The isolation of fungi from laboratory dental pumice.
Samples of used dental laboratory pumice from the two dental laboratories were cultured for the isolation of fungi. The resulting supernatant fluid from sedimentation of each pumice sample after suspension in sterile saline was serially diluted and plated onto Sabouraud agar. After incubation, fungal colonies observed were enumerated, isolated, and identified. The mean number of fungal colonies recovered from 10 pumice samples in laboratories I and II was 51.0 X 10(2) and 22.6 X 10(2), respectively. In both laboratories the predominant fungi recovered were Aspergillus niger and Fusarium sp. Other fungi recovered included Cephalosporium and Penicillium species and A. flavus. Many of these organisms have been involved in human disease. It is suggested that the presence of fungi in used dental laboratory pumice presents an unhygienic condition in the dental laboratory and may place dental laboratory technicians and denture patients at increased risk of fungal sensitization and disease.


microRNA Expression Profiling of Propofol-Treated Developing Rat Hippocampal Astrocytes.
Although propofol exerts toxic effects on the developing central nervous system (CNS), it remains a first-choice anesthetic in the pediatric population. Astrocytes represent a major glial cell population whose role in CNS development is widely appreciated and that has been recently shown to be mediated in large part by microRNAs (miRNAs). In contrast, relatively little is known about the roles of miRNAs in developing astrocytes during propofol treatment. Here, miRNA microarray was used to profile fluctuations in miRNA expression in immature hippocampal astrocytes in response to propofol treatment, and results were subsequently validated using quantitative real-time polymerase chain reaction. Predictive analysis of genes targeted by propofol-regulated miRNAs indicated enrichment of genes in the gene ontology (GO) nervous system development and differentiation category, and in the Kyoto encyclopedia of genes and genomes (KEGG) apoptotic pathway category. A total of 24 (10 short-term dosage and 14 long-term dosage) miRNAs were significantly regulated, one of which was rno-miR-665. Ectopic overexpression and silencing of rno-miR-665 demonstrated its role in the neurotoxic effects of propofol on hippocampal immature astrocytes. We present evidence that the role of rno-miR-665 in anesthesia-induced disturbances in astroglia development may involve direct downregulation of the anti-apoptotic gene Bcl2l1, and subsequent increased caspase-3-mediated apoptosis. Our results shed light on the anesthetic mechanism of propofol and have implications for its use in the clinical setting.


Effect of long-term maternal smoking on the offspring's lung health.
Maternal smoking during pregnancy contributes to long-term health problems in offspring, especially respiratory disorders that can manifest in either childhood or adulthood. Receptors for advanced glycation end products (RAGE) are multiligand receptors abundantly localized in the lung, capable of responding to by-products of reactive oxygen species and proinflammatory responses. RAGE signaling is a key regulator of inflammation in cigarette smoking-related pulmonary diseases. However, the impact of maternal cigarette smoke exposure on lung RAGE signaling in the offspring is unclear. This study aims to investigate the effect of maternal cigarette smoke exposure (SE), as well as mitochondria-targeted antioxidant [mitoquinone mesylate (MitoQ)] treatment, during pregnancy on the RAGE-mediated signaling pathway in the lung of male offspring. Female Balb/c mice (8 wk) were divided into a sham group (exposed to air), an SE group (exposed to cigarette smoke), and an SE + MQ group (exposed to cigarette smoke with MitoQ supplement from mating). The lungs from male offspring were collected at 13 wk. RAGE and its downstream signaling, including nuclear factor-κB and mitogen-activated protein kinase family consisting of extracellular signal-regulated kinase 1, ERK2, c-JUN NH2-terminal kinase (JNK), and phosphorylated JNK, in the lung were significantly increased in the SE offspring. Mitochondrial antioxidant manganese superoxide dismutase was reduced, whereas IL-1β and oxidative stress response nuclear factor (erythroid-derived 2)-like 2 were significantly increased in the SE offspring. Maternal MitoQ treatment normalized RAGE, IL-1β, and Nrf-2 levels in the SE + MQ offspring. Maternal SE increased RAGE and its signaling elements associated with increased oxidative stress and inflammatory cytokines in offspring lungs, whereas maternal MitoQ treatment can partially normalize these changes.


Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells.
Insulin-expressing beta cells, found in pancreatic islets, are capable of generating more beta cells even in the adult. We show that fibroblast-like cells derived from adult human islets donated postmortem proliferate readily in vitro. These mesenchymal-type cells, which exhibit no hormone expression, can then be induced to differentiate into hormone-expressing islet-like cell aggregates, which reestablishes the epithelial character typical of islet cells. Immunohistochemistry, in situ hybridization, and messenger RNA measurements in single cells and cell populations establish the transition of epithelial cells within islets to mesenchymal cells in culture and then to insulin-expressing epithelial cells.


Prospective study of depression and the risk of heavy alcohol use in women.
The authors' goal was to determine whether depression is associated with a greater risk of heavy alcohol consumption in women. The study was based on a 1-year follow-up of the Baltimore cohort of the National Institute of Mental Health Epidemiologic Catchment Area project. The sample consisted of 1,383 women at risk for heavy alcohol use. History of depression and frequency of lifetime-experienced depressive symptoms were assessed at baseline, and incident cases of heavy drinking were identified 1 year later. After calculating descriptive statistics for the sample, the authors developed a series of logistic regression models to estimate the risk of heavy drinking at follow-up associated with depression status. The initial estimate of the risk for heavy drinking in women with a history of depressive disorder was 2.60 times greater than the risk in women with no history of depressive disorder. This estimate did not change markedly after adjustment for age, history of antisocial personality disorder, or father's history of heavy drinking (relative risk=2.2). A higher frequency of depressive symptoms was also found to be associated with an elevation in the risk for heavy alcohol use (relative risk=1.09). These results add to other evidence that depression must be considered in the assessment of vulnerability for heavy alcohol use in women. Further research is needed to clarify the mechanisms of the observed association and to discover whether detection and effective treatment of depression might reduce risk of later alcohol problems.


A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer.
Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care Excellence (NICE) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). A systematic search of MEDLINE, EMBASE and the Cochrane Library for randomised controlled trials (RCTs) published from 2001 to 2010 was carried out. Relative treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using standard meta-analysis and mixed treatment comparison methodology. A total of 23 RCTs were included: 18 trials compared platinum-based chemotherapy, two compared pemetrexed and three compared gefitinib. There are no statistically significant differences in OS between any of the four third-generation chemotherapy regimens. There is statistically significant evidence that pemetrexed+platinum increases OS compared with gemcitabine+platinum. There are no statistically significant differences in OS between gefitinib and docetaxel+platinum or between gefitinib and paclitaxel+platinum. There is a statistically significant improvement in PFS with gefitinib compared with docetaxel+platinum and gefitinib compared with paclitaxel+platinum. Due to reduced generic pricing, third-generation chemotherapy regimens (except vinorelbine) are still competitive options for most patients. This research provides a comprehensive evidence base, which clinicians and decision-makers can use when deciding on the optimal first-line chemotherapy treatment regimen for patients diagnosed with locally advanced or metastatic NSCLC.


Dynamical properties of steric zipper polymorphs formed by a IAPP-derived peptide.
Understanding the molecular basis of neurodegenerative diseases has enormous implications for the development of effective therapeutic strategies. One of the most puzzling features of these pathologies is the occurrence of distinct strains, which are believed to be generated by alternative conformational transitions of the same protein/peptide. Very recently, it has been discovered that small model peptides are able to form alternative tightly packed assemblies (polymorphs) in the crystalline state. Intriguingly, it has been postulated that the different polymorphs of the same polypeptide sequence may be representative of distinct strains. As the organization of crystalline aggregates of small peptides may be heavily biased by crystal packing, we have here performed MD simulations on steric zipper polymorphs formed by of the IAPP-derived fragment SSTNVG. Our analyses show that these aggregates are rather stable also in a non-crystalline environment. This finding corroborates the hypothesis that steric zipper assemblies are good candidates to account for the phenomenon of strain in neurodegenerative diseases. Present investigations also provide clues on the factors that favour the formation of polymorphs. Indeed, the intrinsic stability of individual β-sheets formed by SSTNVG strands is very poor. Therefore, the formation of these aggregates is essentially dictated by inter-sheet interactions established within the steric zipper assembly.


A temporal study of Salmonella serovars from fluff samples from poultry breeder hatcheries in Ontario between 1998 and 2008.
The objectives of this study were to determine the prevalence of Salmonella, trends, major serovars, and their clusters from fluff samples, in poultry hatcheries in Ontario between 1998 and 2008. Multi-level logistic regression modelling with random effects for hatchery and sampling visit (day on which samples were collected from a hatchery) was used to identify factors [poultry breeder type, year (trend), and season] associated with the prevalence of Salmonella and a cluster detection test was used to identify clusters of common serovars. The period prevalence of Salmonella in fluff samples was 8.7% in broiler-breeders, 3.1% in layer-breeders, 13.2% in turkey-breeders, and 11.9% in other-breeder birds, such as ducks, geese, quail, partridges, and pheasants. There was an overall increasing trend in Salmonella prevalence in broiler-breeders and other-breeder birds, and a decreasing trend in layer-breeders. The 4 most common serovars identified were Salmonella Kentucky, Heidelberg, Enteritidis, and Senftenberg in broiler-breeders; Salmonella Heidelberg, Senftenberg, Braenderup, and Typhimurium in layer-breeders; Salmonella Senftenberg, Heidelberg, Saintpaul, and Montevideo in turkey-breeders; and Salmonella Enteritidis, Thompson, Typhimurium, and Heidelberg in other-breeder birds. Temporal clusters were identified for 12 of 13 serovars examined in broiler-breeders, and 4 of 4 serovars in all other poultry-breeders. The seasonal effects varied by year with the highest probability of Salmonella most often occurring in the summer, followed by the fall season. Variance components suggested that control measures should be directed at the hatchery and the sampling visit levels. Further studies are needed to identify risk factors for Salmonella in broiler-breeder, turkey-breeder, and other-breeder bird hatcheries in order to implement necessary control measures.


Still behind the glass wall? Swedish fathers' satisfaction with postnatal care.
To describe new fathers' satisfaction with postnatal care after the introduction of a more family-centered model and to study factors related to fathers' overall satisfaction with postnatal care. Two cohorts of fathers who had a live-born baby during a 15 weeks period in 2004 and 2006. A Swedish hospital. Postnatal care options were traditional postnatal ward, early discharge, cocare at neonatal ward, and from 2006 a family suite on a hotel ward. Two hundred and eighty-four fathers whose babies were born in 2004 and 356 fathers whose babies were born in 2006. Data were collected using a questionnaire and descriptive statistical odds ratios with 95% confidence interval and logistic regression analyses were used. Six hundred and forty (64%) fathers completed the questionnaire. There was no improvement between the 2 years in satisfaction with the content of postnatal care, although fathers who stayed in the family suite on the hotel ward were more satisfied with the postnatal care over all. The following factors were most significant for predicting dissatisfaction with postnatal care: no support from staff, not being treated nicely, dissatisfaction with the environment, lack of medical check-ups for the mother, and visiting hours. A true family perspective should be applied in postnatal care and the new parents viewed as a family unit, not as medical cases only. Staff working in postnatal wards should be given the opportunity to involve fathers in postnatal care.


[Self concept and parental images in patients with affective disorders--a clinical study with the Giessen Test].
The relationship between self, ideal self and normative self was studied in a sample of 139 patients with affective disorders and 73 patients with orthopaedic complaints. The depressive patients showed significant-asymmetric relationships between self and ideal self even after recovery from the clinical depression. Neurotic depressive patients could be distinguished from unipolar depressive patients in this regard. The self-concept of the depressive patients was characterised by means of the bipolar Giessen-test dimensions "insufficiency of performance", "lack of social adjustment" and "lack of social contact" and by means of the GT-dimensions "negative social resonance" and "depressive mood". There were no specific relationships between self-image and parental images in the depressive sample. The results underline the necessity of therapeutic interventions in depressive patients during the so-called symptom-free interval.


Myeloid Protease-Activated Receptor-2 Contributes to Influenza A Virus Pathology in Mice.
Innate immune responses to influenza A virus (IAV) infection are initiated in part by toll-like receptor 3 (TLR3). TLR3-dependent signaling induces an antiviral immune response and an NFκB-dependent inflammatory response. Protease-activated receptor 2 (PAR2) inhibits the antiviral response and enhances the inflammatory response. PAR2 deficiency protected mice during IAV infection. However, the PAR2 expressing cell-types contributing to IAV pathology in mice and the mechanism by which PAR2 contributes to IAV infection is unknown. IAV infection was analyzed in global (Par2-/- ), myeloid (Par2fl/fl;LysMCre+) and lung epithelial cell (EpC) Par2 deficient (Par2fl/fl ;SPCCre+) mice and their respective controls (Par2+/+ and Par2fl/fl). In addition, the effect of PAR2 activation on polyinosinic-polycytidylic acid (poly I:C) activation of TLR3 was analyzed in bone marrow-derived macrophages (BMDM). Lastly, we determined the effect of PAR2 inhibition in wild-type (WT) mice. After IAV infection, Par2-/- and mice with myeloid Par2 deficiency exhibited increased survival compared to infected controls. The improved survival was associated with reduced proinflammatory mediators and reduced cellular infiltration in bronchoalveolar lavage fluid (BALF) of Par2-/- and Par2fl/fl;LysMCre+ 3 days post infection (dpi) compared to infected control mice. Interestingly, Par2fl/fl;SPCCre+ mice showed no survival benefit compared to Par2fl/fl . In vitro studies showed that Par2-/- BMDM produced less IL6 and IL12p40 than Par2+/+ BMDM after poly I:C stimulation. In addition, activation of PAR2 on Par2+/+ BMDM increased poly I:C induction of IL6 and IL12p40 compared to poly I:C stimulation alone. Importantly, PAR2 inhibition prior to IAV infection protect WT mice. Global Par2 or myeloid cell but not lung EpC Par2 deficiency was associated with reduced BALF inflammatory markers and reduced IAV-induced mortality. Our study suggests that PAR2 may be a therapeutic target to reduce IAV pathology.


Nighttime Suckling Behavior in Captive Giraffe (Giraffa camelopardalis reticulata).
Suckling behaviors are useful to better understand mother-offspring relationships. However, in many species, knowledge about nighttime suckling behavior is sparse. In the present study, we investigated suckling behavior in four calves of the reticulated giraffe (Giraffa camelopardalis reticulata) and their mother in the Kyoto City Zoo, Japan, by analyzing video clips of 9614 h. The relation between a calf's age and the mean duration and frequency of suckling were consistent with the results of previous daytime studies: the longest duration (80 ± 4 s) and highest frequency (0.41/h) of suckling occurred when the calves were young, and decreased thereafter. Suckling frequency was lower at night than during the day, probably because the mother spent much of the time resting at night. The mother initiated suckling behavior in offspring until six months of age. Most often, the mother terminated suckling except during the first few weeks after birth. Additionally, we reported that the average weaning period was 448 days (n = 5) and that the last born (sixth) continued to suckle for more than 750 days, which is a rare phenomenon. We believe the present report helps to fill the lack of knowledge about nighttime suckling behavior in giraffe.


Development and validation of the parent-reported Drug Hypersensitivity Quality of Life Questionnaire.
Background. Drug hypersensitivity in children impacts the quality of life of the patients and their caregivers. Measurements of the quality of life in children are different from adults, because children cannot answer the questions. This research aimed to develop and validate the Parent-reported Drug Hypersensitivity Quality of Life Questionnaire (P-DrHy-Q). Methods. The 21-item scale was initially generated by researchers. Then, 3 experts were asked for their opinion about the scale. After adjusting the contents and language, the scale was answered by 97 caregivers. A factor analysis was carried out to select the items for the final scale, and Cronbach's alpha assessed the internal consistency. Finally, we examined the test-retest reliability in another group of 10 caregivers. Results. The 21-item scale was grouped into 6 factors. However, some factors were inappropriate. Therefore, the number of factors was reduced using a statistical analysis. The final 12-item scale included two factors: mental health and social activity. The scale had good internal consistency (Cronbach's á = 0.897) and the test-retest associations were good (R = 0.9439; p minor 0.001). Conclusions. The P-DrHy-Q is the first scale for assessment to consider the interaction of biopsychosocial factors on drug allergy that includes the carer-child dyad. It shows good internal consistency and reliability. Its application might be relevant for future research, and provide clinicians and researchers with a solid tool to define which type of psychosocial support is required to provide more comprehensive care in drug hypersensitivity.


Newspapers foretell health care's future.
This article is based on a two-months snapshot (November 1998 to January 1999) of newspaper articles addressing various health care issues. Newspaper contents reflect the changing market share of competing societal concerns. Health care issues, particularly cost and choice, now preoccupy the American people. Health care trends percolate bottom-up through the pages of newspapers, not top-down from Washington, D.C, policymakers, or health care executives. By reviewing these articles, the author provides a big picture view of the prevailing and emerging health care trends. From the new thrust of consumerism and the public backlash against managed care organizations to the demise of HMOs and PPMCs, these observations signify not only the concerns that are bubbling to the surface but also the direction that health care is headed. Consumers are in the driver's seat and physician executives need to provide them with evidence of the value they desire--and understand what they perceive as value.


Faujasites incorporated tissue engineering scaffolds for wound healing: in vitro and in vivo analysis.
Exploring the possibility of using inorganic faujasites in tissue engineering scaffolds is a prospective approach in regenerative medicine. Novel gelatin/hyaluronic acid (HA)/faujasite porous scaffolds with low surface energy were fabricated by lyophilization. The pore size of gelatin/HA scaffold was 50-2000 μm, whereas it was greatly reduced to 10-250 μm after incorporation of 2.4% (w/w) of faujasites in polymer matrix, GH(2.4%). Micro computed tomography analysis showed that the porosity of GH(2.4%) was 90.6%. The summative effect was ideal for growth of dermal fibroblasts and cellular attachment. XRD analysis revealed that the embedded faujasites maintained their crystallinity in the polymer matrix even though they interacted with the polymers as indicated by FT-IR analysis. Coupling with effective reinforcement of faujasites, GH(2.4%) demonstrated compression modulus of 929 ± 7 Pa and glass transition temperature of 31 ± 0.05 °C. It exhibited controlled swelling and degradation, allowing sufficient space for tissue regrowth. The latter is further supported by capability of faujasites to provide efficient oxygen supply to fibroblast cells. GH(2.4%) showed a cell viability of 91 ± 8% on NIH 3T3 fibroblast cell lines. The in vivo studies on Sprague-Dawley rats revealed its ability to enhance wound healing by accelerating re-epithelization and collagen deposition. These findings indicated its potential as excellent wound dressing material.


Landscape genetic connectivity in a riparian foundation tree is jointly driven by climatic gradients and river networks.
Fremont cottonwood (Populus fremonti) is a foundation riparian tree species that drives community structure and ecosystem processes in southwestern U.S. ecosystems. Despite its ecological importance, little is known about the ecological and environmental processes that shape its genetic diversity, structure, and landscape connectivity. Here, we combined molecular analyses of 82 populations including 1312 individual trees dispersed over the species' geographical distribution. We reduced the data set to 40 populations and 743 individuals to eliminate admixture with a sibling species, and used multivariate restricted optimization and reciprocal causal modeling to evaluate the effects of river network connectivity and climatic gradients on gene flow. Our results confirmed the following: First, gene flow of Fremont cottonwood is jointly controlled by the connectivity of the river network and gradients of seasonal precipitation. Second, gene flow is facilitated by mid-sized to large rivers, and is resisted by small streams and terrestrial uplands, with resistance to gene flow decreasing with river size. Third, genetic differentiation increases with cumulative differences in winter and spring precipitation. Our results suggest that ongoing fragmentation of riparian habitats will lead to a loss of landscape-level genetic connectivity, leading to increased inbreeding and the concomitant loss of genetic diversity in a foundation species. These genetic effects will cascade to a much larger community of organisms, some of which are threatened and endangered.


Magnetic self-assembly of 3D multicellular microscaffolds: A biomimetic brain tumor-on-a-chip for drug delivery and selectivity testing.
In recent years, the need for highly predictive brain cancer models to test new anticancer compounds and experimental therapeutic approaches has significantly increased. Realistic in vitro brain tumor-on-a-chip platforms would allow a more accurate selection of valid candidate drugs and nanomedicines, therefore alleviating the economic and ethical issues of unsuccessful studies in vivo. Here, we present a multi-functional self-assembled brain tumor-on-a-chip model characterized by 3D glioma cultures interfaced both to nonmalignant brain cells of the peritumoral niche and to a 3D-real-scale blood-brain barrier (BBB) microfluidic system. This platform allowed us to screen multiple features, such as BBB crossing capabilities, apoptotic efficacy against GBM cells, and side effects on nonmalignant brain cells of a promising anticancer drug, nutlin-3a, which is fundamental for the treatment of brain cancer.


Navigating the Viral Divide: Sexual and Gender Minority Community Perspectives on Treatment as Prevention.
Since it was established that HIV-positive individuals who maintain an undetectable viral load are unable to sexually transmit HIV (U=U), treatment as prevention (TasP) has become an important biomedical HIV prevention option. Many have remained optimistic that TasP, combined with pre-exposure prophylaxis (PrEP), will help close the "viral divide" between those living with and without HIV. This qualitative interview study of 62 sexual and gender minority (SGM) individuals of mixed serostatuses explored community perspectives regarding TasP, including the meaning of undetectability and how U=U impacts understandings of serodifference. Five key themes emerged from interviews: (1) undetectable does not equal HIV-negative, (2) PrEP is more promoted than TasP, (3) TasP increases openness to serodifferent sex, (4) rejection of TasP absolutism, and (5) the importance of layering prevention strategies. These findings suggest that while TasP is helping to bridge the viral divide, serostatus distinctions remain prevalent and important to many SGM individuals.


Climate warming dominates over plant genotype in shaping the seasonal trajectory of foliar fungal communities on oak.
Leaves interact with a wealth of microorganisms. Among these, fungi are highly diverse and are known to contribute to plant health, leaf senescence and early decomposition. However, patterns and drivers of the seasonal dynamics of foliar fungal communities are poorly understood. We used a multifactorial experiment to investigate the influence of warming and tree genotype on the foliar fungal community on the pedunculate oak Quercus robur across one growing season. Fungal species richness increased, evenness tended to decrease, and community composition strongly shifted during the growing season. Yeasts increased in relative abundance as the season progressed, while putative fungal pathogens decreased. Warming decreased species richness, reduced evenness and changed community composition, especially at the end of the growing season. Warming also negatively affected putative fungal pathogens. We only detected a minor imprint of tree genotype and warming × genotype interactions on species richness and community composition. Overall, our findings demonstrate that warming plays a larger role than plant genotype in shaping the seasonal dynamics of the foliar fungal community on oak. These warming-induced shifts in the foliar fungal community may have a pronounced impact on plant health, plant-fungal interactions and ecosystem functions.


Organ specific gene expression in the regenerating tail of Macrostomum lignano.
Temporal and spatial characterization of gene expression is a prerequisite for the understanding of cell-, tissue-, and organ-differentiation. In a multifaceted approach to investigate gene expression in the tail plate of the free-living marine flatworm Macrostomum lignano, we performed a posterior-region-specific in situ hybridization screen, RNA sequencing (RNA-seq) of regenerating animals, and functional analyses of selected tail-specific genes. The in situ screen revealed transcripts expressed in the antrum, cement glands, adhesive organs, prostate glands, rhabdite glands, and other tissues. Next we used RNA-seq to characterize temporal expression in the regenerating tail plate revealing a time restricted onset of both adhesive organs and copulatory apparatus regeneration. In addition, we identified three novel previously unannotated genes solely expressed in the regenerating stylet. RNA interference showed that these genes are required for the formation of not only the stylet but the whole male copulatory apparatus. RNAi treated animals lacked the stylet, vesicula granulorum, seminal vesicle, false seminal vesicle, and prostate glands, while the other tissues of the tail plate, such as adhesive organs regenerated normally. In summary, our findings provide a large resource of expression data during homeostasis and regeneration of the morphologically complex tail regeneration and pave the way for a better understanding of organogenesis in M. lignano.


[SPECT-99mTc-HMPAO in a case of epilepsia partialis continua and focal encephalitis].
A case of epilepsia partialis continua (EPC) in a eight year old girl is presented. The episode EPC involved the left side of the face and the left arm and leg with progressive neurologic deficit and mental impairment. The focal seizures did not respond to treatment with a wide variety of antiepileptic drugs. The patient was studied with a 99mTc HMPAO-SPECT in addition to EEG, CT and MRI procedures. During the ictal period the SPECT showed an increased cerebral blood flow in the right hemisphere especially in the Rolandic area and the temporal lobe; during the interictal period a decreased flow was seen in the same regions. The EEG showed marked epileptogenic activity consisting of continued spike and slow wave discharges over the right brain hemisphere; the CT scan was normal and the MRI showed an increased signal intensity in the white and gray matter in the right hemisphere, especially in the frontal and temporal lobes. A temporal lobectomy and a frontal corticectomy were done. The pathologic specimens showed changes consistent with viral encephalitis (Rasmussen's syndrome). The patient has not had seizures in the ten months after surgery. She returned to school three months after surgery, and her IQ was normal. This report illustrates the usefulness of the 99mTc HMPAO-SPECT technique for the diagnosis and the management of EPC cases.


Treatment outcome of extraoral implants in the craniofacial region.
Extraoral implants for the retention of facial prosthesis have been used for better support, stability, and retention. Other than the clinical experiences, treatment outcomes of these prostheses should be evaluated for predicting the long-term success. The aim of this study was to evaluate the survival rates and soft tissue responses of extraoral implants. In total, 52 patients were examined, including 16 with auricular defects, 16 with orbital defects, 13 with nasal defects, and 7 with midfacial defects. Data on implant length and location, radiation-treatment history, systemic diseases, and alcohol and cigarette use were collected and assessed, and data on the health of periimplant soft tissue were recorded for all of the defects. Statistical analyses were performed with t and chi2 tests and correlation and regression analyses for the determination of the survival rate. According to results, the defect area has a significant effect on success rate. The overall success rate was found highest in the auricular area and least in the midfacial area. The presence of diabetes, alcohol use, and age were found as significant factors for implant loss, whereas smoking and radiotherapy were found as insignificant.


Characterization of Three Mycobacterium spp. with Potential Use in Bioremediation by Genome Sequencing and Comparative Genomics.
We provide the genome sequences of the type strains of the polychlorophenol-degrading Mycobacterium chlorophenolicum (DSM43826), the degrader of chlorinated aliphatics Mycobacterium chubuense (DSM44219) and Mycobacterium obuense (DSM44075) that has been tested for use in cancer immunotherapy. The genome sizes of M. chlorophenolicum, M. chubuense, and M. obuense are 6.93, 5.95, and 5.58 Mb with GC-contents of 68.4%, 69.2%, and 67.9%, respectively. Comparative genomic analysis revealed that 3,254 genes are common and we predicted approximately 250 genes acquired through horizontal gene transfer from different sources including proteobacteria. The data also showed that the biodegrading Mycobacterium spp. NBB4, also referred to as M. chubuense NBB4, is distantly related to the M. chubuense type strain and should be considered as a separate species, we suggest it to be named Mycobacterium ethylenense NBB4. Among different categories we identified genes with potential roles in: biodegradation of aromatic compounds and copper homeostasis. These are the first nonpathogenic Mycobacterium spp. found harboring genes involved in copper homeostasis. These findings would therefore provide insight into the role of this group of Mycobacterium spp. in bioremediation as well as the evolution of copper homeostasis within the Mycobacterium genus.


Application of atomic force microscopy in cancer research.
Atomic force microscopy (AFM) allows for nanometer-scale investigation of cells and molecules. Recent advances have enabled its application in cancer research and diagnosis. The physicochemical properties of live cells undergo changes when their physiological conditions are altered. These physicochemical properties can therefore reflect complex physiological processes occurring in cells. When cells are in the process of carcinogenesis and stimulated by external stimuli, their morphology, elasticity, and adhesion properties may change. AFM can perform surface imaging and ultrastructural observation of live cells with atomic resolution under near-physiological conditions, collecting force spectroscopy information which allows for the study of the mechanical properties of cells. For this reason, AFM has potential to be used as a tool for high resolution research into the ultrastructure and mechanical properties of tumor cells. This review describes the working principle, working mode, and technical points of atomic force microscopy, and reviews the applications and prospects of atomic force microscopy in cancer research.


Aspiration biopsy cytology of lymph nodes in malignant lymphoma.
The cytologic findings of needle aspiration biopsy of lymph nodes in malignant lymphoma are presented. In 42 of 49 cases, a correct cytologic diagnosis was rendered. There was one false-positive diagnosis. The diagnostic accuracy of needle aspiration cytology is high. It helps to select patients for further investigation and treatment, thereby avoiding unnecessary surgery in patients who present with lymphadenopathy. The technique is also useful in the staging work-up of patients with lymphoma and the diagnosis of recurrent disease during the follow-up period.


Lipoprotein lipase mRNA expression in abdominal adipose tissue is little modified by age and nutritional state in broiler chickens.
Lipoprotein lipase (LPL)-catalyzed hydrolysis of plasma lipoproteins is a rate-limiting step in the transport of lipids into the peripheral tissues of broiler chickens. The aim of the present study was to investigate whether LPL mRNA expression in adipose tissue is affected by age or nutritional treatments, with a view to reducing fat accumulation in broiler chickens. The study found that chicken LPL mRNA expression in abdominal adipose tissue did not differ significantly between chickens aged 4, 6, and 8 wk, but there was less expression of LPL mRNA in 2-wk-old chickens. In nutritional modulation, LPL mRNA levels in abdominal adipose tissues were not modified by 48-h feed deprivation or by subsequent refeeding for 48 h. In addition, expression of LPL mRNA was not significantly altered in chickens fed for 7 d on diets containing 8% olive oil (triolein rich), safflower oil (trilinolein rich), or linseed oil (trilinolenin rich). On the other hand, adipose LPL mRNA expression in chickens force-fed for 12 h with a trilinolenin (18:3) emulsion after 48-h feed deprivation was significantly decreased when compared to that in chickens force-fed with a triolein (18:1) or trilinolein (18:2) emulsion. Changes to LPL immunoreactive protein levels in chicken abdominal adipose tissues brought about by aging and nutritional manipulations were similar to those observed in relation to mRNA expression. These findings suggest that LPL mRNA expression in growing chickens is less responsive to aging and nutritional manipulation than in mammals, thereby indicating specificity of physiological response on broiler chicken LPL.


Emergency Regulatory Procedures, Pharmaceutical Regulatory Politics, and the Political Economy of Vaccine Regulation in the COVID-19 Pandemic.
Regulatory approaches to COVID-19 vaccine authorizations varied substantially across countries. Facing a common public health threat, what accounts for regulatory variation? This study focuses on emergency pharmaceutical and vaccine regulatory procedures, and whether and how regulators' emergency pharmaceutical regulatory procedures going into the pandemic shaped regulatory processes and decisions during the pandemic. An analysis of seven high-impact national and international pharmaceutical regulators, with case studies from Brazil, China, India, Russia, the United Kingdom, the United States, and the European Medicines Agency, and evidence from primary source executive and legislative branch regulations and statutes, national and international scientific and general press reporting, and secondary analysis of scholars, practitioners, and international organizations. Inherited emergency pharmaceutical and vaccine regulatory procedures substantially shaped COVID-19 vaccine regulation during the pandemic. Variation in the presence and content of emergency regulatory procedures affected the quality of pandemic regulatory processes, outcomes, and procedural updates, and differentially empowered policymaking experts and elected politicians. Emergency regulatory procedures affect key features of regulatory political economy and public health practices during crises. To improve future public health crisis responses, the authors provide sets of policy recommendations for 1) Establishing clear emergency pharmaceutical regulatory procedures, and 2) International collaboration.


[Congenital adrenal hyperplasia: a qualitative study on disease and treatment, doubts, anguishes and relationships (part I)].
To understand the meanings/thoughts of a group of parents, patients and physicians regarding congenital adrenal hyperplasia (CAH), and to evaluate their anguishes, doubts and anxieties. We selected 21 subjects: 7 pediatric endocrinologists from five Brazilian Public Health System institutions, 9 parents and 6 patients with CAH, according to the qualitative research model. Three of the studied categories are presented: 'disease and treatment', 'doubts and anguishes' and 'relationships.' Parents' main anguishes relate to the situation of an unnamed sex at birth. A sense of loneliness when dealing with the disease is the major anguish among patients, whereas physicians show hopelessness with the passivity parents and patients. The apparent submissiveness of patients/parents during consultations must be evaluated cautiously. University Hospitals outpatient clinic dynamics have a direct effect on this behavior: physicians do not talk openly with parents who in turn do not talk with their children, whereas patients chose to protect their parents from additional suffering. Thus, some miscommunication is noticeable among these subjects. These observations suggest that a special mindful measure should be built for these patients.


Diet and Activity Assessments and Interventions Using Technology in Older Adults.
This paper reports on the findings and recommendations specific to older adults from the "Tech Summit: Innovative Tools for Assessing Diet and Physical Activity for Health Promotion" forum organized by the North American branch of the International Life Sciences Institute. The summit aimed to investigate current and emerging challenges related to improving energy balance behavior assessment and intervention via technology. The current manuscript focuses on how novel technologies are applied in older adult populations and enumerated the barriers and facilitators to using technology within this population. Given the multiple applications for technology in this population, including the ability to monitor health events and behaviors in real time, technology presents an innovative method to aid with the changes associated with aging. Although older adults are often perceived as lacking interest in and ability to adopt technologies, recent studies show they are comfortable adopting technology and user uptake is high with proper training and guided facilitation. Finally, the conclusions suggest recommendations for future research, including the need for larger trials with clinical outcomes and more research using end-user design that includes older adults as technology partners who are part of the design process. This article is part of a theme issue entitled Innovative Tools for Assessing Diet and Physical Activity for Health Promotion, which is sponsored by the North American branch of the International Life Sciences Institute.


Heterogeneity in COVID-19 Pandemic-Induced Lifestyle Stressors and Predicts Future Mental Health in Adults and Children in the US and UK.
Identifying predictors of mental health symptoms after the initial phase of the pandemic may inform the development of targeted interventions to reduce its negative long-term mental health consequences. In the current study, we aimed to simultaneously evaluate the prospective influence of life change stress, personal COVID-19 impact, prior mental health, worry about COVID-19, state-level indicators of pandemic threat, and socio-demographic factors on mood and anxiety symptoms in November 2020 among adults and children in the US and UK. We used a longitudinal cohort study using the Coronavirus Health Impact Survey (CRISIS) collected at 3 time points: an initial assessment in April 2020 ("April"), a reassessment 3 weeks later ("May"), and a 7-month follow-up in November 2020 ("November"). Online surveys were collected in the United States and United Kingdom by Prolific Academic, a survey recruitment service, with a final sample of 859 Adults and 780 children (collected via parent report). We found subtypes of pandemic-related life change stress in social and economic domains derived through Louvain Community Detection. We assessed recalled mood and perceived mental health prior to the pandemic; worries about COVID-19; personal and family impacts of COVID-19; and socio-demographic characteristics. Levels of mood symptoms in November 2020 measured with the circumplex model of affect. We found 3 life change stress subtypes among adults and children: Lower Social/Lower Economic (adults and children), Higher Social/Higher Economic (adults and children), Lower Social/Higher Economic (adults), and Intermediate Social/Lower Economic (children). Overall, mood symptoms decreased between April and November 2020, but shifting from lower to higher-stress subtypes between time points was associated with increasing symptoms. For both adults and children, the most informative predictors of mood symptoms in November identified by conditional random forest models were prior mood and perceived mental health, worries about COVID, and sources of life change. The relative importance of these predictors was the most prominent difference in findings between adults and children, with lifestyle changes stress regarding friendships being more predictive of mood outcomes than worries about COVID in children. In the US, objective state-level indicators of COVID-19 threat were less predictive of November mood than these other predictors. We found that in addition to the well-established influences of prior mood and worry, heterogeneous subtypes of pandemic-related stress were differentially associated with mood after the initial phase of the pandemic. Greater research on diverse patterns of pandemic experience may elucidate modifiable targets for treatment and prevention.


Ridges and rivers: a test of competing hypotheses of Amazonian diversification using a dart-poison frog (Epipedobates femoralis).
Mitochondrial DNA cytochrome b sequence data from a dart-poison frog, Epipedobates femoralis, were used to test two hypotheses of Amazonian diversification: the riverine barrier and the ridge hypotheses. Samples were derived from sites located on both banks of the Rio Juruá and on both sides of the Iquitos Arch in western Amazonia. The phylogeographic structure was inconsistent with predictions of the riverine barrier hypothesis. Haplotypes from opposite river banks did not form monophyletic clades in any of our phylogenetic analyses, nor was the topology within major clades consistent with the riverine hypothesis. Further, the greatest differentiation between paired sites on opposite banks was not at the river mouth where the strongest barrier to gene flow was predicted to occur. The results instead were consistent with the hypothesis that ancient ridges (arches), no longer evident on the landscape, have shaped the phylogeographic relationships of Amazonian taxa. Two robustly supported clades map onto opposite sides of the Iquitos Arch. The mean haplotypic divergence between the two clades, in excess of 12%, suggests that this cladogenic event dates to between five and 15 million years ago. These estimates span a period of major orogenesis in western South America and presumably the formation of these ancient ridges.


The Rnf Complex Is an Energy-Coupled Transhydrogenase Essential To Reversibly Link Cellular NADH and Ferredoxin Pools in the Acetogen Acetobacterium woodii.
The Rnf complex is a respiratory enzyme that catalyzes the oxidation of reduced ferredoxin to the reduction of NAD+, and the negative free energy change of this reaction is used to generate a transmembrane ion gradient. In one class of anaerobic acetogenic bacteria, the Rnf complex is believed to be essential for energy conservation and autotrophic growth. We describe here a methodology for markerless mutagenesis in the model bacterium of this class, Acetobacterium woodii, which enabled us to delete the rnf genes and to test their in vivo role. The rnf mutant did not grow on H2 plus CO2, nor did it produce acetate or ATP from H2 plus CO2, and ferredoxin:NAD+ oxidoreductase activity and Na+ translocation were also completely lost, supporting the hypothesis that the Rnf complex is the only respiratory enzyme in this metabolism. Unexpectedly, the mutant also did not grow on low-energy substrates, such as ethanol or lactate. Oxidation of these substrates is not coupled to the reduction of ferredoxin but only of NAD+, and we speculated that the growth phenotype is caused by a loss of reduced ferredoxin, indispensable for biosynthesis and CO2 reduction. The electron-bifurcating hydrogenase of A. woodii reduces ferredoxin, and indeed, the addition of H2 to the cultures restored growth on ethanol and lactate. This is consistent with the hypothesis that endergonic reduction of ferredoxin with NADH is driven by reverse electron transport catalyzed by the Rnf complex, which renders the Rnf complex essential also for growth on low-energy substrates.IMPORTANCE Ferredoxin and NAD+ are key electron carriers in anaerobic bacteria, but energetically, they are not equivalent, since the redox potential of ferredoxin is lower than that of the NADH/NAD+ couple. We describe by mutant studies in Acetobacterium woodii that the main function of Rnf is to energetically link cellular pools of ferredoxin and NAD+ When ferredoxin is greater than NADH, exergonic electron flow from ferredoxin to NAD+ generates a chemiosmotic potential. This is essential for energy conservation during autotrophic growth. When NADH is greater than ferredoxin, Rnf works in reverse. This reaction is essential for growth on low-energy substrates to provide reduced ferredoxin, indispensable for biosynthesis and CO2 reduction. Our studies put a new perspective on the cellular function of the membrane-bound ion-translocating Rnf complex widespread in bacteria.


Bilateral agenesis of maxillary permanent canines: Review of the literature.
Oligodontia, or agenesis of six or more teeth, excluding third molars, which involves canine agenesis is rare, and restorative management can be challenging. Bilateral agenesis of a permanent canine in the general population often indicates a several missing adult teeth. The most common sign of it is the primary canine retention beyond its exfoliation age. The multistage restorative management includes the early diagnosis, excluding associated medical problems as well as assessment of patient's malocclusion and facial skeletal pattern, life span of deciduous teeth, possibility of premolar substitution, minimum required number of prosthetic units, patient's preferences, and the cost of treatment. A 10-year-old boy with bilateral agenesis of maxillary permanent canines is described. Some thoughts on the multidisciplinary restorative management of this case are discussed.


Intrauterine Inflammation Alters the Transcriptome and Metabolome in Placenta.
Placental insufficiency is implicated in spontaneous preterm birth (SPTB) associated with intrauterine inflammation. We hypothesized that intrauterine inflammation leads to deficits in the capacity of the placenta to maintain bioenergetic and metabolic stability during pregnancy ultimately resulting in SPTB. Using a mouse model of intrauterine inflammation that leads to preterm delivery, we performed RNA-seq and metabolomics studies to assess how intrauterine inflammation alters gene expression and/or modulates metabolite production and abundance in the placenta. 1871 differentially expressed genes were identified in LPS-exposed placenta. Among them, 1,149 and 722 transcripts were increased and decreased, respectively. Ingenuity pathway analysis showed alterations in genes and canonical pathways critical for regulating oxidative stress, mitochondrial function, metabolisms of glucose and lipids, and vascular reactivity in LPS-exposed placenta. Many upstream regulators and master regulators important for nutrient-sensing and mitochondrial function were also altered in inflammation exposed placentae, including STAT1, HIF1α, mTOR, AMPK, and PPARα. Comprehensive quantification of metabolites demonstrated significant alterations in the glucose utilization, metabolisms of branched-chain amino acids, lipids, purine and pyrimidine, as well as carbon flow in TCA cycle in LPS-exposed placenta compared to control placenta. The transcriptome and metabolome were also integrated to assess the interactions of altered genes and metabolites. Collectively, significant and biologically relevant alterations in the placenta transcriptome and metabolome were identified in placentae exposed to intrauterine inflammation. Altered mitochondrial function and energy metabolism may underline the mechanisms of inflammation-induced placental dysfunction.


Hamstring and gluteal activation during high-speed overground running: Impact of prior strain injury.
This study examined the spatial patterns of hamstring and gluteal muscle activation during high-speed overground running in limbs with and without aprior hamstring strain injury. Ten active males with arecent (<18 month) unilateral biceps femoris long head (BFLH) strain injury underwent functional magnetic resonance imaging before and immediately after arepeat-sprint running protocol. Transverse relaxation (T2) time, an index of muscle activation, of the BFLH and short head (BFSH), semitendinosus (ST), semimembranosus (SM), gluteus maximus (GMAX) and medius (GMED) was assessed pre-post exercise. No significant between-limb differences in running-induced mean T2 changes were observed (p = 0.949), however, decision tree induction revealed that previously injured limbs were characterised by highly variable intramuscular activation of the ST (SD5.3). T2 times increased more for GMAX than all other muscles (all p< 0.001, d= 0.5-2.5). Further, T2 changes were greater for ST than BFSH, SM, GMED, and BFLH (all p≤ 0.001, d= 0.5-2.9); and were greater for BFLH than BFSH, SM, and GMED (all p< 0.001, d= 1.2-1.6). Athletes display heterogenous patterns of posterior thigh activation when sprinting (GMAX>ST>BFLH>GMED>SM>BFSH) and may exhibit altered intramuscular hamstring activation after returning to sport from BFLH strain injury.


Analysis of hepatitis C virus core protein interaction domains.
Hepatitis C virus (HCV) core protein forms the internal viral coat that encapsidates the genomic RNA and is enveloped in a host cell-derived lipid membrane. As the single capsid protein, core should be capable of multimerization but attempts to produce virus-like particles following expression of HCV structural proteins have not been successful. In this study, we have analysed the interaction capacity of full-length and truncated HCV core using the yeast two-hybrid system. Full-length core containing or lacking the translocation signal for the E1 glycoprotein did not interact with full-length or truncated core proteins. Truncation to the N-terminal 122 aa revealed an interaction domain which was mapped to the tryptophan-rich sequence from aa 82-102 and was termed the main homotypic interaction domain. The C-terminal hydrophobic fragment of core (aa 122-172) was incapable of interacting with itself but interacted with the main homotypic interaction domain in trans (the weak heterotypic interaction domain). Core proteins truncated at their N and C termini (aa 46-102) were trans-activating when fused to the DNA-binding domain of GAL4. Based on our results, we suggest that the C-terminal segment may interact in cis with the main homotypic interaction domain and thereby prevent multimerization. Core-core interaction was also observed for in vitro-translated proteins bound to truncated immobilized core 102. However, interaction was less specific in this system suggesting that protein interaction and possibly conformational alteration of core may be dependent on the experimental system.


Validation of preimplantation genetic diagnosis by PCR analysis: genotype comparison of the blastomere and corresponding embryo, implications for clinical practice.
The aim of this study was to validate the overall preimplantation genetic diagnosis (PGD)-PCR procedure and to determine the diagnostic value. Genotyped embryos not selected for embryo transfer (ET) and unsuitable for cryopreservation after PGD were used for confirmatory analysis. The PGD genotyped blastomeres and corresponding embryos were compared, and morphology was scored on Day 4 post fertilization. To establish the validity of the PGD-PCR procedure and the diagnostic value, misdiagnosis rate, false-negative rate and negative predictive value were calculated. Moreover, comparison on the validity was made for the biopsy of one or two blastomeres. For the total embryo group (n = 422), a misdiagnosis rate of 7.1% and a false-negative rate of 3.1% were found. The negative predictive value was 96.1%. Poor morphology Day 4 embryos (Class 1) were over-represented in the embryo group in which the blastomere genotype was not confirmed by the whole embryo genotype. The misdiagnosis rate of Class 1 embryos was 12.5% and the false-negative rate 17.1%. Exclusion of these embryos resulted in a misdiagnosis rate of 6.1%, a false-negative rate of 0.5% and a negative predictive value of 99.3%. The two blastomere biopsies revealed a significant higher positive predictive value, lowering the misdiagnosis rate, whereas the negative predictive value remained the same. In conclusion, the PGD-PCR procedure is a valid diagnostic method to select unaffected embryos for ET. The misdiagnosis and false-negative rates decrease by rejecting Class 1 embryos for ET. The biopsy of a second blastomere improves the positive predictive value, lowering the misdiagnosis rate.


Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle.
Iron is essential for oxygen transport because it is incorporated in the heme of the oxygen-binding proteins hemoglobin and myoglobin. An interaction between iron homeostasis and oxygen regulation is further suggested during hypoxia, in which hemoglobin and myoglobin syntheses have been reported to increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells, mobilizes body iron, and increases hemoglobin concentration. However, contrary to our hypothesis that muscle iron proteins and myoglobin would also be up-regulated during HA, this study shows that HA lowers myoglobin expression by 35% and down-regulates iron-related proteins in skeletal muscle, as evidenced by decreases in L-ferritin (43%), transferrin receptor (TfR; 50%), and total iron content (37%). This parallel decrease in L-ferritin and TfR in HA occurs independently of increased hypoxia-inducible factor 1 (HIF-1) mRNA levels and unchanged binding activity of iron regulatory proteins, but concurrently with increased ferroportin mRNA levels, suggesting enhanced iron export. Thus, in HA, the elevated iron requirement associated with enhanced erythropoiesis presumably elicits iron mobilization and myoglobin down-modulation, suggesting an altered muscle oxygen homeostasis.


Rational design, synthesis, adsorption principles and applications of metal oxide adsorbents: a review.
The shortage of water resources and increasingly serious water pollution have driven the development of high-efficiency water treatment technology. Among a variety of technologies, adsorption is widely used in environmental remediation. As a class of typical adsorbents, metal oxides have been developed for a long time and continued to attract widespread attention, since they have unique physicochemical properties, including abundant surface active sites, high chemical stability, and adjustable shape and size. In this review, the basic principles of the adsorption process will be first elucidated, including affecting factors, evaluation index, adsorption mechanisms, and common kinetic and isotherm models. Then, the adsorption properties of several typical metal oxides, and key parameters affecting the adsorption performance such as particle/pore size, morphology, functionalization and modification, supports and calcination temperature will be discussed, as well as their application in the removal of various inorganic and organic contaminants. In addition, desorption and recycling of the spent adsorbent are summarized. Finally, the future development of metal oxide based adsorbents is also discussed.


Preparation, characterization and magnetic behavior of a spin-labelled physical hydrogel containing a chiral cyclic nitroxide radical unit fixed inside the gelator molecule.
An optically active amphiphilic nitroxide radical compound [(S,S,R)-], which contains a paramagnetic (2S,5S)-2,5-dimethyl-2,5-diphenylpyrrolidine-N-oxyl radical group fixed in the inner position together with a hydrophobic long alkyl chain and a hydrophilic (R)-alanine residue in the opposite terminal positions, was found to serve as a low-molecular-weight gelator in H2O to give rise to a spin-labelled physical hydrogel. Characterization of the hydrogel was performed by microscopic (SEM, TEM and AFM) techniques, XRD and SAXS measurements, and IR, UV and CD spectroscopies. The gel-sol transition temperature was determined by EPR spectral line-width (ΔHpp) analysis. Measurement of the temperature dependence of relative paramagnetic susceptibility (χrel) for the hydrogel and sol phases was achieved by means of the double-integration of VT-EPR spectra.


THE OCCURRENCE OF SPORTS INJURIES AMONG PRE-ADOLESCENTS.
Preschool children's harmonious development, cognitive and communicative abilities are enhanced through physical activities in sports, yet sports training and competition pose a risk of injury to children aged three to seven years due to their physiological and psychological features. Although sports injuries in preschool children are not common, they can be undesirable and unavoidable, and fortunately, these injuries are usually reversible. This review article presents data on the physiological features of the developing musculoskeletal system and its relationship to sports injuries in children, which together determine the nature of children's sports injuries. We also present a classification of sports injuries among preschool children, based on the literature, which considers the type, location, and severity of the trauma as estimated by the duration of mandatory missed practice.


Possibilities and limitations of endoscopic resection for early gastric cancer.
To date, the accepted criteria for endoscopic resection of early gastric cancer have been: a) elevated-type mucosal cancer less than 2 cm in size, and b) depressed-type mucosal cancer without ulceration less than 1 cm in size. In this study, we attempted to expand these indications. Sixty patients with early gastric cancer who did not meet the above criteria underwent endoscopic treatment, and were divided into four groups: those with elevated tumours larger than 2 cm with submucosal invasion (group 1 a); those without submucosal invasion (group 1 b); those with depressed tumours larger than 1 cm (group 2); and those with ulcerated tumours (group 3). The patients were treated with endoscopic resection using a two-channel scope, followed by additional laser irradiation or heater-probe coagulation (combination therapy) if residual cells were found. Follow-up was by endoscopy and biopsy for more than two years. Endoscopic treatment was effective in 87% of the patients (52 of 60), half of whom required combination therapy. In submucosal cancers, endoscopic treatment was effective in 76% of patients (13 of 17). However, tumours with deep invasion into the submucosa could not be cured. Mucosal cancers larger than 20 mm could be completely resected in 44% of patients (eight of 18) using endoscopic resection, but all five patients with tumours larger than 30 mm had incomplete resections. These results indicate that complete resection using endoscopic resection alone is possible in early gastric cancers measuring up to 30 mm in diameter. Tumours larger than 30 mm, and those with deep submucosal invasion, cannot be curatively treated by the current endoscopic modalities.


Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience.
Nipple-sparing mastectomy (NSM) has been gathering increased recognition as an alternative to more traditional mastectomy approaches. Initially, questions concerning its oncologic safety limited the use of NSM. Nevertheless, mounting evidence supporting the practice of NSM for both prophylactic and oncologic purposes is leading to its more widespread use and broadened indications. Using a prospectively maintained database, we reviewed our experience of 353 NSM procedures performed in 200 patients over the past 10 years. The indications for surgery were: 196 prophylactic risk-reduction (55.5%), 74 ductal carcinoma in situ (DCIS) (20.8%), 82 invasive cancer (23.2%), and 1 phyllodes tumor (0.5%). The nipple areolar complex (NAC) was entirely preserved in 341 mastectomies (96.7%). There were 11 patients (3.1%) who were found to have cancer at the nipple margin, warranting further excision. A total of 69 breasts (19.5%) had some degree of skin desquamation or necrosis, but only 12 (3.3%) required operative debridement, of which 3 breasts (1%) necessitated removal of a breast implant. Also, 6 patients (2%) were treated for infection. Of the 196 prophylactic NSMs, 11 specimens (5.6%) were found to harbor occult cancer (8 DCIS and 3 invasive cancers). One patient who underwent NSM for invasive ductal carcinoma in 2006 developed metastatic disease to her brain. No other recurrences are attributable to the 353 NSMs. The trends demonstrate the increasing acceptance of NSM as a prophylactic procedure as well as for therapeutic purposes. Although NSM is not standard, our experience supports the selective use of NSM in both prophylactic and malignant settings.


[Biochemical and molecular genetic mechanisms underlying occupational respiratory diseases].
The article presents materials on diagnostic value of biochemical and molecular genetic methods assessing proteinase inhibitor system. The author specified criteria to evaluate biologic balance in "proteinase--inhibitors" system. Those criteria could serve as markers for lung inflammatory and destructive processes. Findings also are criteria of industrial aerosols' influence on pathology course and on individual risk of occupational respiratory disease development.


L30 binds the nascent RPL30 transcript to repress U2 snRNP recruitment.
The mechanisms of pre-mRNA splicing regulation are poorly understood. Here we dissect how the Saccharomyces cerevisiae ribosomal L30 protein blocks splicing of its pre-mRNA upon binding a kink-turn structure including the 5' splice site. We show that L30 binds the nascent RPL30 transcript without preventing recognition of the 5' splice site by U1 snRNP but blocking U2 snRNP association with the branch site. Interaction of the factors BBP and Mud2 with the intron, relevant for U2 snRNP recruitment, is not affected by L30. Furthermore, the functions of neither the DEAD-box protein Sub2 in the incipient spliceosome nor the U2 snRNP factor Cus2 on branch site recognition are required for L30 inhibition. These findings contrast with the effects caused by binding a heterologous protein to the same region, completely blocking intron recognition. Collectively, our data suggest that L30 represses a spliceosomal rearrangement required for U2 snRNP association with the transcript.


[Further study of the indications for combination cytostatic-anticoagulant-antiaggregation-corticosteroid therapy of chronic glomerulonephritis].
One hundred and twenty-five patients with different morphoclinical variants of chronic glomerulonephritis (CGN) were examined for the efficacy of cytostatic-anticoagulant-antiaggregation (CAA) therapy. The treatment appeared successful in 47 (37%) of patients. The efficacy largely depended on the degree and intensity of the disease clinical manifestations as well as on a dramatic increase in the permeability of the glomerular filter for medium- and high-molecular serum proteins and on superimposition of sclerotic transformation of renal glomeruli. The use of CAA therapy was most successful in GN whatever superimposition of fibroplastic transformation. The treatment was abortive in prolonged (more than 12 months) persistence of pronounced proteinuria combined with hematuria and/or arterial hypertension, in the nephrotic-hypertonic pattern of GN irrespective of the disease stage, in disease patterns manifesting themselves chiefly by hematuria and negligible proteinuria.


The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice.
Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein aggregation. A lead MT, called CLR01, has been demonstrated to inhibit the aggregation and toxicity of multiple amyloidogenic proteins in vitro and in vivo. Previously, we evaluated the effect of CLR01 in the 3 × Tg mouse model of Alzheimer's disease, which overexpresses mutant human presenilin 1, amyloid β-protein precursor, and tau and found that subcutaneous administration of the compound for 1 month led to a robust reduction of amyloid plaques, neurofibrillary tangles, and microgliosis. CLR01 also has been demonstrated to inhibit tau aggregation in vitro and tau seeding in cell culture, yet because in Alzheimer's disease (AD) and in the 3 × Tg model, tau hyperphosphorylation and aggregation are thought to be downstream of Aβ insults, the study in this model left open the question whether CLR01 affected tau in vivo directly or indirectly. To determine if CLR01 could ameliorate tau pathology directly in vivo, we tested the compound similarly using the P301S-tau (line PS19) mouse model. Mice were administered 0.3 or 1.0 mg/kg per day CLR01 and tested for muscle strength and behavioral deficits, including anxiety- and disinhibition-like behavior. Their brains then were analyzed by immunohistochemical and biochemical assays for pathological forms of tau, neurodegeneration, and glial pathology. CLR01 treatment ameliorated muscle-strength deterioration, anxiety-, and disinhibition-like behavior. Improved phenotype was associated with decreased levels of pathologic tau forms, suggesting that CLR01 exerts a direct effect on tau in vivo. Limitations of the study included a relatively short treatment period of the mice at an age in which full pathology is not yet developed. In addition, high variability in this model lowered the statistical significance of the findings of some outcome measures. The findings suggest that CLR01 is a particularly attractive candidate for the treatment of AD because it targets simultaneously the two major pathogenic proteins instigating and propagating the disease, amyloid β-protein (Aβ), and tau, respectively. In addition, our study suggests that CLR01 can be used for the treatment of other tauopathies in the absence of amyloid pathology.


Influence of trust on two different risk perceptions as an affective and cognitive dimension during Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea: serial cross-sectional surveys.
This study aimed to assess the affective and cognitive risk perceptions in the general population of Middle East respiratory syndrome (MERS) during the 2015 MERS coronavirus (MERS-CoV) outbreak in South Korea and the influencing factors. Serial cross-sectional design with four consecutive surveys. Nationwide general population in South Korea. Overall 4010 respondents (aged 19 years and over) from the general population during the MERS-CoV epidemic were included. The main outcome measures were (1) affective risk perception, (2) cognitive risk perception, and (3) trust in the government. Multivariate logistic regression models were used to identify factors (demographic, socioeconomic, area and political orientation) associated with risk perceptions. Both affective and cognitive risk perceptions decreased as the MERS-CoV epidemic progressed. Proportions of affective risk perception were higher in all surveys and slowly decreased compared with cognitive risk perception over time. Females (adjusted OR (aOR) 1.72-2.00; 95% CI 1.14 to 2.86) and lower self-reported household economic status respondents were more likely to perceive the affective risk. The older the adults, the higher the affective risk perception, but the lower the cognitive risk perception compared with younger adults. The respondents who had low trust in the government had higher affective (aOR 2.19-3.11; 95 CI 1.44 to 4.67) and cognitive (aOR 3.55-5.41; 95 CI 1.44 to 9.01) risk perceptions. This study suggests that even if cognitive risk perception is dissolved, affective risk perception can continue during MERS-CoV epidemic. Risk perception associating factors (ie, gender, age and self-reported household economic status) appear to be noticeably different between affective and cognitive dimensions. It also indicates that trust in the government influences affective risk perception and cognitive risk perception. There is a need for further efforts to understand the mechanism regarding the general public's risk perception for effective risk communication.


Performance and feasibility of three different approaches for computer based semi-automated analysis of ventricular arrhythmias in telemetric long-term ECG in cynomolgus monkeys.
Computer-based analysis of long-term electrocardiogram (ECG) monitoring in animal models represents a cost and time-consuming process as manual supervision is often performed to ensure accuracy in arrhythmia detection. Here, we investigate the performance and feasibility of three ECG interval analysis approaches A) attribute-based, B) attribute- and pattern recognition-based and C) combined approach with additional manual beat-to-beat analysis (gold standard) with regard to subsequent detection of ventricular arrhythmias (VA) and time consumption. ECG analysis was performed on ECG raw data of 5 male cynomolgus monkeys (1000 h total, 2 × 100 h per animal). Both approaches A and B overestimated the total number of arrhythmias compared to gold standard (+8.92% vs. +6.47%). With regard to correct classification of detected VA event numbers (accelerated idioventricular rhythms [AIVR], ventricular tachycardia [VT]) approach B revealed higher accuracy compared to approach A. Importantly, VA burden (% of time) was precisely depicted when using approach B (-1.13%), whereas approach A resulted in relevant undersensing of ventricular arrhythmias (-11.76%). Of note, approach A and B could be performed with significant less working time (-95% and - 91% working time) compared to gold standard. In sum, we show that a combination of attribute-based and pattern recognition analysis (approach B) can reproduce VA burden with acceptable accuracy without using manual supervision. Since this approach allowed analyses to be performed with distinct time saving it represents a valuable approach for cost and time efficient analysis of large preclinical ECG datasets.


Mastectomy and oophorectomy by menstrual cycle phase in women with operable breast cancer.
It is unclear whether the phase of the menstrual cycle in which primary surgical treatment occurs influences disease-free survival (DFS) and overall survival (OS) in premenopausal women with breast cancer. We investigated this question in the context of a clinical trial comparing mastectomy alone with mastectomy plus adjuvant oophorectomy and tamoxifen in premenopausal women with operable breast cancer. The date of the first day of the last menstrual period (LMP) was used to estimate the phase of the menstrual cycle when the surgeries were done. Follicular phase was defined as day 1-14 from LMP. Luteal phase was defined as day 15-42 from LMP. DFS and OS statistics were determined and analyzed by Cox proportional hazards ratios and Kaplan-Meier methods. All statistical tests were two-sided. We analyzed results for 565 women who reported an LMP within 42 days before surgery. For women in the mastectomy only arm (n = 289), there were no differences in DFS or OS by menstrual cycle phase. For women in the adjuvant treatment arm (n = 276), those whose surgery occurred during the luteal phase (n = 158) had better DFS (relative risk [RR] = 0.54; 95% confidence interval [CI] = 0.32 to 0.96; P =.02) and OS (RR = 0.53; 95% CI = 0.30 to 0.95; P =.03) than those whose surgery occurred during the follicular phase (n = 118). Moreover, women whose surgery occurred during the luteal phase and who received adjuvant therapy had better 5-year DFS than did women whose surgery occurred during the follicular phase (84%; 95% CI = 78% to 90% versus 67%; 95% CI = 58% to 78%; P =.02); they also had better OS (85%; 95% CI = 78% to 92% versus 75%; 95% CI = 66% to 84%; P =.03). The phase of the menstrual cycle at which surgery was done had no impact on survival for women who received mastectomy only. However, women who received a mastectomy and surgical oophorectomy and tamoxifen during the luteal phase had better outcomes than women who received surgery during the follicular phase.


Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension.
Soy-based diets reduce blood pressure in spontaneously hypertensive rats, but apparently not in hypertensive humans. In the present study, the antihypertensive potential of soy milk (500 mL twice daily) compared with cow's milk was investigated in a 3-mo double-blind randomized study of 40 men and women with mild-to-moderate hypertension. Before initiation of the study, urinary isoflavonoids (measured by HPLC) were undetectable in most cases (for genistein, they were always <100 micromol/L). After 3 mo of soy milk consumption, systolic blood pressure decreased by 18.4 +/- 10.7 mmHg compared with 1.4 +/- 7.2 mmHg in the cow's milk group (P < 0.0001), diastolic blood pressure decreased by 15.9 +/- 9.8 mmHg vs. 3.7 +/- 5.0 mmHg in the cow's milk group (P < 0.0001) and mean blood pressure decreased by 16.7 +/- 9.0 mmHg compared with 3.0 +/- 4.6 mmHg in the cow's milk group (P < 0.0001). Urinary genistein was strongly (r = -0.588) and significantly (P = 0.002) correlated with the decrease in blood pressure, particularly for diastolic values. In conclusion, chronic soy milk consumption had modest, but significant hypotensive action in essential hypertensive subjects. This hypotensive action was correlated with the urinary excretion of the isoflavonoid genistein.


Cardiovascular adaptive responses in rats submitted to moderate resistance training.
The present study investigated the effects of 8 week of resistance training (RT) on hemodynamic and ventricular function on cardiac myosin ATPase activity, and on contractility of papillary muscles of rats. Groups: control (CO), electrically stimulated (ES), trained at 60% (TR 60%) and 75% of one repetition maximum (1RM) (TR 75%). Exercise protocol: 5 sets of 12 repetitions at 60 and 75% of 1RM, 5 times per week. The CO and ES groups had similar values for parameters analyzed (P > 0.05). Blood pressure (BP), heart rate (13%), left ventricle systolic pressure (LVSP 13%) decreased and cardiac myosin ATPase activity increased in the TR 75% group (90%, P < 0.05). The contractile performance of papillary muscles increased in trained rats (P < 0.05). Eight weeks of RT was associated with lowering of resting BP, heart rate and LVSP, improvements in contractility of the papillary muscle and an increase of cardiac myosin ATPase activity in rats.


[Leucoplakia vesicae in females: diagnosis and treatment].
Sixty patients suffering from leucoplakia vesicae (LV) were examined using cystoscopy with biopsy of the urinary bladder wall, blood enzyme immunoassay for detection of antibodies to agents of sexually transmitted infections (STI), uroflowmetry, culture analysis of cervical canal and mucosa samples for STI. As shown by a pathomorphological examination of the vesical mucosa biopsy specimens, long-term persistence of pathogenic (chlamydia, trichomonades) and opportunistic (mycoplasma, ureaplasma, fungi) flora underlies development of LV. Morphogenesis of LV is characterized by hyperplastic reactions of urothelium and its metaplasy in laminated squamous keratosic epithelium, often with para- and dyskeratosis, developing in the presence of inflammatory reactions in the lamina in the presence of persisting infection. In LV, specific infection agents are often found in the urogenital tract. The spectrum of these agents is identical for samples from the cervical canal and vesical mucosa from leucoplakia foci. Vesical mucosa is most frequently contaminated with Mycoplasma hominis (57.2%), Candida albicans (51.4%), Ureaplasma urealiticum (37.1%) and Trichomonas vaginalis (22.9%). Associations of the infection agents are detected in 70% of LV patients. Persistent dysuria is a basic clinical symptom of leucoplakia. The following therapeutic measures should be taken: transurethral coagulation of the vesical mucosa, intravesical therapy, immunocorrection, antibacterial treatment by standard schemes or according to the isolated flora sensitivity.


Genomic architecture and treatment outcome in pediatric acute myeloid leukemia: a Children's Oncology Group report.
Childhood acute myeloid leukemia (AML) is frequently characterized by chromosomal instability. Approximately 50% of patients have disease relapse, and novel prognostic markers are needed to improve risk stratification. We performed genome-wide genotyping in 446 pediatric patients with de novo AML enrolled in Children's Oncology Group (COG) studies AAML0531, AAML03P1, and CCG2961. Affymetrix and Illumina Omni 2.5 platforms were used to evaluate copy-number alterations (CNAs) and determine their associations with treatment outcome. Data from Affymetrix and Illumina studies were jointly analyzed with ASCAT and GISTIC software. An average of 1.14 somatically acquired CNAs per patient were observed. Novel reoccurring altered genomic regions were identified, and the presence of CNAs was found to be associated with decreased 3-year overall survival (OS), event-free survival (EFS), and relapse risk from the end of induction 1 (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.2-2.4; HR, 1.4; 95% CI, 1.0-1.8; and HR, 1.4; 95% CI, 1.0-2.0, respectively). Analyses by risk group demonstrated decreased OS and EFS in the standard-risk group only (HR, 1.9; 95% CI, 1.1-3.3 and HR, 1.7; 95% CI, 1.1-2.6, respectively). Additional studies are required to test the prognostic significance of CNA presence in disease relapse in patients with AML. COG studies AAML0531, AAML03P1, and CCG2961 were registered at www.clinicaltrials.gov as #NCT01407757, #NCT00070174, and #NCT00003790, respectively.


Development of candidate gene markers associated to common bacterial blight resistance in common bean.
Common bacterial blight (CBB), caused by Xanthomonas axonopodis pv. phaseoli (Xap), is a major yield-limiting factor of common bean (Phaseolus vulgaris L.) production around the world. Two major CBB-resistant quantitative trait loci (QTL), linked to the sequence characterized amplified region markers BC420 and SU91, are located at chromosomes 6 and 8, respectively. Using map-based cloning approach, four bacterial artificial chromosome (BAC) clones from the BC420-QTL locus and one BAC clone containing SU91 were sequenced by Roche 454 technique and subsequently assembled using merged assemblies from three different programs. Based on the quality of the assembly, only the sequences of BAC 32H6 and 4K7 were used for candidate gene marker (CGM) development and candidate gene (CG) selection. For the BC420-QTL locus, 21 novel genes were predicted in silico by FGENESH using Medicago gene model, whereas 16 genes were identified in the SU91-QTL locus. For each putative gene, one or more primer pairs were designed and tested in the contrasting near isogenic lines. Overall, six and nine polymorphic markers were found in the SU91- and BC420-QTL loci, respectively. Afterwards, association mapping was conducted in a breeding population of 395 dry bean lines to discover marker-trait associations. Two CGMs per each locus showed better association with CBB resistance than the BC420 and SU91 markers, which include BC420-CG10B and BC420-CG14 for BC420_QTL locus, and SU91-CG10 and SU91-CG11 for SU91_QTL locus. The strong associations between CBB resistance and the CGs 10 and 14 from BC420_QTL locus and the CGs 10 and 11 from SU91_QTL locus indicate that the genes 10 and 14 from the BC420 locus are potential CGs underlying the BC420_QTL locus, whereas the genes 10 and 11 from the SU91 locus are potential CGs underlying the SU91_QTL locus. The superiority of SU91-CG11 was further validated in a recombinant inbred line population Sanilac × OAC 09-3. Thus, co-dominant CGMs, BC420-CG14 and SU91-CG11, are recommended to replace BC420 and SU91 for marker-assisted selection of common bean with resistance to CBB.


The correlation of bone mineral density and histologic data in the early grafted maxillary sinus: a preliminary report.
: Implant success in the grafted maxillary sinus is dependent on the formation of new vital autogenous bone and its mineral density. Different bone graft materials and graft combinations have been used in the sinus augmentation procedure to support dental implants under occlusal loads. The goal of this study was to determine whether it is possible to observe a direct correlation between bone mineral density and histologic data in the grafted maxillary sinus. Based on the observed histological findings, we propose a bone mineral density classification that has 3 rather than 4 types of bone. : A total of 15 patients participated in this study, all of which had only 1 sinus grafted. A total of 34 dental implants were placed in the grafted sinuses. In 7 patients, designated as group A, a 50:50 composite ratio of autogenous and allogeneic bone was used to graft the sinuses. Four patients had the sinuses grafted with a 50:50 composite ratio of a naturally occurring marine algae hydroxyapatite graft material and autogenous bone. One patient had the sinus grafted with 100% autogenous bone. In this group of patients, a total of 25 dental implants were surgically placed 14 to 20 weeks after sinus grafting. The implants were restored 12 weeks later. No implant failures were observed over a 52-week period. The last 3 patients, designated as group B, completed implant surgery beyond the 52-week end point of the study for various reasons. They provided a unique opportunity to histologically observe bone maturation at 68, 88, and 260 weeks, respectively. Using cone beam computed tomography (CT) technology and 3D-CT interactive software, bone mineral density in Hounsfield unit values were recorded during different healing time periods. : In all 15 patients, bone mineral density was observed to steadily increase during the 52-week observation period and beyond, as evidenced by the increase in Hounsfield unit values and the formation of new, vital autogenous trabecular bone. : Histologic and histomorphometric data demonstrate a definite correlation with the formation of new, vital autogenous trabecular bone and bone mineral density (quality) that permits early loading of implants in the grafted maxillary sinus.


Thioredoxin-1 maintains mechanistic target of rapamycin (mTOR) function during oxidative stress in cardiomyocytes.
Thioredoxin 1 (Trx1) is a 12-kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism, and survival. We have shown previously that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown. Using a substrate-trapping mutant of Trx1 (Trx1C35S), we show here that mTOR is a direct interacting partner of Trx1 in the heart. In response to H2O2 treatment in cardiomyocytes, mTOR exhibited a high molecular weight shift in non-reducing SDS-PAGE in a 2-mercaptoethanol-sensitive manner, suggesting that mTOR is oxidized and forms disulfide bonds with itself or other proteins. The mTOR oxidation was accompanied by reduced phosphorylation of endogenous substrates, such as S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) in cardiomyocytes. Immune complex kinase assays disclosed that H2O2 treatment diminished mTOR kinase activity, indicating that mTOR is inhibited by oxidation. Of note, Trx1 overexpression attenuated both H2O2-mediated mTOR oxidation and inhibition, whereas Trx1 knockdown increased mTOR oxidation and inhibition. Moreover, Trx1 normalized H2O2-induced down-regulation of metabolic genes and stimulation of cell death, and an mTOR inhibitor abolished Trx1-mediated rescue of gene expression. H2O2-induced oxidation and inhibition of mTOR were attenuated when Cys-1483 of mTOR was mutated to phenylalanine. These results suggest that Trx1 protects cardiomyocytes against stress by reducing mTOR at Cys-1483, thereby preserving the activity of mTOR and inhibiting cell death.


Methodology for Safe and Effective Subcutaneous Implantation of Wireless Biotelemetry Sensor Devices in Rodents.
In this work, a methodology for assessing the impact of implantation surgery on laboratory mice on behavior was created. The study included the design of several implants fabricated on various printed circuit board (PCB) technologies with overall diameters between 26-28mm and weights between 4.5-6.5g. 11 adult CD1 mice were implanted with the devices and their behavior was analyzed using common behavioral benchmark tests. The results show that implants designed to be 10% of the animal's body weight showed no adverse effects on mobility or social behavior. These results illustrate a method to identify and reduce the adverse behavioral changes inherent to device implantation. Additional considerations for implant surgery are provided. These results are validated with the implantation of a Bluetooth Low Energy (BLE) wireless sensor tag. The implanted wireless tag showed an average Received Signal Strength Indicator (RSSI) of 62.96dBm with a standard deviation of 4.95dBm and a variance of 24.5 dBm2. The high RSSI and variance values show that the implant was working well inside of the mouse's body and that the mouse was fully recovered and readily exploring its surroundings.Clinical Relevance-This work 1) studies the behavioral impact of implantable wireless biopotential devices. This will help clinical researchers conducting behavioral studies using sensor implants. 2) demonstrates a working implanted BLE wireless model inside of a mouse. Various wireless connectivity metrics are studied.


Chaperone control of the activity and specificity of the histone H3 acetyltransferase Rtt109.
Acetylation of Saccharomyces cerevisiae histone H3 on K56 by the histone acetyltransferase (HAT) Rtt109 is important for repairing replication-associated lesions. Rtt109 purifies from yeast in complex with the histone chaperone Vps75, which stabilizes the HAT in vivo. A whole-genome screen to identify genes whose deletions have synthetic genetic interactions with rtt109Delta suggests Rtt109 has functions in addition to DNA repair. We show that in addition to its known H3-K56 acetylation activity, Rtt109 is also an H3-K9 HAT, and we show that Rtt109 and Gcn5 are the only H3-K9 HATs in vivo. Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by Vps75. Another histone chaperone, Asf1, and Vps75 are both required for acetylation of lysine 9 on H3 (H3-K9ac) in vivo by Rtt109, whereas H3-K56ac in vivo requires only Asf1. Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56.


Excision of transposon Tn5 is dependent on the inverted repeats but not on the transposase function of Tn5.
The excision of Tn5 from sites of insertion in the Escherichia coli genome was studied by examining the reversion of lac::Tn5 insertion mutations to lac+. We find that: (i) the frequency of excision depends on the site of Tn5 insertion, (ii) excision occurs efficiently in recA- cells, (iii) excision does not require a Tn5-encoded transposition function, and (iv) efficient excision requires the inverted repeats of Tn5. We propose that excision of Tn5 is similar to the formation of spontaneous deletions and occurs by slippage during DNA synthesis.


[Osteoplastic fixation of the spine].
The combined anterolateral osteoplastic fixation of the spine was carried out on 17 cases out of 73 operated upon for pathological spinal changes of various etiology. The tibial crest rigid homograft and the rib autograft on vasoneuromuscular feeding pedicle were used. Such a combination of bone grafts possessing different mechanic and osteogenic properties permitted to obtain a reliable fixation of the spine for all the period necessary for anatomic and functional reconstruction of the grafts.


[The difference of erythropoietin concentration in various disease].
The serum concentration of erythropoietin in 79 cases with various blood diseases, uremia, chronic obstructive pulmonary disease etc was determined. At comparable degrees of anemia, patients with myelodysplastic syndrome and aplastic anemia had the highest levels of erythropoietin in our study. The high level of erythropoietin titer in patients with aplastic anemia should be taken as the nom for renal synthesis and release of this hormone. The erythropoietin level in patients with uremic anemia was lower than the level in patients with anemia of other causes but still higher than that of the normal controls. Patients suffering from polycystic kidney disease with or without uremia had a high level of erythropoietin due to local hypoxia of remnant kidney tissue resulting from the pressure of cystic formation. Different methods are used to determine the erythropoietin level, which varies with the stage and etiology of the diseases. There are other stimulating or inhibitory factors of erythropoiesis when the assay is processed. Transfusion and administration of certain drugs also influence the growth of erythroid cells, thus the serum titers of erythropoietin differed markedly between patients at comparable hemoglobin concentration.


pH Dependence of the photocycle kinetics of the E46Q mutant of photoactive yellow protein: protonation equilibrium between I1 and I2 intermediates, chromophore deprotonation by hydroxyl uptake, and protonation relaxation of the dark state.
The kinetics of the photocycle of PYP and its mutants E46Q and E46A were investigated as a function of pH. E46 is the putative donor of the chromophore which becomes protonated in the I(2) intermediate. For E46Q we find that I(2) is in a pH-dependent equilibrium with its precursor I(1)' with a pK(a) of 8.15 and n = 1. From this result and from experiments with pH indicator dyes, we conclude that in the I(1)' to I(2) transition one proton is taken up from the external medium. The pK(a) of 8.15 is that of the surface-exposed chromophore in the equilibrium between I(1)' and I(2) and is close to that of the phenolate group of p-hydroxycinnamic acid. The pH-dependent I(1)'/I(2) equilibrium with associated H(+) uptake is reminiscent of the M(I)/M(II) equilibrium in the formation of the signaling state of rhodopsin. Well above this pK(a) no I(2) is formed and I(1)' returns in a pH-independent manner to the initial state P. The decay rate for the return to P via I(2) is between pH 4 and pH 8, exactly proportional to the hydroxide concentration (first order), and the deprotonation of the chromophore in this transition occurs by hydroxide uptake. Well above the pK(a) of 8.15 the apparent rate constant for the return to P is constant due to the branching from I(1)'. Complementary measurements with the pH indicator dye cresol red at pH 8.3 show that the remaining PYP molecules that still cycle via I(2) take up one proton in the formation of I(2). Together, these observations provide compelling evidence that during the photocycle the chromophore in E46Q is protonated and deprotonated from the external medium. For the yellow form of the mutant E46A the apparent rate constant for the return to P is also linear in [OH(-)] below about pH 8.3 and constant above about pH 9.5, with a pK(a) value of 8.8 for I(1)', suggesting a similar mechanism of chromophore protonation/deprotonation as in E46Q. For wild type qualitatively similar observations were made: the amplitude of I(2) decreased at alkaline pH, I(1)' and I(2) were in equilibrium, and I(1)' decayed together with the return to P. Chromophore hydrolysis prevented, however, an accurate determination of the pK(a) of I(1)'. We estimate that its value is above 11. The ground state P is in the dark in a pH-dependent equilibrium with a low-pH bleached form P(bl) with protonated chromophore. The pK(a) values for these equilibria are 4.8 and 7.9 for E46Q and E46A, respectively. When the pH is close to these pK(a)'s, the kinetics of the photocycle contains additional components in the millisecond time range. Using pH-jump stopped-flow experiments, we show that these contributions are due to the relaxation of the P/P(bl) equilibrium which is perturbed by the rapid decrease in the P concentration caused by the flash excitation of P. The condition for the occurrence of this effect is that the relaxation time of the P/P(bl) equilibrium is faster than the photocycle time.


The role of a guanine nucleotide-binding protein in the activation of rat liver plasma-membrane adenylate cyclase by forskolin.
The effects of the photoreactive GTP analogue GTP-gamma-azidoanilide on rat liver plasma-membrane adenylate cyclase are described. U.v. irradiation in the presence of the analogue abolished activation by any effector or combination of effectors that function via the activatory G protein. Partial protection against this inhibition was given by F- and guanosine 5'-[gamma-thio]triphosphate. It is concluded that GTP-gamma-azidoanilide acts by a light-induced covalent reaction with the G protein. In the dark the effects of the analogue were similar to those of GTP. Irradiation in the presence of GTP-gamma-azidoanilide was found to reduce but not to abolish activation of rat liver plasma membrane adenylate cyclase by forskolin. The activation by forskolin and GTP together were greater than the sum of the individual activations. Forskolin doubled adenylate cyclase activity in the presence of glucagon and guanosine 5'-[beta, gamma-imido]triphosphate, which might be expected to activate to the maximum possible extent via the G protein. It is concluded that there are two components to the forskolin activation, a guanine nucleotide-dependent and a guanine nucleotide-independent component.