Cytoskeletal organization, phylogenetic affinities and systematics in the contentious taxon Excavata (Eukaryota).
An overview of the controversial proposal for the major eukaryote taxon "Excavata" is presented. Excavata is predicted to include at least ten distinct groups: jakobids, Malawimonas, Trimastix, Carpediemonas, retortamonads, diplomonads, Heterolobosea, oxymonads, parabasalids and Euglenozoa. These "excavates" have broadly similar flagellar apparatus organizations, for which a "universal" terminology is provided. Most, but not all, of these organisms share a distinctive suspension-feeding groove, as well as some or all of a set of seven other proposed cytoskeletal apomorphies. Cladistic analyses of morphological data do not resolve high-level relationships within Excavata. Excavate-rich molecular phylogenies recover some robust clades, but do not support or strongly refute the monophyly of Excavata. A partial classification for excavates is presented, with phylogenetic diagnoses for Excavata and for two novel taxon names, Fornicata (Carpediemonas, retortamonads, diplomonads) and Preaxostyla (Trimastix, oxymonads).


Hemangioendothelioma of the spine.
A review of the patient files from our institution's oncology department showed that between 1950 and 2000, 11 patients were diagnosed with hemangioendothelioma of the spine, a rare, low-grade malignant vascular tumor. After reevaluation of the diagnoses by orthopaedic oncologists and pathologists, three patients were excluded; therefore eight patients formed the study group. The eight lesions were located in the thoracic (three) or lumbar spine (five, one in each vertebral level). Computed tomography scans revealed expansile lytic process. All lesions involved the vertebral body, but only one was diffuse with spinous process involvement. Treatment included: external beam irradiation alone (one patient), curettage and external beam irradiation (one patient), laminectomy and external beam irradiation (two patients), anterior resection only (two patients), and anterior resection with postoperative external beam irradiation (two patients). Patients without spinal stabilization had chronic low back pain; no patient with spinal stabilization had such pain. One patient who had surgical resection and radiation therapy had a radiation-induced sarcoma develop after 4 years. One patient who was treated with radiation therapy alone had a metastatic lung lesion develop. No other patient had tumor recurrence or progression. Therefore, patients with hemangioendothelioma of the spine may be treated with radiation therapy alone, surgery alone, or a combination thereof. However, because the number of patients in the current series was small, no definitive recommendations regarding treatment may be made. Resection of large lesions and stabilization of vertebral collapse may decrease back pain.


[Dendritic cells and their role in atopic dermatitis].
Dendritic cells in the epidermis have an important role in the skin inmunity since they have an immunogenic capacity. The dendritic cell prototype is Langerhans cell (LC), however, nowadays it is known that there are other dendritic cells in the skin as dermic dendritic cells (DDCs). In this review we examined the functions and characteristics of these cells and their role in the atopic dermatitis.


Reducing Student Nurse Stigmatization of the Patient Who Misuses Opioids: A Scoping Review.
The United States is in the midst of an opioid epidemic. The numbers of opioid-related deaths have been steadily climbing, magnifying the need for innovative intervention. Stigma is a set of preconceived, negative assumptions about a patient population or group. Stigma is a known deterrent to communication and the delivery of healthcare. Nurses serve as a primary contact for many marginalized patients within the healthcare system. The purpose of this scoping review is to gather known data on the use of educational interventions with nursing students to reduce stigmatizing tendencies. Inclusion criteria constituted an educational intervention involving student nurses and an effort to reduce stigmatizing attitudes toward patients who misuse opioids. The intervention must have taken place in an institute of higher learning between the years of 2003 and 2018. Exclusion criteria included community-wide studies. A single study was identified addressing nursing student reduction of stigmatization of the individual who uses opioids, and so, the search was expanded to include any student nursing intervention developed to reduce stigma toward any marginalized population. The following electronic databases were utilized in the search process: Cumulative Index of Nursing and Allied Health Literature, Google Scholar, Journal Storage, Microsoft Academic, and ScienceDirect. Reference pages of selected or related articles were reviewed in an attempt to identify additional pertinent literature through citation mapping. Fifteen studies were identified, each of which utilized a variable methodology for stigma reduction with varying levels of success.


[A young woman from Cameroon with rectal blood loss, intestinal schistosomiasis and rectosigmoid carcinoma].
A 32-year-old woman from Cameroon presented with rectal blood loss due to a focally infiltrating adenocarcinoma of the rectosigmoid in the presence of an active intestinal schistosomiasis (Schistosoma intercalatum). A correlation between chronic intestinal schistosomiasis and the development of colorectal cancer has been suggested in the literature, but is not uniformly accepted. However, the case presented here reinforces this suggestion. In a patient with rectal blood loss who comes from an area where intestinal schistosomiasis is endemic, the possibility of a colorectal carcinoma should be considered in the diagnosis.


Ribosomal protein QM/RPL10 positively regulates defence and protein translation mechanisms during nonhost disease resistance.
Ribosomes play an integral part in plant growth, development, and defence responses. We report here the role of ribosomal protein large (RPL) subunit QM/RPL10 in nonhost disease resistance. The RPL10-silenced Nicotiana benthamiana plants showed compromised disease resistance against nonhost pathogen Pseudomonas syringae pv. tomato T1. The RNA-sequencing analysis revealed that many genes involved in defence and protein translation mechanisms were differentially affected due to silencing of NbRPL10. Arabidopsis AtRPL10 RNAi and rpl10 mutant lines showed compromised nonhost disease resistance to P. syringae pv. tomato T1 and P. syringae pv. tabaci. Overexpression of AtRPL10A in Arabidopsis resulted in reduced susceptibility against host pathogen P. syringae pv. tomato DC3000. RPL10 interacts with the RNA recognition motif protein and ribosomal proteins RPL30, RPL23, and RPS30 in the yeast two-hybrid assay. Silencing or mutants of genes encoding these RPL10-interacting proteins in N. benthamiana or Arabidopsis, respectively, also showed compromised disease resistance to nonhost pathogens. These results suggest that QM/RPL10 positively regulates the defence and translation-associated genes during nonhost pathogen infection.


Pharyngeal airway dimensions after chin cup treatment in Class III malocclusion subjects.
The objective of this study was to examine if chin cup therapy have any adverse effect on the sagittal pharyngeal dimensions in Class III malocclusion patients. Twenty patients (10 girls and 10 boys; mean age 10.31 +/- 1.15 years) with skeletal Class III malocclusion, and an untreated control group (8 girls and 10 boys, mean age 9.89 +/- 1.55 years) were evaluated. The chin cup appliance and an occlusal bite plate with 600 grams totally was used for 9.78 +/- 0.93 months. Linear, angular and area measurements were evaluated on the cephalometric radiographs taken before and after observation and treatment periods. Treatment changes showed significant increases in maxillary forward position, effective length of the maxilla and the mandible, and vertical facial height measurements. The mandible showed a clockwise rotation revealed by the decrease in SNB and the increase in mandibular plane angles. Significant increase in the nasopharyngeal area was found when the treatment and control groups were compared. The nasopharyngeal airway area was affected by chin cup treatment, without any adverse effect on the pharyngeal airway dimensions in the short term.


Prospective identification of adolescent suicide ideation using classification tree analysis: Models for community-based screening.
Although a large number of risk markers for suicide ideation have been identified, little guidance has been provided to prospectively identify adolescents at risk for suicide ideation within community settings. The current study addressed this gap in the literature by utilizing classification tree analysis (CTA) to provide a decision-making model for screening adolescents at risk for suicide ideation. Participants were N = 4,799 youth (Mage = 16.15 years, SD = 1.63) who completed both Waves 1 and 2 of the National Longitudinal Study of Adolescent to Adult Health. CTA was used to generate a series of decision rules for identifying adolescents at risk for reporting suicide ideation at Wave 2. Findings revealed 3 distinct solutions with varying sensitivity and specificity for identifying adolescents who reported suicide ideation. Sensitivity of the classification trees ranged from 44.6% to 77.6%. The tree with greatest specificity and lowest sensitivity was based on a history of suicide ideation. The tree with moderate sensitivity and high specificity was based on depressive symptoms, suicide attempts or suicide among family and friends, and social support. The most sensitive but least specific tree utilized these factors and gender, ethnicity, hours of sleep, school-related factors, and future orientation. These classification trees offer community organizations options for instituting large-scale screenings for suicide ideation risk depending on the available resources and modality of services to be provided. This study provides a theoretically and empirically driven model for prospectively identifying adolescents at risk for suicide ideation and has implications for preventive interventions among at-risk youth. (PsycINFO Database Record


Durability of antibody responses after receipt of the monovalent 2009 pandemic influenza A (H1N1) vaccine among HIV-infected and HIV-uninfected adults.
Human immunodeficiency virus (HIV)-infected persons are at risk for severe influenza infections. Although vaccination against the H1N1 pandemic influenza strain is recommended, currently there are no data on the durability of post-vaccination antibody responses in this population. HIV-infected and HIV-uninfected adults (18-50 years old) received a single dose of monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1). Antibody levels to the 2009 H1N1 pandemic strain were determined at day 0, day 28, and 6 months by hemagglutination-inhibition assay. A seroprotective response was a post-vaccination titer of ≥1:40 among those with a pre-vaccination level of ≤1:10. Geometric mean titers (GMT) and factors associated with higher levels were also evaluated. We studied 127 participants with a median age of 35 (interquartile range (IQR) 28, 42) years. Among the HIV-infected arm (n=63), the median CD4 count was 595 (IQR 476, 819)cells/mm(3) and 83% were receiving HAART. Thirty-five percent of all participants had a pre-vaccination level of >1:10. HIV-infected compared to HIV-uninfected adults were less likely to generate a seroprotective response at day 28 (54% vs. 75%, adjusted OR 0.23, p=0.021) or have a durable response at 6 months post-vaccination (28% vs. 56%, adjusted OR 0.19, p=0.005). Additionally, although pre-vaccination GMT were similar in both arms (median 7 vs. 8, p=0.11), the GMT at 6 months was significantly lower among HIV-infected versus HIV-uninfected adults (median 20 vs. 113, p=0.003). Among HIV-infected persons, younger age (p=0.035) and receipt of HAART (p=0.028) were associated with higher GMTs at 6 months. Despite vaccination, most HIV-infected adults do not generate durable seroprotective antibody responses to the 2009 influenza A (H1N1) virus, and hence may remain vulnerable to infection. In addition to HAART use, more immunogenic vaccines are likely needed for improving protection against influenza in this population.


[Involvement of tetrahydrobiopterin in local change of endothelium-dependent vasorelaxation in pulmonary hypertension].
A deficiency of tetrahydrobiopterin (BH4), a NO-synthase co-factor, results in reactive oxygen species synthesis by NO-synthase. It leads to disturbances of endothelium-dependent vasorelaxation. We performed our study on the monocrotaline model of pulmonary hypertension. A decrease in endothelium-dependent relaxation was observed only in intrapulmonary arteries of monocrotaline-treated rats. A perfusion of BH4 (0.1 mol/liter) increased significantly endothelium-dependent dilation of hypertensive pulmonary arteries (p < 0.01). But BH4 did not influence the relaxation of systemic vessels and the dilation responses of pulmonary and systemic arteries of control rats. Measuring of superoxide by lucigenin-mediated chemiluminescence showed five-fold O2- production in intrapulmonary arteries of pulmonary hypertensive rats, that was activated by acetylcholine and inhibited by a nonselective NO-synthase blocker (L-NAME). However, activity of NO-synthase measured as [H3]arginine to [H3]citrulline conversion and assessed in pulmonary vessels and aortic tissue, did not differ in control and monocrotaline-treated groups. These data suggest, that there is a local deficiency of BH4--in pulmonary vessels, without significant changes of systemic circulation.


Important features of retail shoes for women with rheumatoid arthritis: A Delphi consensus survey.
Footwear management aims to preserve foot function, reduce the burden of foot pain and maintain joint mobility in women with rheumatoid arthritis (RA). Whilst retail footwear is commonly recommended by health professionals, there is no current consensus on recommended features of retail footwear for women with RA. This study aimed to determine consensus from health professionals about the important features of retail footwear for women with RA. An international Delphi exercise using online survey software was conducted with 39 participants from health care backgrounds. Three iterative rounds were conducted. In the first round, participants listed features of retail footwear that would be important for women with RA. Responses of the first round, combined with results of a scoping review of patient-reported outcome measures used in assessing footwear in arthritis and a qualitative analysis of female patients' perspectives of retail footwear in RA were used to create items for the second round. Items were scored by a 9-point rating scale with consensus defined by the RAND/UCLA disagreement index. The third round consisted of items which did not reach consensus or scored >1 on the RAND/UCLA disagreement index from round two. Fifty-eight items (n = 58) were generated for rating and at the end of three iterative rounds, there was agreement that thirty-eight items were important, that two were not important, and there was no agreement for a further eighteen items. Item themes reaching consensus included footwear characteristics and acceptability and psychosocial aspects of footwear. Footwear characteristics related to heel height, shape, cushioning, toe box size, adjustable fastening, removable insoles, mid-foot support and soft accommodative uppers. Acceptability and psychosocial aspects included affordability, comfort, aesthetic, style, colour and impact on femininity. This consensus exercise has identified the important features of retail footwear for women with RA.


Oxygen consumption in human, tissue-engineered myobundles during basal and electrical stimulation conditions.
During three-dimensional culture of skeletal muscle in vitro, electrical stimulation provides an important cue to enhance skeletal muscle mimicry of the in vivo structure and function. However, increased respiration can cause oxygen transport limitations in these avascular three-dimensional constructs, leading to a hypoxic, necrotic core, or nonuniform cell distributions in larger constructs. To enhance oxygen transport with convection, oxygen concentrations were measured using an optical sensor at the inlet and outlet of an 80 μl fluid volume microphysiological system (MPS) flow chamber containing three-dimensional human skeletal muscle myobundles. Finite element model simulations of convection around myobundles and oxygen metabolism by the myobundles in the 80 μl MPS flow chamber agreed well with the oxygen consumption rate (OCR) at different flow rates, suggesting that under basal conditions, mass transfer limitations were negligible for flow rates above 1.5 μl s-1. To accommodate electrodes for electrical stimulation, a modified 450 μl chamber was constructed. Electrical stimulation for 30 min increased the measured rate of oxygen consumption by the myobundles to slightly over 2 times the basal OCR. Model simulations indicate that mass transfer limitations were significant during electrical stimulation and, in the absence of mass transfer limitations, electrical stimulation induced about a 20-fold increase in the maximum rate of oxygen consumption. The results indicate that simulated exercise conditions increase respiration of skeletal muscle and mass transfer limitations reduce the measured levels of oxygen uptake, which may affect previous studies that model exercise with engineered muscle.


How does low-molecular-weight polystyrene dissolve: osmotic swelling vs. surface dissolution.
By means of multiscale hierarchical modeling we study the real time evolution of low-molecular-weight polystyrene, below the glass transition temperature, in contact with its solvent, toluene. We observe two concurrent phenomena taking place: (1) the solvent diffuses into the polymer by a Case II mechanism, leading to osmotic driven swelling and progressive chain dilution (inside-out mechanism); (2) polymer chains are solvated, detach from the interface and move into the solvent before the film is completely swollen (outside-in mechanism). From our simulations we conclude that, below the entanglement length, a thin swollen layer, also observed in previous experiments, forms almost instantaneously, which allows for the outside-in mechanism to start a few tens of nanoseconds after the polymer-solvent initial contact. After this initial transient time the two mechanisms are concurrent. We furthermore observe that the presence of the solvent significantly enhances the mobility of the polymer chains of the surface layer, but only in the direction parallel to the interface.


The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application.
A novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019. There is limited support for many of its key epidemiologic features, including the incubation period for clinical disease (coronavirus disease 2019 [COVID-19]), which has important implications for surveillance and control activities. To estimate the length of the incubation period of COVID-19 and describe its public health implications. Pooled analysis of confirmed COVID-19 cases reported between 4 January 2020 and 24 February 2020. News reports and press releases from 50 provinces, regions, and countries outside Wuhan, Hubei province, China. Persons with confirmed SARS-CoV-2 infection outside Hubei province, China. Patient demographic characteristics and dates and times of possible exposure, symptom onset, fever onset, and hospitalization. There were 181 confirmed cases with identifiable exposure and symptom onset windows to estimate the incubation period of COVID-19. The median incubation period was estimated to be 5.1 days (95% CI, 4.5 to 5.8 days), and 97.5% of those who develop symptoms will do so within 11.5 days (CI, 8.2 to 15.6 days) of infection. These estimates imply that, under conservative assumptions, 101 out of every 10 000 cases (99th percentile, 482) will develop symptoms after 14 days of active monitoring or quarantine. Publicly reported cases may overrepresent severe cases, the incubation period for which may differ from that of mild cases. This work provides additional evidence for a median incubation period for COVID-19 of approximately 5 days, similar to SARS. Our results support current proposals for the length of quarantine or active monitoring of persons potentially exposed to SARS-CoV-2, although longer monitoring periods might be justified in extreme cases. U.S. Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases, National Institute of General Medical Sciences, and Alexander von Humboldt Foundation.


LDH isozymes in skeletal muscles of endurance and strength trained athletes.
Muscle biopsy samples were obtained from arm and leg muscles of endurance and strength trained athletes, respectively. Total LDH activity as well as occurrence and activity of LDH isozymes were determined. Comparing the results from the athletes with those from non-trained subjects with corresponding fibre compositions, it was found that the endurance athletes had a lower total LDH activity, a higher relative activity of the most heart-specific isozymes. LDH (1 + 2), and, on electrophoretic separation, a complete absence of LDH (4 + 5) in both arm and leg muscles. As compared to the untrained material the strength trained athletes tended to have a higher total LDH activity, a similar distribution of relative isozyme activities, and, in the leg muscles, a strong electrophoretic band corresponding to LDH 5, the most skeletal muscle specific isozyme.


Femtosecond laser bone ablation with a high repetition rate fiber laser source.
Femtosecond laser pulses can be used to perform very precise cutting of material, including biological samples from subcellular organelles to large areas of bone, through plasma-mediated ablation. The use of a kilohertz regenerative amplifier is usually needed to obtain the pulse energy required for ablation. This work investigates a 5 megahertz compact fiber laser for near-video rate imaging and ablation in bone. After optimization of ablation efficiency and reduction in autofluorescence, the system is demonstrated for the in vivo study of bone regeneration. Image-guided creation of a bone defect and longitudinal evaluation of cellular injury response in the defect provides insight into the bone regeneration process.


Inflammatory polyarthritis in the community is not a benign disease: predicting functional disability one year after presentation.
To predict which patients with early inflammatory polyarthritis presenting to primary care will be functionally disabled one year after presentation, in order to inform treatment and referral decisions. The study population consisted of 381 patients notified to the Norfolk Arthritis Register, a primary care based inception cohort of patients with inflammatory polyarthritis. Patients were regarded as functionally disabled if they had a Health Assessment Questionnaire (HAQ) score of one or more. Clinical, laboratory, and demographic variables easily measured at baseline were analyzed for their ability to predict future disability. Recursive partitioning was used to create a simple decision tree to predict those patients who would be disabled at one year. A logistic regression model was generated on a sample of 277 patients and tested on an independent sample of 104 patients. This was compared with other models, one of which consisted of the 1987 ARA criteria. 112 (29%) patients had a HAQ score of at least 1 at one year. The strongest predictors of future disability were a high baseline HAQ, large joint involvement, female sex, and longer disease duration. The decision tree predicted disability accurately in 67% of patients. It is possible to predict functional outcome at one year among patients with early inflammatory polyarthritis presenting to primary care using simple clinical variables measured at baseline. Satisfying the 1987 ARA criteria could not be used to predict future disability.


Economic dependency, health services, and health: the case of Lesotho.
This article is concerned with two factors affecting the health status of the people of Lesotho: (1) the nation's function as a reserve labor economy (that is, the primary source of income for about half the country's male labor force is employment in South Africa); and (2) the health care system (its size, composition, accessibility, and efficiency). Although such apparently diverse factors usually are analyzed independently, they might be combined to provide a more complete understanding of the determinants of health and disease. The paper reaches the conclusion that any substantive solutions to the problems of Lesotho will be found primarily in the wider southern Africa setting, and not within the context of small, dependent national states. At the same time, these small, dependent national states must make development decisions considering existing geopolitical realities. Foresightful decision making on these issues could both contribute immediately to the health of the people of Lesotho, and also increase in longer-term possibilities for a better life for all the people of southern Africa.


Interstitial lung disease associated with gefitinib.
Although pulmonary toxicity associated with gefitinib, an epidermal growth factor receptor inhibitor, has been reported recently, the accumulation of clinical information and the underlying mechanisms of gefitinib-induced interstitial lung disease (ILD) remain insufficient and unclear. After retrospectively reviewing the clinical records and chest X-rays of 489 lung cancer patients who were treated with gefitinib, we diagnosed four cases of gefitinib-induced ILD who underwent fiberoptic bronchoscopy and bronchoalveolar lavage (BAL). We found that the period of time from starting gefitinib to the onset of ILD was short, and concluded that a careful and close observation of a chest imaging study and a collection of respiratory symptoms was recommended. All four patients were treated with a high dose of corticosteroids, and ILD was resolved. We detected high levels of interferon-inducible protein-10 in BAL fluid, although we could not demonstrate the characteristic features of laboratory findings or BAL fluid cell analysis. We speculated that a Th1 type of lung tissue inflammation or lung injury might be involved as a part of mechanisms underlying gefitinib-induced ILD.


Surgical treatment for nonunion of the scaphoid.
Fracture of the scaphoid is the most common injury of the carpal bones. Most scaphoid fractures heal after immobilization. When the fracture does not unite, degenerative arthritic changes and disability may occur. Twenty-four symptomatic nonunions treated surgically were reviewed. Based on presence of union, percent of normal motion, and patients' symptoms, results were rated good in 19 cases and fair in five. Nine of ten patients treated with bone grafting and styloidectomy had union of fractures with good results. All five patients with bone grafting and internal fixation had union. Excision of proximal fragments of more than one third to one half of the scaphoid, and internal fixation alone, had unsatisfactory results. A styloidectomy should excise approximately one half of the radius articulating with the scaphoid. If not enough styloid is excised, osteophytic overgrowth will occur; if too much is excised, the carpus will sublux radially.


Changes in lipid membranes may trigger amyloid toxicity in Alzheimer's disease.
Amyloid-beta peptides (Aβ), implicated in Alzheimer's disease (AD), interact with the cellular membrane and induce amyloid toxicity. The composition of cellular membranes changes in aging and AD. We designed multi-component lipid models to mimic healthy and diseased states of the neuronal membrane. Using atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM) and black lipid membrane (BLM) techniques, we demonstrated that these model membranes differ in their nanoscale structure and physical properties, and interact differently with Aβ1-42. Based on our data, we propose a new hypothesis that changes in lipid membrane due to aging and AD may trigger amyloid toxicity through electrostatic mechanisms, similar to the accepted mechanism of antimicrobial peptide action. Understanding the role of the membrane changes as a key activating amyloid toxicity may aid in the development of a new avenue for the prevention and treatment of AD.


Evaporative cooling and coherent axial oscillations of highly charged ions in a penning trap.
Externally, in an electron beam ion trap, generated Ar16+ ions were retrapped in a Penning trap and evaporatively cooled in their axial motion. The cooling was observed by a novel extraction technique based on the excitation of a coherent axial oscillation which yields short ion bunches of well-defined energies. The initial temperature of the ion cloud was decreased by a factor of more than 140 within 1 s, while the phase-space density of the coldest extracted ion pulses was increased by a factor of up to about 9.


A collagen-rich arch in the urochordate notochord coordinates cell shaping and multi-tissue elongation.
Cell and tissue reshaping is crucial for coordinating three-dimensional pattern formation, in which the size and shape of the cells must be accurately regulated via signal transport and communication among tissues. However, the identity of signaling and transportation mechanisms in this process remains elusive. In our study, we identified an extracellular matrix (ECM) structure with a vertebra-like shape surrounding the central notochord tissue in the larval tail of the urochordate Ciona. Additionally, we verified that the ECM structure was formed de novo, mainly from collagens secreted by notochord cells. Fluorescence recovery after photobleaching and simulation results revealed that this structure was formed via diffusional collagen flow from a notochord that was restricted and molded in the spaces among tail tissues. We revealed that the collagen structure was essential for notochord cell arrangement and elongation. Furthermore, we observed that the central notochord connects with the epidermis through this ECM structure. The disruption of this structure by collagen knockdown and loss-of-collagen function caused the failure of notochord elongation. More importantly, the epidermis could not elongate proportionally with notochord, indicating that the collagen-rich structure serves as a scaffold to coordinate the concurrent elongation of the tail tissues. These findings provide insights into how the central tissue forms and molds its surrounding ECM structure, by not only regulating its own morphogenesis but also functioning as a scaffold for signal transmission to orchestrate the coordinated morphologic reshaping of the surrounding tissues.


Inert fluorinated gas MRI: a new pulmonary imaging modality.
Fluorine-19 ((19)F) MRI of the lungs using inhaled inert fluorinated gases can potentially provide high quality images of the lungs that are similar in quality to those from hyperpolarized (HP) noble gas MRI. Inert fluorinated gases have the advantages of being nontoxic, abundant, and inexpensive compared with HP gases. Due to the high gyromagnetic ratio of (19)F, there is sufficient thermally polarized signal for imaging, and averaging within a single breath-hold is possible due to short longitudinal relaxation times. Therefore, the gases do not need to be hyperpolarized prior to their use in MRI. This eliminates the need for an expensive polarizer and expensive isotopes. Inert fluorinated gas MRI of the lungs has been previously demonstrated in animals, and more recently in healthy volunteers and patients with lung diseases. The ongoing improvements in image quality demonstrate the potential of (19)F MRI for visualizing the distribution of ventilation in human lungs and detecting functional biomarkers. In this brief review, the development of inert fluorinated gas MRI, current progress, and future prospects are discussed. The current state of HP noble gas MRI is also briefly discussed in order to provide context to the development of this new imaging modality. Overall, this may be a viable clinical imaging modality that can provide useful information for the diagnosis and management of chronic respiratory diseases.


Marcy's priority in the development of inguinal herniorrhaphy.
Conflicting claims regarding priority for the development of the modern operation for inguinal herniation have been made on behalf of Bassini, Halsted, and Marcy. The evidence is reviewed with special emphasis on the latter. It is concluded that Bassini was first and foremost.


Repetition Blindness for Faces: A Comparison of Face Identity, Expression, and Gender Judgments.
Repetition blindness (RB) refers to the impairment in reporting two identical targets within a rapid serial visual presentation stream. While numerous studies have demonstrated RB for words and picture of objects, very few studies have examined RB for faces. This study extended this research by examining RB when the two faces were complete repeats (same emotion and identity), identity repeats (same individual, different emotion), and emotion repeats (different individual, same emotion) for identity, gender, and expression judgment tasks. Complete RB and identity RB effects were evident for all three judgment tasks. Emotion RB was only evident for the expression and gender judgments. Complete RB effects were larger than emotion or identity RB effects across all judgment tasks. For the expression judgments, there was more emotion than identity RB. The identity RB effect was larger than the emotion RB effect for the gender judgments. Cross task comparisons revealed larger complete RB effects for the expression and gender judgments than the identity decisions. There was a larger emotion RB effect for the expression than gender judgments and the identity RB effect was larger for the gender than for the identity and expression judgments. These results indicate that while faces are subject to RB, this is affected by the type of repeated information and relevance of the facial characteristic to the judgment decision. This study provides further support for the operation of separate processing mechanisms for face gender, emotion, and identity information within models of face recognition.


Nacre calcification in the freshwater mussel Unio pictorum: carbonic anhydrase activity and purification of a 95 kDa calcium-binding glycoprotein.
The formation of the molluscan shell is finely tuned by macromolecules of the shell organic matrix. Previous results have shown that the acid-soluble fraction of the nacre matrix of the freshwater paleoheterodont bivalve Unio pictorum shell displays a number of remarkable properties, such as calcium-binding activity, the presence of extensive glycosylations and the capacity to interfere at low concentration with in vitro calcium carbonate precipitation. Here we have found that the nacre-soluble matrix exhibits a carbonic anhydrase activity, an important function in calcification processes. This matrix is composed of three main proteinaceous discrete fractions. The one with the highest apparent molecular weight is a 95 kDa glycoprotein that is specific to the nacreous layer. P95, as it is provisionally named, is enriched in Gly, Glx and Asx and exhibits an apparent pI value of approximately 4, or approximately 7 when chemically deglycosylated. Furthermore, its glycosyl moiety, consisting of sulfated polysaccharides, is involved in calcium binding. Purified fractions of the three main proteins were digested with trypsin, and the resulting peptides were analysed by mass spectrometry. Our results suggest that identical peptides are constitutive domains of the different proteins. Partial primary structures were obtained by de novo sequencing and compared with known sequences from other mollusc shell proteins. Our results are discussed from an evolutionary viewpoint.


Engineering the embryoid body microenvironment to direct embryonic stem cell differentiation.
Embryonic stem cells (ESCs) are pluripotent cells capable of differentiating into all somatic and germ cell types. The intrinsic ability of pluripotent cells to generate a vast array of different cells makes ESCs a robust resource for a variety of cell transplantation and tissue engineering applications, however, efficient and controlled means of directing ESC differentiation is essential for the development of regenerative therapies. ESCs are commonly differentiated in vitro by spontaneously self-assembling in suspension culture into 3D cell aggregates called embryoid bodies (EBs), which mimic many of the hallmarks of early embryonic development, yet the 3D organization and structure of EBs also presents unique challenges to effectively direct the differentiation of the cells. ESC differentiation is strongly influenced by physical and chemical signals comprising the local extracellular microenvironment, thus current methods to engineer EB differentiation have focused primarily on spatially controlling EB size, adding soluble factors to the media, or culturing EBs on or within natural or synthetic extracellular matrices. Although most such strategies aim to influence differentiation from the exterior of EBs, engineering the microenvironment directly within EBs enables new opportunities to efficiently direct the fate of the cells by locally controlling the presentation of morphogenic cues.


Biparametric MRI and 41 sector map for MRI/Transrectal ultrasound fusion biopsy to increase diagnostic accuracy of prostate cancer.
Optimizing the number of prostate biopsy (PB) cores in the initial diagnosis of prostate cancer is still an open question. Increasing the number of cores can expectedly lead to a higher cancer detection rate but more frequent, and greater number of adverse effects should be considered. It is necessary to limit the number of PBs, obtained from tumor areas and areas with a high suspect of malignancy. Simplified Prostate Imaging Reporting and Data System (PIRADS) using biparametric MR imaging (bpMRI) protocol identifies 4 categories indicating the management for each one. We suggest targeted biopsy for category 3b [lesion with a volume ≥0.5 cc, homogeneous or inhomogeneous, mild/moderately or markedly hypointense on T2-weighted, hyperintense on high b value diffusion-weighted (DW) imaging and moderately hypointense on apparent diffusion coefficient (ADC) map] and category 4 (homogeneous or heterogeneous lesion intra- or extraglandular, mild/moderately or markedly hypointense on T2-weighted, hyperintense on high b value DW imaging and markedly hypointense on ADC map). For a precise localization of the suspected prostate lesions we used a model of 41 sectors/regions map. BpMRI/Transrectal ultrasound fusion-targeted biopsy and the 41 sectors map represent a valid alternative model to the core biopsy of 10-12 systematic transrectal or transperineal peripheral zone biopsies.


Leptospiral renal colonization status in asymptomatic rural population of Tiruchirapalli district, Tamilnadu, India.
Humans are known to excrete leptospires in their urine after recovery from illness and there are reports showing development of asymptomatic leptospiruria in settings of high disease transmission. In this regard, we sought to evaluate the asymptomatic renal carriage status of humans in the highly endemic region of Tiruchirapalli district, Tamilnadu, India. A total of 245 asymptomatic participants were included. Urine and blood samples were collected and the extent of leptospiral infection was characterized by MAT, qPCR, 16S rRNA, and dot blot assay. The qPCR screening with urine DNA identified 129 (52.7%) positive samples further confirmed by nested PCR. The dot blot assay marked 30.2% (74/245) as true positives. The phylogenetic analysis showed the sequences to cluster with pathogenic Leptospira spp. Serological results showed 50 people with urine positivity to be negative for MAT and can probably be classified as 'asymptomatic individuals.' In conclusion, it can be speculated that in endemic regions there is a greater possibility of humans as maintenance host rather than incidental hosts.


Induced radioresistance in four strains of Escherichia coli, two with lambda lysogens.
Cells of E. coli that are recA+ and lex+ show a phenomenon of induced radioresistance. A preexposure to ultraviolet light, or ionizing radiation followed by incubation to allow protein synthesis, followed by treatment with rifampin to prevent further induction, renders the cells resistant to further doses of radiation. When this is attempted with lambda lysogens of the same strains, no radioresistance is seen, even though the preexposure is too small to induce lambda itself. If the lysogens are ind-, namely lambda C1857, about the normal radioresistance can be developed by pretreatment. These findings suggest that the lambda repressors can bind to single-strand breaks caused by the inducing agent and can modify the course of induction.


Pharmacological Interactions on Blood Pressure Control in Arterial Hypertension, An Issue not to be Overlooked.
Our vision of long-term treatment strategies for the prevention of target organ damage and eventually cardiovascular morbidity and mortality in essential arterial hypertension needs to be continually monitored and updated for at least three issues: 1--the achievement of target pressure required to obtain the expected benefit needs continuous monitoring, a dose adjustment of the drug and, often, the use of combination therapies; 2--the chronic use of certain drugs, even in combination, is associated with the possible onset of side effects; 3--increasing of population life expectancy is inevitably associated with in an increase in drugs use with the unavoidable occurrence of adverse drug reactions, some of which can interfere with blood pressure control. These issues, still poorly studied, pose considerable problems in applying proper strategies for prevention. In this review, we will evaluate the goals of antihypertensive therapy, and its weak spots, such as the frequent side effects, that lead to poor therapy compliance. Moreover, we will review the interactions between antihypertensive and drugs used for other common disease, and their importance in not achieving the expected blood pressure reduction.


Multiple cartilaginous exostoses in the dog.
The clinicopathologic aspects of multiple cartilaginous exostoses (MCE) in 2 dogs were compared with those in 9 previously reported cases of MCE in dogs. Although a familial tendency is probable, there is apparently no sex or breed predilection. Only bones that developed by endochondral ossification were affected. The vertebrae, ribs, and long bones were the most frequent location of exostoses. Bones of the carpal and tarsal joints and the skull were not affected in the cases evaluated. Physical examination and radiography may provide strong supportive evidence for a diagnosis of MCE, but a definitive diagnosis must be based on microscopic evaluation of osseous lesions. Treatment is unnecessary unless growth of exostoses results in clinical sequelae. Surgical extirpation of lesions should be considered if dysfunction of the skeletal, muscular, or neurologic systems develops. The prognosis is variable, being dependent on the location and number of lesions, the age of the patient at the time of diagnosis, and the presence or absence of clinical complications.


Formulation of Mesoporous Silica Nanoparticles for Controlled Release of Antimicrobials for Stone Preventive Conservation.
The biotic deterioration of artifacts of archaeological and artistic interest mostly relies on the action of microorganisms capable of thriving under the most disparate environmental conditions. Thus, to attenuate biodeterioration phenomena, biocides can be used by the restorers to prevent or slow down the microbial growth. However, several factors such as biocide half-life, its wash-out because of environmental conditions, and its limited time of action make necessary its application repeatedly, leading to negative economic implications. Sound and successful treatments are represented by controlled release systems (CRSs) based on porous materials. Here, we report on the design and development of a CRS system based on mesoporous silica nanoparticles (MSNs), as a carrier, and loaded with a biocide. MSNs, with a diameter of 55 nm and cylindrical pores of ca. 3-8 nm arranged as parallel arrays concerning the NP diameter, and with 422 m2/g of specific surface area were synthesized by the sol-gel method assisted by oil in water emulsion. Biocide loading and release were carried out in water and monitored by UV-Vis Spectroscopy; in addition, microbiological assay was performed using as control the MCM-41 mesoporous silica loaded with the same biocide. The role of specific supramolecular interaction in regulating the release is discussed. Further, we demonstrated that this innovative formulation was useful in inhibiting the in vitro growth of Kocuria rhizophila, an environmental Gram-positive bacterial strain. Besides, the CRS here prepared reduced the bacterial biomass contaminating a real case study (i.e., stone derived from the Santa Margherita cave located in Sicily, Italy), after several months of treatment thus opening for innovative treatments of deteriorated stone artifacts.


Correlates of Late Presentation to HIV care in a South Indian Cohort.
Late presentation to healthcare by HIV infected patients' is common in India despite access to free combination antiretroviral therapy (cART). We assessed risk factors for late presentation among patients with a recent HIV diagnosis in an academic university-based antiretroviral treatment center. This retrospective study included 474 recently diagnosed HIV-infected patients registered for cART between 2012 and 2013. Subjects with CD4+ T-lymphocyte (CD4) count ≤ 350 cells/μL or with an AIDS defining event were defined as late presenters (LP) and patients with CD4 count ≤ 200 cells/μL or with an AIDS defining event were defined as LP with advanced HIV disease (LPAD). Multivariable logistic regression analysis was used to investigate factors associated with late presentation. Of the 474 patients, 356 (75.1%) were LP. Of these, 299 (83.99%) were LPAD and 57 (16.01%) LP were AIDS-free. Median CD4 count among LP was 134 cells/μL (interquartile range 72.25-219). Mean age of LP was 42.50 ± 8.88 years; 256 (71.9%) were males. Increasing age (> 51 years; Adjusted odds ratio [aOR] 4.19; P = 0.014) and rural residence (aOR 3.19; P = < 0.001) were independently associated with late presentation. HIV-positive housewives (aOR 0.34; P = 0.027), HIV-positive individuals with negative partners (aOR 0.48; P = 0.006), and partners with unknown HIV status (aOR 0.43; P = 0.007) were less likely to present late compared with positive partners of people living with HIV/AIDS (PLWHA). Most patients were LP despite free access to cART. Rural population and older PLWHA should be targeted while implementing HIV care. There is a need to strengthen the HIV care cascade by linking PLWHA to cART immediately after diagnosis.


Carotid cutdown for surgical retrieval of a guidewire introducer: an unusual complication after mitral valve repair.
With the use of endovascular techniques and indwelling catheters, potential complications can include embolization of fragments or components of various systems. The authors describe the surgical retrieval of a guidewire introducer from the right common carotid artery (CCA). A 64-year-old man was found to have a foreign body within the right CCA on CT angiography after he had presented with a transient ischemic attack. He had undergone a complex mitral valve repair several months before presenting to the authors' facility. That procedure involved a femoral artery cutdown and the insertion of an endovascular aortic balloon for cardiac bypass. As in most endovascular procedures, guidewire introducers were probably used to facilitate the introduction of the guidewire into the system during the procedure. Although rare, iatrogenic embolization of the introducer probably occurred during use of the guidewire. The guidewire introducer was successfully retrieved without complication by using a standard carotid cutdown approach. It is extraordinarily unusual for an extracorporeal part of an implantable system to embolize to the carotid circulation. To the authors' knowledge, this is the only reported case of an embolized guidewire introducer and the use of a carotid exposure to retrieve an intraluminal foreign body. This case demonstrates that a carotid cutdown approach can be used successfully for the retrieval of intraluminal extracranial carotid artery foreign bodies.


Biochemical Basis of Anti-Cancer-Effects of Phloretin-A Natural Dihydrochalcone.
Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2',4',6'-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a wide array of preclinical studies. The efficacy of phloretin in suppressing xenograft tumor growth in athymic nude mice implanted with a variety of human cancer cells, and the ability of the compound to interfere with cancer cells signaling, have made it a promising candidate for anti-cancer drug development. Mechanistically, phloretin has been reported to arrest the growth of tumor cells by blocking cyclins and cyclin-dependent kinases and induce apoptosis by activating mitochondria-mediated cell death. The blockade of the glycolytic pathway via downregulation of GLUT2 mRNA and proteins, and the inhibition of tumor cells migration, also corroborates the anti-cancer effects of phloretin. This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent.


Re-appraisal of topical 1% voriconazole and 5% natamycin in the treatment of fungal keratitis in a randomised trial.
To compare the efficacy of topical 1% voriconazole vs 5% natamycin for the treatment of fungal keratitis. In a prospective, double-masked, randomised, controlled, registered clinical trial, 118 patients with fungal keratitis were treated using identical dosage schedule with either voriconazole (58) or natamycin (60) as inpatients for 7 days and followed up weekly. The outcome measures were percentage of patients with healed or resolving ulcer and final visual acuity at last follow-up (primary) and on day 7 (secondary) in each group. More patients (p=0.005) on natamycin (50/56, 89.2%) had healed or resolving ulcer compared with voriconazole (34/51, 66.6%) at last follow-up. The improvement in vision was marginally greater in patients in the natamycin group compared with the voriconazole group at day 7 (p=0.04) and significantly greater at final visit (p=0.01). In univariate analysis, drug, age and mean size of corneal infiltrate and epithelial defect had a significant effect on the final visual outcome. In multivariate analysis, the effect of drug (voriconazole vs natamycin, adjusted coefficient 0.27 (-0.04 to 0.57), p=0.09) was marginal while the effect of age and epithelial defect was significant (p<0.001 for both). In the group treated with natamycin, the final visual acuity was significantly better (p=0.005, Wilcoxon signed-rank test) in patients with Fusarium keratitis but not with Aspergillus keratitis (p=0.714, paired t test). When compared with voriconazole, natamycin was more effective in the treatment of fungal keratitis, especially Fusarium keratitis. Clinical Trial Registry India (2010/091/003041).


Hexokinase II: cancer's double-edged sword acting as both facilitator and gatekeeper of malignancy when bound to mitochondria.
A key hallmark of many cancers, particularly the most aggressive, is the capacity to metabolize glucose at an elevated rate, a phenotype detected clinically using positron emission tomography (PET). This phenotype provides cancer cells, including those that participate in metastasis, a distinct competitive edge over normal cells. Specifically, after rapid entry of glucose into cancer cells on the glucose transporter, the highly glycolytic phenotype is supported by hexokinase (primarily HK II) that is overexpressed and bound to the outer mitochondrial membrane via the porin-like protein voltage-dependent anion channel (VDAC). This protein and the adenine nucleotide transporter move ATP, newly synthesized by the inner membrane located ATP synthase, to active sites on HK II. The abundant amounts of HK II bind both the ATP and the incoming glucose producing the product glucose-6-phosphate, also at an elevated rate. This critical metabolite then serves both as a biosynthetic precursor to support cell proliferation and as a precursor for lactic acid, the latter exiting cancer cells causing an unfavorable environment for normal cells. Although helping facilitate this chemical warfare, HK II via its mitochondrial location also suppresses the death of cancer cells, thus increasing their possibility for metastasis and the ultimate death of the human host. For these reasons, targeting this key enzyme is currently being investigated in several laboratories in a strategy to develop novel therapies that may turn the tide on the continuing struggle to find effective cures for cancer. One such candidate is 3-bromopyruvate that has been shown recently to eradicate advanced stage, PET positive hepatocellular carcinomas in an animal model without apparent harm to the animals.


Morphogenic effects of alpha-factor on Saccharomyces cerevisiae a cells.
Saccharomyces cerevisiae mating type a cells enlarged and elongated when exposed to alpha-factor, a sex pheromone produced by mating-type alpha cells. This morphogensis required exogenous-D-glucose, nitrogen, and phosphate, and cells in exponential phase responded better than stationary-phase cells. Morphogenesis was blocked by cycloheximide and by inhibitors of cell wall biosynthesis such as 2-deoxy-D-glucose, 2-deoxy-2-fluoro-D-glucose, and 2-deoxy-2-fluoro-D-mannose, but not by polyoxin D. One to two hours after addition of pheromone, a cells became more susceptible to lysis by glucanases, a change that was dependendent on the dose of alpha-factor and was blocked by drugs that block morphogenesis. On the other hand, treatment with alpha-factor did not increase susceptibility to attack by trypsin, subtilisin, or exo-alpha-mannanase. Radioactive label, incorporated into cell wall polysaccharides during treatment with alpha-factor, was not secreted into the medium during morphogenesis. Analysis of the labeled wall polymers showed that alpha-factor-treated cells contain more glucan and less mannan than control cells, and that the mannan of treated cells contains an increased proportion of shorter side chains and unsubstituted backbone mannose units. Thin-section electron microscopy of treated cells revealed that the cell wall possesses a diffuse outer layer in the extension and is thinner at the tip.


[Primary structure of tRNA2Leu from the bovine udder. Determination of the oligonucleotide structure of the pyrimidyl-RNAse hydrolysate of tRNA2Leu by microspectrophotometric methods].
tRNA2Leu from cow mammary gland has been degraded with pancreatic ribonuclease, and the fragments obtained were separated by DEAE-cellulose micro-column chromatography in 7 M urea at pH 7,5. Rechromatography was performed on a DEAE-cellulose micro-column at pH 3,7 and also on Dowex 1 X 2 in a formiate system. Nucleotide analysis was carried out with the aid of T2-RNase hydrolysis followed by chromatography on anion-exchanger AG 1 X 8. Nucleosides were separated on Aminex A-6 at pH 9,8. 15 minor components were shown to be present: T, 2 psi, 2Um, 2D, m5C, ac4C, m1G, 2m2G, m22G, m1A and N, the N is not identified so far. The structure of oligonucleotides was established by terminal analysis, hydrolysis with T1-RNase and also using incomplete hydrolysis by the snake venom phosphodiesterase.


Prognostic assessment of the acute complications of bone marrow transplantation requiring intensive therapy.
Patients with bone marrow transplant may present with acute, life-threatening complications which frequently (40% of our cases) require intensive care unit treatment and result in an increased mortality (76% in this series). In an attempt to reach a more objective prognostic assessment, we have analyzed those factors related to the worst outcome in the 25 patients with bone marrow transplant admitted into our intensive care unit. Respiratory failure was the most frequent complication (72%), with an 83% mortality. Graft-versus-host disease and neutropenia led to a greater number of infectious complications with a poor outcome. Failure of more than three organ systems, septic shock and mechanical ventilation were statistically associated with mortality (p less than 0.05), and all patients who required mechanical ventilation for more than seven days or needed intensive therapy for more than 10 days died. The presence of septic shock, multisystem failure and severe neutropenia on admission should be considered as initial indicators of a poor prognosis. More than 7 days of mechanical ventilation and an intensive care unit stay of more than 10 days could be critical points in the reassessment of the intensity and prolongation of treatment.


Association Between Aerobic Fitness And High Blood Pressure in Adolescents in Brazil: Evidence for Criterion-Referenced Cut-Points.
Criterion-referenced cut-points for health-related fitness measures are lacking. This study aimed to determine the associations between aerobic fitness and high blood pressure levels (HBP) to determine the cut-points that best predict HBP among adolescents. This cross-sectional school-based study with sample of 875 adolescents aged 14-19 years was conducted in southern Brazil. Aerobic fitness was assessed using the modified Canadian Aerobic Fitness Test (mCAFT). Systolic and diastolic blood pressure were measured by the oscillometric method with a digital sphygmomanometer. Analyses controlled for sociodemographic variables, physical activity, body mass and biological maturation. Receiver Operating Characteristic (ROC) curves demonstrated that mCAFT measures could discriminate HBP in both sexes (female: AUC = 0.70; male: AUC = 0.63). The cut-points with the best discriminatory power for HBP were 32 mL·kg-1·min-1 for females and 40 mL·kg-1·min-1 for males. Females (OR = 8.4; 95% CI: 2.1, 33.7) and males (OR: 2.5; CI 95%: 1.2, 5.2) with low aerobic fitness levels were more likely to have HBP. mCAFT measures are inversely associated with BP and cut-points from ROC analyses have good discriminatory power for HBP.


Distribution of espM and espT among enteropathogenic and enterohaemorrhagic Escherichia coli.
Enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) translocate dozens of type III secretion system effectors, including the WxxxE effectors Map, EspM and EspT that activate Rho GTPases. While map, which is carried on the LEE pathogenicity island, is absolutely conserved among EPEC and EHEC strains, the prevalence of espM and espT is not known. Here we report the results of a large screen aimed at determining the prevalence of espM and espT among clinical EPEC and EHEC isolates. The results suggest that espM, detected in 51 % of the tested strains, is more commonly found in EPEC and EHEC serogroups that are linked to severe human infections. In contrast, espT was absent from all the EHEC isolates and was found in only 1.8 % of the tested EPEC strains. Further characterization of the virulence gene repertoire of the espT-positive strains led to the identification of a new zeta2 intimin variant. All the espT-positive strains but two contained the tccP gene. espT was first found in Citrobacter rodentium and later in silico in EPEC E110019, which is of particular interest as this strain was responsible for a particularly severe diarrhoeal outbreak in Finland in 1987 that affected 650 individuals in a school complex and an additional 137 associated household members. Comparing the protein sequences of EspT to that of E110019 showed a high level of conservation, with only three strains encoding EspT that differed in 6 amino acids. At present, it is not clear why espT is so rare, and what impact EspM and EspT have on EPEC and EHEC infection.


Analysis of microRNAs in pancreatic fine-needle aspirates can classify benign and malignant tissues.
MicroRNAs (miRNAs) are RNA molecules that are involved in the regulation of many cellular processes, including those related to human cancers. The aim of this study was to determine, as a proof of principle, whether specific candidate miRNAs could be detected in fine-needle aspirate (FNA) biopsies of pancreatic ductal adenocarcinoma (PDAC) and could accurately differentiate malignant from benign pancreatic tissues. We used TaqMan(R) assays to quantify miRNA levels in FNA samples collected in RNARetain (n = 16) and compared the results with a training set consisting of frozen macrodissected pancreatic samples (n = 20). Quantitative reverse-transcription PCR analysis confirmed that miRNA levels are affected in PDAC FNAs and correlate well with the changes observed in the training set of frozen pancreatic samples. Analysis of the amounts produced for a few specific miRNAs enabled identification of PDAC samples. The combination of miR-196a and miR-217 biomarkers further improved the ability to distinguish between healthy tissue, PDAC, and chronic pancreatitis in the training set (P = 8.2 x 10(-10)), as well as segregate PDAC FNA samples from other FNA samples (P = 1.1 x 10(-5)). Furthermore, we showed that miR-196a production is likely specific to PDAC cells and that its incidence paralleled the progression of PDAC. To the best of our knowledge, this study is the first to evaluate the diagnostic potential of miRNAs in a clinical setting and has shown that miRNA analysis of pancreatic FNA biopsy samples can aid in the pathologic evaluation of suspicious cases and may provide a new strategy for improving the diagnosis of pancreatic diseases.


Inhalation exposure of children to fragrances present in scented toys.
When utilized in the perfuming of children's toys, fragrances capable of inducing contact allergy in human skin may also become bioavailable to children via the inhalation route. The aim of this study was to determine the area-specific emission rates of 24 fragrances from a plasticized PVC reference material that was meant to mimic a real plastic toy. This material was introduced into an emission chamber for 28 days at handling conditions or at worst-case conditions. As a result, fragrances can be separated into three categories according to their emission rates ranging from 0.0041 to 16.2 mg/m² × h, i.e., highly volatile, semivolatile, and low-volatile compounds. Compounds of the first and second categories were monitored with decreasing emission rates. Substances of the third category were detected with increasing emission rates over time. Further, higher temperatures led to higher emission rates. The emission concentration of fragrances from four real scented toys varied between 1.10 and 107 μg/m³ at day 1 in the test chamber. Therefore, short-term inhalation exposure to fragrances originating from toys was in the range of 0.53-2700 ng/kg BW/d for the children of age 1 and older. Long-term exposure to these fragrances was calculated in the range of 2.2-220 ng/kg BW/d. Besides household products and cosmetics, fragrances can be found in toys for children. Some fragrances are known contact allergens in the skin, but there is a lack of information on their effects in the human respiratory tract. Here, we analyzed and categorized fragrances present in a plasticized PVC reference material according to their emission profiles and volatility. We also demonstrate that volatile fragrances are being emitted from real toys and thus may get inhaled under consumer conditions to different extents.


Desertihabitans aurantiacus gen. nov., sp. nov., a novel member of the family Propionibacteriaceae.
The taxonomic position of an actinobacterium isolated from a desert soil sample collected from Badain Jaran Desert, designated as CPCC 204711T, was established using a polyphasic approach. Cells of the isolate were Gram-staining-positive, aerobic, non-motile cocci. Good growth was observed at 28 °C (range 20-40 °C), pH 7.0 (range pH 6.0-8.0) and 0-1 % NaCl concentration (range 0-5 %, w/v). Galactose, arabinose and ribose were detected as the sugar compositions in the whole cell hydrolysates. The peptidoglycan type was A3gamma (ll-Dpm-Gly). MK-9(H4) was detected as the predominant menaquinone, and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, several unidentified glycolipids, and one unidentified amino-glycolipid were detected as the major polar lipids. The predominant fatty acid was anteiso-C15 : 0. The genomic DNA G+C content was 73.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204711T affiliated to the family Propionibacteriaceae, in which the strain formed a distinct phylogenetic lineage next to the genus Mariniluteicoccus, with the highest 16S rRNA gene sequence similarity of 96.0 % to Mariniluteicoccus endophyticus YIM 2617T. Both phylogenetic analysis and phenotypic characteristics supported that strain CPCC 204711T represents a novel species of a new genus in the family Propionibacteriaceae, for which the name Desertihabitans aurantiacus gen. nov., sp. nov. is proposed, with CPCC 204711T (=KCTC 39977T=DSM 105431T) as the type strain.


A randomized trial of genotype-guided dosing of warfarin.
The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.).


Antidepressant medications and change in mammographic density in postmenopausal women.
Several studies suggest antidepressant medications can increase prolactin levels. Some, but not all, studies suggest prolactin levels are positively associated with mammographic breast density, an established risk factor for breast cancer. We evaluated 29,284 women with two routine screening mammograms 9 to 28 months apart between 1996 to 2006 to examine whether antidepressant use was associated with changes in mammographic breast density. Mammographic breast density was assigned by radiologists and coded according the Breast Imaging Reporting and Data System classification. Exposure to antidepressants was ascertained based on electronic pharmacy dispensing data, including dispensings from claims data. We used polytomous logistic regression to estimate the odds of an increase or decrease in density categories between mammograms associated with antidepressant initiation, continuation, and discontinuation compared with nonusers of any antidepressants. Initiation, continuation, and discontinuation of antidepressant medications were not associated with changes in mammographic density. The lack of association between antidepressant use and breast density is consistent with recent studies that do not suggest an association between antidepressant use and breast cancer risk.


Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts.
Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts.


[E-learning and the continuing professional development in medicine].
E-learning is widely used in continuing medical education but three main problems still face health decision makers: the substantial heterogeneity among the characteristics of the web-based educational projects; the concerns about the e-learning effectiveness; the variety of outcomes used to evaluate the effectiveness. Systematic reviews suggest e-learning has effectiveness similar to traditional educational methods.The attention should now be given to how and when can we use e-learning to improve the health workers' performance and better healthcare.


Characterisation of Zea mays L. plastidial transglutaminase: interactions with thylakoid membrane proteins.
Chloroplast transglutaminase (chlTGase) activity is considered to play a significant role in response to a light stimulus and photo-adaptation of plants, but its precise function in the chloroplast is unclear. The characterisation, at the proteomic level, of the chlTGase interaction with thylakoid proteins and demonstration of its association with photosystem II (PSII) protein complexes was accomplished with experiments using maize thylakoid protein extracts. By means of a specific antibody designed against the C-terminal sequence of the maize TGase gene product, different chlTGase forms were immunodetected in thylakoid membrane extracts from three different stages of maize chloroplast differentiation. These bands co-localised with those of lhcb 1, 2 and 3 antenna proteins. The most significant, a 58 kDa form present in mature chloroplasts, was characterised using biochemical and proteomic approaches. Sequential fractionation of thylakoid proteins from light-induced mature chloroplasts showed that the 58 kDa form was associated with the thylakoid membrane, behaving as a soluble or peripheral membrane protein. Two-dimensional gel electrophoresis discriminated, for the first time, the 58-kDa band in two different forms, probably corresponding to the two different TGase cDNAs previously cloned. Electrophoretic separation of thylakoid proteins in native gels, followed by LC-MS mass spectrometry identification of protein complexes indicated that maize chlTGase forms part of a specific PSII protein complex, which includes LHCII, ATPase and pSbS proteins. The results are discussed in relation to the interaction between these proteins and the suggested role of the enzyme in thylakoid membrane organisation and photoprotection.


A mechanistic study of the antibacterial effect of silver ions on Escherichia coli and Staphylococcus aureus.
To investigate the mechanism of inhibition of silver ions on microorganisms, two strains of bacteria, namely Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), were treated with AgNO(3) and studied using combined electron microscopy and X-ray microanalysis. Similar morphological changes occurred in both E. coli and S. aureus cells after Ag(+) treatment. The cytoplasm membrane detached from the cell wall. A remarkable electron-light region appeared in the center of the cells, which contained condensed deoxyribonucleic acid (DNA) molecules. There are many small electron-dense granules either surrounding the cell wall or depositing inside the cells. The existence of elements of silver and sulfur in the electron-dense granules and cytoplasm detected by X-ray microanalysis suggested the antibacterial mechanism of silver: DNA lost its replication ability and the protein became inactivated after Ag(+) treatment. The slighter morphological changes of S. aureus compared with E. coli recommended a defense system of S. aureus against the inhibitory effects of Ag(+) ions.


Cameleon calcium indicator reports cytoplasmic calcium dynamics in Arabidopsis guard cells.
Cytoplasmic free calcium ([Ca2+]cyt) acts as a stimulus-induced second messenger in plant cells and multiple signal transduction pathways regulate [Ca2+]cyt in stomatal guard cells. Measuring [Ca2+]cyt in guard cells has previously required loading of calcium-sensitive dyes using invasive and technically difficult micro-injection techniques. To circumvent these problems, we have constitutively expressed the pH-independent, green fluorescent protein-based calcium indicator yellow cameleon 2.1 in Arabidopsis thaliana (Miyawaki et al. 1999; Proc. Natl. Acad. Sci. USA 96, 2135-2140). This yellow cameleon calcium indicator was expressed in guard cells and accumulated predominantly in the cytoplasm. Fluorescence ratio imaging of yellow cameleon 2.1 allowed time-dependent measurements of [Ca2+]cyt in Arabidopsis guard cells. Application of extracellular calcium or the hormone abscisic acid (ABA) induced repetitive [Ca2+]cyt transients in guard cells. [Ca2+]cyt changes could be semi-quantitatively determined following correction of the calibration procedure for chloroplast autofluorescence. Extracellular calcium induced repetitive [Ca2+]cyt transients with peak values of up to approximately 1.5 microM, whereas ABA-induced [Ca2+]cyt transients had peak values up to approximately 0.6 microM. These values are similar to stimulus-induced [Ca2+]cyt changes previously reported in plant cells using ratiometric dyes or aequorin. In some guard cells perfused with low extracellular KCl concentrations, spontaneous calcium transients were observed. As yellow cameleon 2.1 was expressed in all guard cells, [Ca2+]cyt was measured independently in the two guard cells of single stomates for the first time. ABA-induced, calcium-induced or spontaneous [Ca2+]cyt increases were not necessarily synchronized in the two guard cells. Overall, these data demonstrate that that GFP-based cameleon calcium indicators are suitable to measure [Ca2+]cyt changes in guard cells and enable the pattern of [Ca2+]cyt dynamics to be measured with a high level of reproducibility in Arabidopsis cells. This technical advance in combination with cell biological and molecular genetic approaches will become an invaluable tool in the dissection of plant cell signal transduction pathways.


A study of root canal morphology of human primary molars using computerised tomography: an in vitro study.
Knowledge of the size, morphology and variation of the root canals of primary teeth are useful in visualizing the pulp cavity during treatment. This study was carried out to investigate the applicability of Computed Tomography in studying the root canal morphology of the primary molars. A total of 60 primary molars.without any macroscopic root resorption were collected and divided into four groups. The samples were arranged in wax block and then scanned for evaluation in the CT Scanner both in axial and coronal plane. The results obtained from the scanned images were statistically analyzed to know the frequency, mean and standard deviation for all the groups. The images showed the complexity of the root canals of the primary molars and also several capabilities of the CT Scan in advance Endodontic research in primary teeth were observed.


Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma.
Small-cell lung carcinoma (SCLC) is a neuroendocrine subtype of lung cancer. Although SCLC patients often initially respond to therapy, tumors nearly always recur, resulting in a 5-year survival rate of less than 10%. A mouse model has been developed based on the fact that the RB and p53 tumor suppressor genes are mutated in more than 90% of human SCLCs. Emerging evidence in patients and mouse models suggests that p130, a gene related to RB, may act as a tumor suppressor in SCLC cells. To test this idea, we used conditional mutant mice to delete p130 in combination with Rb and p53 in adult lung epithelial cells. We found that loss of p130 resulted in increased proliferation and significant acceleration of SCLC development in this triple-knockout mouse model. The histopathologic features of the triple-mutant mouse tumors closely resembled that of human SCLC. Genome-wide expression profiling experiments further showed that Rb/p53/p130-mutant mouse tumors were similar to human SCLC. These findings indicate that p130 plays a key tumor suppressor role in SCLC. Rb/p53/p130-mutant mice provide a novel preclinical mouse model to identify novel therapeutic targets against SCLC.


A microsphere coupler for a nanowire waveguide plasmonic probe for molecular imaging.
Highly forward scattering of light by a silica microsphere is predicted by Mie theory. Finite-difference time-domain simulations are used to examine the use of a silica microsphere for coupling light into a ZnO nanowire terminated with a gold nanoparticle (NP) tip, intended for near-field imaging of single molecules immobilized on a gold substrate or gold nanoparticle-labeled cell membranes. The results show that plasmonic coupling at the Au tip is dependent on the incident angle of the excitation. Pre-conditioning the signal with the microsphere amplifies the coupling while reducing background energy levels, significantly boosting the signal-to-noise ratio.


Defensins impair phagocytic killing by neutrophils in biomaterial-related infection.
The implantation of foreign material carries a risk of infection which frequently is resistant to all treatment short of removing the implant. We have previously shown that these materials activate neutrophils by contact, leading to production of oxygen free radicals accompanied by release of granule products. Such activation further results in depletion of local host defenses, including the capacity of biomaterial-activated neutrophils to kill bacteria. Among the granule products released from neutrophils are small cationic antibacterial peptides (human neutrophil peptides [HNP]) known as defensins. Here we tested the hypothesis that defensins, released from activated neutrophils onto the surface of biomaterials, might play a role in the deactivation of subsequent neutrophil populations. Incubation of neutrophils with purified HNP resulted in a dose-related impairment of stimulus-induced oxygen radical production and of phagocytic killing. Furthermore, fresh neutrophils added to biomaterial-associated neutrophils exhibited impaired phagocytic killing. This impairment could be abrogated by antibody to HNP but not by an irrelevant antibody. Taken together, these observations support the idea that neutrophils activated at a material surface can create, by means of HNP release, an environment hostile to their microbicidal function and that of their infiltrating brethren.


Characterization of formulated microbial products by denaturing gradient gel electrophoresis, total cellular fatty acid analysis, and DNA microarray analysis.
Two commercial products, Biotize and Cycle, containing bacteria as an active ingredient were characterized for species identification and batch-to-batch variation by denaturing gradient gel electrophoresis (DGGE), total cellular fatty acid analysis (FAA), and a taxonomic DNA microarray. DGGE was useful at assessing the stability of consortia in different batches, and cluster analysis differentiated each batch even when only slight differences in species composition were observed. DGGE, FAA, and DNA microarray results indicated little batch-to-batch variation in Biotize and some batch variation in Cycle. The 3 methods agreed well with species identification in Biotize but generated conflicting results in the species composition of Cycle. This multi-method approach was useful in determining if the observed bacterial species present in the products matched the expected species composition.


Timing of life-threatening arrhythmias detected by implantable cardioverter-defibrillators in relation to changes in cosmophysical factors.
Studies have linked the natural history of many pathologies with environmental physical activity. This study investigated the relationship between the occurrence of ventricular tachycardia/fibrillation (VT/VF) recorded by implantable cardioverter defibrillators (ICD) and geomagnetic and cosmic ray (neutron) activity. The study group included 85 patients (73 men) with cardiomyopathy (80% ischemic) who underwent ICD placement in the years 1995-2006; 74% had a left ventricular ejection fraction of < 30%. Data on the days on which VT/VF occurred (total number of days: 284) and the days on which the patients were treated (total number of treatments: 580) were collected from the ICD records. The findings were analyzed against levels of geomagnetic activity (GMA) (I degree -IV degree) and cosmic ray activity (CRA), derived from international observatories, on the same days and throughout the study period. On days of VT/VF, daily values of GMA level averaged 1.5 +/- 0.7, consistent with level I degree (quiet). The ratios of daily VT/VF episodes and treatment to GMA level for the whole study period were as follows: 1.2 level I; 0.9 level II; 0.69 level III; 0.78 level IV (r = -0.974; p = 0.02). Mean CRA on days of VT/VF was 9246.8 +/- 299.0 imp/min, and for all 4383 days studied, 8805.33 +/- 411.4 imp/min (p < 0.0001). In patients with predominantly ischemic cardiomyopathy and severe left ventricular dysfunction, VT/VF occurs more often on days of low GMA and high CRA. Further studies are needed to determine the underlying mechanism of the effect of neutron activity on cardiac electrical instability.


Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.
Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection.


Proteomic Analysis of Inflammatory Biomarkers Associated With Breast Cancer Recurrence.
Breast cancer is the most frequent cancer detected for women, and while our ability to treat breast cancer has improved substantially over the years, recurrence remains a major obstacle. Standard screening for new and recurrent breast cancer involves clinical breast imaging. However, there is no clinically approved noninvasive body fluid test for the early detection of recurrent breast cancer. Materials and Method: In this study, we analyzed serum samples from both recurrent and nonrecurrent breast cancer patients by different proteomics methods to identify biomarkers in patients with recurrence of disease. Comparative data analysis identified several histone deacetylase (HDAC) proteins, which were found at significantly higher levels in the serum of recurrent breast cancer patients: HDAC9 (C-term) (P = 0.0035), HDAC5 (C-term) (P = 0.013), small ubiquitin-like modifier 1 (N-term) (P = 0.017), embryonic stem cell-expressed Ras (inter) (P = 0.018), and HDAC7 (C-term) (P = 0.020). Chronic inflammation plays a critical role in the development of the breast cancer recurrence, and we identified several proinflammatory cytokines that were present at elevated levels only in recurrent breast cancer patient serum. Our data indicated that the epigenetic regulation of inflammatory processes plays a critical role in breast cancer recurrence. The identified proteins could lay the groundwork for the development of a serum-based breast cancer recurrence assay.


Tetrahydrobiopterin improves coronary endothelial function, but does not prevent coronary spasm in patients with vasospastic angina.
Reduced bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, and the resulting decrease in NO in the coronary circulation may be involved in the pathogenesis of coronary spasm. The present study investigated the effects of BH4 on the vascular response to acetylcholine (ACh) in 28 patients with vasospastic angina (VA) using quantitative angiography. After recording the vascular responses to ACh (3 and 30 microg/min), either BH4 (1 mg/min) or saline was infused into the coronary artery for 2 min before and during a subsequent infusion of ACh. With the 3 microg/min dose of ACh, BH4 attenuated the ACh-induced decrease in coronary diameter in both the nonspastic segments (-1.1 +/- 2.2% ACh vs 6.0 +/- 2.8% ACh+BH4) and spastic segments (-6.3 +/- 2.7% ACh vs 2.9 +/- 2.7% ACh+BH4), but did not influence the ACh-induced coronary spasm at 30 microg/min (-57.3 +/-2.4% ACh vs -55.3 +/- 2.4% ACh+BH4). In the control patients, saline did not influence either the spastic or nonspastic vasoconstrictor responses to ACh. Acute administration of BH4 improves coronary endothelial function, but does not prevent coronary spasm in patients with VA.


MiRNAs and neural stem cells: a team to treat Parkinson's disease?
Parkinson's disease (PD) is a common neurodegenerative disorder with no proven neuroprotective or neurorestorative therapies. During disease progression, degeneration of dopaminergic neurons of the central nervous system occurs. Therefore, therapies that either aim on the inhibition of this degeneration or on the replacement of the degenerated neurons are needed. On the one hand, arrest of degeneration might be achievable through specific inhibition of disease associated genes like α-Synuclein or Leucine rich repeat kinase 2 (LRRK2). On the other hand, based on neural stem cells that bear the ability to generate new dopaminergic neurons, replacement of degenerated cells could be accomplished. Since both approaches can be regulated by micro-RNAs, these molecules have an enormous therapeutic potential. In this review, we will focus on the neurobiological and neurodegenerative implications of miRNAs and highlight their role in stem cell fate decisions. Finally, we will discuss their potential as therapeutic agents and targets for Parkinson's disease.


Differential impact of preschool models on development and early learning of inner-city children: a three-cohort study.
Three different preschool models operating in an urban school district were identified through cluster analysis of teacher responses to the Pre-K Survey of Beliefs and Practices. The language, self-help, social, motor, and adaptive development, along with mastery of basic skills, of 721 4-year-olds randomly selected from these models were compared. Children in the child-initiated model demonstrated greater mastery of basic skills than did children in programs in which academics were emphasized and skills were taught. Children in the combination model did significantly poorer on all measures except self-help and development of social coping skills compared with children in either the child-initiated or academically directed models. Girls outperformed boys in all areas except gross motor development and play and leisure skills. Implications for educational policymakers are discussed.


Health professionals' experiences of providing care for women survivors of sexual violence in psychiatric inpatient units.
Survivors of sexual violence, who are predominantly women, commonly access mental health services. Psychiatric inpatient units in Australia are predominately mixed gender and may further retraumatise these women. Sexual violence is under-recognised by mental health professionals and there is a lack of adequate policy or direction for mental health service services. To date, only a small amount of research has focused on health professionals' experiences of providing trauma-informed care to women in psychiatric settings, with most studies focused on specific practices or interventions. Qualitative data is particularly lacking on this topic. This is a critical gap in the knowledge given that health professionals are key to detecting and addressing victimisation. The aim of this study was to gain an in-depth understanding of healthcare professionals' experiences and perceptions in providing care to women who are survivors of sexual violence in psychiatric inpatient units. This qualitative study utilised semi-structured interviews with 40 health professionals recruited from four psychiatric inpatient units within a large Australian public mental health organisation. Data were examined using thematic analysis. Three main typologies were developed to describe participants' experiences of the care provided to women; 1) Dismissing and denying; 2) Acknowledging but unprepared; 3) Empathising but despairing. Gender, professional training, adherence to the biomedical model, and level of experience influenced health professionals' experiences. Health professionals in this study held varying attitudes towards female consumers and responses to sexual violence. Our findings suggest the need to address individual staff perception and promote trauma-informed and gender-sensitive care across all disciplines, genders, and levels of experience.


Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells.
Addition of 0.4-25 microM extracellular ATP results in transient, dose-dependent increases in cytosolic free calcium measured in Ehrlich ascites tumor cells. In cells incubated with 1 mM extracellular Ca2+, ATP induces a triphasic Ca2+ transient: an initial rapid increase (2-3 s), a second, slower phase of increase (60-90 s), and, finally, a gradual return to near resting [Ca2+]i (4-5 min). Several findings demonstrate that the initial, rapid phase of Ca2+ transient results from a mobilization of Ca2+ from a non-mitochondrial intracellular store, while the second, slow phase of increase is produced by enhanced influx of Ca2+ across the plasma membrane. Successive additions of extracellular ATP can elicit repetitive Ca2+ transients if the initially added ATP is removed either through the action of native ecto-ATPase activity or exogenous hexokinase. Other adenine nucleotides, including non-hydrolyzable ATP analogs, neither alter cytosolic [Ca2+] nor antagonize the ATP-induced effects. Conversely, other nucleotide triphosphates (ITP, UTP, and GTP) induce Ca2+ transients which are identical to those produced by ATP. A variety of experimental results indicate that these actions of ATP and other nucleotide triphosphates are not due to a generalized increase in plasma membrane permeability. The results suggest that, in these transformed cells, ATP may act in a manner similar to other Ca2+ mobilizing hormones and growth factors.


Evaluation of environmental scanning electron microscopy for analysis of Proteus mirabilis crystalline biofilms in situ on urinary catheters.
Proteus mirabilis is a common cause of catheter-associated urinary tract infections and frequently leads to blockage of catheters due to crystalline biofilm formation. Scanning electron microscopy (SEM) has proven to be a valuable tool in the study of these unusual biofilms, but entails laborious sample preparation that can introduce artefacts, undermining the investigation of biofilm development. In contrast, environmental scanning electron microscopy (ESEM) permits imaging of unprocessed, fully hydrated samples, which may provide much insight into the development of P. mirabilis biofilms. Here, we evaluate the utility of ESEM for the study of P. mirabilis crystalline biofilms in situ, on urinary catheters. In doing so, we compare this to commonly used conventional SEM approaches for sample preparation and imaging. Overall, ESEM provided excellent resolution of biofilms formed on urinary catheters and revealed structures not observed in standard SEM imaging or previously described in other studies of these biofilms. In addition, we show that energy-dispersive X-ray spectroscopy (EDS) may be employed in conjunction with ESEM to provide information regarding the elemental composition of crystalline structures and demonstrate the potential for ESEM in combination with EDS to constitute a useful tool in exploring the mechanisms underpinning crystalline biofilm formation.


Carbohydrate and fat have different effects on plasma leptin concentrations and adipose tissue leptin production.
Leptin is secreted by adipocytes and plays a role in the regulation of food intake. However, the regulation of leptin production by adipose tissue is unclear. We have investigated whether a mixed meal or a high-fat load given orally, or a pure fat load given intravenously, stimulates adipose tissue leptin production. Six volunteers were studied on two occasions following an overnight fast. On one occasion they consumed tomato soup containing 40 g of triacylglycerol (as Intralipid) and 9.6 g of carbohydrate; on the other occasion Intralipid was infused intravenously over 4 h to give the same fat load. A further eight subjects consumed a mixed meal (containing 37 g of fat and 100 g of carbohydrate) after an overnight fast. Paired blood samples were obtained from an arterialized hand vein and a vein draining subcutaneous adipose tissue at baseline and for 6 h following the meals or the start of the infusion. After both the intravenous and oral fat loads, the arterialized and adipose venous plasma leptin concentrations decreased over 6 h (both P<0.001), as did the leptin veno--arterial difference (P=0.01). Following the mixed meal, there was a slight increase in the arterialized plasma leptin concentration (P=0.02) and a more marked increase in the adipose venous plasma leptin concentration (P=0.03) and in the adipose tissue leptin veno--arterial difference (P=0.01), all peaking at 240 min. We conclude that the increase in plasma leptin concentration observed after meals is not simply a result of an energy load, but is in response to a signal that is not present following a fat load without carbohydrate.