Cyclic-di-GMP signalling meets extracellular polysaccharide synthesis in Bacillus subtilis.
In order to resist harmful environmental conditions, many bacteria form multicellular aggregates called biofilms. In these biofilms, they protect themselves in a self-produced matrix consisting of extracellular polysaccharides, proteins and DNA. In many bacteria, biofilm formation is stimulated in the presence of the second messenger cyclic di-GMP. In this issue of Environmental Microbiology Reports, Bedrunka and Graumann have studied matrix production by the proteins encoded in the Bacillus subtilis ydaJKLMN operon. For the first time, they were able to provide a link between c-di-GMP signalling and matrix production in this bacterium. The work demonstrates that the c-di-GMP receptor protein YdaK forms a membrane-bound complex with the YdaM and YdaN proteins, and that this interaction with YdaK is required for polysaccharide production by YdaL, YdaM and YdaN.


Theoretical study of the nuclear spin-molecular rotation coupling for relativistic electrons and non-relativistic nuclei.
A theoretical study of the relation between the relativistic formulation of the nuclear magnetic shielding and spin-rotation tensors is presented. To this end a theoretical expression of the relativistic spin-rotation tensor is formulated, considering a molecular Hamiltonian of relativistic electrons and non-relativistic nuclei. Molecular rotation effects are introduced considering the terms of the Born-Oppenheimer decomposition, which couple the electrons and nuclei dynamics. The loss of the simple relation linking both spectral parameters in the non-relativistic formulation is further analyzed carrying out a perturbative expansion of relativistic effects by means of the linear response within the elimination of the small component approach. It is concluded that relativistic effects on the spin-rotation tensor are less important than those of the nuclear magnetic shielding tensor.


Psychopathological profile and quality of life of patients with oral lichen planus.
Oral lichen planus (OLP) is a chronic, multifocal, sometimes painful, inflammatory disease of the oral mucosa. OLP can predispose development of psycho-emotional disorders. Until now, the relationship between the severity of lichen planus and the psychological profile of patients (psychological well-being, perceived stress and pain coping strategies) has never been studied. Study was conducted on 42 OLP patients. Number of sites involved, severity and activity score of OLP were evaluated. Psychological tests were used to evaluate patients' psycho-emotional condition. The mean duration time of symptomatic OLP was 43 months. We detected that the longer the duration of subjective symptoms, the poorer the quality of life and the higher the level of perceived stress (PSS). Also, the higher the PSS results, the greater the anxiety and depression on Hospital Anxiety and Depression Scale (HADS). Likewise, higher level of depression in HADS was strongly correlated with worse quality of life. (p≤0.05). In this study, we detected a relationship between duration of the disease, level of perceived stress and quality of life. The longer the disease lasts, the higher it tends to catastrophize. This may influence development or increase of the anxiety and depression and may decrease patients' quality of life.


The role of familiarity in the recognition of static and dynamic objects.
Although the perception of our world is experienced as effortless, the processes that underlie object recognition in the brain are often difficult to determine. In this chapter, we review the effects of familiarity on the recognition of moving or static objects. In particular, we concentrate on exemplar-level stimuli such as walking humans, unfamiliar objects and faces. We found that the perception of these objects can be affected by their familiarity; for example the learned view of an object or the learned dynamic pattern can influence object perception. Deviations in the viewpoint from the familiar viewpoint, or changes in the temporal pattern of the objects can result in some reduction of efficiency in the perception of the object. Furthermore, more efficient sex categorization and crossmodal matching were found for familiar than for unfamiliar faces. In sum, we find that our perceptual system is organized around familiar events and that perception is most efficient with these learned events.


A collaborative approach to managing student malingering.
The authors present a case study of a successful collaborative effort to reduce student malingering in a school-based health center and to address the academic and social problems related to overuse of center services. School-based health centers have been identified as important sources of support for teenagers who have emotional and psychological problems, and, in this case, the overuse of a school-based health center is linked to such challenges for a substantial subset of students. It demonstrates that it is possible to identify, based on their status as frequent center users, students with potentially serious academic, family, or personal problems who are at risk for academic failure. The case involves multiple professionals, from a variety of disciplines, who dealt successfully with the problems associated with overuse of center services.


Development of New Reactions Driven by N-O Bond Cleavage: from O-Acyl Hydroxylamines to Tetrodotoxin.
This Account describes new reactions that have been developed in the Johnson laboratories at UNC Chapel Hill enabled by considerations of N-O bond cleavage. Three main case studies are highlighted: the metal-catalyzed electrophilic amination of O-acyl hydroxyl amines, multihetero-Cope rearrangements driven by O-N bond breakage, and merged dearomatization/N=O cycloadditions for the synthesis of complex 4-aminocyclohexanols such as those found in the natural product tetrodotoxin.


Sleep-waking cycle and behaviour after diethyldithiocarbamate in the rat.
Young adult Louis rats were implanted for chronic sleep recording to test the effect of diethyldithiocarbamate (DDC) on sleep. Recordings of EEG and EMG were done continuously for 12 h during the 12 consecutive days. There were 2 days of baseline recording, 3 days of recording with a single daily injection of placebo, 3 days of recording with a single daily injection of DDC (500 mg/kg i.p.), and 3 days of DDC withdrawal recording with placebo injection. Placebo injections did not change the proportion of time spent in different behavioural states. With daily injection of DDC there was an increase in wakefulness, no change in slow-wave sleep and elimination or drastic reduction in paradoxical sleep (PS). There was no PS rebound during the DDC withdrawal days. These results suggest that the reduction of PS produced by DDC and the absence of PS rebound may be due to a lowering in norepinephrine in the brain. In other experiments rats were injected with DDC (500 mg/kg i.p.) daily for 3 days and whole brains were analysed chemically. Norepinephrine was significantly decreased, while 5-hydroxytryptamine, 5-hydroxyindolacetic acid, dopamine and homovanilic acid were unchanged. Seizure activity appeared during relaxed wakefulness in all rats treated with DDC. Taken together it seems that lowering of brain NE is responsible for the appearance of seizure activity and also, for PS reduction. PS reduction might, per se, produce seizure activity.


Correlations between dynamic urethral profilometry and perivaginal pelvic muscle activity.
Of 208 ambulatory female subjects evaluated for complaints of urinary incontinence, complete history, physical findings, and urodynamic data were available on 163 patients allowing correlation of measures of perivaginal muscle activity to urethral profilometry measurement of sphincter strength. Perivaginal measures include pelvic digital exam score as well as vaginal electromyography with a modified perinometer. Urethral profilometry was performed at rest and during pelvic muscle contractions in both supine and standing positions. There was a moderate and significant correlation (r = 0.19 to 0.32) between profilometry measures of voluntary sphincter contractions and perivaginal EMG parameters of endurance peak and area, as well as to the digital test parameters of pressure and displacement. The correlation values between the vaginal EMG and the Digital Test scale of perivaginal strength were higher (r = 0.28 to 0.74). When the patients with pure stress incontinence were stratified by degrees of incontinence (mild, moderate, severe), urethral prolfilometry measures were a more accurate indicator of severity of incontinence than measures of perivaginal strength or the degree of bladder neck mobility as measured by the Q-tip test.


Self-reported alcohol consumption and association to carbohydrate-deficient transferrin and gamma-glutamyltransferase in a random sample of the general population in the Republic of Karelia, Russia and in North Karelia, Finland.
In the present study, alcohol consumption was estimated in a population survey in Pitkäranta in the Republic of Karelia, Russia (RUS) and in the neighbouring province of North Karelia in Finland (FIN) in the spring of 1997 in connection with the National FINRISK Study. Alcohol consumption was evaluated by self-report and by the biological markers carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT). In RUS, elevated CDT values were observed in 36.6% of the men and 17.6% of the women. In FIN, the respective rates were 9.6% and 9.4%, which are similar to average European rates. The prevalence of elevated CDT values seen in RUS is the highest prevalence ever reported in general population surveys. However, the self-reported alcohol consumption was similar in the two regions. These results suggest that alcohol consumption especially in Russia may not be reliably estimated by self-reporting, and that alcohol consumption is relatively high, especially among men, in RUS.


QT Interval in Pregnant and Non-pregnant Women.
Prolongation of QT interval might result in dangerous cardiac arrhythmias, including Torsades de Pointes (TdP), consequently leading to syncope or death. A limited number of studies carried out in this respect to date have shown that QT interval might increase during pregnancy. On the other hand, it has been shown that each pregnancy might result in an increase in the risk of cardiac accidents in patients with long QT interval. Therefore, the present study was undertaken to compare QT intervals in pregnant and non-pregnant women. Pregnant women group consisted of 40 women in the second and third trimesters of pregnancy and the non-pregnant control group consisted of healthy women 18-35 years of age. All the patients underwent standard 12-lead electrocardiogram (ECG). The QT interval was measured for each patient at lead II. The mean corrected QT interval (QTc) and QT dispersions (QTd) were compared between the two groups. Mean heart rates in the pregnant and non-pregnant groups were 98.55±14.09 and 72.53±13.17 beats/minutes (P<0.001). QTd and QTc means were in the normal range in both groups; however, these variables were 49.50±12.80 and 43.03±18.47 milliseconds in the pregnant group and 39.5±9.59 and 40.38±17.20 milliseconds in the control group, respectively (P<0.001). The QT interval was longer in pregnant women compared to non-pregnant women; however, it was in the normal range in both groups. Therefore, it is important to monitor and manage risk factors involved in prolongation of QT interval and prevent concurrence of these factors with pregnancy.


Clinical experience with typhoid vaccine in Thailand.
A brief report of the typhoid vaccine trials in Thailand is reviewed, and discussed in relation to other clinical and field studies.


Critical review of surface-enhanced Raman spectroscopy applications in the pharmaceutical field.
Surface-enhanced Raman spectroscopy (SERS) is a sensitive analytical tool used in the pharmaceutical field in recent years. SERS keeps all the advantages of classical Raman spectroscopy while being is more sensitive allowing its use for the detection and the quantification of low-dose substances contained in pharmaceutical samples. However, the analytical performance of SERS is limited due to the difficulty to implement a quantitative methodology correctly validated. Nevertheless, some studies reported the development of SERS quantitative methods especially in pharmaceutical approaches. In this context, this review presents the main concepts of the SERS technique. The different steps that need to be applied to develop a SERS quantitative method are also deeply described. The last part of the present manuscript gives a critical overview of the different SERS pharmaceutical applications that were developed for a non-exhaustive list of pharmaceutical compounds with the aim to highlights the validation criteria for each application.


Dumbbell structure probe-triggered rolling circle amplification (RCA)-based detection scaffold for sensitive and specific neonatal infection-related small extracellular vesicle (sEV) detection.
Small extracellular vesicles (sEVs) have been reported to play important roles in cell-to-cell communication and are promising biomarkers for the early diagnosis of infections. Therefore, it is in high demand to develop a method that can integrate easy-to-operate sEV isolation and sensitive quantification. We herein propose a novel detection scaffold for sEV isolation via low-speed centrifugation and the quantification of sEVs through DNAzyme-based signal amplification. The detection scaffold is established through dumbbell probe-based RCA (rolling circle amplification), containing repeated CD63 aptamer sections and DNAzyme sections. The original state of the DNAzyme section is locked in a hairpin structure in the detection scaffold. In the presence of sEVs, the CD63 aptamer recognizes and binds with sEVs, leading to the aggregation of sEVs, which can be isolated by low-speed centrifugation and the exposure of the DNAzyme section. After the catalytic fluorescence signal generation from the DNAzyme-based molecular beacon (MB) cleavage, the method exhibited a detection range of 102 to 106 particles per μL. Considering the high sensitivity and wash-free and easy-to-operate features, the strategy reported herein paves a new avenue for the effective determination of sEVs and other membrane biomolecules in fundamental and applied research.


Microring resonator photodetector for enhancement in L-band performance.
We proposed a microring resonator (MRR) enhanced photodetector (PD) structure. Resonance wavelength enhanced by the MRR amplifies the PD response. At L-band wavelengths, responsivity was doubled for an ultra-short germanium PD of 4 µm employing the MRR structure. Data rates of up to 40 Gb/s were also demonstrated at 1600 nm.


Novel Synthesized Nanofibrous Scaffold Efficiently Delivered hBMP-2 Encoded in Adenoviral Vector to Promote Bone Regeneration.
Treatment of bone defect, especially large bone defect, is still a challenge for physicians clinically. Bone morphogenetic protein 2 (BMP-2) can induce osteoblast differentiation and promote new bone formation. Recently, nanomaterials have been widely used as a carrier to hold and deliver biomolecules, like human bone morphogenetic protein 2 gene (hBMP-2) in target cells/tissues. Most nanomethods, however, need further modification in order to work more reliably in clinical applications. Therefore, in this study, we created a novel poly(lactic-co-glycolic acid [PLGA]) nanofibrous scaffold using an electrospinning technique; then, using a lyophilization process to allow nanofibrous scaffold to adsorb hBMP-2 adenoviral vector, AdCMV-hBMP2. Results indicate that the lyophilized poly(lactic-co-glycolic acid) nanofibrous scaffold/AdCMVhBMP2 can efficiently release and transduce cells in vitro and in vivo, and secrete functional hBMP-2 to promote osteogenic differentiation in vitro, and new bone generation in vivo. Importantly, the amount of newly formed bone covered >80% of the bone defect area 8 weeks post-implantation in vivo, in which the defect could not be repaired without any treatment in general. Our data demonstrate that the lyophilized PLGA nanofibrous scaffold/AdCMV-hBMP2 created herein stably and efficiently release functional viral vector to transduce local cells, resulting in secretion of hBMP-2 and promote new bone formation in vivo. Our new nanodelivery method has potential clinical application for the repair of large bone defects.


Effect of polyelectrolyte structure on protein-polyelectrolyte coacervates: coacervates of bovine serum albumin with poly(diallyldimethylammonium chloride) versus chitosan.
Electrostatic interactions between synthetic polyelectrolytes and proteins can lead to the formation of dense, macroion-rich liquid phases, with equilibrium microheterogeneities on length scales up to hundreds of nanometers. The effects of pH and ionic strength on the rheological and optical properties of these coacervates indicate microstructures sensitive to protein-polyelectrolyte interactions. We report here on the properties of coacervates obtained for bovine serum albumin (BSA) with the biopolyelectrolyte chitosan and find remarkable differences relative to coacervates obtained for BSA with poly(diallyldimethylammonium chloride) (PDADMAC). Coacervation with chitosan occurs more readily than with PDADMAC. Viscosities of coacervates obtained with chitosan are more than an order of magnitude larger and, unlike those with PDADMAC, show temperature and shear rate dependence. For the coacervates with chitosan, a fast relaxation time in dynamic light scattering, attributable to relatively unrestricted protein diffusion in both systems, is diminished in intensity by a factor of 3-4, and the consequent dominance by slow modes is accompanied by a more heterogeneous array of slow apparent diffusivities. In place of a small-angle neutron scattering Guinier region in the vicinity of 0.004 A-1, a 10-fold increase in scattering intensity is observed at lower q. Taken together, these results confirm the presence of dense domains on length scales of hundreds of nanometers to micrometers, which in coacervates prepared with chitosan are less solidlike, more interconnected, and occupy a larger volume fraction. The differences in properties are thus correlated with differences in mesophase structure.


Design and synthesis of a novel series of 1,2-disubstituted cyclopentanes as small, potent potentiators of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors.
2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) potentiators are ligands that act as positive allosteric modulators at the AMPA receptors. We recently disclosed a novel series of 2-arylpropylsulfonamides that were potent potentiators of responses mediated through AMPA receptors. To further define the structural requirements for activity in this series, new ring-constrained analogues were prepared and a new stereocenter was introduced. The potentiating activity was highly dependent on the stereochemistry at the 2-position of the disubstituted cyclopentane and was independent of the relative stereochemistry at the 1-position. Compound (R,R)-10 represents a potent, novel potentiator of iGluR4 flip receptors (EC(50) = 22.6 nM).


RNA Interference as a Therapeutic Strategy for the Treatment of Liver Diseases.
RNA interference has emerged as an innovative technology for gene silencing that degrades mRNAs complementary to the antisense strands of double-stranded, short interfering RNAs (siRNAs). Its therapeutic application has important advantages over small-molecule drugs since offers the possibility of targeting virtually all genes and allows selective silencing of one or several genes. So far, a relative small proportion of cellular proteins can bind and respond to chemical drugs. Based on that, RNA interference-mediated gene silencing is widely considered as a crucial breakthrough in molecular biology with a direct translation to medicine. The liver has been widely chosen as a model system for the development of RNA interference therapy due to the convenience and availability of effective delivery into this tissue. Numerous preclinical models have revealed promising results, but the safety of this technology remains the primary challenge in developing siRNA based treatments. Liver diseases comprise a broad spectrum of genetic and non-genetic pathologies including acute fulminant liver injury that demands urgent medical care, or chronic pathologies such as nonalcoholic fatty liver (NAFLD), alcoholic liver disease, liver cirrhosis, viral hepatitis and hepatocellular carcinoma (HCC). In some cases restoration of liver function is not possible and alternatives to liver transplantation offering novel and efficient therapeutic approaches are urgently needed. In this review, we describe recent insights on the advantages of using RNA interference in preclinical settings as a targeted strategy with potential to markedly improve the treatment of liver diseases.


[Strategy for treatment of acute myocardial infarction after coronary revascularization with integrative medicine].
Since 1980s, the treatment of acute myocardial infarction (AMI) has entered the era of revascularization of infarction-related artery. There is still shortness of ideal strategy in modern medicine for comprehensive intervention aiming at the complex pathological links such as myocardial no-reflow, slow-reflow and reperfusion injury after revascularization. Therefore, combining traditional Chinese medicine with modern medicine, selecting effective drugs or prescriptions, and exploring their effective ingredients and portions of them as well as the mechanisms of the combinations in promoting myocardial capillary angiogenesis and cardiac muscle cell differentiation, and regulating the repairing process of inflammatory reaction will provide new intervening target directions and comprehensive intervening patterns for the prevention and treatment of AMI.


Behçet: the syndrome.
Behçet's syndrome (BS) is a systemic vasculitis characterized by a relapsing and remitting course. It can involve the skin, mucosa, joints, vessels (arteries and/or veins), eyes, and nervous and gastrointestinal systems, and so is referred to as a syndrome rather than as a unique and nosologically distinct condition. These involvements may present alone or co-exist in the same patient. Although all the possible combinations of the above-mentioned manifestations may occur, clusters of commonly co-existing involvements (also referred to as 'disease phenotypes') have been suggested, namely 'mucocutaneous and articular', 'peripheral vascular and extra-parenchymal neurological' and 'parenchymal neurological and ocular' phenotypes have been described. Patient-specific demographic and genetic features have been described as positively or negatively associated with specific disease phenotypes. This review will focus on the different clinical features of Behçet's syndrome, summarizing current evidence on the distinct disease manifestations as well as the major phenotypes.


[D-penicillamine--a retrospective view].
D-penicillamine was discovered in 1943. At the beginning of the 1960s it was introduced into the treatment of rheumatoid arthritis. Since then, its efficacy and adverse effects have become very well known. According to this experience, D-penicillamine, similarly to gold, is acknowledged as a disease-modifying drug in the treatment of rheumatoid arthritis.


Effectiveness of oral health education methods on oral hygiene in children and adolescents with visual impairment: A systematic review.
Conventional methods of oral health education (OHE) are not suitable for children with visual impairment, as these methods usually involve visual demonstration with models or plaque-disclosing dyes. To systematically review the literature to support the best approach for providing OHE to children and adolescents with visual impairment. A systematic search of five electronic databases and grey literature was conducted. Randomized controlled trials that compared different OHE methods in children and adolescents with visual impairment were included. The Cochrane risk-of-bias tool (RoB 2) was used for the risk-of-bias assessment. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to determine the certainty of evidence. Nine randomized controlled trials with a total of 804 participants were included in this review. Seven OHE methods were compared. Seven studies were assessed to be at high risk of bias, one study was assessed to have some concerns, and one study was assessed to be at low risk of bias. The overall certainty of evidence was very low according to GRADE. There was insufficient evidence to recommend a particular method of OHE as more effective in improving the oral hygiene of children with visual impairment, but combination methods may show similar or better results.


Two-Year Complete Remission of Diffuse Large B-Cell Lymphoma in an Immunological Nonresponder HIV-Infected Patient: Case Report.
HIV-infected patients are affected significantly more frequently by all types of lymphoma, with diffuse large B-cell lymphoma (DLBCL) as the most prevalent histological type. Since the introduction of combination antiretroviral therapy (cART) morbidity and mortality of DLBCL has been markedly reduced, which is primarily interpreted as a result of the drug-mediated immune reconstitution. We present a previously healthy, 44-year-old HIV-infected man with DLBCL of the oral cavity, treated with immunochemotherapy and cART. During HIV-directed treatment, despite the successful virologic response, a satisfactory immunological response was not achieved. However, the patient had a 2-year complete remission after first-line treatment of DLBCL. Response to cART strongly predicts outcome in patients with DLBCL. Close monitoring of HIV-directed therapy efficacy, especially as to achievement of successful virologic response, independently associated with prolonged survival, is essential for estimating future DLBCL treatment strategies.


Draft Genome Sequence of Carbaryl-Degrading Soil Isolate Pseudomonas sp. Strain C5pp.
We report the draft genome sequence of carbaryl-degrading Pseudomonas sp. strain C5pp. Genes encoding salicylate and gentisate metabolism, large amounts of oxygenase, nitrogen metabolism, and heavy metal tolerance were identified. The sequence will provide further insight into the biochemical and evolutionary aspects of carbaryl degradation.


Tissue shrinkage and stereological studies.
Shrinkage often takes place in biological tissues during the different phases of preparation for microscopy. This can have detrimental effects on the stereological estimates, even when unbiased procedures are used. There are different types of shrinkage, and an awareness of them is essential when designing stereological studies. Some forms of shrinkage can be taken into account to ensure the unbiasedness of an estimator, but some cannot and should be avoided. Dimensional changes that take place during fixation, embedding, sectioning, mounting, and staining can seriously compromise one's ability to make assumption-free estimates of length and surface, but there are steps that can be taken to reduce the impact of these changes on estimates of object number and size. This article describes types of shrinkage and the effects of shrinkage on estimators of object number. It gives an example of how to make a number-weighted correction of section thickness and also discusses the consequences of shrinkage for the validity of estimates of object size.


Epilepsy and intellectual disability linked protein Shrm4 interaction with GABABRs shapes inhibitory neurotransmission.
Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABAB receptors (GABABRs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABABR activity causing increased anxiety-like behaviour and susceptibility to seizures. Moreover, Shrm4 influences hippocampal excitability by modulating tonic inhibition in dentate gyrus granule cells, in a process involving crosstalk between GABABRs and extrasynaptic δ-subunit-containing GABAARs. Our data highlights a role for Shrm4 in synaptogenesis and in maintaining GABABR-mediated inhibition, perturbation of which may be responsible for the involvement of Shrm4 in cognitive disorders and epilepsy.


Harnessing nursing to diminish ageism.
The common practice of making fun of aging and older people demonstrates that ageism towards older people is socially acceptable. It is so accepted that even those of us who are aging or have moved into the 'third act' believe and fear the negative stereotypes that growing old is linked with physical and mental deterioration, dependence, and less social value. Ageism is evident in work places, family relationships, when older people purchase goods and services, in health and social institutions and extends throughout professions that work with older people. We explore how nurses-the largest group of healthcare professions- may be inadvertently perpetuating negative perceptions about older people in nursing practice, nursing education, and through common misconceptions about what gerontological nursing means. This is discussion paper using the literature. We suggest that nursing education is well situated to diminish negative perspectives of ageing by incorporating theories of life-course and harmonious aging into the holistic perspective of individuals that nursing is well known for. Greater understanding about the diversity of ageing and the context that have influenced older persons could encourage nurses to treat them holistically with dignity, which would ultimately improve older people's experiences. Improving older persons' experiences is like paying it forward, as we all are ageing and if we are to have a different experience when we are old, it is necessary to diminish stereotypes about ageing, and work towards inclusion of older people in social and healthcare institutions. It is important for nurses, particularly those in nursing education, to support the incorporation of a life course and harmonious view of aging in which the social, political, and environmental context of individuals are viewed as part of the difference of ageing.


Cytomegalovirus antigenemia is observed more frequently following allogeneic peripheral blood stem cell transplantation compared to bone marrow transplantation.
One of the major complications following hematopoietic stem cell transplantation (HSCT) is cytomegalovirus (CMV) infection. In our institution, three methods have been applied routinely for the diagnosis of CMV antigenemia (CMV-Ag): 1. Direct immunofluorescence microscopic (IFM) examination; 2. Flow cytometric (FC) analysis; and 3. Serological investigation. We were able to detect CMV-Ag by FC in 18 out of 75 transplanted cases. In 14 of these, positivity was confirmed by IFM as well. CMV-Ag was detected as positive by FC in samples from peripheral blood (14 cases) and/or bronchoalveolar lavage (BAL) fluid (4 cases). Eighteen patients had been transplanted [peripheral blood stem cell transplantation (PBSCT)/bone marrow transplantation (BMT): 16/2]. CMV-Ag was detected in 34% of PBSCTs and 7% of BMTs (p<0.008). Antigenemia was observed at a median of 4.5 months. In most of the patients, graft-versus-host disease (GVHD) was accompained by CMV-Ag. The ratio of acute GVHD/chronic GVHD was 6/10. Out of 18 CMV-Ag positive patients, 16 also had signs of infection. They were all positive by IFM as well. The two methods of CMV-Ag detection were correlated (r=0.619, p<0.0001). An important finding is the higher frequency of CMV-Ag and GVHD in patients who had received PBSCT.


A six-month evaluation of the VivaSight™ video double-lumen endotracheal tube after introduction into thoracic anaesthetic practice at a single institution.
For a six-month period, all airway options used for non-emergent patients undergoing thoracic surgery requiring one-lung ventilation at a single institution were assessed after introduction of the VivaSight™ double-lumen endotracheal tube (VivaSight-DL), a novel double-lumen tube with an integrated camera. This device displays a continuous view of the position of the tube relative to the carina. A total of 72 patients had lung separation with the VivaSight-DL. Lung separation was achieved on first attempt without additional manipulation in 85% of cases. In only three cases (4%) was a fibreoptic bronchoscope required, in each instance to reposition the tube after intraoperative dislodgement. The VivaSight-DL represents a novel method of one-lung ventilation allowing rapid identification of intraoperative airway problems and reducing the need for fibreoptic bronchoscopy.


Grifolin induces autophagic cell death by inhibiting the Akt/mTOR/S6K pathway in human ovarian cancer cells.
Grifolin, a secondary metabolic product isolated from the mushroom Albatrellus confluence, has been reported to possess antitumor activities in various tumors. To date, no report exists on the role of autophagy in grifolin-treated human ovarian cancer cells. In the present study, we investigated the effect and the mechanism of autophagy in ovarian cancer. Ovarian cancer cell lines A2780 and SKOV3 were treated with grifolin. Cell proliferation was assessed by MTT assay and the autophagic effect was determined using flow cytometry, electron microscopy, immunofluorescence staining and GFP-LC3 puncta formation assay. The expression of autophagy markers and the main autophagy-associated Akt/mTOR/S6K pathway proteins were measured by western blot analysis. MTT assay indicated that grifolin inhibits the proliferation of human ovarian cancer cell lines A2780 and SKOV3. Flow cytometry, electron microscopy, immunofluorescence and GFP-LC3 puncta formation assay proved that grifolin induces autophagic cell death in human ovarian cancer. The results of the western blot analysis suggested that grifolin treatment leads to upregulation of autophagy markers LC3B, Atg7, Beclin-1 along with downregulation of P62. In addition, the proteins of the pathways p-Akt, p-mTOR, p-p70S6K and p-4E-BP1 were downregulated while the total of these proteins remained unaffected. The present study indicated that grifolin could induce autophagic cell death in human ovarian cancer by inhibiting the Akt/mTOR/S6K pathway.


Use of antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary prosthetic vascular graft infections.
This study was conducted to assess the efficacy of antibiotic-loaded polymethylmethacrylate (PMMA) beads in the management of lower extremity extracavitary prosthetic arterial graft infection. This was a retrospective review of 34 patients treated for vascular surgical site (VSS) infections involving 36 prosthetic lower extremity arterial bypasses using antibiotic-loaded PMMA beads and culture-specific parenteral antibiotics for 4 to 6 weeks. Sites of graft infection were explored, debrided, and cultured. As determined from the results of Gram's stains of VSS purulence, PMMA powder was polymerized with an antibiotic (vancomycin, daptomycin, or tobramycin/gentamicin, or a combination), molded into a chain of beads, and implanted adjacent to the infected graft after debridement and pulsed-spray antibacterial lavage. All wounds were closed primarily with planned exploration to verify sterilization before a graft preservation or in situ replacement procedure. Treatment outcomes, including wound sterilization, were analyzed based on tissue culture isolates, procedures for persistent infection, and freedom from graft infection. Cultures isolated 42 pathogens, (32 gram-positive, 9 gram-negative, 1 Candida albicans) with methicillin-resistant Staphylococcus aureus (MRSA) cultured from 16 (44%) of 36 surgical site infections. As determined from the initial operative Gram's stain or a prior culture result, vancomycin PMMA beads were implanted in 29 of 36 VSS infections at the first procedure; daptomycin (n = 4) or tobramycin (n = 3) beads were implanted in the rest. Repeat VSS exploration and culture results led to an average of 2.5 antibiotic bead replacements before definitive treatment. A sterile (no growth on tissue culture) VSS was achieved in 87% of cases before a graft preservation (n = 16) or in-situ replacement of an infected graft (n = 20) procedure. No patient deaths occurred. Early and late limb salvage was 100%. Infection recurred in 4 (11%) VSSs during a mean 23-month follow-up period, one within 3 months owing to unrecognized bowel injury associated with in situ replacement of an aortofemoral graft limb. Antibiotic-loaded PMMA beads may be a useful adjunct in the contemporary surgical management of VSS infection involving a prosthetic graft. Wound sterilization was achieved in most VSSs before graft preservation or an in-situ replacement procedure, including infections caused by MRSA, a pathogen isolated in half of the extracavitary prosthetic graft infections. This preliminary trial shows the potential benefit of this new technique, but further study is required to prove efficacy.


Genome-wide DNA methylation at birth in relation to in utero arsenic exposure and the associated health in later life.
In utero arsenic exposure may alter fetal developmental programming by altering DNA methylation, which may result in a higher risk of disease in later life. We evaluated the association between in utero arsenic exposure and DNA methylation (DNAm) in cord blood and its influence in later life. Genome-wide DNA methylation in cord blood from 64 subjects in the Taiwanese maternal infant and birth cohort was analyzed. Robust regressions were applied to assess the association of DNA methylation with in utero arsenic exposure. Multiple testing was adjusted by controlling false discovery rate (FDR) of 0.05. The DAVID bioinformatics tool was implemented for functional annotation analyses on the detected CpGs. The identified CpGs were further tested in an independent cohort. For the CpGs replicated in the independent cohort, linear mixed models were applied to assess the association of DNA methylation with low-density lipoprotein (LDL) at different ages (2, 5, 8, 11 and 14 years). In total, 579 out of 385,183 CpGs were identified after adjusting for multiple testing (FDR = 0.05), of which ~60% were positively associated with arsenic exposure. Functional annotation analysis on these CpGs detected 17 KEGG pathways (FDR = 0.05) including pathways for cardiovascular diseases (CVD) and diabetes mellitus. In the independent cohort, about 46% (252 out of 553 CpGs) of the identified CpGs showed associations consistent with those in the study cohort. In total, 11 CpGs replicated in the independent cohort were in the pathways related to CVD and diabetes mellitus. Via longitudinal analyses, we found at 5 out of the 11 CpGs methylation was associated with LDL over time and interactions between DNA methylation and time were observed at 4 of the 5 CpGs, cg25189764 (coeff = 0.157, p-value = 0.047), cg04986899 (coeff. For interaction [coeff.int] = 0.030, p-value = 0.024), cg04903360 (coeff.int = 0.026, p-value = 0.032), cg08198265 (coeff.int = -0.063, p-value = 0.0021), cg10473311 (coeff.int = -0.021, p-value = 0.027). In utero arsenic exposure was associated with cord blood DNA methylation at various CpGs. The identified CpGs may help determine pathological epigenetic mechanisms linked to in utero arsenic exposure. Five CpGs (cg25189764, cg04986899, cg04903360, cg08198265 and cg10473311) may serve as epigenetic markers for changes in LDL later in life.


Cross-reactivity in flavivirus serology: new implications of an old finding?
To investigate the influence of pre-existing antibodies against tick-borne encephalitis (TBE) or yellow fever (YF) viruses on dengue virus antibody test results, we examined sera from vaccinees and from individuals with previous TBE virus infection. Distinct IgG antibody cross-reactivity was found in about 15.1% in the YF-vaccinated group and in about 9.5% in the TBE-vaccinated group. Altogether 15 out of a total of 80 samples tested (18.8%) had detectable dengue virus IgG antibody titres. The serum samples from patients with acute TBE virus infection not only had the highest anti-TBE virus antibodies but were also highly cross-reactive against dengue virus antigens. The high cross-reactivity rate of YF and TBE antibody-positive sera in dengue virus antibody assays should be taken into account in the interpretation of laboratory tests for the diagnosis of flavivirus infections and when undertaking seroepidemiological surveys.


Electrocardiographic changes following intracranial haemorrhage: a retrospective cohort study.
To improve the understanding of the association between electrocardiographic (ECG) abnormalities and clinical outcomes of patients with all types of intracranial hemorrhage (ICH). A retrospective cohort study was conducted in a tertiary healthcare hospital on patients with ICH without cardiac disease or renal disease requiring dialysis. Demographic and clinical data were collected from hospital records. ECG record were obtained within 24 hours of presentation and prior to treatment. Records were interpreted for this study by a cardiologist blinded to other data. Assessment of 291 patients (228 adults and 63 children) showed that subdural hemorrhage was the most common type of ICH (31.6%) followed by intraparenchymal hemorrhage (23.0%). ECG records were available for 98 patients. ECG abnormalities were most commonly nonspecific ST-segment changes (32.6%). In adults, history of neurological disease was associated with atrioventricular block (p=.004) and QTc prolongation (p=.041). Pediatric patients exhibited associations between ST-segment changes (p=.045) and sinus tachycardia (p=.027) and type of ICH. However, ECG changes were not statistically associated with clinical outcomes in adults or children. Significant ECG changes frequently occurred in patients with all types of ICH but did not consistently predict the outcome in this study. Close observation of patients is still recommended to detect ECG changes that could affect the treatment.


Unravelling Peritoneal Carcinomatosis Using Cross-Sectional Imaging Modalities.
Peritoneal carcinomatosis (PC) refers to malignant epithelial cells that spread to the peritoneum, principally from abdominal malignancies. Until recently, PC prognosis has been considered ill-fated, with palliative therapies serving as the only treatment option. New locoregional treatments are changing the outcome of PC, and imaging modalities have a critical role in early diagnosis and disease staging, determining treatment decision making strategies. The aim of this review is to provide a practical approach for detecting and characterizing peritoneal deposits in cross-sectional imaging modalities, taking into account their appearances, including the secondary complications, the anatomical characteristics of the peritoneal cavity, together with the differential diagnosis with other benign and malignant peritoneal conditions. Among the cross-sectional imaging modalities, computed tomography (CT) is widely available and fast; however, magnetic resonance (MR) performs better in terms of sensitivity (92% vs. 68%), due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR mainly depends on the primary tumour histology; in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights into the tumour origin. The timepoint of tumour evolution, previous or ongoing treatments, and the peritoneal spaces in which they occur also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is essential in the detection and characterisation of peritoneal deposits. Several benign and malignant conditions show similar imaging features that overlap those of PC, making differential diagnosis challenging. Knowledge of peritoneal anatomy and primary tumour histology is crucial, but one must also consider clinical history, laboratory findings, and previous imaging examinations to achieve a correct diagnosis. In conclusion, to correctly diagnose PC in cross-sectional imaging modalities, knowledge of peritoneal anatomy and peritoneal fluid flow characteristics are mandatory. Peritoneal deposit features reflect the primary tumour characteristics, and this specificity may be helpful in its identification when it is unknown. Moreover, several benign and malignant peritoneal conditions may mimic PC, which need to be considered even in oncologic patients.


Subchronic hepatotoxicity evaluation of 2,3,4,6-tetrachlorophenol in sprague dawley rats.
Male Sprague Dawley rats were exposed to 2,3,4,6-tetrachlorophenol (TCP) for 5 days, 2 weeks, 4 weeks, or 13 weeks. TCP was administered by gavage at doses of 0, 10, 25, 50, 100, or 200 mg/kg/day. Endpoints evaluated included clinical observations, body weights, liver weights, serum chemistry, blood TCP, gross pathology, and liver histopathology. There were no TCP exposure-related clinical signs of toxicity. Mean body weight decreased 12-22% compared to control in the 100 and 200 mg/kg/day groups. Serum ALT concentrations were increased in rats of the 200 mg/k/day. Liver weight increases were both dose- and exposure time-related and statistically significant at ≥25 mg/kg/day. Incidence and severity of centrilobular hepatocytic vacuolation, hepatocyte hypertrophy, and single cell hepatocytic necrosis were related to dose and exposure time. Following 13 weeks of exposure, bile duct hyperplasia and centrilobular and/or periportal fibrosis were observed in rats primarily of the highest TCP dose group. Blood TCP concentrations increased with dose and at 13 weeks ranged from 1.3 to 8.5 μg/mL (10 to 200 mg/kg/day). A NOAEL of 10 mg/kg/day was selected based on the statistically significant incidence of hepatocyte hypertrophy at doses ≥25 mg/kg/day.


Structural basis of potent and broad HIV-1 fusion inhibitor CP32M.
CP32M is a newly designed peptide fusion inhibitor possessing potent anti-HIV activity, especially against T20-resistant HIV-1 strains. In this study, we show that CP32M can efficiently inhibit a large panel of diverse HIV-1 variants, including subtype B', CRF07_BC, and CRF01_AE recombinants and naturally occurring or induced T20-resistant viruses. To elucidate its mechanism of action, we determined the crystal structure of CP32M complexed with its target sequence. Differing from its parental peptide, CP621-652, the (621)VEWNEMT(627) motif of CP32M folds into two α-helix turns at the N terminus of the pocket-binding domain, forming a novel layer in the six-helix bundle structure. Prominently, the residue Asn-624 of the (621)VEWNEMT(627) motif is engaged in the polar interaction with a hydrophilic ridge that borders the hydrophobic pocket on the N-terminal coiled coil. The original inhibitor design of CP32M provides several intra- and salt bridge/hydrogen bond interactions favoring the stability of the helical conformation of CP32M and its interactions with N-terminal heptad repeat (NHR) targets. We identified a novel salt bridge between Arg-557 on the NHR and Glu-648 of CP32M that is critical for the binding of CP32M and resistance against the inhibitor. Therefore, our data present important information for developing novel HIV-1 fusion inhibitors for clinical use.


Rapid characterization of chemical constituents of Platycodon grandiflorum and its adulterant Adenophora stricta by UPLC-QTOF-MS/MS.
Platycodon grandiflorum (PG) is extensively used for treating cough, excessive phlegm, sore throat, bronchitis and asthma, whereas Adenophora stricta (AS) is commonly used to reduce phlegm, clear lung and tonify stomach. Due to similar appearances, PG is sometimes adulterated with cheap AS so as to gain profits. And this will inevitably result in different pharmacological property. In order to further clarify the differences in the chemical composition of these two Chinese herbs, the ultra-high performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry coupled with UNIFI platform was used to establish a reliable, simple, sensitive and rapid analytical method. Seventy-five compounds, including triterpenoid saponins, organic acids, flavonoids, steroids, phenols, etc., were identified from PG based on MSE data and retention time under the optimized conditions. Meanwhile, 57 compounds including triterpenoid saponins, organic acids, steroids, phenols, alkaloids, etc. were identified from AS. Among all the identified compounds, there were only 14 common components (mainly organic acids) existing in two herbs, and most of the other chemical compositions are totally different between the two herbs. Based on the results, AS cannot substitute for PG. In addition, PG adulterated with AS will lead a poor efficacy in clinical application. In addition, the systematic comparison of similarities and differences between two Chinese herbs will provide reliable characterization profiles to clarify the pharmacological fundamental substances.


Comparative study on heat stability and functionality of camel and bovine milk whey proteins.
Heat stability, emulsifying, and foaming properties of camel whey have been investigated and compared with that of bovine whey. Camel whey is similar to bovine whey in composition, but is deficient in beta-lactoglubulin (beta-LG), a major component of bovine whey. Whether the deficiency in beta-LG will affect stability and functional properties is not yet known. Substantial information on the functional properties of bovine milk whey proteins is available; however, there is little research done on functional properties of camel whey proteins. Therefore, the objective of this study was to investigate the heat stability, emulsifying, and foaming characteristics of camel whey proteins. Calorimetric studies showed no significant difference in heat stability between bovine and camel whey proteins in liquid form. Upon drying, thermograms indicated that the 2 proteins are different in composition and thermal stability. The difference is represented in the absence of beta-LG and the occurrence of protein denaturation peak at a lesser temperature in camel whey. The first marginal thermal transition in bovine whey appeared at 81 degrees C, followed by 2 other transitions at 146 and 198 degrees C. For camel whey, the transitions appeared at 139, 180, and 207 degrees C respectively. The first marginal denaturation peak in bovine whey is due to beta-LG, which is essentially absent in camel whey, while the second peak is due to the mixture of alpha-lactalbumin, serum albumin, and possibly part of the partially stabilized beta-LG structure during the denaturation process. Because camel whey is deficient in beta-LG, the denaturation peak at 139 must be due to the mixture of alpha-lactalbumin and camel serum albumin. In both proteins, the highest thermal transition is due to sugars such as lactose. The solubility study has shown that camel whey is more sensitive to pH than bovine milk whey and that heat stability is lowest near the isoelectric point of the proteins at pH 4.5. The sensitivity to pH resulted in partial denaturation and increased tendency to aggregate, which caused poor and unstable emulsion at pH 5. Both bovine and camel whey proteins have demonstrated good foaming properties; however, the magnitudes of these properties were considerably greater in bovine milk for all of the conditions studied.


Aryl Hydrocarbon Receptor-interacting Protein-like 1 Is an Obligate Chaperone of Phosphodiesterase 6 and Is Assisted by the γ-Subunit of Its Client.
Phosphodiesterase 6 (PDE6) is the effector enzyme in the phototransduction cascade and is critical for the health of both rod and cone photoreceptors. Its dysfunction, caused by mutations in either the enzyme itself or AIPL1 (aryl hydrocarbon receptor-interacting protein-like 1), leads to retinal diseases culminating in blindness. Progress in research on PDE6 and AIPL1 has been severely hampered by failure to express functional PDE6 in a heterologous expression system. Here, we demonstrated that AIPL1 is an obligate chaperone of PDE6 and that it enables low yield functional folding of cone PDE6C in cultured cells. We further show that the AIPL1-mediated production of folded PDE6C is markedly elevated in the presence of the inhibitory Pγ-subunit of PDE6. As illustrated in this study, a simple and sensitive system in which AIPL1 and Pγ are co-expressed with PDE6 represents an effective tool for probing structure-function relationships of AIPL1 and reliably establishing the pathogenicity of its variants.


Seasonal changes in gene expression represent cell-type composition in whole blood.
Seasonal patterns in behavior and biological parameters are widespread. Here, we examined seasonal changes in whole blood gene expression profiles of 233 healthy subjects. Using weighted gene co-expression network analysis, we identified three co-expression modules showing circannual patterns. Enrichment analysis suggested that this signal stems primarily from red blood cells and blood platelets. Indeed, a large clinical database with 51 142 observations of blood cell counts over 3 years confirmed a corresponding seasonal pattern of counts of red blood cells, reticulocytes and platelets. We found no direct evidence that these changes are linked to genes known to be key players in regulating immune function or circadian rhythm. It is likely, however, that these seasonal changes in cell counts and gene expression profiles in whole blood represent biological and clinical relevant phenomena. Moreover, our findings highlight possible confounding factors relevant to the study of gene expression profiles in subjects collected at geographical locations with disparaging seasonality patterns.


Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward.
The recreational drug, Salvinorin A, derived from the plant of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. The abuse of selective k-agonists is a novel phenomenon, the mechanism of which is not fully understood. We investigated salvinorin A given SC on the conditioned place preference (.05-160 microg/kg) and intracerebroventricular (ICV) self-administration (.01-1 microg/infusion) paradigms, in Wistar rats. The present results demonstrate the rewarding effects of Salvinorin A in a range of doses between .1 and 40 microg/kg SC for conditioned place preference test and .1-.5 microg/infusion for ICV self-administration. Highest doses (160 microg/kg for conditioned place preference test and 1 microg/infusion for ICV self-administration) were aversive. The rewarding effect was antagonized by intraperitoneal (IP) pretreatment with the cannabinoid CB(1) receptor antagonist, rimonabant [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro phenyl)-4 methyl pyrazole 3-carboxamide] (1 mg/kg), and the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) (10 mg/kg). In the shell of nucleus accumbens, dopamine extracellular levels were increased after administration of salvinorin A (40 microg/kg SC), reaching a maximum value of about 150%. These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-opioid and (endo)cannabinoid system in rats.


Mg-Zr Cosubstituted Ta3N5 Photoanode for Lower-Onset-Potential Solar-Driven Photoelectrochemical Water Splitting.
In p/n photoelectrochemical (PEC) cell systems, a low onset potential for the photoanode, as well as a high photocurrent, are critical for efficient water splitting. Here, we report a Mg-Zr cosubstituted Ta3N5 (Ta3N5:Mg+Zr) photoanode, designed to provide a more negative onset potential for PEC water splitting. The anodic photocurrent onset on Ta3N5:Mg+Zr was 0.55 V(RHE) under AM 1.5G-simulated sunlight, which represented a negative shift from the ca. 0.8 V(RHE) for pure Ta3N5. This negative shift in the onset potential of PEC water splitting was attributed to the change in the bandgap potential due to partial substitution by the foreign ions Mg(2+) and/or Zr(4+).


Expression of P1-450 and P3-450 DNA coding sequences as enzymatically active cytochromes P-450 in mammalian cells.
Two cDNA clones representing the mRNA coding sequences for mouse cytochromes P1-450 and P3-450 were inserted into the thymidine kinase gene of the wild-type vaccinia virus under the control of the vaccinia virus promoter. Murine and human cells infected with each of the resulting infectious recombinant viruses efficiently expressed their respective P-450 proteins. The newly synthesized protein products are translocated into the microsomes, and their characterization by immunochemical analysis indicates that the sizes of the polypeptides expressed were indistinguishable from their cytochrome P-450 counterparts found in mammalian liver microsomes. Functional analysis of each of the proteins by spectral and enzymatic analysis indicates that the expressed proteins have incorporated heme, and the holoenzymes displayed catalytic activities characteristic of their respective cytochrome P-450 enzymes. Thus, this system can be used to produce properly processed and catalytically active P-450 gene products in a wide variety of cells. The remarkable fidelity of expression and processing of these enzymes suggests that the vaccinia virus recombinants can be used for a wide variety of studies, including analysis of the effects of defined mutations produced in vitro, and directly correlate the structure/activity relationships of the cytochrome P-450 enzymes.


Block duplications of a zeta-zeta-alpha-theta gene set in the rabbit alpha-like globin gene cluster.
In order to understand the coordinate regulation between the alpha-like and beta-like globins during the developmental switches in hemoglobin synthesis, we have studied the rabbit alpha-like globin gene family. A cluster of six linked genes arranged 5'-zeta 1-alpha 1-theta 1-zeta 2-zeta 3-theta 2-3' has been isolated as a set of overlapping clones from a library of rabbit genomic DNA. Blot-hybridization analysis of genomic DNA not only confirms this linkage arrangement but also reveals the presence of additional zeta and theta genes. We propose that this gene cluster was generated by a block duplication of a set of alpha-like genes; the proposed duplication unit is zeta-zeta-alpha-theta. Further duplications of a zeta-zeta-theta set are also proposed to have occurred. As expected for a duplicated locus, the rabbit alpha-like gene cluster contains long blocks of internal homology. The Z homology block is about 7.2 kilobase pairs long and contains the zeta genes; the T homology block is about 4.7 kilobase pairs long and contains a theta gene. Surprisingly, both Z and T homology blocks are flanked by a common junction sequence (J) which contains a region very similar to the 3'-untranslated sequence of an alpha-globin gene. Analysis of the J sequences suggests a recombination mechanism by which the alpha gene could have been deleted from the second set of genes in the cluster (zeta 2-zeta 3-theta 2). The relationships among the genes in characterized alpha-like gene clusters in mammals are summarized. The rabbit gene cluster differs from those of other mammals principally in the loss of a gene orthologous to the human psi alpha 1 and in the block duplication of the zeta-zeta-alpha-theta gene set.


The structure of NoRC-associated RNA is crucial for targeting the chromatin remodelling complex NoRC to the nucleolus.
Silencing of ribosomal RNA genes (rDNA) requires binding of the chromatin remodelling complex NoRC to RNA that is complementary to the rDNA promoter. NoRC-associated RNA (pRNA) folds into a conserved stem-loop structure that is required for nucleolar localization and rDNA silencing. Mutations that disrupt the stem-loop structure impair binding of TIP5, the large subunit of NoRC, to pRNA and abolish targeting of NoRC to nucleoli. Binding to pRNA results in a conformational change of TIP5, as shown by enhanced sensitivity of TIP5 towards trypsin digestion. Our results indicate an RNA-dependent mechanism that targets NoRC to chromatin and facilitates the interaction with co-repressors that promote heterochromatin formation and rDNA silencing.


Human auditory steady state potentials.
The auditory steady state potentials may be an important technique in objective audiometry. The effects of stimulus rate, intensity, and tonal frequency on these potentials were investigated using both signal averaging and on-line Fourier analysis. Stimulus presentation rates of 40 to 45/sec result in a 40 Hz sinusoidal response which is about twice the amplitude of the 10 and 60/sec responses. No significant effects of subject age or sex were seen. The 40/sec response shows a linear decrease in amplitude and a linear increase in latency when stimulus intensity is decreased from 90 to 20 dB normal hearing level. This response is recordable to within a few decibels of behavioral threshold. Stimuli of different tonal frequency give similar amplitude/rate functions, with absolute amplitude decreasing with increasing tonal frequency. Signal averaging and Fourier analysis provide nearly identical amplitude/rate, amplitude/intensity, and latency/intensity functions. Both methods of analysis may be used, therefore, to record the 40 Hz steady state potential. Fourier analysis, however, may be the faster and less expensive method. Furthermore, techniques ("zoom") are available with Fourier analysis to study the effects of varying stimulus parameters on-line with the Fourier analysis procedure.


Fibular lengthening for malunited ankle fractures.
Malunited ankle fractures are uncommon. They produce symptoms of persistent pain, joint effusion, limitation of dorsiflexion and eventually lead to ankle arthritis. We feel that correction of the ankle alignment can improve the final outcome and present our results. From May 2004 to April 2006, seven patients with a malunited fibular fracture aged 25 to 62 years (male:female ratio, 5:2) were treated in our institute. All patients were referred for persistent pain. The delay between injury and the operative intervention was 3 to 16 months. All patients were assessed with a clinical examination, AOFAS ankle hindfoot score and plain radiographs. A transverse fibular osteotomy was made just above the ankle joint and below the tibiofibular syndesmosis. A tricortical iliac bone graft and a lateral fibular plate were applied. Fibular length and restoration of the ankle mortise was successful in all the cases. All patients showed radiological evidence of bony union on followup. The average AOFAS score was 82 (pain: 31, function: 41, and alignment: 10). Patients were followed up for an average period of 11 (range, 6 to 24) months after the surgery. We present our early experience with a simpler fibular osteotomy to correct the ankle joint alignment for malunited fibular fractures which was successful at short-term followup.


Glutathione S-conjugate formation and metabolism in HepG2 cells: a cell model of mercapturic acid biosynthesis.
Mercapturic acid biosynthesis is mediated by a series of at least four enzymatic steps and three cell membrane transport events, and is believed to require the interorgan shuttling of the various metabolic intermediates. To identify a single cell type that can carry out all of these metabolic and transport steps, the present study examined whether HepG2 cells, a human hepatoma-derived cell line, can convert an electrophilic chemical (1-chloro-2,4-dinitrobenzene, CDNB) to its corresponding mercapturic acid (S-dinitrophenyl-N-acetylcysteine, DNP-NAC). The results demonstrate that HepG2 cells are able to convert CDNB to DNP-NAC in a dose- and time-dependent fashion. Intracellular conjugation with glutathione occurred rapidly, and the resulting glutathione S-conjugate was promptly transported into the culture medium, where it was sequentially degraded to the cysteinylglycine and cysteine S-conjugates. The cysteine conjugate was then presumably reabsorbed, and N-acetylated intracellularly to form the mercapturic acid. The mercapturic acid was found to accumulate slowly in the culture medium, such that after 4 h of incubation, 4-10% of the CDNB dose was recovered as the mercapturic acid. These data provide the first demonstration that a single cell type can carry out all of the transport and enzymatic steps required for mercapturic acid biosynthesis. HepG2 cells may provide a useful model system for studying this important detoxification pathway.


A Case Report: Two Young Children with Long QT Syndrome Type-2 Diagnosed by Presymptomatic Genetic Testing.
Long QT syndromes (LQTSs) can lead to sudden cardiac death, yet these syndromes are often asymptomatic and clinically undetected, despite the prolongation of the QT interval. Currently, when a disease-causing variant is identified in an individual, presymptomatic genetic testing is available and can form part of the recommended cascade testing to identify other family members at risk. We herein report the cases of two daughters who received presymptomatic genetic testing in infancy when the proband mother had been diagnosed with LQTS type 2 (LQT2; c.1171C > T, p.Q391X in KCNH2) after suffering from cardiac arrhythmia at 30 years of age. The daughters had a normal QTc interval, but they carried the same disease-causing variant as their mother. Children with family members who have genetically confirmed LQTS have a high risk of suffering from cardiac events later in life, so genetic testing is required. This poses a complex problem, as guidelines for medical intervention and follow-up systems among asymptomatic children with LQTS have yet to be established. Genetic testing should only be performed after adequate counseling to support children later in life. Individualized long-term genetic counseling is required for both parents and children at stages throughout life.


[Cesarean section using single-layer transisthmic uterine sutures].
Since 1972 the authors performed 1865 caesarean sections and used only a transisthmic suture of the uterine wound in one layer. No maternal mortality and no severe complications (rupture and dehiscence of the uterus, sepsis) were observed. An analysis of 1062 operations of the years 1978-1982 resulted in a course without complications (no fever, no transfusion) in 81.9 per cent. --These favourable results are likely to be attributed to the modification used.


Inhibition of Monoacylglycerol Lipase Decreases Angiogenic Features of Endothelial Cells via Release of Tissue Inhibitor of Metalloproteinase-1 from Lung Cancer Cells.
Despite the well-described anticarcinogenic effects of endocannabinoids, the influence of the endocannabinoid system on tumor angiogenesis is still debated. In the present study, conditioned medium (CM) from A549 and H358 lung cancer cells treated with ascending concentrations of the monoacylglycerol lipase (MAGL) inhibitor JZL184 and 2-arachidonoylglycerol (2-AG), a prominent MAGL substrate, caused a concentration-dependent reduction in human umbilical vein endothelial cell (HUVEC) migration and tube formation compared with CM from vehicle-treated cancer cells. Comparative experiments with MAGL inhibitors JW651 and MJN110 showed the same results. On the other hand, the angiogenic properties of HUVECs were not significantly altered by direct stimulation with JZL184 or 2-AG or by exposure to CM of JZL184- or 2-AG-treated non-cancerous bronchial epithelial cells (BEAS-2B). Inhibition of HUVEC migration and tube formation by CM of JZL184- and 2-AG-treated A549 cells was abolished in the presence of the CB1 antagonist AM-251. Increased release of tissue inhibitor of metalloproteinase-1 (TIMP-1) from JZL184- or 2-AG-stimulated A549 or H358 cells was shown to exert an antiangiogenic effect on HUVECs, as confirmed by siRNA experiments. In addition, JZL184 caused a dose-dependent regression of A549 tumor xenografts in athymic nude mice, which was associated with a decreased number of CD31-positive cells and upregulation of TIMP-1-positive cells in xenograft tissue. In conclusion, our data suggest that elevation of 2-AG by MAGL inhibition leads to increased release of TIMP-1 from lung cancer cells, which mediates an antiangiogenic effect on endothelial cells.


Anti-HLA antibodies and kidney allograft outcomes in recipients with donor bone marrow cell infusion.
Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concurrent donor bone marrow cell infusion (DBMI). Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre- and post-transplant (days 14, 30, and 90) sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA specific panel for antibody specification. Of 40 patients, 9 (22.5%) experienced acute rejection episodes (ARE) (6/20 cases in non-infused versus 3/20 in DBMI patients). The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones (88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively). A total of 10% (4/40) of patients developed donor specific anti-HLA antibodies (DSA) and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Our findings reveal an association between pre- and post-transplant anti-HLA antibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts.


A pH-responsive prodrug delivery system of 10-HCPT for controlled release and tumor targeting.
We synthesized a pH-responsive conjugate of 10-hydroxycamptothecin-thiosemicarbazide-linear polyethylene glycol 2000 (PEG2000). The conjugate was confirmed by matrix-assisted laser desorption time of flight mass spectrometry, 1H NMR, and 13C NMR. The water solubility of the prodrug was increased by over 3,000 times; much longer body circulation time, higher tumor-targeting ability, and reduced toxicity were observed, compared with commercial 10-HCPT injection. The linker contains a pH-sensitive hydrazone bond, which breaks under low pH conditions in the tumor microenvironment. The conjugates showed good stability in phosphate-buffered saline (pH 7.4) and rat plasma. This amphiphilic conjugate could self-assemble into nanosized micelles of 80-100 nm. Cytotoxicity assay results indicate significantly higher efficacy of the conjugate (IC50 [half maximal inhibitory concentration] =0.117 µM on SW180 cells) than 10-HCPT solution (IC50 =0.241 µM on SW480 cells). Cellular uptake analysis suggested its rapid internalization and nuclear transport. Pharmacokinetic analysis of the conjugates demonstrated that the conjugate circulated for a longer time in the blood circulation system (T2/1 =10.516±1.158 h) than did 10-HCPT solution (T2/1 =1.859±1.385 h), and that it also enhanced the targeting and mean residence time (MRT0-inf =39.873±4.549 h) in the tumor site, compared with 10-HCPT (MRT0-inf =9.247±1.026 h). Finally, the conjugate demonstrated an increased tumor growth inhibition effect (TIR =82.66%±7.175%) in vivo and lower side effects than 10-HCPT (TIR =63.85%±5.233%). This prodrug holds great promise in improving therapeutic efficacy and overcoming multidrug resistance.


Spintronic Integrate-Fire-Reset Neuron with Stochasticity for Neuromorphic Computing.
Spintronics has been recently extended to neuromorphic computing because of its energy efficiency and scalability. However, a biorealistic spintronic neuron with probabilistic "spiking" and a spontaneous reset functionality has not been demonstrated yet. Here, we propose a biorealistic spintronic neuron device based on the heavy metal (HM)/ferromagnet (FM)/antiferromagnet (AFM) spin-orbit torque (SOT) heterostructure. The spintronic neuron can autoreset itself after firing due to the exchange bias of the AFM. The firing process is inherently stochastic because of the competition between the SOT and AFM pinning effects. We also implement a restricted Boltzmann machine (RBM) and stochastic integration multilayer perceptron (SI-MLP) using our proposed neuron. Despite the bit-width limitation, the proposed spintronic model can achieve an accuracy of 97.38% in pattern recognition, which is even higher than the baseline accuracy (96.47%). Our results offer a spintronic device solution to emulate biologically realistic spiking neurons.


YKL-40 in asthmatic patients, and its correlations with exacerbation, eosinophils and immunoglobulin E.
The chitinase-like protein YKL-40, which binds chitin but lacks chitinase activity, has been found to be either the cause or a biomarker for asthma. The aim of our study was to investigate whether serum YKL-40 levels are increased in Chinese patients with asthma and identify its correlation to acute exacerbation, total serum immunoglobulin (Ig)E, the percentage of peripheral blood eosinophils and lung function. We quantified serum YKL-40 levels, total IgE levels and peripheral blood eosinophil percentages in patients with asthma, as well as in controls from the communities surrounding our hospital. The lung function of asthma subjects was also measured. Our data showed that the serum YKL-40 levels were significantly elevated in patients with asthma compared with controls and, when the asthma subjects were stratified, serum YKL-40 levels in the exacerbation group were higher than those in the stable and control groups. In addition, serum YKL-40 levels correlated positively with total serum IgE levels and the percentage of peripheral blood eosinophils, but correlated inversely with lung functions. Thus, we conclude that YKL-40 is found in increased quantities in the serum of Chinese patients with asthma, and its level correlates with exacerbation attacks, indicating that high levels of serum YKL-40 may be a biological characteristic of the exacerbation of asthma.


Blood glucose amplitude variability in critically ill patients.
While the discussion on the optimal blood glucose (BG) level target in critically ill patients is on-going, attention shifts towards other aspects of the BG signal, such as hypoglycemia and blood glucose amplitude variability (BGAV). A large number of observational and mostly retrospective studies have demonstrated an association between increased BGAV and worse outcomes. This observed association could partially be explained by endogenous factors such as changes in the status of the patient that cannot be externally influenced. On the other hand, exogenous factors such as insulin and caloric infusions could play a role in increasing or decreasing BGAV. In this review article, intuitive concept of "variability" will be clarified, and possible metrics to quantify BGAV are discussed. Whether it is feasible to actively minimize BGAV in order to improve the outcome of critically ill patients, is questionable.


A Review of the Motion Planning and Control Methods for Automated Vehicles.
The motion planning and control method of automated vehicles, as the key technology of automated vehicles, directly affects the safety, comfort, and other technical indicators of vehicles. The planning module is responsible for generating a vehicle driving path. The control module is responsible for driving the vehicle. In this study, we review the main methods and achievements in motion planning and motion control for automated vehicles. The advantages and disadvantages of various planning and control methods are comparatively analyzed. Finally, some predictions and summaries based on the existing research results and trends are proposed. Through this analysis, it is believed that various types of algorithms will be further integrated in the future to complement each other's strengths and weaknesses. The next area of research will be to establish more accurate vehicle models to describe vehicle motion, improve the generalization-solving ability of algorithms, and enhance the planning and control of integrated 'human-vehicle-road' traffic systems.


Concealed conduction in accessory atrioventricular pathways: an important determinant of the expression of arrhythmias in patients with Wolff-Parkinson-White syndrome.
Concealed conduction into accessory atrioventricular pathways has been postulated to explain variability of R-R intervals during atrial fibrillation in patients with Wolff-Parkinson-White syndrome. We examined the occurrence of concealed conduction into atrioventricular pathways using extrastimulus techniques in 26 consecutive patients undergoing electrophysiologic studies for the Wolff-Parkinson-White syndrome. Anterograde pathway concealment was demonstrated (10 patients) by introducing a second atrial extrastimulus (A3) after block in the accessory pathway occurred following the first extrastimulus (A2). The apparent effective refractory period (ERP) of the atrioventricular pathway with A3 (after A2 blocked in the pathway), or ERPB, was always greater than the ERP of the atrioventricular pathway (505 +/- 100 vs 323 +/- 105 msec, mean +/- SD; p less than .001), a finding explained by concealment into the pathway by the blocked A2. A measure of the apparent prolongation of refractoriness due to anterograde concealment (delta ERPB), defined as the difference between ERP and ERPB at a given cycle length, was derived. The average R-R interval in atrial fibrillation correlated better with delta ERPB (r = .8, p less than .01) than with the ERP (r = .6, p = NS), supporting the influence of anterograde atrioventricular pathway concealment in modulating the ventricular response during atrial fibrillation. By similar techniques, concealed retrograde conduction in the atrioventricular pathway could be demonstrated in 16 of 26 patients. In two of these patients "bystander" atrioventricular pathway conduction during orthodromic reciprocating tachycardia that did not involve the atrioventricular pathway did not occur, even though the ERP of the pathway should have permitted it, a finding readily explained by repetitive retrograde concealment into the atrioventricular pathway during tachycardia. Concealed conduction can be demonstrated in most patients with Wolff-Parkinson-White syndrome and is an important factor in the clinical expression of their arrhythmias.


Intracellular production of virus particles and viral components in NIH/3T3 cells chronically infected with Moloney murine leukemia virus: effect of interferon.
The effect of interferon on the biochemical properties and the maturation process of intracellular viral particles isolated from the cytoplasmic fraction of NIH/3T3 cells chronically infected with Moloney murine leukemia virus was investigated. By labeling these virions with either [35S]methionine or [3H]glucosamine, we demonstrated that they contain the same viral proteins and glycoproteins found in extracellular virions. Interferon treatment was found to reduce the rate of intracellular virus assembly. This effect was not a consequence of an interferon inhibition of viral RNA synthesis or its translation or a consequence of an interference with the posttranslational cleavage processing of viral precursor proteins, since all of these steps were not affected by interferon. However, the reduced rate of virus assembly could be attributed to the inhibition of viral protein glycosylation observed in interferon-treated cells. Nevertheless, despite this reduced rate, virus particles accumulated in interferon-treated cells. This accumulation was probably due to the strong inhibition of their final release from such cells.


Public image of the profession is associated with the choice of nursing career among Arab high school students: A cross-sectional study.
The aim of this study is to examine (a) public image of nursing and the intention to choose nursing as a future career and (b) the relationship between the public image, gender roles and the choice of the nursing career among Arab high school students. School graduates from the Arab sector represent an important social group with the potential to provide quality candidates for the nursing profession in Israel. In this cross-sectional study, 138 high school students from two Arab schools in Israel completed a structured questionnaire. One third of the sample intended to choose nursing as a future career. Students from families with a higher level of paternal education and those exposed to the work of nurses perceived nursing as more positive. The profession's public image contributed to the explanation of 21% of the variance of the intention to choose a nursing career. A positive public image of nursing contributes to decisions about choosing a nursing career in the future among Arab high school students. School graduates may be influenced by providing information and presenting the role of a nurse as significant, as well as by emphasizing the positive image of nursing to parents and influential people in the Arab community.


The efficiency of removal of lead and other elements from domestic drinking waters using a bench-top water filter system.
The efficiency of removal of lead (Pb) and other elements from natural drinking waters using a bench-top water filter system was evaluated in three recently-built houses in Sydney, Australia, and two from rural centres. In addition, one filter system was tested for copper (Cu), Pb and cadmium (Cd) under rigorously-controlled laboratory conditions using Sydney water. For two Sydney houses, the efficiency was evaluated using special filter cartridges concomitant with the ordinary filters. Waters after passing through the filter, was sampled when the filter had been exposed to '0', 50, 100, 150, 200, and 250 l respectively and were analysed for lead isotopes and lead concentrations by high precision isotope dilution mass spectrometry. Samples that passed through the filter after '0', 50, 150 and 250 l collections were analysed for four anions and 39 cations by various methods. Sydney water was fairly uniform in its anion and cation composition, whereas water from the two rural areas contained higher concentrations of Ca, Mg and HCO3. Effects of the filter on the water compositions can be summarised into three groups: (1) elements removed during filtration--Ca, Mg, Sr, Ba, Cu, Pb, Zn and Ni. With 'age' of the filter, the efficiency of removal for Pb was maintained in the two houses with Pb concentrations greater than 10 micrograms/l in the first flush water and was maintained for Cu through all concentrations. Ca, Mg, Sr and Ba were largely removed in the first 50 1 of usage. (2) Elements added during filtration--K, Rb, Ag and P. Except for Ag, which was present throughout the testing period, these elements were added only in the first filtration. (3) Elements unaffected by filtration--Al, Si, Na, Fe, Cl and F. Efficiency of Pb removal from tap water by this system depends generally on the initial Pb content in the water. However, it also seems to depend, to some extent, on Pb speciation and water composition, as found in earlier studies of natural waters. The control in filtering efficiency as a function of Pb speciation and chemical composition becomes more important at low initial Pb concentrations in the water. However, the Pb concentrations at which speciation and water composition appear to play a role in filter efficiency are so low that these factors, though scientifically interesting, have no relevance from a practical point of view, especially the impact on human health. Acidification of six sets of duplicate water samples, one sample immediately after collection and the other acidified after more than 2 weeks, showed negligible changes in Pb or Cu concentrations between duplicates.


Frequency of Hyponatremia and Its Impact on Prognosis in Ischemic Stroke.
Background Hyponatremia, often encountered in hospitalized patients, is associated with adverse outcomes in ischemic stroke patients. In this study, we investigated the frequency of hyponatremia and its impact on prognosis and clinical outcomes in ischemic stroke patients from a tertiary care hospital. Methodology A total of 289 patients admitted to the hospital with ischemic stroke from September 2022 to February 2023 were considered in this cross-sectional study. Serum sodium level was measured on admission, and hyponatremia was defined as sodium less than 135 mmol/L. The primary outcome of the study was assessed by the National Institutes of Health Stroke Scale (NIHSS) score on admission and discharge and inpatient mortality. Data were analyzed using SPSS version 20 (IBM Corp., Armonk, NY, USA), and multivariate logistic regressions were conducted using variables identified as having a relationship with hyponatremia. Results Our study shows that among 289 patients with ischemic stroke, the mean age was 61 ± 8.53 years. Hyponatremia was observed in 101 (35%) patients, and all baseline characteristics and risk factors for stroke were similar between patients with and without hyponatremia. The patients with hyponatremia had higher NIHSS scores on admission (p = 0.041) and at discharge (p = 0.039). In the resultant multivariate analysis, hyponatremia was an independent predictor of mortality rates during the hospital stay. The cumulative incidence rates of in-hospital mortality for hyponatremia and normal sodium level were 16.8% and 10.1%, respectively. Conclusions Hyponatremia is prevalent in ischemic stroke and is independently associated with in-hospital mortality and worse NIHSS scores at admission and discharge.


Electroconvulsive Therapy in Children and Adolescents: A Systematic Review of Current Literature and Guidelines.
There is a lack of studies regarding the efficacy of electroconvulsive therapy (ECT) in children and adolescents. In this study, we aimed to assess benefits and harms of ECT in children and adolescents with major psychiatric diseases. We conducted a systematic search in PubMed, EMBASE, and PsycINFO for peer-reviewed articles written in English regarding the use of ECT as treatment for major psychiatric diseases in children and adolescents. This study consists of 192 articles, mostly case studies (n = 50), reviews and overview articles (n = 52), and retrospective studies (n = 30). We present an overview of evidence for ECT in children and adolescents with mood disorders, catatonia, schizophrenia, intellectual disability, self-injurious behavior, and other indications. This article is also a summary of international guidelines regarding the use of ECT in children and adolescents. We evaluated the overall quality of evidence by using Grading of Recommendations, Assessment, Development and Evaluations and found the overall level of evidence to be of low quality. There are no absolute contra indications for ECT in children and adolescents. Fears regarding cognitive dysfunction have not been reproduced in studies. Electroconvulsive therapy should be considered in severe, treatment-resistant mood disorders, catatonia, and schizophrenia, especially in older adolescents. High-quality studies are warranted to assess the efficacy of ECT, especially in these potentially life-threatening diseases.


Heat Generation and Efficiency of a New Modified Phaco Tip and Sleeve.
To compare a modified phacoemulsification tip with the established micro tip, in terms of temperature at the corneal wound, efficiency, and chatter events, using the Centurion® Vision system. Eighty porcine eyes were randomized into 4 groups: 1)sleeveless conventional 45D MiniFlared ABS® Kelman tip (1.1-mm incision); 2)sleeveless new modified 45D ABS® INTREPID® balanced tip(1.1-mm incision); 3) Kelman tip with own sleeve (2.2-mm incision); 4)Balanced tip with modified 4-rib sleeve (2.2-mm incision). Measurements were taken with 2 settings: longitudinal(power 40% and 70%) and torsional mode (power 40% and 100%). Peak temperatures were measured 0, 10, 30, and 60 seconds after continuous ultrasound power. For the efficiency test, porcine lens nuclei were formalin soaked and cut into 2.0 mm3 cubes. Efficiency and chatter were examined. In all longitudinal settings, the sleeveless groups(1 and 2) showed lower temperatures than the sleeved groups(3 and 4) (P = 0.003). In 100% torsional mode, groups 3 and 4 produced significantly different temperatures(37.13 ± 1.44 and 35.14 ± 0.54, respectively; P = 0.007).The efficiency, in a 100% power torsional setting, was13.52 ± 2.60 sec for group 4, and 44.45± 14.75 sec for group 3 (P<0.001). The two different bare tips show no significant differences in thermogenesis. However, the balanced tip with sleeve produces lower temperaturesat100% torsional power and better efficiency than the Kelman tip.


Lipid nanocapsules loaded with an organometallic tamoxifen derivative as a novel drug-carrier system for experimental malignant gliomas.
Ferrocenyl diphenol tamoxifen derivative (Fc-diOH) is one of the most active molecules of a new class of organometallic drugs, showing in vitro antiproliferative effects on both hormone-dependent and independent breast cancer cells. For the first time, Fc-diOH was tested on a 9L glioma model according to two encapsulation strategies: lipid nanocapsules (LNC) and swollen micelles. LNC showed a higher drug loading capacity because of a larger oily core in their structure and were able to be up taken by glioma cells. The large amount of PEG present at the micellar interface prevented interaction with cytoplasm membrane which led to a low level of micelle cell uptake and no biological activity. On the contrary, Fc-diOH cytostatic activity was conserved after its encapsulation in LNC and was very effective on 9L-glioma cells as the IC(50) was about 0.6 microM. Interestingly, Fc-diOH-loaded LNC showed low toxicity levels when in contact with healthy cells, conferring a functional specificity of this compound on tumour cells. Finally, Fc-diOH LNC treatment was able to lower significantly both tumour mass and volume evolution after 9L-cell implantation into rats which evidenced for the first time the in vivo efficacy of this new kind of organometallic compound.


Inflammatory aneurysm of the ascending aorta.
The gold standard to clarify an acute pathology of the ascending aorta is transesophageal echocardiography or contrast-enhanced computed tomography. Neither of these methods led to the correct finding in our case of an inflammatory aneurysm of the ascending aorta. Both assessments resulted in the diagnosis of an acute dissection of the ascending aorta.


Simultaneous Enrichment Analysis of all Possible Gene-sets: Unifying Self-Contained and Competitive Methods.
Studying sets of genomic features is increasingly popular in genomics, proteomics and metabolomics since analyzing at set level not only creates a natural connection to biological knowledge but also offers more statistical power. Currently, there are two gene-set testing approaches, self-contained and competitive, both of which have their advantages and disadvantages, but neither offers the final solution. We introduce simultaneous enrichment analysis (SEA), a new approach for analysis of feature sets in genomics and other omics based on a new unified null hypothesis, which includes the self-contained and competitive null hypotheses as special cases. We employ closed testing using Simes tests to test this new hypothesis. For every feature set, the proportion of active features is estimated, and a confidence bound is provided. Also, for every unified null hypotheses, a $P$-value is calculated, which is adjusted for family-wise error rate. SEA does not need to assume that the features are independent. Moreover, users are allowed to choose the feature set(s) of interest after observing the data. We develop a novel pipeline and apply it on RNA-seq data of dystrophin-deficient mdx mice, showcasing the flexibility of the method. Finally, the power properties of the method are evaluated through simulation studies.


Lymph node dissection in patients with kidney cancer: when is it indicated?
It is necessary to consider the potential risks and benefits of performing a lymph node dissection (LND) at the time of radical nephrectomy. LND may lead to more accurate staging, a decrease in local recurrence, and an increase in survival for patients with metastatic disease limited to the resected lymph nodes. However, there are risks associated with the treatment that must be considered. The advantages of LND vary among patients, depending on the location and extent of disease progression. For patients with stage T3 or T4 disease, we recommend a limited LND. Patients with T3 or T4 disease with grossly positive nodes with or without hematogenous metastasis should undergo a more extensive LND.


Expertise in cognitive psychology: testing the hypothesis of long-term working memory in a study of soccer players.
This experiment compared several theories of expertise and exceptional performances in cognitive psychology. One current conception assumes that experts in a specific domain have developed a long-term working memory, which accounts for the difference in memory performance between experts and novices. The principal characteristics of this memory are the speed with which processes of storage and retrieval function and the existence of retrieval structures that allow a temporary activation of the knowledge store in long-term memory. Other authors such as Vicente and Wang argue this notion does not account for memory performance that is not intrinsic to the domain of expertise. We attempt to clarify the two viewpoints and to focus on this debate by testing the hypothesis of long-term working memory using soccer as the domain of expertise and by comparing the cognitive performance of participants who have different expertise (novices, supporters, players, and coaches). 35 male participants were administered a new version of the Reading Span test to assess their long-term working memory according to two conditions. In the first condition (structured condition), the last word of each sentence was related to the soccer domain, and these words were related to each other in such a manner that they represented a part of the game. In the second condition (unstructured condition), the last word of each sentence was related to soccer but these words did not represent part of the game. Analysis showed that the sentence span increased as a function of expertise for the structured condition but not for the unstructured condition. The results were interpreted in the framework of the constraint attunement hypothesis proposed by Vicente in 1992 and the long-term working memory hypothesis proposed by Ericsson and Kintsch in 1995.


Renewal of driving license in India and glaucoma: A study of prevalent practice and its lacunae.
Glaucoma affects different aspects of vision including visual field. This prospective observational study aims to collect details of driving license (DL) renewal procedure (in an urban metro in India) among patients with diagnosed glaucoma and the method of reporting of vision-related requirements during renewal. One-hundred patients with diagnosed glaucoma above 40 years, having valid DL (with at least one renewal cycle), were included. Patients with other ocular comorbidities were excluded. Driving Habits Questionnaire and a questionnaire about license renewal were administered. Driving eligibility was compared to international guidelines. Study population included patients with 69% early, 29% moderate, and 2% advanced glaucoma. Sixteen percent of patients had stopped driving. Legal license renewal procedure was bypassed by 45%. Form-1 was not submitted by 43% and 49% did not submit Form-1A at the time of renewal. Only 7.01% mentioned about glaucoma in the self-declaration form. None were asked about their visual field during renewal. Among 61 patients who submitted a medical certificate, the undersigning doctor was an ophthalmologist in only six patients. Thirty percent patients with valid Indian DL would not have satisfied International College of Ophthalmologists guidelines. Driving difficulties were experienced by 44%, more so in advanced glaucoma (F (1, 82) = 22.12, P < 0.001). Vision-related testing at the time of renewal of DL is inadequate in India. Chronic eye diseases such as glaucoma are commonly not self-declared or detected at pre-renewal testing. Clear-cut guidelines about visual requirements and implementation are required to prevent road traffic events because of vision-related errors.