Open tube thoracoscopy for removal of intrapleural foreign bodies.
Failure to remove all sponges and surgical instruments from the operative field after thoracic surgical procedures can lead to serious complications. Fortunately this occurrence is rare and preventable. Two patients are described in whom intrapleural foreign bodies were successfully removed by open tube thoracoscopy, a technique that the authors recommend as the procedure of choice in such cases.


[Longitudinal assessment of hematological parameters in the elderly].
Red blood cell count (RBC), hemoglobin level (Hb), hematocrit value (Ht), and white blood cell count (WBC) were determined periodically in 499 subjects (274 males, 225 females) aged 60 and over. RBC, Hb, and Ht showed a significant decrease after 5 years in both younger (60-64) and older (65 and over) male groups, and in the female groups except for the Hb level in the older group. Comparison between the younger and older group (cross-sectional study), revealed that the older male group showed lower levels of RBC, Hb, Ht than the younger male group, but the situation was completely the reverse in the females. No significant age-related changes were observed in WBC, but it was significantly higher in both the younger and older male groups than in the female groups. A significant decline with age was observed in both male and female MCV values. On the contrary, from a cross-sectional standpoint, the MCV values in the older female group were higher than those in the younger group. These findings revealed a completely reverse outcome in some parameters, when studied longitudinally and cross-sectionally. Therefore, the data should be evaluated longitudinally to elucidate the real effect of aging. It is pertinent to apply the WHO criteria (male 13 g/dl, female 12 g/dl) to the diagnosis of anemia of elderly people.


Post-Partum Depression Effect on Child Health and Development.
While studies have shown the disastrous effects of post-partum depression (PPD) on children's behaviors, there is relatively lack of reliable data in Asian countries. This study examined the relative significance of maternal PPD in children's developmental disabilities at age four. In a longitudinal study design (2009), 1801 pregnant women attending in primary health centers of Mazandaran province in the north of Iran provided self-reports of depression from two to twelve postpartum weeks using Edinburgh Postnatal Depression Scale (EPDS). Approximately four years later, the women experiencing PPD and twice as the ones who did not experience this disorder were considered as case (N=204) and control (N=467) groups. The association between maternal depression at different times and childhood developmental disabilities based on Ages and Stages Questionnaire (ASQ) and other health problems reported by the child were analyzed using two-sample t-test, chi-square test, and logistic regression models. The presence of PPD only was not a predictor of child's developmental disabilities at age four. Childhood developmental disabilities in communication, gross motor and personal-social domains of ASQ were associated with the current and concurrent maternal depressive symptoms (OR=2.59, 95% CI=1.16-5.78; OR=4.34, 95% CI=2.10-8.96; OR=5.66, 95% CI=1.94-16.54 and OR=3.35, 95% CI=1.31-8.58; OR=4.15, 95% CI=2.72-13.87; OR=6.17, 95% CI=1.95-19.53 respectively). PPD, the current depressive symptoms, and depression at both occasions were associated with more health problems in children. Childhood developmental disabilities in some domains of ASQ were significantly related to the maternal depression chronicity or recurrence. Also, child's difficulties were more prevalent in association with maternal depression regardless of onset time.


Expression and the Peculiar Enzymatic Behavior of the Trypanosoma cruzi NTH1 DNA Glycosylase.
Trypanosoma cruzi, the etiological agent of Chagas' disease, presents three cellular forms (trypomastigotes, epimastigotes and amastigotes), all of which are submitted to oxidative species in its hosts. However, T. cruzi is able to resist oxidative stress suggesting a high efficiency of its DNA repair machinery.The Base Excision Repair (BER) pathway is one of the main DNA repair mechanisms in other eukaryotes and in T. cruzi as well. DNA glycosylases are enzymes involved in the recognition of oxidative DNA damage and in the removal of oxidized bases, constituting the first step of the BER pathway. Here, we describe the presence and activity of TcNTH1, a nuclear T. cruzi DNA glycosylase. Surprisingly, purified recombinant TcNTH1 does not remove the thymine glycol base, but catalyzes the cleavage of a probe showing an AP site. The same activity was found in epimastigote and trypomastigote homogenates suggesting that the BER pathway is not involved in thymine glycol DNA repair. TcNTH1 DNA-binding properties assayed in silico are in agreement with the absence of a thymine glycol removing function of that parasite enzyme. Over expression of TcNTH1 decrease parasite viability when transfected epimastigotes are submitted to a sustained production of H2O2.Therefore, TcNTH1 is the only known NTH1 orthologous unable to eliminate thymine glycol derivatives but that recognizes and cuts an AP site, most probably by a beta-elimination mechanism. We cannot discard that TcNTH1 presents DNA glycosylase activity on other DNA base lesions. Accordingly, a different DNA repair mechanism should be expected leading to eliminate thymine glycol from oxidized parasite DNA. Furthermore, TcNTH1 may play a role in the AP site recognition and processing.


Long-term Clinical Outcome of Teeth Obturated with Resilon.
Although Resilon has been in clinical use as an endodontic obturation material for more than a decade, there is a lack of long-term clinical outcome studies. The purpose of this retrospective case-control study was to compare long-term clinical outcomes in teeth obturated with Resilon/RealSeal SE (RS) and GP/AH Plus (GP). One hundred teeth treated at Texas A&M University College of Dentistry between 2007 and 2012 were included; 50 teeth were obturated with RS and 50 with GP. All cases were initial treatments without preoperative periapical radiolucencies. Success and failure were assessed on the basis of clinical signs and symptoms and/or the presence of periapical radiolucency. Chi-square test and odds ratio were used to determine the association between the obturation material and outcome. Potential prognostic factors were evaluated including age, sex, tooth location, preoperative diagnosis, and one versus multiple visits. The average recall time for RS was 5.8 years and 6.6 years for GP. Fifty-six percent of RS-obturated teeth were classified as successful at recall compared with 88% of GP-obturated teeth. RS had 5.7 times greater odds of failure compared with GP (P < .001). When periapical radiolucencies were present, they tended to be larger and involve multiple roots in the RS group compared with GP group. None of the prognostic factors examined were found to have any significant effect on outcome. Within the limitations of this study, teeth obturated with RS had 5.7 times greater chance of failure compared with teeth obturated with GP.


EGR1 regulates hepatic clock gene amplitude by activating Per1 transcription.
The mammalian clock system is composed of a master clock and peripheral clocks. At the molecular level, the rhythm-generating mechanism is controlled by a molecular clock composed of positive and negative feedback loops. However, the underlying mechanisms for molecular clock regulation that affect circadian clock function remain unclear. Here, we show that Egr1 (early growth response 1), an early growth response gene, is expressed in mouse liver in a circadian manner. Consistently, Egr1 is transactivated by the CLOCK/BMAL1 heterodimer through a conserved E-box response element. In hepatocytes, EGR1 regulates the transcription of several core clock genes, including Bmal1, Per1, Per2, Rev-erbα and Rev-erbβ, and the rhythm amplitude of their expression is dependent on EGR1's transcriptional function. Further mechanistic studies indicated that EGR1 binds to the proximal region of the Per1 promoter to activate its transcription directly. When the peripheral clock is altered by light or feeding behavior transposition in Egr1-deficient mice, the expression phase of hepatic clock genes shifts normally, but the amplitude is also altered. Our data reveal a critical role for EGR1 in the regulation of hepatic clock circuitry, which may contribute to the rhythm stability of peripheral clock oscillators.


A paediatric home therapy programme for developmental progress in severely handicapped infants.
An effort has been made to influence the development of severely handicapped infants and improve the quality of life for their families in one health care district. Weekly visits to the homes by a 'developmental therapist' for 2 years after the initial suspicion of major developmental delay have taken place. The visits have been carried out by senior professional staff in the therapeutic professions who normally deal with a young handicapped population working within a closely knit team directed by a paediatrician and a psychologist. Success and difficulties met by children, families, therapists and team are described. Appreciation of the child's individual characteristics and his family's particular accommodation to them has been the task of therapists, who appear to have successfully crossed the parent-professional barrier. Evaluation of maternal attitudes in this group and a comparison group from another health care district is being carried out. This paper is the first of three. The next two will describe the observed effects in the children and the families respectively.


Nursing practice environment in intensive care unit and professional burnout.
To evaluate and compare the nursing practice environments in Intensive Care Units of a public and private hospital and the prevalence of burnout among nursing professionals. Cross-sectional, descriptive study with a quantitative approach to the data. The data collection took place between October 2018 and March 2019, and it was carried out through a questionnaire with socio-occupational variables and with metrics of intensity. The practice environment was assessed through the Nursing Work Index Revised (NWI-R); and the burnout was assessed by the Maslach Burnout Inventory (IBM). We included professionals with, at least, six months of employment, and those who were on leave or on a fixed-term employment contract were excluded. The sample consisted of 296 professionals. We found Favorable environments in both institutions, however, low results in the subscales autonomy, control and organizational support in the private hospital. The prevalence of burnout among nurses was 2.5% in the public hospital and 9.1% in the private hospital, and among nursing technicians, it was 9.5% and 8.5%, respectively. The control of the environment, autonomy and support were considered critical points, referring to the importance of assessing institutions factors, that can improve the working conditions for the nursing team.


Understanding telecardiology success and pitfalls by a systematic review.
Cardiology is the clinical area where death causes are more frequent than in any other clinical area, and it could benefit from telemedicine. At present, assessment about telecardiology application are hard to find, and sometimes can be found in review article about telemedicine, but there is a lack of review on telecardiology application literature. So we reviewed studies regarding telemedicine applications on cardiology specialty.Sixty-one articles were selected, searching the PubMed database for all years the database were available. All considered articles were published on peer reviewed telemedicine and biomedical journals, from 1992 to 2004. We defined an evaluation grid for the articles in our research result set. Each article was reviewed and catalogued, identifying: 1) Article identification, 2) Content description, 3) Telemedicine manifesto classification, 4) Telemedicine system paradigm, 5) Involved actors.Most of the analysed literature referred only to feasibility studies, pilot projects and to short-term outcomes, for example only 21 cases reported a project duration greater than one year. The method proposed can be used to analyse literature on others telemedicine specialties.


Hierarchical structure of the energy landscape of proteins revisited by time series analysis. II. Investigation of explicit solvent effects.
Time series analysis tools are employed on the principal modes obtained from the C(alpha) trajectories from two independent molecular-dynamics simulations of alpha-amylase inhibitor (tendamistat). Fluctuations inside an energy minimum (intraminimum motions), transitions between minima (interminimum motions), and relaxations in different hierarchical energy levels are investigated and compared with those encountered in vacuum by using different sampling window sizes and intervals. The low-frequency low-indexed mode relationship, established in vacuum, is also encountered in water, which shows the reliability of the important dynamics information offered by principal components analysis in water. It has been shown that examining a short data collection period (100 ps) may result in a high population of overdamped modes, while some of the low-frequency oscillations (<10 cm(-1)) can be captured in water by using a longer data collection period (1200 ps). Simultaneous analysis of short and long sampling window sizes gives the following picture of the effect of water on protein dynamics. Water makes the protein lose its memory: future conformations are less dependent on previous conformations due to the lowering of energy barriers in hierarchical levels of the energy landscape. In short-time dynamics (<10 ps), damping factors extracted from time series model parameters are lowered. For tendamistat, the friction coefficient in the Langevin equation is found to be around 40-60 cm(-1) for the low-indexed modes, compatible with literature. The fact that water has increased the friction and that on the other hand has lubrication effect at first sight contradicts. However, this comes about because water enhances the transitions between minima and forces the protein to reduce its already inherent inability to maintain oscillations observed in vacuum. Some of the frequencies lower than 10 cm(-1) are found to be overdamped, while those higher than 20 cm(-1) are slightly increased. As for the long-time dynamics in water, it is found that random-walk motion is maintained for approximately 200 ps (about five times of that in vacuum) in the low-indexed modes, showing the lowering of energy barriers between the higher-level minima.


Platycodon grandiflorus Root Extract Improves Learning and Memory by Enhancing Synaptogenesis in Mice Hippocampus.
Platycodon grandiflorus (Jacq.) A.DC. (PG) has long been used as an ingredient of foods and is known to have beneficial effects on cognitive functions as well. The present study examined the effect of each PG extract (PGE) from root, aerial part, and seeds on cognitive functions in mice. Changes in spatial learning and memory using a Y-maze test, and markers of adult hippocampal neurogenesis and synaptogenesis were examined. Moreover, changes in neuritogenesis and activation of the ERK1/2 pathway were investigated. Results indicated that mice administered PGE (root) showed increased spontaneous alternation in the Y-maze test and synaptogenesis in the hippocampus. In addition, PGE (root) and platycodin D, the major bioactive compound from the PG root, significantly stimulated neuritic outgrowth by phosphorylation of the ERK1/2 signaling pathway in vitro. These results indicate that the PGE (root), containing platycodin D, enhances cognitive function through synaptogenesis via activation of the ERK1/2 signaling pathway.


Transcriptomic and proteomic analyses of mouse cerebellum reveals alterations in RasGRF1 expression following in vivo chronic treatment with delta 9-tetrahydrocannabinol.
We have applied transcriptomic and proteomic techniques to identify changes in the RNA and the protein levels in the mouse cerebellum after chronic treatment with Delta(9)-tetrahydrocannabinol (THC). Among approximately 14,000 transcripts in a mouse cDNA microarray library, we found 11 genes with altered expression. RasGRF1, a neuron-specific Ras guanine nucleotide exchange factor, showed a reduction both at the RNA and protein levels with a specific decrease of the protein pool associated to cell membranes. In addition, proteomic analysis on cerebellum obtained from chronically THC-treated mice detected quantitative changes of additional 27 spots, mostly in the membranous fraction. We found enrichment of alpha (Galphao, Galphaq) and beta subunits (beta4/beta2 and beta5) of guanine nucleotide-binding proteins and of two calcium-binding proteins, calretinin and hippocalcin-like protein-1. In addition, we also detected a significant increase in the membrane fraction of proteins involved in exo-endocytosis such as septins, dynamin-1, and vesicle protein sorting 29. By western blotting, we confirmed increased membrane localization of calretinin and of dynamin-1 isoforms with higher isoelectric point, indicative for an underphosphorylated state of the molecule. In conclusion, our results indicate that chronic THC modulates the expression and subcellular localization of proteins implicated in Ras signaling, calcium-buffering potential, and trafficking.


Bidirectional transcription of the Epstein-Barr virus major internal repeat.
In latently infected cell lines, the Epstein-Barr virus BamHI W fragment (major internal repeat) is transcribed in a rightward direction to yield exons common to several alternatively spliced messages which encode the six known viral nuclear antigens. A substantial steady-state population of very large (up to 20-kilobase) rightward transcripts is nuclear, much of it being polyadenylated. We report a rise in the levels of rightward transcripts hybridizing to BamHI-W sequences upon phorbol ester treatment of the clone-13 Burkitt's lymphoma cell line. We also report large (up to 15-kilobase) leftward transcripts hybridizing to BamHI-W sequences which occurred late in the viral lytic cycle in B95-8 and clone-13 cells. These leftward transcripts may antagonize the expression of the viral nuclear antigen messages by the formation of RNA duplexes.


A brief review about melatonin, a pineal hormone.
Melatonin is a ubiquitous molecule in nature, being locally synthesized in several cells and tissues, besides being a hormone that is centrally produced in the pineal gland of vertebrates, particularly in mammals. Its pineal synthesis is timed by the suprachiasmatic nucleus, that is synchronized to the light-dark cycle via the retinohypothalamic tract, placing melatonin synthesis at night, provided its dark. This unique trait turns melatonin into an internal synchronizer that adequately times the organism's physiology to the daily and seasonal demands. Besides being amphiphilic, melatonin presents specific mechanisms and ways of action devoted to its role as a time-giving agent, being widely spread in the organism. The present review aims to focus on melatonin as a pineal hormone with specific mechanisms and ways of action, besides presenting the clinical syndromes related to its synthesis and/or function disruptions.


Protozoan predation as a driver of diversity and virulence in bacterial biofilms.
Protozoa are eukaryotic organisms that play a crucial role in nutrient cycling and maintaining balance in the food web. Predation, symbiosis and parasitism are three types of interactions between protozoa and bacteria. However, not all bacterial species are equally susceptible to protozoan predation as many are capable of defending against predation in numerous ways and may even establish either a symbiotic or parasitic life-style. Biofilm formation is one such mechanism by which bacteria can survive predation. Structural and chemical components of biofilms enhance resistance to predation compared to their planktonic counterparts. Predation on biofilms gives rise to phenotypic and genetic heterogeneity in prey that leads to trade-offs in virulence in other eukaryotes. Recent advances, using molecular and genomics techniques, allow us to generate new information about the interactions of protozoa and biofilms of prey bacteria. This review presents the current state of the field on impacts of protozoan predation on biofilms. We provide an overview of newly gathered insights into (i) molecular mechanisms of predation resistance in biofilms, (ii) phenotypic and genetic diversification of prey bacteria, and (iii) evolution of virulence as a consequence of protozoan predation on biofilms.


Action, emotion, and music-colour synaesthesia: an examination of sensorimotor and emotional responses in synaesthetes and non-synaesthetes.
Synaesthesia has been conceptualised as a joining of sensory experiences. Taking a holistic, embodied perspective, we investigate in this paper the role of action and emotion, testing hypotheses related to (1) changes to action-related qualities of a musical stimulus affect the resulting synaesthetic experience; (2) a comparable relationship exists between music, sensorimotor and emotional responses in synaesthetes and the general population; and (3) sensorimotor responses are more strongly associated with synaesthesia than emotion. 29 synaesthetes and 33 non-synaesthetes listened to 12 musical excerpts performed on a musical instrument they had first-hand experience playing, an instrument never played before, and a deadpan performance generated by notation software, i.e., a performance without expression. They evaluated the intensity of their experience of the music using a list of dimensions that relate to sensorimotor, emotional or synaesthetic sensations. Results demonstrated that the intensity of listeners' responses was most strongly influenced by whether or not music is performed by a human, more so than familiarity with a particular instrument. Furthermore, our findings reveal a shared relationship between emotional and sensorimotor responses among both synaesthetes and non-synaesthetes. Yet it was sensorimotor intensity that was shown to be fundamentally associated with the intensity of the synaesthetic response. Overall, the research argues for, and gives first evidence of a key role of action in shaping the experiences of music-colour synaesthesia.


Studies on the Condensation Pathway to and Properties of Diiron Azadithiolate Carbonyls.
Reaction of Fe(2)(SH)(2)(CO)(6) and HCHO, which gives Fe(2)[(SCH(2))(2)NH](CO)(6) in the presence of NH(3), affords the possible intermediate Fe(2)(SCH(2)OH)(2)(CO)(6), which has been characterized crystallographically as its axial-equatorial isomer. Fe(2)(SCH(2)OH)(2)(CO)(6) was shown to react with ammonia and amines to give Fe(2)[(SCH(2))(2)NR](CO)(6) (R = H, alkyl). Related hemithioacetal intermediates were generated by treatment of Fe(2)(SH)(2)(CO)(6) with RC(O)C(O)R (R = H, Ph, 4-F-C(6)H(4)) to give cycloadducts. The benzil derivative Fe(2)[S(2)C(2)(OH)(2)Ph(2)](CO)(6), a C(2)-symmetric species, was also characterized crystallographically. The acylated azadithiolate Fe(2)[(SCH(2))(2)NAc](CO)(6) was prepared by reaction of Li(2)Fe(2)S(2)(CO)(6) with (ClCH(2))(2)NC(O)Me. DNMR experiments show that the free energies of activation for rotation of the amide bond are the same for Fe(2)[(SCH(2))(2)NAc](CO)(6) and Fe(2)[(SCH(2))(2)NAc](CO)(4)(PMe(3))(2), which implies that the ligands on the iron centers do not strongly affect the basicity of the nitrogen. As a control, we showed that the thioamide Fe(2)[(SCH(2))(2)NC(S)Me](CO)(6) does exhibit a significantly higher barrier to rotation, attributable to the increased double-bond character of the N-C(S) bond.


HeartCareII: home care support for patients with chronic cardiac disease.
Systematic engagement of patients in disease management requires design and deployment of innovative technologies that complement and extend professional nursing services. We describe here a model of nursing practice that capitalizes on a web-based resource (HeartCareII) to support patient self-management, symptom interpretation, and self-monitoring. Research staff provided computers and technical assistance; visit nurses trained patients in the components of the HeartCareII Website most relevant to their care needs. This paper describes the nursing practice model and the web resource, and reports the experience of patients recruited in the early phase of the study.


Zero-lag synchronization and multiple time delays in two coupled chaotic systems.
Zero-lag synchronization (ZLS) between two chaotic systems coupled by a portion of their signal is achieved for restricted ratios between the delays of the self-feedback and the mutual coupling. We extend this scenario to the case of a set of multiple self-feedbacks {Ndi} and a set of multiple mutual couplings {Ncj}. We demonstrate both analytically and numerically that ZLS can be achieved when SigmaliNdi+igmamjNcj=0, where li,mj(epsilon)Z. Results which were mainly derived for Bernoulli maps and exemplified with simulations of the Lang-Kobayashi differential equations, indicate that ZLS can be achieved for a continuous range of mutual coupling delay. This phenomenon has an important implication in the possible use of ZLS in communication networks.


Ultrastructural localization of acidic glycoconjugates with the low iron diamine method.
The present study has applied the low iron diamine (LID) method at the ultrastructural level to demonstrate acid glycoconjugates. We have examined rat epiphyseal cartilage, human bone marrow, rat tracheal glands, and mouse sublingual glands stained with LID prior to embedment. The LID staining appeared to require postosmication for adequate visualization at the electron microscope level. Thiocarbohydrazide-silver proteinate (TCH-SP) staining of thin sections variably enhanced LID reactive sites. LID-TCH-SP stained carboxyl and sulfate groups of glycosaminoglycans in the extracellular cartilage matrix, secretory granules, and expanded Golgi saccules of chondrocytes. In human bone marrow, LID-TCH-SP variably stained the cytoplasmic granules, known to contain sulfated glycosaminoglycans, and the external surface of the plasma membrane of leukocytes. Moderately strong LID staining was observed in secretory granules in mucous tubules of rat tracheal glands, known to contain sulfated glycoproteins, and in acinar cells of mouse sublingual glands, known to contain a sialoglycoprotein. The lack of sulfated glycoconjugates in acinar cells of the mouse sublingual gland was confirmed by their failure to stain with the high iron diamine method. Thus these studies indicate that the LID and LID-TCH-SP methods are useful for the ultrastructural localization of carboxylated and sulfated glycoconjugates in extracellular and intracellular sites.


Transfusion-associated bacterial sepsis.
The incidence of sepsis caused by transfusion of bacterially contaminated blood components is similar to or less than that of transfusion-transmitted hepatitis C virus infection, yet significantly exceeds those currently estimated for transfusion-associated human immunodeficiency and hepatitis B viruses. Outcomes are serious and may be fatal. In addition, transfusion of sterile allogenic blood can have generalized immunosuppressive effects on recipients, resulting in increased susceptibility to postoperative infection. This review examines the frequency of occurrence of transfusion-associated sepsis, the organisms implicated, and potential sources of bacteria. Approaches to minimize the frequency of sepsis are discussed, including the benefits and disadvantages of altering the storage conditions for blood. In addition, the impact of high levels of bacteria on the gross characteristics of erythrocyte and platelet concentrates is described. The potentials and limitations of current tests for detecting bacteria in blood are also discussed.


Objective quality of vision in presbyopic and non-presbyopic patients after pseudoaccommodative advanced surface ablation.
To analyze the objective quality of vision at 6 months postoperatively after pseudoaccommodative (presbyopic) advanced surface ablation (PASA). The study comprised 62 eyes of 35 patients with 6-month follow-up that underwent primary or secondary treatments using PASA. Pre- and postoperative results of distance and near uncorrected visual acuity (UCVA), spherical aberration (coefficient of the Z12 Zernike polynomial), and the asphericity (Q) index were reviewed. The corresponding wavefront maps (total, low, and high order aberrations) and the corresponding point spread function and modulation transfer function (MTF) were also calculated. Our results show that PASA improves distance and near mean UCVA, increases negative spherical aberration and negative asphericity index, and improves the corresponding MTF. Pseudoaccommodative advanced surface ablation is a promising approach for the surgical correction of presbyopia with distance refractive error (myopia and hyperopia with or without astigmatism). This PASA technique could theoretically be used in non-presbyopic patients with refractive error or post cataract patients with monofocal intraocular lenses. The increase in negative spherical aberration and asphericity/eccentricity index seems to increase the depth of focus of the eye, improving the near vision and compensating the age-related lens changes. Rather than creating a multifocal cornea, PASA appears to create an improved aspheric (prolate) ablation profile.


Pituitary corticotroph adenoma containing many apoptotic cells: a histologic, immunohistochemical, ultrastructural and molecular study.
Apoptosis regulates cell turnover in normal tissues and occurs during the neoplastic process. Owing to difficulties in recognizing apoptotic cells by histology alone, several complementary approaches have been introduced, which disclosed the presence of cells with typical nuclear and cytoplasmic changes characteristic of apoptosis. Electron microscopy remains the most conclusive method to reveal the structural changes. Identification of caspase cleaved keratin 18 intermediate filament rearrangements can contribute to the identification of early apoptotic changes. The authors present here an unusual case of a pituitary corticotroph adenoma removed surgically from a young woman with Cushing disease. The tumor contained many apoptotic cells identified by histology. In addition, the apoptotic events were investigated using various morphologic techniques, including electron microscopy, the in situ end-labeling technique, and immunohistochemistry to confirm the caspase-cleaved keratin 18 rearrangements.


Various clinical presentations of tuberculosis in heart transplant recipients.
The purpose of this study was to clarify the various clinical presentations, incidence, and complications associated with tuberculosis (TB), as well as patient survival in heart transplantation (HTx) recipients. A retrospective review of 177 case records of HTx recipients from May 1989 to April 2003 were evaluated for their clinical course, diagnostic procedures, treatment, and survival. TB was diagnosed by culture. TB was proven in five (2.8%) patients. There were three pulmonary lesions and two extrapulmonary lesions. TB was diagnosed at 3.5 to 85 months after HTx. Pulmonary lesions were detected by cultures of sputum, bronchoalveolar lavage, or pleural effusion. For extrapulmonay lesions, one subject had neck lymphadenopathy shown by biopsy and culture to be TB; another suffered from swelling of the finger joints which upon culture of the aspirate proved to be TB. Treatment consisted of isoniazid (INH), rifampin (RIF), ethambutol, pyrazinamide, streptomycin (STR), ciprofloxacin (Ciproxin), and levofloxacin (Cravit). During the use of RIF, the daily dosage of cyclosporine (CsA) or tacrolimus was increased to maintain appropriate levels. Because of severe hepatotoxicity and interference with CsA, RIF was withdrawn and STR given in the last three patients. In addition, ciprofloxacin was given in the patient with miliary TB. Levofloxacin was given to the other two patients. All patients survived the TB infection under treatment with at least three drugs. There were five clinical presentations of TB in our HTx recipients. Because of the high incidence of hepatitis and severe drug interaction with CsA or tacrolimus on RIF treatment, avoiding the use of RIF but treatment with at least three drugs is recommended.


Caffeine and D2O medium interact in affecting the expression of radiation-induced potentially lethal damage.
Earlier work (Ben-Hur et al. 1980) has been extended to compare the killing of log-phase V79 Chinese hamster cells by ionizing radiation when they are treated immediately after irradiation with medium containing either caffeine or 90% D2O. The object was to determine if the enhanced killing due to post-treatment with caffeine, or D2O, resulted from action on the same sector of potentially lethal damage as appeared to be the case for hypertonic shock and D2O medium. The treatments by themselves were not toxic to unirradiated cells. We found that the enhanced expression of potentially lethal damage by post-treatment with caffeine or D2O medium is similar. For example, the kinetics of the repair of the potentially lethal damage expressible by either post-treatment was similar, and an additive enhancement of potentially lethal damage occurred when the two treatments were administered sequentially. These findings suggest that caffeine and D2O medium affect the same sector of potentially lethal damage. When the two treatments were combined, however, they competed with each other. That is, exposures to caffeine, which by themselves did not enhance killing (up to 1 mM for 2 h), decreased the enhanced killing due to D2O medium, Reciprocally, D2O medium reduced the enhanced killing due to high concentrations of caffeine (greater than 1 mM). Thus, although caffeine and D2O medium act on the same sector of potentially lethal damage they do so differently, suggesting that more than one pathway of the expression of radiation damage can result in the same phenotypic effect.


Graph-Based Hub Gene Selection Technique Using Protein Interaction Information: Application to Sample Classification.
Classification of samples of gene expression profile plays a significant role in prediction and diagnosis of diseases. In the task of sample classification, a robust feature selection algorithm is very much essential to identify the important genes from the high dimensional gene expression data. This paper explores the information of protein-protein interaction with a graph mining technique for finding a proper subset of features (genes), which further takes part in sample classification. Here, our contribution for feature selection is three-fold: first, all the genes are grouped into different clusters based on the integrated information of the gene expression values and their protein interactions using a multi-objective optimization based clustering approach. Second, the confidence scores of the protein interactions are incorporated in a popular graph mining algorithm namely Goldberg algorithm to find out the relevant features. These features are the topologically and functionally significant genes, named as hub genes. Finally, these hub genes are identified varying the degrees of the nodes, and those are utilized for the sample classification task. Different machine learning classifiers are exploited for this purpose, and the classification performance is measured with respect to various performance metrics namely accuracy, sensitivity, specificity, precision, F-measure, and Mathews coefficient correlation. Comparative analysis with respect to two baselines and several existing approaches proves the efficiency of the proposed approach. Furthermore, the robustness of the identified hub-gene modules is endorsed using some strong biological significance analysis.


Advance consent for dementia research.
Informed consent is a fundamental ethical concern for dementia research that involves the participation of human subjects. The central dilemma is how to obtain valid informed consent from a population of potential subjects who are losing their decision-making capacity while still providing adequate protection for this vulnerable group of people. One model for informed consent for dementia research would be to obtain consent in advance of the loss of decision-making capacity, perhaps using written advance directives similar to those used for clinical decisions on life-sustaining treatments. This article examines the advance consent model, contrasts the life-sustaining treatment arena with dementia research issues, and suggests that written advance consent should not be required to conduct dementia research. Instead, an argument is presented in favor of a more informal advance consent process that builds upon the existing practice of using subject assent plus proxy consent.


Differential Pattern of Cell Death and ROS Production in Human Airway Epithelial Cells Exposed to Quinones Combined with Heated-PM2.5 and/or Asian Sand Dust.
The combined toxicological effects of airborne particulate matter (PM), such as PM2.5, and Asian sand dust (ASD), with surrounding chemicals, particularly quinones, on human airway epithelial cells remain underexplored. In this study, we established an in vitro combination exposure model using 1,2-naphthoquinones (NQ) and 9,10-phenanthroquinones (PQ) along with heated PM (h-PM2.5 and h-ASD) to investigate their potential synergistic effects. The impacts of quinones and heated PM on tetrazolium dye (WST-1) reduction, cell death, and cytokine and reactive oxygen species (ROS) production were examined. Results revealed that exposure to 9,10-PQ with h-PM2.5 and/or h-ASD dose-dependently increased WST-1 reduction at 1 μM compared to the corresponding control while markedly decreasing it at 10 μM. Higher early apoptotic, late apoptotic, or necrotic cell numbers were detected in 9,10-PQ + h-PM2.5 exposure than in 9,10-PQ + h-ASD or 9,10-PQ + h-PM2.5 + h-ASD. Additionally, 1,2-NQ + h-PM2.5 exposure also resulted in an increase in cell death compared to 1,2-NQ + h-ASD and 1,2-NQ + h-PM2.5 + h-ASD. Quinones with or without h-PM2.5, h-ASD, or h-PM2.5 + h-ASD significantly increased ROS production, especially with h-PM2.5. Our findings suggest that quinones, at relatively low concentrations, induce cell death synergistically in the presence of h-PM2.5 rather than h-ASD and h-PM2.5 + h-ASD, partially through the induction of apoptosis with increased ROS generation.


The establishment of IL-2 producing cells by genetic engineering.
Expression plasmids containing human interleukin-2(IL-2) cDNA under the control of viral promoters (SV40 early region, MuLV LTR, HTLV-I LTR, and ASV (Y73) LTR) were introduced into TK- mouse L cells and human FL cells to establish IL-2 producing cells. The highest levels of IL-2 producing clones were obtained in TK+ mouse L cells transformed with a recombinant plasmid having MuLV LTR as a promoter, whereas transformed cells of human FL cells (G418r) were revealed to produce IL-2 at the highest level when the cells were transfected with a plasmid containing HTLV LTR as a promoter. These results suggest that these promoter/enhancer regions possess different cell specificities in gene expression. To obtain higher levels of IL-2 production using gene amplification, the hybrid plasmids containing the hamster DHFR and human IL-2 genes were constructed and transfected into DHFR- CHO cells. DHFR+ colonies produced IL-2 at about the same level as that produced by TK+ L cells transformed with the recombinants containing MuLV LTR. Selection of methotrexate-resistant cells resulted in a 5- to 30-fold increase of IL-2 production. These cells produced IL-2 stably for at least 3 months, even in the absence of methotrexate.


Depletion of the surface CD4 molecule by the envelope protein of human immunodeficiency virus expressed in a human CD4+ monocytoid cell line.
A CD4+ human monocytoid cell line, U937, was transfected with a constructed plasmid which has the envelope gene of human immunodeficiency virus under the transcriptional control of the human metallothionein IIA promoter and was cloned thereafter. These cloned cell lines (EH and EL cells) expressed the viral gp160 in the cytoplasm. The expression of surface CD4 antigen examined by Leu3a and OKT4 monoclonal antibodies, however, disappeared completely in EH cells, which produce a larger amount of gp160, while diminishing only partly in EL cells, which produce a smaller amount of gp160. These results indicate that the level of expression of surface CD4 antigen correlates inversely with the amount of intracellular gp160. Moreover, immunoprecipitation studies using lysate from EH cells showed that OKT4 monoclonal antibody precipitated a significant number of CD4 molecules even after surface CD4 disappeared. However, Leu3a monoclonal antibody, which recognizes the binding site for envelope protein, could not precipitate any CD4 molecules in the same cell lysate. Taken together, these results suggested that CD4 molecules are still synthesized normally after the augmented production of gp160 in the cells but form a complex with the envelope protein in the cytoplasm and become unable to be transported to the cell surface, resulting in the observed depletion of surface CD4 antigen. This mechanism may explain the decrease or absence of surface CD4 antigens in human lymphocytes infected with human immunodeficiency virus.


Prevention of spinal cord injury after cross-clamping of the thoracic aorta.
Paraplegia has been a devastating and unpredictable complication following surgical procedures involving temporary occlusion of the thoracic aorta. This study was undertaken to determine the effect of the pressure gradient between the aortic pressure distal to the occluding aortic clamp and cerebrospinal fluid pressure, defined as "Relative spinal cord perfusion pressure" (RSPP) on the development of the ischemic spinal cord injury. In twelve mongrel dogs, the thoracic aorta just distal to the left subclavian artery was cross-clamped. Somatosensory evoked potentials (SEP) were generated by peripheral stimulation of the bilateral peroneal nerves. After complete loss of SEP was evident, six dogs, Group 1, were subjected to occlusion of the descending thoracic aorta for a period of 20 minutes with maintenance of 0 mmHg of RSPP, by an injection of normal saline into the subarachnoid space. Six other dogs, Group 2, likewise underwent 40 minutes of aortic occlusion, keeping the RSPP at 15 mmHg by withdrawal of cerebrospinal fluid. All the dogs in Group 1 developed paraplegia, whereas all the dogs in Group 2 demonstrated complete postoperative recovery without any neurological sequelae. Thus, RSPP is a most important factor in the development of the ischemic spinal cord injury during the temporary thoracic aortic occlusion.


Mechanistic pathway(s) of acquired von willebrand syndrome with a continuous-flow ventricular assist device: in vitro findings.
In patients with a ventricular assist device (VAD), diminished high-molecular-weight von Willebrand factor (vWF) multimers may contribute to a bleeding diathesis. The mechanistic pathway(s) of vWF degradation and the role of ADAMTS-13, the vWF-cleaving metalloproteinase, are unknown. The objective of this study was to investigate the molecular mechanisms of VAD-induced vWF impairment in an in vitro system.Simple, mock circulatory loops (n = 4) were developed with a clinically approved, paracorporeal continuous-flow VAD. The loops were primed with anticoagulated, whole bovine blood (750 ml). The VAD was operated at constant blood flow and pressure. Blood samples were drawn at baseline and hourly for 6 hours. vWF multimers and ADAMTS-13 protein were quantified by agarose and polyacrylamide gel electrophoresis with immunoblotting. Plasma platelet factor 4 (PF4), a marker of platelet activation, was quantified via ELISA.Within 120 minutes, high-molecular-weight vWF multimers decreased, and low-molecular-weight multimers increased. Multiple low-molecular-weight vWF fragments emerged (~140, 176, 225, and 310 kDa). Total plasma ADAMTS-13 increased by 13 ± 3% (p < 0.05). Plasma PF4 increased by 21 ± 7% (p = 0.05).During VAD support, vWF degradation occurred quickly. Multiple mechanisms were responsible and included vWF cleavage by ADAMTS-13 (140 and 176 kDa fragments), and what may have been mechanical demolition of endogenous plasma vWF (225 kDa fragments) and nascent vWF (225 and 310 kDa fragments) from platelets. A modest increase in plasma ADAMTS-13 from activated platelets may have contributed to this process but was not the major mechanism. Mechanical demolition was likely the dominant process and warrants further evaluation.


First array of enriched Zn[Formula: see text]Se bolometers to search for double beta decay.
The R&D activity performed during the last years proved the potential of ZnSe scintillating bolometers to the search for neutrino-less double beta decay, motivating the realization of the first large-mass experiment based on this technology: CUPID-0. The isotopic enrichment in [Formula: see text]Se, the Zn[Formula: see text]Se crystals growth, as well as the light detectors production have been accomplished, and the experiment is now in construction at Laboratori Nazionali del Gran Sasso (Italy). In this paper we present the results obtained testing the first three Zn[Formula: see text]Se crystals operated as scintillating bolometers, and we prove that their performance in terms of energy resolution, background rejection capability and intrinsic radio-purity complies with the requirements of CUPID-0.


Modulating nitric oxide release by S-nitrosothiol photocleavage: mechanism and substituent effects.
The photochemistry and photophysics of a series of S-nitrosothiols (RSNOs) have been studied computationally. The photocleavage mechanism of the model compound CH(3)SNO to release CH(3)S· and ·NO was studied at the CASPT2 level resulting in a barrierless process when irradiating in the visible region (S(1)), in the near UV region (S(2)) and for photosensitized (T(1)) reaction. The absorption energy required to initiate photocleavage was calculated at the CASPT2 and B3P86 levels showing the possibility of the modulation of NO release by RSNO photoactivation as a function of the substituent R. Good correlations between the wavelengths of the lowest energy (1)(n,π*) and (1)(π,π*) transitions of aryl S-nitrosothiols and the corresponding Hammett constants of the substituents have been obtained.


Incarcerated gravid uterus - A systematic review.
Incarcerated gravid uterus (IGU) is a serious complication of pregnancy that leads to adverse obstetric outcomes. The aim of this review was to describe this entity in detail. We also aimed to understand if pregnancies with predisposing risk factors that increase the risk of developing IGU had a difference in their clinical manifestations, treatment, and obstetric outcomes. The PubMed, MEDLINE, Embase, Scopus databases and clinicaltrials.gov were searched from inception to July 2023. Case reports and series that provided all the details of the pregnancy and IGU outcome were included. Study quality and risk of bias were assessed using a tool that is an adaptation from criteria listed by Pierson, Bradford Hills and Newcastle Ottawa scale modification. Patients with the condition of interest included in this review were grouped into those with documented, identified risk factors and no risk factors. The two groups were compared to understand the difference in obstetric outcome and presentation of IGU. Data were analyzed and summarized descriptively, categorical variables were assessed by chi-squared test or Fisher's exact test, and continuous variables by the Wilcoxon Mann Whitney test. Of 236 articles found, 62 articles with 80 cases were included in the final analysis. The median age was 32 [27-35] years. The median gestational age of diagnosis was 17 [14-26] weeks. The most common risk factor was fibroids (N = 22, 27.5 %). Most common presentation was urinary complaints and lower abdomen pain (N = 47, 58.6 %). Twenty-seven patients (33.6 %) needed more than one visit for the diagnosis to be made. Conservative management was the first step to treat IGU in most patients. Most common complication was fetal malpresentation (N = 13, 40.6 %). Patients with or without risk factors developing IGU had no statistical difference in- parity, median gestational age of diagnosis, delay in diagnosis, increased chance of misdiagnosis, management of IGU or in obstetric outcome (all p > 0.05). It is important to recognize this entity early to prevent obstetric complications especially when patients report urinary retention and abdomen pain. The presence of risk factors does not change the management course or obstetric outcome in patients with IGU. Hence it is reasonable to start with conservative management of IGU regardless of presence of risk factors or the gestational age of diagnosis, in clinical practice.


Regulation of DENND3, the exchange factor for the small GTPase Rab12 through an intramolecular interaction.
The Rab family of small GTPases functions in multiple aspects of cellular membrane trafficking. Proteins bearing a differentially expressed in normal and neoplastic cells (DENN) domain have emerged as the largest family of Rab-activating guanine nucleotide exchange factors (GEFs). Rab12 functions in the initiation of starvation-induced autophagy, and our previous work revealed that its activator, DENN domain-containing protein 3 (DENND3), is phosphorylated and activated upon starvation. However, how the GEF activity of DENND3 toward Rab12 is regulated at the molecular level is still not understood. Here, we combine size-exclusion chromatography, Förster resonance energy transfer, pulldown, and in vitro GEF assays to demonstrate that regulation of GEF activity is achieved through an intramolecular interaction that is controlled by a key residue in DENND3, tyrosine 940. Our study sheds light on the regulation of Rab12 activation and lays the groundwork for characterizing the regulation of other DENN domain-containing proteins.


Effect of surfaces on fluid-phase prekallikrein activation.
The activation of prekallikrein by factor XII fragments (XIIf), during incubation in plastic tubes was previously noted to be increased by high molecular weight (HMW) kininogen as well as other plasma proteins. In this report, we investigated the mechanism responsible for this increase. Although we confirmed that HMW kininogen, bovine serum albumin, fibrinogen, cold insoluble globulin, and mixed phospholipids apparently increased prekallikrein activation, we found that the product of prekallikrein activation (kallikrein) lost substantial activity in less than 0.5 min after exposure to a variety of fresh surfaces. This loss was partially prevented by the presence of various proteins and phospholipids. Similar protection against inactivation of XIIf, the enzyme in this reaction, was also found. In contrast, no loss of the substrate, prekallikrein, was observed during incubation. The loss of kallikrein activity was found to be proportional to the surface area of the incubation vessel as well as the concentration of kallikrein. Further loss of kallikrein activity could also be prevented by pretreating the vessel with kallikrein. We therefore conclude that various substances apparently affect prekallikrein activation in a purified system by preventing the enzyme and product in the reaction mixture from losing activity due to adsorption to a surface.


Plasma levels of lipophilic antioxidant vitamins in acute ischemic stroke patients: correlation to inflammation markers and neurological deficits.
Acute ischemic stroke is a clinical condition accompanied by inflammation and oxidative stress. In this study, we compared levels of plasma lipophilic antioxidants and inflammation markers between patients with stroke and healthy controls and assessed the associations of antioxidants, inflammation markers, and neurologic deficits among patients with stroke. We measured plasma levels of lipophilic antioxidant vitamins (retinol, lycopene, alpha-carotene, beta-carotene, alpha-tocopherol, and gamma-tocopherol), inflammation markers (high-sensitivity C-reactive protein [hs-CRP], fibrinogen, erythrocyte sedimentation rate, and white blood cell count), and neurologic deficits (indicated by the score of the National Institute of Health Stroke Scale) in 68 patients with acute ischemic stroke within 48 h after stroke onset in comparison with 41 normal controls. Plasma alpha- and beta-carotene concentrations were lower and levels of inflammation markers were higher among patients with acute ischemic stroke compared with normal controls. Levels of alpha- and beta-carotene in patients with stroke were negatively associated with hs-CRP level (R = -0.29 and -0.41, respectively, P < 0.01) and with neurologic deficits (R = -0.28 and -0.27, respectively, P < 0.05). The negative association between neurologic deficits and combined plasma levels of alpha- and beta-carotene remained after adjustment for age and sex (P = 0.04). However, the magnitude of association decreased after adjustment of hs-CRP (P = 0.08). Plasma concentrations of alpha- and beta-carotene are lower in patients with acute ischemic stroke than in healthy controls and are negatively correlated with hs-CRP level and neurologic deficits. The negative association between neurologic deficits and combined plasma alpha- and beta-carotene levels is confounded by hs-CRP.


Knowledge, Attitudes, and Stigma Related to Dementia Among Illiterate and Literate Older Adults in Shanghai.
China has the largest population of patients with dementia worldwide, no assessment of illiterate old population's dementia knowledge, attitudes, stigma have been conducted so far in China. This study focused on the impact of education on knowledge, attitudes, and stigma related to dementia. The community-based sample used in this study was recruited using multi-stage random sampling from residents aged ≥60 years registered in Shanghai. We used the Geriatric Depression Scale (GDS-30) to identify depression, and the Ascertain Dementia 8 questionnaire (AD8) for evaluating participants' cognitive impairment. Knowledge, Attitude, Belief, and Practice scale, Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) were used for measuring dementia knowledge, attitudes, stigma. We separated the population into illiterate and literate group, propensity score matching based on age, sex, depression, and cognitive impairment. We calculated the difference of knowledge, attitudes, and stigma related to dementia between illiterate and literate groups. Two thousand five hundred and eighteen participants completed the survey. After propensity score matching, 186 pairs of matched participants left. The overall correct rate of dementia knowledge was 70.34%. The illiterate group had a lower percentage of correct answers for each knowledge item. The item "Dementia is not a disease, it is forgetfulness due to aging" had the lowest accuracy rate in both groups (38.71% vs. 50.54%, p=0.022). Illiterate older adults were less accepting of dementia than literate older adults. The majority of participants did not agree that: "There is no need to visit a doctor when older people have memory loss, difficulty communicating, or finding words" (56.99% vs. 68.28%). Illiterate older adults had higher scores for the items assessing stigma toward dementia than literate older adults. Dementia-related knowledge and attitudes among community-dwelling older adults in Shanghai may be related to literacy.


Modulation of resistance to anticancer drugs by inhibition of metallothionein synthesis.
The expression of metallothionein (MT) in certain tumor cells has been associated with resistance to anticancer drugs. In the present study, we examined the effects of inhibition of MT synthesis on resistance to anticancer drugs of human bladder tumor which were inoculated in nude mice. The results show that pretreatment of tumor-bearing mice with zinc salts increased MT content, both in normal and tumor tissues, with a marked reduction in the antitumor activity of cisplatin, Adriamycin, and melphalan. Injection of propargylglycine, an inhibitor of cystathionase, decreased MT induction by zinc in the tumor and diminished the resistance to these drugs. These results suggest a role for MT in drug resistance in tumors, and injection of propargylglycine may provide a potential means to overcome drug resistance caused by elevation of MT levels in certain tumors.


Initial treatment of transplant-eligible patients in multiple myeloma.
Induction therapy followed by intensification with ASCT is the standard of care in younger patients with multiple myeloma. Three-drug induction regimens combining novel agents (VTD, VRD, VCD, PAD) have shown a high CR rate both, pretransplant and posttransplant. Patients with high-risk cytogenetics continues to have an inferior outcome even when treated with novel agents. The role of tandem autologous stem cell transplant (ASCT) is not well established, although some studies show a better outcome with tandem ASCT as compared to single auto. The high response rate obtained with novel agents also raises the question if autologous transplant has a role in front-line therapy or if it should be used as savage therapy after relapse.


Preparation of carbamazepine-Soluplus solid dispersions by hot-melt extrusion, and prediction of drug-polymer miscibility by thermodynamic model fitting.
Hot-melt extrusion (HME) is a dust- and solvent-free continuous process enabling the preparation of a variety of solid dosage forms containing solid dispersions of poorly soluble drugs into thermoplastic polymers. Miscibility of drug and polymer is a prerequisite for stable solid dispersion formation. The present study investigates the feasibility of forming solid dispersions of carbamazepine (CBZ) into polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus) by hot-melt extrusion. Physicochemical properties of the raw materials, extrudates, co-melted products, and corresponding physical mixtures were characterized by thermo-gravimetric analysis (TGA), differential scanning calorimetry (DSC), attenuated total reflectance infrared (ATR-FTIR) spectroscopy and hot stage microscopy (HSM), while miscibility of CBZ and Soluplus was estimated on the basis of the Flory-Huggins theory, Hansen solubility parameters, and solid-liquid equilibrium equation. It was found that hot-melt extrusion of carbamazepine and Soluplus is feasible on a single-screw hot-melt extruder without the addition of plasticizers. DSC analysis and FTIR spectroscopy revealed that a molecular dispersion is formed when the content of CBZ does not exceed ∼5% w/w while higher CBZ content results in a microcrystalline dispersion of CBZ form III crystals, with the molecularly dispersed percentage increasing with extrusion temperature, at the risk of inducing transformation to the undesirable form I of CBZ. Thermodynamic modeling elucidated potential limitations and temperature dependence of solubility/dispersibility of carbamazepine in Soluplus hot-melt extrudates. The results obtained by thermodynamic models are in agreement with the findings of the HME processing, encouraging therefore their further application in the HME process development.


Identification of Escherichia coli O157:H7 and other enterohemorrhagic serotypes by EHEC- hlyA targeting, strand displacement amplification, and fluorescence polarization.
Human disease caused by enterohemorrhagic E. coli O157:H7 and other serotypes (EHEC) has been associated with bovine fecal contamination of food and the environment. The range of serotypes, low infectious dose, and numerous transmission vehicles for EHEC render development of detection methods for this pathogen complex. In this study, the hemolysin gene (EHEC- hly A) was targeted with oligonucleotides, and probe-target hybrids were amplified using strand displacement amplification (SDA). Amplicons were resolved in the complete reaction mix through changes in the fluorescence polarization (FP) of a fluorescein-labeled detector probe hybridized to the amplicons during amplification. Results combining EHEC- hly A, SDA, and FP were obtained within 35 min of reaction initiation. The test specificity was determined on EHEC strains representing 13 serotypes (49 isolates); and control uropathogenic, commensal, and other organisms (10 isolates). Statistical analysis of results indicated a sensitivity in the reaction vessel to 4.3 bacteria (95% confidence interval), and a specificity for EHEC (n=59) at 100% (P=5.11E-17; i.e. P<<0.05). Detection based on combining EHEC- hly A, SDA, and FP was compatible with water sources directly associated with human infection (drinking and recreational supplies), and bovine drinking trough water representing an environmental matrix linked to the maintenance of an EHEC animal reservoir.


Evaluation of resveratrol and piceatannol cytotoxicity in macrophages, T cells, and skin cells.
The cytotoxicity of resveratrol and of piceatannol, a structural analog of resveratrol, was examined in cultured cells. Using a MTT-based assay, which measures the conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) to a colored formazan product in living cells, resveratrol was found to inhibit the viability of transformed mouse macrophages, tumor-derived human T cells and human epidermoid carcinoma cells in a concentration-dependent manner, with the effect decreasing in the order: T cells (LC50 approximately 27 micromol L(-1), 24 h; approximately 9 micromol L(-1); 48 h)>macrophages (LC50 approximately 29 micromol L(-1), 24 h; 39 micromol L(-1), 48 h)>skin cells (LC50 approximately 91 micromol L(-1), 24 h; approximately 66 micromol L(-1), 48 h). Paradoxically, a high concentration of resveratrol (50 micromol L(-1)) inhibited the proliferation of all three cell types, and a low concentration (5 micromol L(-1)) stimulated the proliferation of macrophages. The viability of macrophages was also decreased by piceatannol in a concentration-dependent manner. The stimulation of macrophages with zymosan lowered the cytotoxicity of both resveratrol and piceatannol. Scanning electron microscopy of cells treated with resveratrol revealed changes in cellular morphology that were consistent with toxicity. In macrophages and skin cells, resveratrol (50 micromol L(-1)) induced a time-dependent increase in reduced glutathione levels but did not alter the background levels of thiobarbituric acid-reactive substances. Taken together, the present data indicate that resveratrol is toxic to cultured macrophages, T cells and skin cells at concentrations>or=25 micromol L(-1), and that the cytotoxicity occurs via a mechanism that does not involve oxidative stress. Furthermore, the degree of toxicity of both resveratrol and piceatannol towards macrophages depends on the activation status of these cells, with zymosan-activated cells appearing more resistant than nonstimulated cells.


Non-ketotic hyperglycinemia as the cause of infant seizures--the case study.
Non-ketotic hyperglycinemia is a disease that causes serious functional disorders of CNS and the degradation of its structure. The frequency of recognition of this disease is disproportionally low with relation to the number of unexplained deaths of the neonates. We present a case of a neonate in whom the seizures occurred during the first 24 hours of life. A detailed subsequent diagnosis of the seizures by excluding inflammatory reasons, electrolyte disorders and primary neurological reasons was done. The final diagnosis of NKH was based on high concentration of glycine in the blood serum, craniospinal fluid and elevated value of Scriver index, lack of ketosis, changes in EEG tests, (initially the record of "discharge-silence" type, and next the record of hypsarrhythmia type), hypotony of the muscular system and imaging tests of CNS. The taken up treatment decreased the intensity and the frequency of seizure attacks, caused the increase of muscular tone and of motor activity of the child.


Defining and monitoring indwelling catheter-related urinary tract infections.
Defining and monitoring infection rates in home care is of major importance with the implementation of Adverse Event Outcome Reports. This study identifies the collective effort of home care quality improvement nurses in defining standard indicators for urinary tract infections and the ways to monitor these infections within and across home care agencies for evaluation and benchmarking.


Divergent Pathogenic Properties of Circulating Coxsackievirus A6 Associated with Emerging Hand, Foot, and Mouth Disease.
Coxsackievirus A6 (CV-A6) is an emerging pathogen associated with hand, foot, and mouth disease (HFMD). Its genetic characterization and pathogenic properties are largely unknown. Here, we report 39 circulating CV-A6 strains isolated in 2013 from HFMD patients in northeast China. Three major clusters of CV-A6 were identified and related to CV-A6, mostly from Shanghai, indicating that domestic CV-A6 strains were responsible for HFMD emerging in northeast China. Four full-length CV-A6 genomes representing each cluster were sequenced and analyzed further. Bootscanning tests indicated that all four CV-A6-Changchun strains were most likely recombinants between the CV-A6 prototype Gdula and prototype CV-A4 or CV-A4-related viruses, while the recombination pattern was related to, yet distinct from, the strains isolated from other regions of China. Furthermore, different CV-A6 strains showed different capabilities of viral replication, release, and pathogenesis in a mouse model. Further analyses indicated that viral protein 2C contributed to the diverse pathogenic abilities of CV-A6 by causing autophagy and inducing cell death. To our knowledge, this study is the first to report lethal and nonlethal strains of CV-A6 associated with HFMD. The 2C protein region may play a key role in the pathogenicity of CV-A6 strains.IMPORTANCE Hand, foot, and mouth disease (HFMD) is a major and persistent threat to infants and children. Besides the most common pathogens, such as enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16), other enteroviruses are increasingly contributing to HFMD. The present study focused on the recently emerged CV-A6 strain. We found that CV-A6 strains isolated in Changchun City in northeast China were associated with domestic origins. These Changchun viruses were novel recombinants of the CV-A6 prototype Gdula and CV-A4. Our results imply that measures to control CV-A6 transmission are urgently needed. Further analyses revealed differing pathogenicities in strains isolated in a neonatal mouse model. One of the possible causes has been narrowed down to the viral protein 2C, using phylogenetic studies, viral sequences, and direct tests on cultured human cells. Thus, the viral 2C protein is a promising target for antiviral drugs to prevent CV-A6-induced tissue damage.


Context-dependent third-party intervention in agonistic encounters of male Przewalski horses.
One mechanism to resolve conflict among group members is third party intervention, for which several functions, such as kin protection, alliance formation, and the promotion of group cohesion have been proposed. Still, empirical research on the function of intervention behaviour is rare. We studied 40 cases of intervention behaviour in a field study on 13 semi-wild bachelor horses (Equus ferus przewalskii) in (a) standard social situations, and (b) when new horses joined the group (i.e. introductions). Only interventions in agonistic encounters were analysed. Eight of 13 animals directed intervention behaviour toward threatening animal in agonistic encounters of group members. One stallion was particularly active. The stallions did not intervene to support former group mates or kin and interventions were not reciprocated. In introduction situations and in standard social situations, the interveners supported animals which were lower in rank, but targeted, threatening animals of comparable social rank. After introductions, stallions received more affiliative behaviour from animals they supported and thus appeared to intervene for alliance formation. In standard social situations, interveners did not receive more affiliative behaviour from animals they supported and may primarily have intervened to promote group cohesion and to reduce social disruption within the group.


Outbreaks Associated with Untreated Recreational Water - California, Maine, and Minnesota, 2018-2019.
Outbreaks associated with fresh or marine (i.e., untreated) recreational water can be caused by pathogens or chemicals, including toxins. Voluntary reporting of these outbreaks to CDC's National Outbreak Reporting System (NORS) began in 2009. NORS data for 2009-2017 are finalized, and data for 2018-2019 are provisional. During 2009-2019 (as of May 13, 2020), public health officials from 31 states voluntarily reported 119 untreated recreational water-associated outbreaks, resulting at least 5,240 cases; 103 of the outbreaks (87%) started during June-August. Among the 119 outbreaks, 88 (74%) had confirmed etiologies. The leading etiologies were enteric pathogens: norovirus (19 [22%] outbreaks; 1,858 cases); Shiga toxin-producing Escherichia coli (STEC) (19 [22%]; 240), Cryptosporidium (17 [19%]; 237), and Shigella (14 [16%]; 713). This report highlights three examples of outbreaks that occurred during 2018-2019, were caused by leading etiologies (Shigella, norovirus, or STEC), and demonstrate the wide geographic distribution of such outbreaks across the United States. Detection and investigation of untreated recreational water-associated outbreaks are challenging, and the sources of these outbreaks often are not identified. Tools for controlling and preventing transmission of enteric pathogens through untreated recreational water include epidemiologic investigations, regular monitoring of water quality (i.e., testing for fecal indicator bacteria), microbial source tracking, and health policy and communications (e.g., observing beach closure signs and not swimming while ill with diarrhea).


Description and Phylogeny of Urostyla grandis wiackowskii subsp. nov. (Ciliophora, Hypotricha) from an Estuarine Mangrove in Brazil.
Interphase specimens, aspects of physiological reorganization and divisional morphogenesis were investigated in a strain of a hypotrichous ciliate highly similar to Urostyla grandis Ehrenberg, (type species of Urostyla), collected from a mangrove area in the estuary of the Paraíba do Sul river (Rio de Janeiro, Brazil). The results revealed that albeit interphase specimens match with the known morphologic variability in U. grandis, morphogenetic processes have conspicuous differences. Parental adoral zone is entirely renewed during morphogenesis, and marginal cirri exhibit a unique combination of developmental modes, in which left marginal rows originate from multiple anlagen arising from innermost left marginal cirral row, whereas right marginal ciliature originates from individual within-row anlagen. Based on such characteristics, a new subspecies, namely U. grandis wiackowskii subsp. nov. is proposed, and consequently, U. grandis grandis Ehrenberg, stat. nov. is established. Bayesian and maximum-likelihood analyses of the 18S rDNA unambiguously placed U. grandis wiackowskii as adelphotaxon of a cluster formed by other U. grandis sequences. The implications of such findings to the systematics of Urostyla are discussed.


[Advances in pathogenesis of psoriasis].
The pathogenesis of psoriasis recently made great advancement due to the introduction of transgenic mouse model. K14-VEGF transgenic mouse showed many of the cellular and molecular features of psoriasis, including angiogenesis in dermis, altered epidermal proliferation and differentiation. Psoriasis of early onset and severe disease showed significantly increased frequency of the +405CC genotype and the C allele. Transgenic mice with keratinocytes expressing active Stat3 (K5. Stat3C mice) developed a skin phenotype closely resembling psoriasis. Stat 3 may link activated keratinocytes and immunocytes required for development of psoriasis. More recently, a novel mouse model with epidermal specific double-knockout of the c-Jun and JunB genes showed developments of psoriasis-like skin phenotype and arthritic lesions. All these data provided more profound understanding in pathogenesis and therapy of psoriasis.


Exploring the Potential of Natural Products as Antiparasitic Agents for Neglected Tropical Diseases.
Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.


Development of bacterial resistance to several biocides and effects on antibiotic susceptibility.
The aims of this study were to investigate the development of bacterial resistance to eugenol, thymol, trichlorocarbanalide (TCC), didecyldimethylammonium chloride (DDDMAC) and C10-16-alkyldimethyl, N-oxides (ADMAO) and subsequent effects on antibiotic susceptibility. An agar minimum inhibitory concentration (MIC) method was used to assess the activity of the biocides against standard bacterial strains and laboratory mutants. A range of techniques including disk diffusion and gradient plate experiments were used to attempt to develop bacterial 'resistance' or tolerance to the biocides. The mutants produced were examined for cross-resistance to the other biocides and to antibiotics via disk diffusion and gradient plate MIC methods. Outer membrane proteins of the mutants were extracted and examined using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Escherichia coli triclosan-resistant mutants were not cross-resistant to eugenol, thymol, TCC, DDDMAC and ADMAO. Mutants with elevated MICs to DDDMAC (E. coli and Pseudomonas aeruginosa), thymol (E. coli) and eugenol (E. coli) were isolated, but all remained sensitive to higher concentrations of the agents. Bacteria with elevated MICs to TCC and ADMAO were not obtained. Some low-level cross-resistance between DDDMAC, eugenol and thymol was observed with the E. coli gradient plate mutants, as well as reduced susceptibility to antibiotics, most notably chloramphenicol. The lack of cross-resistance of the triclosan mutants suggested that the mode of action of triclosan is not shared with the other biocides studied. SDS-PAGE results indicated that the DDDMAC P. aeruginosa mutant had a reduced amount (or absence) of one outer membrane protein in comparison with the standard strain. In conclusion, under laboratory conditions, bacterial exposure to thymol, eugenol and DDDMAC can lead to reduced susceptibility between selected biocidal agents and antibiotics, more specifically, chloramphenicol. However, further studies are required to determine if this is of clinical significance.


Pattern of adult leukemias at Al-Jomhori Educational Hospital, Sana'a, Yemen.
There is lack of information about leukemias in Yemen. The purpose of this study is to evaluate the pattern of adult leukemias at Al-Jomhori Educational Hospital in Sana'a, Yemen and to compare it with available data from Saudi Arabia. Data concerning age, sex, area of residence whether rural or urban and the type of leukemia were collected and analyzed. The age range of patients was 15 to 96 years. Diagnosis was based on bone marrow aspiration cytology and cytochemistry. Between November 1999 and November 2003 a total of 169 cases of leukemia were diagnosed. AML was the most common (39.1%) followed in descending order by CML (25.4%), ALL (23.7%) and CLL (11.8%). The male to female ratio was 1.14: 1 for all the types, 1.06: 1 for AML, 2.64: 1 for ALL, 0.65: 1 for CML and 1: 1 for CLL. AML was most common among patients aged 40-59 years old (30.3%) followed by ≥ 60 years old (25.8%). ALL was most common among young patients < 20 years old and CLL among elderly patients whereas CML was most common among middle aged patient. The rural to urban residence ratio was 2.8: 1 for all the types. Leukemia is an important health problem in Yemen and the pattern of adult leukemias is comparable in certain aspects to that reported from different regions of Saudi Arabia. The study recommends implementation of preventive, diagnostic and therapeutic strategies for leukemias in Yemen.


Serum lipoproteins during chemical carcinogenesis.
1. The serum-protein and -lipoprotein patterns of rats, given a purified diet containing 0%, 0.005% or 0.03% 2-acetamidofluorene, have been determined by disk electrophoresis. 2. An abnormal high-density lipoprotein was detected from the first week of the experiment in the serum of the animals given the carcinogen. The low-density lipoproteins also increased on prolonged feeding with the carcinogen.


Identification of DELLA gene family in head cabbage and analysis of mRNA transport in the heterograft.
DELLA gene family is involved in the regulation of signal transduction of plant hormones. mRNAs of GA insensitive (GAI), the member of DELLA gene family, are also signaling molecules of long-distance transport in plants. Genome-wide identification and mRNA transport analysis of the members of DELLA gene family in head cabbage (Brassica oleracea var. capitata) can provide basic data for their application in head cabbage. In this study, five members of DELLA gene family (BoRGA1, BoRGA2, BoRGL1, BoRGL2, and BoRGL3) were identified in head cabbage using genome and transcriptome data. However, head cabbage lacked a GAI gene in its genome. The scion (head cabbage, inbred line G27) and the rootstock Chinese flowering cabbage (Brassica campestris L. ssp. chinensis var. utilis Tsen et Lee) (sijiucaixin) were cleft-grafted together to produce the heterograft. Inflorescence stem of the rootstock and the corresponding inflorescence stem in Chinese flowering cabbage seedlings (as controls) were purified and analyzed with transcriptome sequencing. The total of 8, 9, 3, 5, and 1 exogenous read(s), derived respectively from BoRGA1, BoRGA2, BoRGL1, BoRGL2, and BoRGL3, were identified in the transcriptomes of the rootstocks. Nevertheless, mRNA transport of DELLA family genes from scion to rootstock did not increase the transcriptional level of the members of DELLA gene family in the rootstocks. Correlation analysis suggested that mRNA transport efficiency of the DELLA family genes was correlated with the sequence and the transcriptional level of the respective DELLA gene in the scion (head cabbage). This study lays the foundation for further investigation on the molecular mechanism of mRNA transport of the members of DELLA gene family in head cabbage.


Leukocyte- and platelet-rich fibrin as an adjuvant to the surgical approach for osteoradionecrosis: a case report.
We present a case of osteoradionecrosis treated with leukocyte- and platelet-rich fibrin (LPRF) and surgery and followed up with clinical and tomographic investigations. A 65-year-old woman presented with pain in the posterior region of the right palate. Her medical history included cardiovascular disease and squamous cell carcinoma in the anterior region of the floor of the mouth that had been treated with intensity-modulated radiation therapy. Measurements of isodose curves showed a full dosage of 6,462.6 cGy in the anterior mandibular region, whereas that in the posterior region on the right side of the maxilla reached 5,708.1 cGy. Osteotomy was performed using rotary instruments, and debridement and placement of two LPRF membranes were also carried out. New gum tissue with no bone exposure was noted 14 days postoperatively. Tissue repair was complete, and the patient had no further complaints. During a 39-month follow-up period, the oral mucosa remained intact, and the patient was rehabilitated with a new upper denture. Since there is no consensus regarding the best protocol to treat osteoradionecrosis, LPRF might be an interesting adjuvant to a surgical approach. The use of LPRF is simple and reduces operational costs, time of handling, probability of technical failure, and associated morbidities for patients with osteoradionecrosis.


QSAR study of natural, synthetic and environmental endocrine disrupting compounds for binding to the androgen receptor.
A large data set of 146 natural, synthetic and environmental chemicals belonging to a broad range of structural classes have been tested for their relative binding affinity (expressed as log (RBA)) to the androgen receptor (AR). These chemicals commonly termed endocrine disrupting compounds (EDCs) present a variety of adverse effects in humans and animals. As assays for binding affinity remains a time-consuming task, it is important to develop predictive methods. In this work, quantitative structure-activity relationships (QSARs) were determined using three methods, multiple linear regression (MLR), radical basis function neural network (RBFNN) and support vector machine (SVM). Five descriptors, accounting for hydrogen-bonding interaction, distribution of atomic charges and molecular branching degree, were selected from a heuristic method to build predictive QSAR models. Comparison of the results obtained from three models showed that the SVM method exhibited the best overall performances, with a RMS error of 0.54 log (RBA) units for the training set, 0.59 for the test set, and 0.55 for the whole set. Moreover, six linear QSAR models were constructed for some specific families based on their chemical structures. These predictive toxicology models, should be useful to rapidly identify potential androgenic endocrine disrupting compounds.


The use and uptake of pupillometers in the Intensive Care Unit.
Traumatic brain injury (TBI) is a significant public health issue. Assessing pupil reactivity is a crucial aspect of its management and the pupillometer has been shown to be a more objective tool compared to the standard penlight. Its use, however, is not widespread. To investigate the paucity in uptake, we examined the frequency of use of pupillometers (NeurOptics®NPi-100™) amongst Intensive Care Unit (ICU) doctors and nurses, evaluated its user-friendliness and explored barriers to its use. An online cross-sectional survey. Surveys were distributed five months after the introduction of pupillometers (in May 2015) to ICU doctors and nurses working in a quaternary referral centre providing state services for trauma. The survey included sections on: questions on demographics and experience, methods of conventional pupillary assessment in patients with TBI, experience of using the pupillometer, and questions on barriers to its use. Responses were collated as discrete variables and summarised using counts and proportions. Comparisons among proportions were undertaken using the chi-squared test and reported with 95% confidence intervals. A total of 79 responses were recorded, predominantly 94.9% (n=75) from nursing staff. A total of 50 (63.3%) responders were using the pupillometers, with a mean frequency-of-use rating of 4.67 out of 10 and a mean user-friendliness rating of 6.28 out of 10. There was no association between frequency of use and user-friendliness (p=0.36). The main identified barriers to its use included a lack of education with regards to its use, a perceived lack of clinical significance, a lack of standardisation of documenting findings, and difficulties with access to disposable patient shields (Smartguards). There was good adoption of the technology in the early phases of ICU implementation with user-friendliness rated favourably. In this paper we identify barriers to use and discuss possible solutions to increase clinical utility.


Salicylic acid attenuates gentamicin-induced nephrotoxicity in rats.
Gentamicin (GM) is a widely used antibiotic against serious and life-threatening infections, but its usefulness is limited by the development of nephrotoxicity. The present study was designed to determine the protective effect of salicylic acid (SA) in gentamicin-induced nephrotoxicity in rats. Quantitative evaluation of gentamicin-induced structural alterations and degree of functional alterations in the kidneys were performed by histopathological and biochemical analyses in order to determine potential beneficial effects of SA coadministration with gentamicin. Gentamicin was observed to cause a severe nephrotoxicity which was evidenced by an elevation of serum urea and creatinine levels. The significant increases in malondialdehyde (MDA) levels and protein carbonyl groups indicated that GM-induced tissue injury was mediated through oxidative reactions. On the other hand, simultaneous SA administration protected kidney tissue against the oxidative damage and the nephrotoxic effect caused by GM treatment. Exposure to GM caused necrosis of tubular epithelial cells. Necrosis of tubules was found to be prevented by SA pretreatment. The results from our study indicate that SA supplement attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation in gentamicin-treated rats.


A compositional mediation model for a binary outcome: Application to microbiome studies.
The delicate balance of the microbiome is implicated in our health and is shaped by external factors, such as diet and xenobiotics. Therefore, understanding the role of the microbiome in linking external factors and our health conditions is crucial to translate microbiome research into therapeutic and preventative applications. We introduced a sparse compositional mediation model for binary outcomes to estimate and test the mediation effects of the microbiome utilizing the compositional algebra defined in the simplex space and a linear zero-sum constraint on probit regression coefficients. For this model with the standard causal assumptions, we showed that both the causal direct and indirect effects are identifiable. We further developed a method for sensitivity analysis for the assumption of the no unmeasured confounding effects between the mediator and the outcome. We conducted extensive simulation studies to assess the performance of the proposed method and applied it to real microbiome data to study mediation effects of the microbiome on linking fat intake to overweight/obesity. An R package can be downloaded from https://github.com/mbsohn/cmmb. Supplementary files are available at Bioinformatics online.


Dynamic structures of motor proteins myosin and kinesin, and switch protein troponin as detected by SDSL-ESR.
We have studied biological nano-machines, motor and switch proteins operating as supramolecular complexes by electron spin resonance (ESR) and found key features of their molecular movements. In all the systems, the specific movements of elements or domains were detected and quite dynamic at nanometer scale. We have observed two broad but distinct orientations, separated by a 25 degrees axial rotation, of a spin label attached specifically to the light chain (LC) domain of myosin motor in the muscle fibers. The distribution became only narrower upon muscle activation. ESR spectrum from the spin label of the neck-linker of dimeric kinesin motor consisted of immobilized and mobilized components and did not exhibit nucleotide-dependent mobility change. The distance between two labels of kinesin dimer was also measured by spin dipole-dipole interaction, showing a broad distribution and a nucleotide-dependent change on the nanometer scale (>1.5 nm). These results suggest that two LC domains of myosin and two neck linkers of kinesin play a similar role for sliding movement using two conformations. The spin label of the skeletal (Tn)-I regulatory domain (TnIreg) showed a large mobility change by Ca2+ ion suggesting a Ca-induced switch movement of TnIreg. Spin dipole-dipole interaction showed that in reconstituted muscle fibers both skeletal and cardiac TnC undergo Ca2+-induced structural change that is thought to be essential for TnIreg movement. We also succeeded in fixing the newly-synthesized bifunctional spin label rigidly on the TnC molecule in solution, indicating that we can determine the precise coordinate of the spin principal axis of troponin on the oriented filament.


The evolution of payoff matrices: providing incentives to cooperate.
Most of the work in evolutionary game theory starts with a model of a social situation that gives rise to a particular payoff matrix and analyses how behaviour evolves through natural selection. Here, we invert this approach and ask, given a model of how individuals behave, how the payoff matrix will evolve through natural selection. In particular, we ask whether a prisoner's dilemma game is stable against invasions by mutant genotypes that alter the payoffs. To answer this question, we develop a two-tiered framework with goal-oriented dynamics at the behavioural time scale and a diploid population genetic model at the evolutionary time scale. Our results are two-fold: first, we show that the prisoner's dilemma is subject to invasions by mutants that provide incentives for cooperation to their partners, and that the resulting game is a coordination game similar to the hawk-dove game. Second, we find that for a large class of mutants and symmetric games, a stable genetic polymorphism will exist in the locus determining the payoff matrix, resulting in a complex pattern of behavioural diversity in the population. Our results highlight the importance of considering the evolution of payoff matrices to understand the evolution of animal social systems.


Advanced pairwise structure alignments of proteins and analysis of conformational changes.
Comparing the 3D structures of two proteins or analyzing the structural changes undergone by a protein upon ligand binding or when it crystallizes under different conditions, can be both tricky and tedious, especially when the two proteins are distantly related, or when the structural changes are complex. Readily accessible tools for performing these tasks automatically and reliably should therefore be welcome. We describe a web interface to several automatic procedures for performing pairwise structure superposition in a flexible manner, for detailed analyses of conformational changes and for displaying the results in a pictorial fashion. This interface can be accessed at the Brussels and Cuba Web sites, respectively: http://www.ucmb.ulb.ac.be/SCMBB/Tools.htmland http://bio.cigb.edu.cu.


The use of isotretinoin in low doses and unconventional treatment regimens in different types of acne: a literature review.
High effectiveness of isotretinoin treatment for severe types of acne resistant to antibiotics has been widely recognized. However, the recommended doses in conventional therapy, according to consensus of the Polish Dermatological Society, may cause serious adverse effects. Thus, research into less stressful, alternative treatment regimens with the use of low doses of isotretinoin has been carried out. The aim of the paper was to review the selected papers where authors present the results of their studies on different regimens with the use of isotretinoin in low doses in patients with acne, evaluate their efficacy, patient satisfaction, frequency of adverse effects, recurrences and also treatment costs.


Mesenchymal hamartoma of the liver in a late-term equine fetus.
Mesenchymal hamartoma of the liver is a rare congenital disorder of biliary tract development. During the necropsy of a late-term equine fetus, a markedly enlarged liver of more than two times normal weight was found. Light microscopic review revealed that the normal hepatic parenchyma had been obliterated, replaced, and expanded by abnormal bile ducts surrounded by abundant, myxoid stroma. The lesion was diagnosed as a mesenchymal hamartoma. Small portions of the liver had bridging septa of fibrosis and proliferations of small-caliber abnormal bile ducts, resembling another congenital biliary abnormality termed congenital hepatic fibrosis.


Effects of catalyst pore structure and acid properties on the dehydration of glycerol.
Hierarchical porous catalysts have recently attracted increasing interest because of the enhanced accessibility to active sites on such materials. In this context, previously reported hierarchically mesoporous ASN and ASPN materials are evaluated by applying them to the dehydration of glycerol, and demonstrate excellent catalytic performance. In addition, a comprehensive understanding of the effects of pore structures and the acid properties on the reaction through comparative studies with microporous HZSM-5 and mesoporous AlMCM-41 is provided.


Molecular evaluation of phylogenetic significances in the highly divergent karyotypes of the genus Gonocephalus (Reptilia: Agamidae) from tropical Asia.
The Oriental large-bodied crested dragons of the genus Gonocephalus are known to include two distinct karyomorphs. To evaluate their phylogenetic significances, we conducted phylogenetic analyses of the genus together with other agamid genera on the basis of 862 base positions of mitochondrial 12S and 16S rRNA genes. Results suggested the presence of two distinct lineages within Gonocephalus, of which one, represented by G. robinsonii that has a 2n = 32 karyotype, was closer to other Oriental agamid genera than to the other congeneric lineage. Monophyly of the latter, characterized by unique chromosomal arrangement among agamid genera (2n = 42 karyotype), was confirmed. It is thus likely that states of morphological characters shared between the two lineages are derived through convergence, or represent symplesiomorphy. Our results also suggest that the karyological similarity between G. robinsonii and several Australian agamids, pointed out in a previous study, is actually attributable to homoplasy rather than their recent common ancestry.


Drug release behavior from nanoporous anodic aluminum oxide.
In this study, we developed a new drug delivery system using anodic oxidation. The growth of a porous oxide layer on aluminum under anodic bias in various electrolytes has been studied for more than 40 years. Anodic Aluminum Oxide (AAO) has many uniform nanopores on its surface. This nanoporous surface can be used for drug storage. The effects of the diameter and depth of the AAO on the release characteristics of a drug were investigated. Paclitaxel was used for the drug loading and release test. Paclitaxel was loaded on the inside of the AAO by ultrasonication. The amount of the drug released from the AAO was analyzed by high performance liquid chromatography (HPLC). The pore size did not affect the drug release behavior. However, the depth of the pores had a significant influence on the release rate of the drug.


A Role for the RSC chromatin remodeler in regulating cohesion of sister chromatid arms.
The precise segregation of chromosomes is critical for the proliferation and development of living organisms. Defects in this process can result in tumorigenesis and hereditary diseases. The four-subunit cohesin complex plays an essential role in chromosome segregation and genome integrity. Recently, we reported that the association of cohesin with centromeres and chromosome arms is differentially regulated by the ATP-dependent RSC chromatin-remodeling complex. Here, we propose two models to explain why the cell should have evolved special mechanisms for centromeric and sister arm cohesion and why RSC differentially regulates these processes.


A family intervention to reduce delirium in hospitalised ICU patients: A feasibility randomised controlled trial.
Family members could play an important role in preventing and reducing the development of delirium in Intensive Care Units (ICU) patients. This study sought to assess the feasibility of design and recruitment, and acceptability for family members and nurses of a family delivered intervention to reduce delirium in ICU patients. A single centre randomised controlled trial in an Australian medical/surgical ICU was conducted. Sixty-one family members were randomised (29 in intervention and 32 in non-intervention group). Following instructions, the intervention comprised the family members providing orientation or memory clues (family photographs, orientation to surroundings) to their relative each day. In addition, family members conducted sensory checks (vision and hearing with glasses and hearing aids); and therapeutic or cognitive stimulation (discussing family life, reminiscing) daily. Eleven ICU nurses were interviewed to gain insight into the feasibility and acceptability of implementing the intervention from their perspective. Recruitment rate was 28% of eligible patients (recruited n=90, attrition n=1). Following instruction by the research nurse the family member delivered the intervention which was assessed to be feasible and acceptable by family members and nurses. Protocol adherence could be improved with alternative data collection methods. Nurses considered the activities acceptable. The study was able to recruit, randomise and retain family member participants. Further strategies are required to assess intervention fidelity and improve data collection.


Displacement profile of charge density waves and domain walls at critical depinning.
The influence of a strong surface potential on the critical depinning of an elastic system driven in a random medium is considered. If the surface potential prevents depinning completely the curvature C of the displacement profile exhibits at zero temperature a pronounced rhombic hysteresis curve of width 2f(c) with the bulk depinning threshold f(c). The hysteresis disappears at nonzero temperatures if the driving force is changed adiabatically. If the surface depins by the applied force or thermal creep, C is reduced with increasing velocity. The results apply, e.g., to driven magnetic domain walls, fluxline lattices, and charge-density waves.