Potential application of a bioemulsifier-producing actinobacterium for treatment of vinasse.
Vinasse is a complex effluent created during production of ethyl alcohol, which can present serious pollution hazard in areas where it is discharged. A variety of technologies, many based upon recovery of the effluent via microbial pathways, are continually being evaluated in order to mitigate the pollution potential of vinasse. The present work reports on initial advances related to the effectiveness of the actinobacterium Streptomyces sp. MC1 for vinasse treatment. Alternative use of raw vinasse as a substrate for producing metabolites of biotechnological interest such as bioemulsifiers, was also evaluated. The strain was able to grow at very high vinasse concentrations (until 50% v/v) and remove over 50% of the biodegradable organic matter in a time period as short as 4 d. Potentially toxic metals such as Mn, Fe, Zn, As, and Pb were also effectively removed during bacterial growth. Decrease in the pollution potential of treated vinasse compared to raw effluent, was reflected in a significant increase in the vigour index of Lactuca sativa (letucce) used as bioremediation indicator. Finally, significant bioemulsifier production was detected when this strain was incubated in a vinasse-based culture medium. These results represent the first advances on the recovery and re-valuation of an actual effluent, by using an actinobacterium from our collection of cultures.


Echocardiography and angiocardiography for detection of left atrial thrombosis.
Diagnostic capabilities for detection of the left atrial clot in patients with mitral stenosis were compared between echocardiography and angiocardiography. Large clots in the left atrial body were correctly diagnosed either by echocardiography or by angiocardiography. Clots in the left atrial appendage were not disclosed by echocardiography. Left atrial visualization with pulmonary arteriography offers only possible diagnosis of the clot in the appendage. Definite diagnosis of the clot in this location requires transseptal left atriography.


Context and methodological decontextualization in nursing research with examples from phenomenography.
In both human science and nursing research the concept of context is important. However, context can be understood in different ways. The aim of this article is to elucidate, discuss and problematize context, decontextualization and recontextualization in some health care-related phenomenographical studies. A further aim is to problematize the concept of context in a wider perspective of human science, in order to gain a better understanding of phenomenographical research related to nursing care. Our analysis indicates that the complex phenomena which characterize nursing research demand a broad contextual understanding. Both the local or immediate context and the global or mediated context must be considered, as they are dialectically related. This includes the informants' experiences of the phenomenon of interest as well as the socio-cultural discourse. A balance between openness and pliability to the phenomenon is suggested. Reflection is considered an important tool in this process. Within phenomenography, the interest is directed towards conceptions of certain aspects of the world. Thus, context in a wider sense is given a subordinate role. Accordingly, phenomenography is considered to have limited applicability in nursing research when complex phenomena are to be studied.


Improved risk stratification for patients with high-grade urothelial carcinoma following application of the Paris System for Reporting Urinary Cytology.
The Paris System for Reporting Urinary Cytology (TPS) requires 4 cytomorphologic criteria for a definitive diagnosis of high-grade urothelial carcinoma (HGUC) in urinary tract cytology (UTC) specimens: an elevated nuclear-to-cytoplasmic (N/C) ratio (at or above 0.7), markedly atypical nuclear borders, moderate to severe hyperchromasia, and coarse chromatin. However, malignant UTC specimens often contain degenerative changes, and this limits the number of malignant cells meeting all 4 TPS cytomorphologic criteria. One hundred twelve UTC specimens from patients with a subsequent diagnosis of HGUC were reviewed and reclassified according to TPS criteria. The presence of TPS cytomorphologic criteria for HGUC in each specimen was recorded, as was the proportion of atypical cells meeting all 4 criteria. The number of specimens definitively diagnosed as HGUC did not significantly change upon reclassification. However, approximately 40% of indeterminate specimens (21 of 51) were reclassified into a higher risk category. The most restrictive cytomorphologic criterion was an N/C ratio of 0.7 or higher (seen in 78% of specimens), and approximately half of specimens containing all 4 cytomorphologic criteria did not meet TPS's numerical criterion for HGUC (at least 5 malignant cells). In the majority of specimens qualifying for HGUC by TPS standards, only a small fraction of atypical cells (10%-20%) met all the criteria. When applied to malignant UTC specimens, TPS criteria improved specimen risk stratification by upgrading approximately 40% of indeterminate specimens into higher risk categories while not significantly changing the frequency of HGUC diagnoses. Cancer Cytopathol 2017;125:427-34. © 2017 American Cancer Society.


Risk of high blood pressure associated with objective insomnia and self-reported insomnia complaints in major depression: A study on 703 individuals.
Since few studies have investigated the risk of high blood pressure associated with objective insomnia and self-reported insomnia complaints in major depression, the aim of this study was to examine this risk in a large sample of individuals with major depression. Data from 703 individuals with major depression recruited from the research database of the sleep laboratory of the Erasme Hospital were analysed. High blood pressure status was defined by the presence of one of the following: self-reports at interview of either a physician-diagnosis or taking antihypertensive medication; or an average systolic blood pressure ≥140 mmHg or an average diastolic blood pressure ≥90 mmHg during at least two medical examinations. Logistic regression analyses were conducted to examine the risk of high blood pressure associated with objective insomnia and self-reported insomnia complaints in major depression. After adjustment for major confounding factors associated with high blood pressure, multivariate logistic regression analysis revealed that severe objective insomnia, low complaints of repeated nighttime awakenings or early morning awakening, and intermediate or low self-reported insomnia complaints were significant risk factors of high blood pressure in major depression. In major depression, severe objective insomnia and lower self-reported insomnia complaints are associated with higher risk of high blood pressure, which justifies a better management of objective insomnia and a better assessment of insomnia complaints in this particular subpopulation to avoid the negative consequences related to the co-occurrence of high blood pressure and major depression. Abbreviations: AHI, Apnea-Hypopnea Index; BDI, Beck Depression Inventory; BMI, Body Mass Index; DSM IV-TR, Diagnostic and Statistical Manual of Mental Disorders fourth edition - Text Revision; ESS, Epworth Sleepiness scale; ISI, Insomnia Severity Index; HBP, High Blood Pressure; OSA, Obstructive Sleep Apnea Syndrome; REM, rapid eye movement sleep.


[Doppler sonography assessment of renal arteries against the cardiovascular risk factors in young men--preliminary report].
The purpose of this study was to find out a relationship between cardiovascular risk factors (CVRF) and abnormal results of Duplex Doppler sonography (DD), suggesting renal artery stenosis (RAS). The group of 30 potentially healthy men (age: 35.5 +/- 7.9) randomly selected from population of 200 young men, underwent DD of renal arteries. Abnormal results of DD study, suggesting RAS were found in 19 of 30 men (63%). In this group, occurrence of 3 or more CVRF was significantly higher (15/19) than in the group with normal results of DD (5/11; p < 0.05). The significantly higher (77%; p < 0.05) occurrence of the abnormal DD and the significantly longer (p < 0.001) duration of habitual tobacco smoking were also found out in the group with RR > or = 130/85 mm Hg, in comparison to the group with RR < 130/85 mm Hg. Emphasizing preliminary character of this study and the need of confirmation on larger population, it seems reasonable to consider the assessment of renal arteries with DD in the population of men with cardiovascular risk factors.


Hierarchical macroscopic fibrillar adhesives: in situ study of buckling and adhesion mechanisms on wavy substrates.
Nature uses hierarchical fibrillar structures to mediate temporary adhesion to arbitrary substrates. Such structures provide high compliance such that the flat fibril tips can be better positioned with respect to asperities of a wavy rough substrate. We investigated the buckling and adhesion of hierarchically structured adhesives in contact with flat smooth, flat rough and wavy rough substrates. A macroscopic model for the structural adhesive was fabricated by molding polydimethylsiloxane into pillars of diameter in the range of 0.3-4.8 mm, with up to three different hierarchy levels. Both flat-ended and mushroom-shaped hierarchical samples buckled at preloads one quarter that of the single level structures. We explain this behavior by a change in the buckling mode; buckling leads to a loss of contact and diminishes adhesion. Our results indicate that hierarchical structures can have a strong influence on the degree of adhesion on both flat and wavy substrates. Strategies are discussed that achieve highly compliant substrates which adhere to rough substrates.


GPU-Accelerated State-Averaged Complete Active Space Self-Consistent Field Interfaced with Ab Initio Multiple Spawning Unravels the Photodynamics of Provitamin D3.
Excited-state molecular dynamics is essential to the study of photochemical reactions, which occur under nonequilibrium conditions. However, the computational cost of such simulations has often dictated compromises between accuracy and efficiency. The need for an accurate description of both the molecular electronic structure and nuclear dynamics has historically stymied the simulation of medium- to large-size molecular systems. Here, we show how to alleviate this problem by combining ab initio multiple spawning (AIMS) for the nuclear dynamics and GPU-accelerated state-averaged complete active space self-consistent field (SA-CASSCF) for the electronic structure. We demonstrate the new approach by first-principles SA-CASSCF/AIMS nonadiabatic dynamics simulation of photoinduced electrocyclic ring-opening in the 51-atom provitamin D3 molecule.


Drug-class-specific changes in the volume and cost of antidiabetic medications in Poland between 2012 and 2015.
to investigate the drug-class-specific changes in the volume and cost of antidiabetic medications in Poland in 2012-2015. This retrospective analysis was conducted based on the National Health Fund database covering an entire Polish population. The volume of antidiabetic medications is reported according to ATC/DDD methodology, costs-in current international dollars, based on purchasing power parity. During a 4-year observational period the number of patients, consumption of antidiabetic drugs and costs increased by 17%, 21% and 20%, respectively. Biguanides are the basic diabetes medication with a 39% market share. The insulin market is still dominated by human insulins, new antidiabetics (incretins, thiazolidinediones) are practically absent. Insulins had the largest share in diabetes medications expenditures (67% in 2015). The increase in antidiabetic medications costs over the analysed period of time was mainly caused by the increased use of insulin analogues. The observed tendencies correspond to the evidence-based HTA recommendations. The reimbursement status, the ratio of cost to clinical outcomes and data on the long-term safety have a deciding impact on how a drug is used.


Egg size, embryonic development time and ovoviviparity in Drosophila species.
Lengths, widths and volumes of eggs from 11 species of Drosophila whose genomes have been fully sequenced exhibit significant variation that is not explained by their phylogenetic relationships. Furthermore, egg size differences are unrelated to embryonic development time in these species. In addition, two of the species, Drosophila sechellia and, to a lesser degree, D. yakuba, both ecological specialists, exhibit ovoviviparity, suggesting that female control over oviposition in these species differs from what is observed in D. melanogaster. The interspecific differences in these reproductive characters, coupled with the availability of whole genome sequences for each, provide an unprecedented opportunity to examine their evolution.


[Inflammatory malignant fibrous histiocytoma of the spermatic cord infiltrating an inguinal leiomyoma. Case report with conceptual and bibliographic reviews].
To study paratesticular malignant fibrous histiocytomas (FHM) from the clinical, histological, immunohistochemical and histogenetic, point of view. Through Medline and not index-linked search of international scientific literature we have found a total of 77 cases of paratesticular FHM that globally create diagnostic, terminological and therapeutic problems. We include the case number 78 of FHM of spermatic cord, that presents a few special characteristics (not described before) of cutaneous fistula and infiltration of an inguinal leiomyoma, with histological and immunohistochemical confirmation. We performed a conceptual review of this type of tumours, including the evaluation of contradictions and reclassifications that has undergone from its first description, which causes that they are underestimated and their real prevalence in international series is very variable: from 7 to 37% of paratesticular sarcomas. Also, the fact of their low incidence has determined the lack of protocols for diagnosis and treatment. Paratesticular tumours, although infrequent, have a high rate of malignancy. The FHM concept has varied throughout the last 15 years. Today, this term is synonymous of pleomorphic undifferentiated sarcoma and has been an exclusion diagnosis (Vimentin [+]/ CD 68 [+]--occasionally--without ultrastructural differences), reserving the inflammatory subtype for which they have an inflammatory and histiocytic component. The accomplishment of an intraoperatory biopsy is essential in this location, since it is even difficult to know preoperatively, if a lesion is benign or malignant. The differential diagnosis is only solved after microscopic and inmunohistochemical study. Leiomyoma next to this location (inguinal) could be diagnosed and confused with a nodule of the main FHM. Their immunophenotype allowed us to diagnose it not only as leiomyoma (myogenic markers were positive -non skeletal muscle-), but also to observe the infiltration by the FHM.


Locating consciousness: We are conflicted by the role of conflict.
What is consciousness for? Consciousness allows us to handle conflict, a promising proposal by Morsella et al. However, they provide little evidence as to why consciousness is particularly valuable in resolving conflict, nor do they limit the role of consciousness to only conflicting experiences. We attempt to clarify their possible positions and offer several solutions for how these might be formulated and tested.


Biological characterization of 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) as a selective sphingosine kinase-2 inhibitor and anticancer agent.
In our effort to develop selective sphingosine kinase-2 (SphK2) inhibitors as pharmacological tools, a thiazolidine-2,4-dione analogue, 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145), was synthesized and biologically characterized. Biochemical assay results indicate that K145 is a selective SphK2 inhibitor. Molecular modeling studies also support this notion. In vitro studies using human leukemia U937 cells demonstrated that K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of down-stream ERK and Akt signaling pathways. K145 also significantly inhibited the growth of U937 tumors in nude mice by both intraperitoneal and oral administration, thus demonstrating its in vivo efficacy as a potential lead anticancer agent. The antitumor activity of K145 was also confirmed in a syngeneic mouse model by implanting murine breast cancer JC cells in BALB/c mice. Collectively, these results strongly encourage further optimization of K145 as a novel lead compound for development of more potent and selective SphK2 inhibitors.


A Review of 20 Years of Research on Overdiagnosis and Underdiagnosis in the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) Project.
The Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project represents an integration of research methodology into a community-based outpatient practice affiliated with an academic medical centre. The MIDAS project is the largest clinical epidemiological study using semi-structured interviews to assess a wide range of psychiatric disorders in a general clinical outpatient practice. In an early report from the MIDAS project, we found that across diagnostic categories clinicians using unstandardized, unstructured clinical interviews underrecognized diagnostic comorbidity, compared with the results of semi-structured interviews. Moreover, we found that the patients often wanted treatment for symptoms of disorders that were diagnosed as comorbid, rather than principal, conditions. This highlighted the importance, from the patient's perspective, of conducting thorough diagnostic interviews to diagnose disorders that are not related to the patient's chief complaint because patients often desire treatment for these additional diagnoses. While several of the initial papers from the MIDAS project identified problems with the detection of comorbid disorders in clinical practice, regarding the diagnosis of bipolar disorder we observed the emergence of an opposite phenomenon-clinician overdiagnosis. The results from the MIDAS project, along with other studies of diagnosis in routine clinical practice, have brought to the forefront the problem with diagnosis in routine clinical practice. An important question is what do these findings suggest about the community standard of care in making psychiatric diagnoses, and whether and how the standard of care should be changed? The implications are discussed.


Time-resolved pulsed fluorescence immunometric assays of carcinoembryonic antigen.
A time-resolved pulsed fluorescence immunometric assay (TR-PFIA) for carcinoembryonic antigen is described in which either Eu(III) or Tb(III) chelate is used as label. Described in detail is the assay involving the well-documented format of microtiter matrix and Eu(III) fluorescence enhanced with a beta-diketone and quantified in a commercial time-resolving fluorometer. We have also used the same basic assay, but one with a Tb(III) chelate as label, and we read the fluorescence signal directly off a surface without the application of enhancement solution. The Tb(III) fluorescence is then brought into solution by using an analog of dipicolinic acid in an enhancement solution. The latter approach demonstrates the scope of the methodology, which invokes the extra complexity of enhancement only when increased sensitivity might be required. The power and versatility of the enhancement methodology are demonstrated.


The Hidden Curriculum in Postgraduate Medical Education: a Commentary.
The hidden curriculum is the set of implicit influences which occur within health care organizations. The hidden curriculum has a tremendous impact on medical trainees and practicing physicians alike due to its influence in the domains of policy development, evaluation, resource allocation and institutional slang. We explore and reflect on the various ways in which the hidden curriculum impacts medical trainees and professionals in academic medical institutions.


The Escherichia coli Hemolysin.
The Escherichia coli hemolysin, earlier referred to as the hemolysin, is the best-characterized repeats in toxin (RTX) secreted by a type I exoprotein secretion system. The E. coli hemolysin is a significant virulence factor in murine models of peritonitis and ascending urinary tract infection, which suggests it is likely to be an important cytotoxin in human, extraintestinal E. coli diseases. Among E. coli or Salmonella strains there are no known examples of strict RTX leukotoxins in which lytic activity is limited to white blood cells. The general gene organization of the Vibrio cholerae RTX locus is similar to that seen with either of the E. coli hly and ehx loci with C, B, and D RTX homologs, clearly indicating it is a member of the RTX family. The hemolysin occurs less frequently in cystitis strains and only rarely among normal fecal strains. Among the extraintestinal E. coli isolates, the hlyCABDgenes were among the first virulence factors localized to unique, tRNA-associated segments of E. coli chromosomes. The hemolysin genes were eventually linked to P-type pilin and cytotoxic necrotizing factor-1 genes. Recent progress with its study has slowed down because of the difficulty in deriving the physical structure of the hemolysin protein or other RTX toxins and establishing its precise cytotoxic mechanism and role in pathogenesis of extraintestinal E. coli disease. Genomic sequencing has revealed that there are additional RTX-like genes found among many different pathogens; perhaps new efforts to discover their functions will aid progress in the RTX toxin field.


Active community surveillance of the impact of different tuberculosis control measures, Tiruvallur, South India, 1968-2001.
Tuberculosis is curable, but community surveys documenting epidemiological impact of the WHO-recommended DOTS strategy on tuberculosis prevalence have not been published. We used active community surveillance to compare the impact of DOTS with earlier programmes. We conducted tuberculosis disease surveys using random cluster sampling of a rural population in South India approximately every 2.5 years from 1968 to 1986, using radiography as a screening tool for sputum examination. In 1999, DOTS was implemented in the area. Prevalence surveys using radiography and symptom screening were conducted at the start of DOTS implementation and after 2.5 years. From 1968 to 1999, culture-positive and smear-positive tuberculosis declined by 2.3 and 2.5% per annum compared with 11.9 and 5.6% after DOTS implementation. The 2.5 year period of DOTS implementation accounted for one-fourth of the decline in prevalence of culture-positive tuberculosis over 33 years. Multivariate analysis showed that prevalence of culture-positive tuberculosis decreased substantially (10.0% per annum, 95% CI: 2.8-16.6%) owing to DOTS after only slight declines related to temporal trends (2.1% annual decline, 95% CI: 1.1-3.2%) and short-course chemotherapy (1.5% annual decline, 95% CI: -9.7% to 11.5%). Under DOTS, the proportion of total cases identified through clinical care increased from 81 to 92%. Following DOTS implementation, prevalence of culture-positive tuberculosis decreased rapidly following a gradual decline for the previous 30 years. In the absence of a large HIV epidemic and with relatively low levels of rifampicin resistance, DOTS was associated with rapid reduction of tuberculosis prevalence.


The importance of the evaluation of expectations and perceptions to improve the dental service quality.
Purpose The purpose of this paper is to evaluate the use of SERVQUAL to assess service quality in Dentistry, by evaluating patients' expectations and perceptions of dental care and their association to patients' sociodemographic data. Design/methodology/approach The sample constituted of 379 subjects in the first assessment and 155 in the second phase. All employees of the companies that were clients of the dental insurance participated, a total of four companies in two states (São Paulo and Minas Gerais) of Brazil. SERVQUAL questionnaires about expectations and sociodemographic data were dispatched in the first phase, and in a second phase SERVQUAL questionnaires about perceptions. Those who had not yet received dental treatment and had agreed to participate filled out their survey in the first phase. In the second phase, the respondents had to have completed their treatment. Findings When the value gap is considered, Reliability (as a dimension) had the smallest score (-3.71). This means that it was the worst result, i.e. there is a higher difference between expectations and perceptions, and problems can be identified here. t-test confirmed that all the dimensions had some statistically significant difference with p<0.05 in relation to expectations and perceptions. Women presented higher prevalence of dissatisfaction (Tangible and Reliability dimensions), as well as the oldest participants (Empathy dimension) and those with lower parental literacy (Assurance and Empathy dimensions). The only dimension that was not significantly associated was Responsiveness. Originality/value This research suggests that the patients evaluated the physical characteristics of the premises and the interaction with the staff as the priority issues that need special attention in this service. Moreover, the use of SERVQUAL was extremely relevant for the oral health service, because it assessed the users' subjective perceptions.


Antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae collected from patients across the USA, in 2001-2002, as part of the PROTEKT US study.
The PROTEKT US (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin in the United States) surveillance programme was started in 2000, to chart the emergence and spread of antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae from across the USA. In 2001-2002 (Year 2 of PROTEKT US) 242 centres from 46 states and the territory of Puerto Rico submitted a total of 10 012 S. pneumoniae, 4508 S. pyogenes and 3296 H. influenzae isolates from community-acquired respiratory tract infections (CARTIs). Susceptibility testing was performed and interpreted using NCCLS methodology and criteria. Overall, 35.4% of S. pneumoniae were non-susceptible to penicillin (14.2% intermediate, MIC 0.12-1 mg/L; 21.2% resistant, MIC > or =2 mg/L) and 27.9% were resistant to erythromycin (MIC > or =1 mg/L) (0.2% intermediate, MIC 0.5 mg/L). A total of 105 (1.0%) isolates were resistant to levofloxacin (MIC > or =8 mg/L). More than 99.2% of isolates were susceptible to telithromycin (MIC < or =1 mg/L) irrespective of penicillin and/or erythromycin resistance. All S. pyogenes isolates were susceptible to penicillin (MIC < or =0.12 mg/L) and 5.7% were resistant to erythromycin (MIC > or =1 mg/L) (0.3% intermediate, MIC 0.5 mg/L). The MIC90 of telithromycin for S. pyogenes was 0.03 mg/L. A total of 27.5% of H. influenzae isolates were beta-lactamase producers. Overall, 27.8% were resistant (MIC > or =4 mg/L) and 1.1% were intermediate to ampicillin (MIC 2 mg/L). A total of 96.3% of H. influenzae isolates were susceptible to telithromycin (MIC < or =4 mg/L). Antimicrobial resistance continues to be a problem in the USA. The ketolide telithromycin continues to show high activity against common CARTI pathogens, including those resistant to beta-lactams and macrolides.


Acceptance and Commitment Therapy for weight control: Model, evidence, and future directions.
Behavioral weight loss programs achieve substantial short-term weight loss; however attrition and poor weight loss maintenance remain significant problems. Recently, Acceptance and Commitment Therapy (ACT) has been used in an attempt to improve long-term outcomes. This conceptual article outlines the standard behavioral and ACT approach to weight control, discusses potential benefits and obstacles to combing approaches, briefly reviews current ACT for weight control outcome research, and highlights significant empirical questions that remain. The current evidence suggests that ACT could be useful as an add-on treatment, or in a combined format, for improving long-term weight loss outcomes. Larger studies with longer follow-up are needed as well as studies that aim to identify how best to combine standard treatments and ACT and also who would benefit most from these approaches.


A new 'advanced' test of theory of mind: evidence from children and adolescents with Asperger syndrome.
The aim of the present study was to assess the ability of children and adolescents with Asperger syndrome (AS) (N = 21) to infer physical versus mental states on a new 'advanced' test of theory-of-mind - Stories from Everyday Life. The participants in the AS group were of normal intelligence and were compared with an age-matched control group (N = 20) of normally developing children and adolescents. The test materials comprised 26 short stories or 13 pairs of different types of stories. This contextually complex theory-of-mind battery aimed to record the participants' ability to make inferences about physical as well as mental states. The first part of each story described a physical or mechanical event, and a test question then tested the participants' ability to make an inference about a physical state. The last part of the stories contained two questions, testing the ability to infer a mental state from the story context, e.g., understanding social communication such as a lie, white lie, figure of speech, misunderstanding, double bluff, irony, persuasion, contrary emotions, forgetting, jealousy, intentions, empathy and social blunders. The participants' reaction time and number of prompt questions were also recorded. The participants in the AS group showed significantly more problems attributing mental state inferences relative to the control group. They performed considerably better on tasks involving a physical state, but still did less well than the controls. They had a tendency to interpret behaviour and utterances literally, without regard to context, and to choose a physical explanation when a mental state answer was more appropriate. They also needed significantly more prompt questions and used significantly more time than the controls to solve the tasks, especially those involving mental state inference. This study supports earlier findings that individuals with AS/HFA have difficulties attributing mental states in context, but seem to have significantly fewer difficulties inferring physical states. The fact that the clinical group also used significant longer reaction time and needed significantly more prompt questions to solve the tasks relative to the control group may also be related to their problems in understanding mental states. However, the possibility remains that these difficulties could represent a separate factor - or a distinct 'cognitive style'- suggesting that at least some individuals with AS may be generally slow in solving cognitive tasks.


An Arthritis-Suppressive and Treg Cell-Inducing CD4+ T Cell Epitope Is Functional in the Context of HLA-Restricted T Cell Responses.
We previously showed that mycobacterial Hsp70-derived peptide B29 induced B29-specific Treg cells that suppressed experimental arthritis in mice via cross-recognition of their mammalian Hsp70 homologs. The aim of the current study was to characterize B29 binding and specific CD4+ T cell responses in the context of human major histocompatibility complex (MHC) molecules. Competitive binding assays were performed to examine binding of peptide B29 and its mammalian homologs to HLA molecules. The effect of B29 immunization in HLA-DQ8-transgenic mice with proteoglycan-induced arthritis was assessed, followed by ex vivo restimulation with B29 to examine the T cell response. Human peripheral blood mononuclear cells were used to investigate the presence of B29-specific T cells with immunoregulatory potential. The binding affinity of the B29 peptide was high to moderate for multiple HLA-DR and HLA-DQ molecules, including those highly associated with rheumatoid arthritis. This binding was considered to be functional, because B29 immunization resulted in the suppression of arthritis and T cell responses in HLA-DQ8-transgenic mice. In humans, we demonstrated the presence and expansion of B29-specific CD4+ T cells, which were cross-reactive with the mammalian homologs. Using HLA-DR4+ tetramers specific for B29 or the mammalian homolog mB29b, we showed expansion of cross-reactive T cells, especially the human FoxP3+ CD4+CD25+ T cell population, after in vitro stimulation with B29. These results demonstrated a conserved fine specificity and functionality of B29-induced Treg cell responses in the context of the human MHC. Based on these findings, a path for translation of the experimental findings for B29 into a clinical immunomodulatory therapeutic approach is within reach.


Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation.
Tacrolimus is an immunosuppressive drug that is a substrate of cytochrome P450 3A (CYP3A) enzymes and P-glycoprotein (P-gp). After transplantation, many pharmacological interactions have been described. Corticosteroids induce both CYP3A and P-gp activity. This study was designed to investigate the presence of a clinically significant interaction between steroids and tacrolimus after renal transplantation. We studied 83 renal transplant recipients receiving tacrolimus after transplantation. Patients were divided into three groups, according to steroid dose (low: 0-0.15 mg/kg/day; intermediate: 0.16-0.25 mg/kg/day; and high: >0.25 mg/kg/day). All other medications, including those known to interact with CYP3A and/or P-gp, were recorded. Steroid dosage, tacrolimus dosage, tacrolimus trough concentration (C0) and tacrolimus concentration/dose ratio [C0 divided by the 24 h dosage (mg/kg)] were assessed for each dosage group after 1 and 3 months of tacrolimus treatment. The three groups were not different as regards the use of non-immunosuppressive treatments or clinical events. At 1 and 3 months, the tacrolimus doses and concentration/dose ratios differed significantly in the three steroid dosage groups. With the higher doses, higher tacrolimus doses were needed to achieve the blood tacrolimus targeted trough level. We demonstrated that pharmacokinetic interaction occurs between steroids and tacrolimus in renal transplant patients. The higher the steroid dosage, the higher the dosage of tacrolimus needed to achieve target trough levels in these patients. The most likely interaction mechanism is specific enzymatic induction of CYP3A and/or P-gp. Interaction is present, even when the steroid dosage is low. The clinical events liable to occur during steroid sparing or tapering must be taken into account because it may be associated with episodes of tacrolimus-related nephrotoxicity.


Cholinergic neurons in the rat septal complex: ultrastructural characterization and synaptic relations with catecholaminergic terminals.
Physiological and pharmacological studies have suggested that catecholamines modulate cholinergic neurons in the medial septal and diagonal band nuclei (i.e., the septal complex). Thus, the ultrastructural morphology of neurons containing choline acetyltransferase (ChAT), the biosynthetic enzyme for acetylcholine, and their relation to catecholaminergic terminals exhibiting immunoreactivity for the catecholamine synthesizing enzyme tyrosine hydroxylase (TH) were examined in the rat septal complex. Dual immunoautoradiographic and peroxidase anti-peroxidase labeling methods were used to simultaneously localize antibodies raised in rabbits against TH and from rat-mouse hybridomas against ChAT in single sections. At least two types of perikarya with ChAT-immunoreactivity (ChAT-I) were observed. The first type were large (20-30 microns), elongated or round, and contained a small indented nucleus with an abundant cytoplasm and an occasional lamellar body. The second type was also either ovoid or round but was medium-sized (15-20 microns) and contained a larger indented nucleus and a smaller amount of cytoplasm than the first type. Both types of perikarya as well as dendrites with ChAT-I were surrounded by astrocytic processes apposed to most of their plasmalemmal surfaces. The distribution and types of terminal associations (i.e., asymmetric synapses, symmetric synapses and appositions which lacked a membrane specialization in the plane of section analyzed) with ChAT-labeled perikarya and dendrites were quantitatively evaluated. The majority (68% of 197) of the presynaptic terminals were unlabeled; the remaining terminals were immunoreactive for TH (25%) or ChAT (7%). All three types of terminals contacted primarily the shafts of small dendrites and more rarely ChAT-labeled perikarya and large dendrites. ChAT-labeled terminals: (1) formed associations with unlabeled perikarya and dendrites (31% of 176); (2) formed associations with perikarya and dendrites with ChAT-I (7%); (3) contacted the same unlabeled perikarya and dendrite as a TH-containing terminal (21%); (4) were in apposition to TH-labeled terminals (25%); or (5) were either in apposition to unlabeled or ChAT-labeled terminals or lacked associations with any processes. The majority of associations formed by the terminals with ChAT-I were on the shafts of small dendrites. Moreover, most of the associations formed were either symmetric synapses or appositions not separated by astrocytes in the plane of section analyzed. These findings provide cellular substrates in the septal complex (1) for sparse synaptic input relative to astrocytic investment of cholinergic neurons and (2) for direct synaptic modulation of cholinergic and non-cholinergic neurons by catecholamines and/or acetylcholine. These findings have direct relevance to catecholaminergic-cholinergic interactions and to the neuropathological basis for Alzheimer's disease.


Prevention of overuse: A view on upper gastrointestinal endoscopy.
Many upper gastrointestinal (GI) endoscopies worldwide are performed for inappropriate indications. This overuse of healthcare negatively affects healthcare quality and puts pressure on endoscopy services. Dyspepsia is one of the most common inappropriate indications for upper GI endoscopy as diagnostic yield is low. Reasons for untimely referral are: unfamiliarity with dyspepsia guidelines, uncertainty about etiology of symptoms, and therapy failure. Unfiltered open-access referrals feed upper GI endoscopy overuse. This review highlights strategies applied to diminish use of upper GI endoscopies for dyspepsia. First, we describe the impact of active guideline implementation. We found improved guideline adherence, but resistance was encountered in the process. Secondly, we show several forms of clinical assessment. While algorithm use reduced upper GI endoscopy volume, effects of referral assessment of individual patients were minor. A third strategy proposed Helicobacter pylori test and treat for all dyspeptic patients. Many upper GI endoscopies can be avoided using this strategy, but outcomes may be prevalence dependent. Lastly, empirical treatment with Proton pump inhibitors achieved symptom relief for dyspepsia and avoided upper GI endoscopies in about two thirds of patients. Changing referral behavior is complex as contributing factors are manifold. A collaboration of multiple strategies is most likely to succeed.


Stem cell stories: from bedside to bench.
The stem cell story is not a simple story but a complex narrative: one that requires careful analysis in order to identify major themes and plots. This paper offers an analysis of the ethics of the clinical application of stem cells and argues that even quite risky therapies can be ethical. These arguments cannot be used to justify all aspects of contemporary stem cell science, including human embryonic stem cell science, which remains theoretical and speculative. It is argued that the homogenisation of stem cell science obscures the distinction between clinical application and experimental laboratory science in a morally problematic way.


MTOR Suppresses Environmental Particle-Induced Inflammatory Response in Macrophages.
Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Alveolar macrophages represent a major type of innate immune responses to foreign substances. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and RAW264.7 cells. Pharmacological inhibition or genetic knockdown of MTOR in bone marrow-derived macrophages leads to an amplified cytokine production upon PM exposure, and mice with specific knockdown of MTOR or ras homolog enriched in brain in myeloid cells exhibit significantly aggregated airway inflammation. Mechanistically, PM activated MTOR through modulation of ERK, AKT serine/threonine kinase 1, and tuberous sclerosis complex signals, whereas MTOR deficiency further enhanced the PM-induced necroptosis and activation of subsequent NF κ light-chain-enhancer of activated B cells (NFKB) signaling. Inhibition of necroptosis or NFKB pathways significantly ameliorated PM-induced inflammatory response in MTOR-deficient macrophages. The present study thus demonstrates that MTOR serves as an early adaptive signal that suppresses the PM-induced necroptosis, NFKB activation, and inflammatory response in lung macrophages, and suggests that activation of MTOR or inhibition of necroptosis in macrophages may represent novel therapeutic strategies for PM-related airway disorders.


Do functional and phylogenetic nestedness follow the same mechanisms as taxonomic nestedness? Evidence from amphibians in the largest archipelago of China.
Nested subset pattern (nestedness) has been raised to explain the distribution of species on islands and habitat fragments for over 60 years. However, previous studies on nestedness focused on species richness and composition and overlooked the role of species traits and phylogeny in generating and explaining nestedness. To address this gap, we sampled amphibians on 37 land-bridge islands in the largest archipelago of China, the Zhoushan Archipelago, to explore nestedness as well as the underlying causal processes through three facets of diversity, that is, taxonomic, functional and phylogenetic diversity. The taxonomic nestedness was measured through organizing the species incidence matrix to achieve a maximum value, while the functional and phylogenetic nestedness were quantified by incorporating the similarity of species in terms of their ecological traits and phylogeny. We also obtained six island characteristics and seven species traits as predictors of nestedness. Amphibian metacommunities were significantly nested in these three facets of diversity. When relating different predictors to nestedness, island area, habitat diversity and species traits were highly correlated with taxonomic nestedness. Moreover, island area and habitat diversity significantly influenced functional and phylogenetic nestedness. Therefore, the results support the selective extinction and habitat nestedness hypotheses. Interestingly, although we did not observe significant influences of island isolation on taxonomic nestedness, functional and phylogenetic diversities were significantly higher than expected when matrices were ordered by increasing distance to mainland. The result suggests that there are more functionally and phylogenetically diverse species on less-isolated islands, reflecting a selective colonization process overlooked by the traditional analysis of taxonomic nestedness. Although the three facets of nestedness and underlying processes were largely congruent, we detected the distance-related functional and phylogenetic nestedness for amphibian assemblages. Therefore, we highlight that a framework that simultaneously considers taxonomic, functional and phylogenetic nestedness can contribute to a complementary understanding of nestedness processes. In addition, it also improves our ability to conserve insular biodiversity from different perspectives.


Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study.
There are limited studies investigating the use of fecal microbial transplant (FMT) in dogs with inflammatory bowel disease (IBD). The aim of this preliminary study was to assess the feasibility of adding FMT to standard therapy (corticosteroids and a hypoallergenic diet) for dogs with IBD and to and to describe the changes in measured outcomes after 30 days of treatment. Thirteen client-owned dogs with IBD were enrolled in this double blinded, randomized clinical trial. All dogs received corticosteroid therapy and a hypoallergenic diet; dogs were randomized to receive either placebo or FMT. Measured outcomes included the canine chronic enteropathy clinical activity index (CCECAI) at 1 week and 1 month after enrolment. Fecal microbiota were analyzed after extracting DNA from fecal samples and profiling using 16S amplicon sequencing. Dogs in the placebo group not responding to treatment after 1 month were offered FMT. The CCECAI significantly decreased over time in both groups (p = 0.001). There were no significant differences between the CCECAI of the placebo and FMT group at each time point (F test from ANOVA, p = 0.40). No adverse effects were reported in the 30 days following FMT. The addition of FMT to standard therapy for IBD was feasible. No significant differences were observed in the CCECAI between groups at each time point. Large scale clinical trials can be performed using these methods to evaluate the longer term effect of FMT on clinical signs, microbial diversity, and other outcomes.


Infection control in moving and handling.
Hospitals are obliged to provide moving and handling equipment to protect staff health and prevent back disorders. The use of this equipment has opened up new risks to patients of cross contamination and iatrogenic infection. Hospitals need to address this problem in a systematic way.


Practice of postponing human aging.
People want to be wealthy, attractive, young, and healthy, and they integrate these wishes into most of their activities. As a result, aging processes are somewhat postponed in the human organism. Both average life expectancy and expected life in good health increase by 0.15-0.2 years every year in most developed countries. Studies show that using contemporary knowledge enables an increase in life expectancy up to 90 years in these countries, and much more in the future. Increases in life expectancy depend on the interest of society in these problems and on the amount of scientific research directed at postponing aging and rejuvenation.


[A photo-optical observation of gallbladder motility in dogs (author's transl)].
A photo-optical observation on gallbladder motility was made with the 16 mm cine-cholangiography. The subjects studied were thirty two mongrel dogs. The gallbladder was exposed by a short upper midline abdominal incision under pentothal anesthesia. Gallbladder bile was aspirated and contrast medium was given into the bladder, through a transhepatic route. The cine-cholangiography was done by an image intensifier at a speed of one frame every 2 to 4 seconds. The cinefilms taken were observed repeatedly by the screen projection at various speeds. The drawings were made by tracing the outline of the image of the gallbladder on each frame and were overlapped. Moreover, a contraction curve was made by the cholecystometry using of film motion analyzer in every case. At the same time bile flow into the duodenum was recorded to study a relationship between the gallbladder contraction and motility of the terminal common bile duct. The results obtained are as follows: 1. In a resting state any contraction of the gallbladder was not seen during 30 minutes, and a peristalsis-like movements of the neck portion was observed. However, there was not a relationship between the contraction curve of the gallbladder and the bile flow into the duodenum. 2. Immediately after giving Caerulein, the contrast medium injected into the gallbladder was rapidly discharged into the common bile duct by a peristalsis-like movement of the neck. The size of the gallbladder was markedly decreased into three fifths of the initial state three minutes after administration. At the same time contrast medium was continuously discharged into the duodenum. 3. After giving pilocarpine a marked contraction with forceful movement of the neck and body was observed, and the size of the gallbladder was decreased into three quarters ot the initial state. Bile discharge into the duodenum was markedly increased with an active open- and closing movement of the terminal common bile duct.


Prevalence of anti-synthetase antibodies among systemic sclerosis patients.
we aimed to estimate the prevalence of Amino acyl-transfer ribonucleic acid synthetase antibodies (Anti-ARS); myositis specific antibodies, among patients with systemic sclerosis (SSc), to evaluate the clinical associations of anti-ARS antibodies in SSc patients and to identify risk factors for development of interstitial lung disease (ILD) in SSc. A prospective study of 71 systemic sclerosis patients in our rheumatology clinic in Israel. Sera were tested for myositis antibodies. Data on patients clinical and serological manifestations and treatment were collected and compared according to anti-ARS antibodies and ILD. Prevalence of anti-ARS antibodies was 6% (4/71) with anti PL-7, anti- OJ and Jo-1 positivity. Anti Ro-52 was found in 27%, anti-PM/Scl 75, anti-PM/Scl 100 and anti-SRP in 6%, anti-Ku in 3%, anti-Mi-2 beta and anti-Mi-2 alfa in 4%, anti- NXP2 and anti-TIF1gamma in 1%. ILD complication was observed in 42% of patients and was associated with anti RNAP-III, anti Scl-70 and Anti-ARS antibodies. In multiple logistic regression, anti Scl-70 was associated with 6-fold higher risk for ILD. Anti-ARS antibodies were observed in 6% of SSc patients. All of them had ILD. Due to the low prevalence of anti-ARS, this study could not describe clinical associations of anti-ARS antibodies in SSc patients.


Comparison between external fixation and elastic stable intramedullary nailing for the treatment of femoral shaft fractures in children younger than 8 years of age.
The main objective of this study was to compare external fixation (EF) with elastic stable intramedullary nailing (ESIN) for the treatment of femoral shaft fractures in children aged 8 or younger. Fifteen children with femoral shaft fractures treated by EF and 23 children with femoral shaft fractures treated by ESIN were retrospectively reviewed. All patients were pain free at the last follow-up, with good ranges of motion in the hip and knee. Partial and full weight bearing occurred sooner in patients treated with EF than with ESIN, although more polytrauma patients were present in the ESIN group. In conclusion, EF and ESIN can be considered as safe and effective methods for femoral shaft fracture treatment in children younger than 8 years of age.


Prophage Integrase Typing Is a Useful Indicator of Genomic Diversity in Salmonella enterica.
Salmonella enterica is a bacterial species that is a major cause of illness in humans and food-producing animals. S. enterica exhibits considerable inter-serovar diversity, as evidenced by the large number of host adapted serovars that have been identified. The development of methods to assess genome diversity in S. enterica will help to further define the limits of diversity in this foodborne pathogen. Thus, we evaluated a PCR assay, which targets prophage integrase genes, as a rapid method to investigate S. enterica genome diversity. To evaluate the PCR prophage integrase assay, 49 isolates of S. enterica were selected, including 19 clinical isolates from clonal serovars (Enteritidis and Heidelberg) that commonly cause human illness, and 30 isolates from food-associated Salmonella serovars that rarely cause human illness. The number of integrase genes identified by the PCR assay was compared to the number of integrase genes within intact prophages identified by whole genome sequencing and phage finding program PHASTER. The PCR assay identified a total of 147 prophage integrase genes within the 49 S. enterica genomes (79 integrase genes in the food-associated Salmonella isolates, 50 integrase genes in S. Enteritidis, and 18 integrase genes in S. Heidelberg). In comparison, whole genome sequencing and PHASTER identified a total of 75 prophage integrase genes within 102 intact prophages in the 49 S. enterica genomes (44 integrase genes in the food-associated Salmonella isolates, 21 integrase genes in S. Enteritidis, and 9 integrase genes in S. Heidelberg). Collectively, both the PCR assay and PHASTER identified the presence of a large diversity of prophage integrase genes in the food-associated isolates compared to the clinical isolates, thus indicating a high degree of diversity in the food-associated isolates, and confirming the clonal nature of S. Enteritidis and S. Heidelberg. Moreover, PHASTER revealed a diversity of 29 different types of prophages and 23 different integrase genes within the food-associated isolates, but only identified four different phages and integrase genes within clonal isolates of S. Enteritidis and S. Heidelberg. These results demonstrate the potential usefulness of PCR based detection of prophage integrase genes as a rapid indicator of genome diversity in S. enterica.


Colorimetric detection of biological hydrogen sulfide using fluorosurfactant functionalized gold nanorods.
As a well-known environmental pollutant but also an important gaseous transmitter, the specific detection of hydrogen sulfide (H2S) is significant in biological systems. In this study, fluorosurfactant functionalized gold nanorods (FSN-AuNRs) have been proposed to act as selective colorimetric nanoprobes for H2S. With the combination of strong gold-S interactions and small FSN bilayer interstices, FSN-AuNRs demonstrate favorable selectivity and sensitivity toward H2S over other anions and small biological molecules. The practical application of the present method in biological H2S detection was validated with human and mouse serum samples. Moreover, the proposed nanoprobe can also be used for evaluating the activity of H2S synthetase.


Nature of long-range correlations of density fluctuations in glass-forming liquids.
Based on a concise review of the experimental data, a theory of the structural, kinetic, and dynamic features of the Fischer cluster is put forward. This theory is based on the idea of heterophase fluctuations of glass-forming liquids. According to these ideas in a one-component liquid the solidlike and fluidlike transient associations of molecules (fluctuons) are formed. The fluctuons differ in the short-range order and, consequently, in the free energy. They form a random free energy landscape. The random field free energy functional of the Ginzburg-Landau type, which accounts for the free energy landscape, is deduced. Based on this, the phase equilibrium, critical behavior, and ordering phenomena of the heterophase liquid are considered. It is shown that in the critical region an effective attractive interaction of the fluctuons results in their gravitation and formation of correlated fractal aggregations. The aggregation consists of the fluctuons of similar short-range order. The fractal aggregation formation is a special structural state of the liquid above the glass transition temperature. The condition at which the aggregations are formed is formulated. Thus it is shown that the Fischer cluster is an array of fractal aggregations of fluctuons. The growth kinetics and dynamics of the Fischer cluster are described. The experimental data are analyzed and discussed using the theory that is put forward.


Transient expression of neurofascin by oligodendrocytes at the onset of myelinogenesis: implications for mechanisms of axon-glial interaction.
Cell adhesion molecules (CAMs) must play a crucial role in both the initiation and signalling of axon-glial contact. However, the proteins that permit myelinating oligodendrocytes to recognize the axons that they ensheath in the developing CNS are unknown. By a subtractive cDNA library strategy, we have identified neurofascin as a powerful candidate for such a molecule. Neurofascin is strongly but transiently up-regulated in oligodendrocytes at the onset of myelinogenesis. Once oligodendrocytes have engaged their target axons the protein plays no further part, since the expression of the gene declines precipitously, in contrast to that of the major myelin component proteolipid protein, which remains elevated. After the initial surge of neurofascin expression in oligodendrocytes, there is a shift to a predominantly neuronal localization that persists into adulthood. Hence neurofascin in oligodendrocytes is unlikely to serve a function in the stabilization of the multilamellar sheath around the axon. The major neurofascin isoform of oligodendrocytes contains the third fibronectin type 3 (FNIII) repeat but lacks the mucin-like domain which supports the view that neurofascin isoforms are differentially expressed in the nervous system. Among the genes that are up-regulated during the terminal differentiation of the oligodendrocyte, neurofascin is unique in displaying a transient pattern of expression at the early stages of myelination. We propose that this CAM not only has a role in mediating axon recognition but also signals axonal contact through its links with the actin cytoskeleton.


Effects of chronic dietary exposure to trace elements on banded water snakes (Nerodia fasciata).
Little currently is known about the accumulation or effects of contaminants on reptiles. To date, most studies examining reptile exposure to trace elements report tissue burdens of field-captured animals, but seldom provide insight into the dose, duration, or mode of exposure involved. For two years, we fed juvenile banded water snakes (Nerodia fasciata) prey items collected from a coal ash-contaminated site that contained elevated levels of As, Cd, Cu, Se, Sr, and V. With the exception of Cu, snakes accumulated significant concentrations of elements, usually in a dose-dependent manner. Accumulation varied significantly among liver, kidney, and gonads, and in most cases between sexes. Selenium accumulation was most notable, greatly exceeding established toxicity thresholds for other vertebrates. Despite the high concentrations of pollutants accumulated, snakes exposed to the contaminated diet survived through the study and exhibited normal food consumption, growth, condition factor, overwinter survival and mass loss, metabolic rate, and gonadosomatic index. The results of this study confirm that diet can be a significant route of exposure to trace elements in snakes and indicate that further studies on snakes are warranted to better understand their responses to contaminants.


Hantaviral antigens and antibodies in wild rodents in Portugal.
Small rodents of the species Rattus norvegicus and Rattus rattus have been captured between 1986 and 1988 in several areas of Southern Portugal. A total of 135 animal specimens were examined for hantaviral antigens in lung sections and 5 have been found positive. Some of the rodents were shown to have serum antibodies as detected by immunofluorescence in titres up to 1:256. This investigation proves for the first time the presence of Hantavirus in wild rodent populations of Portugal.


Fractionation of bagasse into cellulose, hemicelluloses, and lignin with ionic liquid treatment followed by alkaline extraction.
Lignocellulose materials are potentially valuable resources for transformation into biofuels and bioproducts. However, their complicated structures make it difficult to fractionate them into cellulose, hemicelluloses, and lignin, which limits their utilization and economical conversion into value-added products. This study proposes a novel and feasible fractionation method based on complete dissolution of bagasse in 1-butyl-3-methylimidazolium chloride ([C(4)mim]Cl) followed by precipitation in acetone/water (9:1, v/v) and extraction with 3% NaOH solution. The ionic liquid [C(4)mim]Cl was easily recycled after concentration and treatment with acetonitrile. (1)H NMR analysis confirmed that there was no obvious difference between the recycled [C(4)mim]Cl and fresh material. Bagasse was fractionated with this method to 36.78% cellulose, 26.04% hemicelluloses, and 10.51% lignin, accounting for 47.17 and 33.85% of the original polysaccharides and 54.62% of the original lignin, respectively. The physicochemical properties of the isolated fractions were characterized by chemical analysis, high-performance anion exchange chromatography (HPAEC), gel permeation chromatography (GPC), Fourier transform infrared (FT-IR), and (1)H and 2D (13)C-(1)H correlation (HSQC) nuclear magnetic resonance spectroscopy. The results showed that the acetone-soluble lignin and alkaline lignin fractions had structures similar to those of milled wood lignin (MWL). The easy extraction of the noncellulose components from homogeneous bagasse solution and amorphous regenerated materials resulted in the relatively high purity of cellulosic fraction (>92%). The hemicellulosic fraction was mainly 4-O-methyl-D-glucuronoxylans with some α-L-arabinofuranosyl units substituted at C-2 and C-3.


Prophylaxis of deep venous thromboembolism. Literature review.
The prophylaxis of deep venous thrombosis is critically related to potentially life-threatening pulmonary embolism. Each of the available agents has benefits and drawbacks which are reviewed in this article. While the search for the ideal method of prophylaxis continues, the appropriate agent appears to be one that balances the risk of complication with the potential risk of development of thromboembolism. Recommendations for acceptable prophylaxis are made for various procedures.


A rare imaging presentation with multisystemic clinicopathological features of Langerhans cell histiocytosis: Case report and literature review.
Langerhans cell histiocytosis (LCH) is a kind of rare disease in which dendritic cells proliferate abnormally. It often occurs in children and can involve any tissue and organ. The affected sites usually include bone, skin, pituitary gland, and lungs, while the thyroid gland and external auditory canal are rarely observed. The perineal and labial involvement of this disease has not been reported yet. A 47-year-old female patient experienced a swelling of the anterior neck area without an obvious inducement. She noticed a quail egg-like mass on the left side, and the mass increased progressively within 3 months. The anterior neck area was found to be swollen, and some flaky red rashes were seen on the scalp and bilateral external auditory canals. Imaging examination showed enlarged thyroid and cervical lymph nodes, multiple low-density nodules in the liver, and reduced signal in the posterior pituitary gland. The biopsy pathological result of the increased left cervical lymph node indicated that LCH was detected. VP regimen (vincristine, dexamethasone per os) and related supportive treatments were given as inducing chemotherapy for 6 weeks. After the second chemotherapy, the rash on the scalp and external auditory canal improved, and the neck mass was significantly reduced. After the third chemotherapy, the rash was mostly disappeared, while the neck lumps increased during chemotherapy. Thus, clatribine chemotherapy was recommended as the follow-up. Imaging examinations played an important role in the diagnosis and follow-up of the disease, especially 18F-FDG PET/CT, which could show multiple involving organs at the same time. When a patient suffering from diabetes insipidus, skin rash, or fever, has a high FDG uptake PET/CT result in multiple tissues and organs throughout the body, it is necessary to consider the possibility of LCH.


Alpha 2-adrenoceptors inhibit a nociceptive response in neonatal rat spinal cord.
Alpha 2-Adrenoceptors mediate analgesia in vivo. The present study explored the actions of the alpha 2-adrenoceptor agonists dexmedetomidine and clonidine on a nociceptive response in isolated neonatal rat spinal cord. Stimulation of a dorsal root generates a slow ventral root potential (slow VRP) at the corresponding ipsilateral ventral root. The slow VRP meets several criteria for a nociceptive response. Dexmedetomidine (10 nM) and clonidine (200 nM) depressed the slow VRP by approximately 80%. Dexmedetomidine's action was approximately linear over the concentration range 0.5-500 nM, whereas clonidine (20 nM-5 microM) exerted biphasic effects. The profile of agonist and antagonist effectiveness characterized the receptor(s) as alpha 2-adrenoceptors; the subtype could not be identified as either alpha 2A or alpha 2B. Naloxone pretreatment partially blocked dexmedetomidine's effect, suggesting a possible endogenous opiate involvement. Dexmedetomidine (0.5-2.0 nM) also depressed the VRP evoked by application of substance P to the cord, implicating postsynaptic as well as possible presynaptic actions. At high concentrations, dexmedetomidine (50-500 nM) depressed the monosynaptic reflex, probably through non-alpha 2-receptor(s). Results from the neonatal spinal cord correlate well with those from in vivo analgesia studies. They suggest an important direct spinal contribution to alpha 2-adrenoceptor-mediated analgesia.


Gene expression profile of ewing sarcoma cell lines differing in their EWS-FLI1 fusion type.
The t(11;22)(q24;q12) translocation is present in up to 95% of Ewing tumor patients and results in the formation of an EWS-FLI-1 fusion gene that encodes a chimeric transcription factor. Many alternative forms of EWS-FLI-1 exist because of variations in the location of the EWS and FLI-1 genomic breakpoints. Previous reports have shown that the type 1 fusion is associated with a significantly better prognosis than the other fusion types. It has been suggested that the observed clinical discrepancies result from different transactivation potentials of the various EWS-FLI-1 fusion proteins. In an attempt to identify genes whose expression levels are differentially modulated by structurally different EWS-FLI-1 transcription factors, we have used microarray technology to interrogate 19,000 sequence genes to compare gene expression profile of type 1 or non-type 1 Ewing sarcoma cell lines. Data analysis showed few qualitative differences on gene expression; expression of only 41 genes (0.215% of possible sequences analyzed) differed significantly between Ewing tumor cell lines carrying EWS-FLI-1 fusion type 1 with respect to those with non-type 1 fusion.


Factors Influencing the Choice between DOACs and LMWHs: A Survey of German Physicians on the Treatment of Cancer-Associated Venous Thromboembolism.
Recently direct-acting oral anticoagulants (DOACs) have become a new therapeutic option besides parenteral anticoagulants to treat cancer-associated venous thromboembolism (VTE). With this survey we wanted to identify factors influencing the choice between low-molecular-weight heparin and DOACs among physicians treating cancer patients. A questionnaire was presented at several medical educational activities on cancer care and VTE management between August 2018 and January 2019. One hundred fifteen physicians returned their surveys. The two most compelling arguments pro DOAC were when the patient had no chemotherapy and when he expressed unwillingness to apply injections. The two most important arguments against DOACs were if the patient had problems with taking oral medications or when he had a history of severe bleeding. This survey shows that future studies need to consider many more factors, particularly patient preferences and physician concerns on bleeding risk, to improve their applicability in daily practice.


Purification, crystallization and preliminary X-ray diffraction data of UDP-galactopyranose mutase from Aspergillus fumigatus.
Aspergillus fumigatus UDP-galactopyranose mutase (AfUGM) is a potential drug target involved in the synthesis of the cell wall of this fungal pathogen. AfUGM was recombinantly produced in Escherichia coli, purified and crystallized by the sitting-drop method, producing orthorhombic crystals that diffracted to a resolution of 3.25 Å. The crystals contained four molecules per asymmetric unit and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 127.72, b = 134.30, c = 173.84 Å. Incorporation of selenomethionine was achieved, but the resulting crystals did not allow solution of the phase problem.


Random walks on simplicial complexes and harmonics.
In this paper, we introduce a class of random walks with absorbing states on simplicial complexes. Given a simplicial complex of dimension d, a random walk with an absorbing state is defined which relates to the spectrum of the k-dimensional Laplacian for 1 ≤ k ≤ d. We study an example of random walks on simplicial complexes in the context of a semi-supervised learning problem. Specifically, we consider a label propagation algorithm on oriented edges, which applies to a generalization of the partially labelled classification problem on graphs. © 2016 Wiley Periodicals, Inc. Random Struct. Alg., 49, 379-405, 2016.


A network biology approach to identify crucial host targets for COVID-19.
The ongoing global pandemic of COVID-19, caused by SARS-CoV-2 has killed more than 5.9 million individuals out of ∼43 million confirmed infections. At present, several parts of the world are encountering the 3rd wave. Mass vaccination has been started in several countries but they are less likely to be broadly available for the current pandemic, repurposing of the existing drugs has drawn highest attention for an immediate solution. A recent publication has mapped the physical interactions of SARS-CoV-2 and human proteins by affinity-purification mass spectrometry (AP-MS) and identified 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Here, we taken a network biology approach and constructed a human protein-protein interaction network (PPIN) with the above SARS-CoV-2 targeted proteins. We utilized a combination of essential network centrality measures and functional properties of the human proteins to identify the critical human targets of SARS-CoV-2. Four human proteins, namely PRKACA, RHOA, CDK5RAP2, and CEP250 have emerged as the best therapeutic targets, of which PRKACA and CEP250 were also found by another group as potential candidates for drug targets in COVID-19. We further found candidate drugs/compounds, such as guanosine triphosphate, remdesivir, adenosine monophosphate, MgATP, and H-89 dihydrochloride that bind the target human proteins. The urgency to prevent the spread of infection and the death of diseased individuals has prompted the search for agents from the pool of approved drugs to repurpose them for COVID-19. Our results indicate that host targeting therapy with the repurposed drugs may be a useful strategy for the treatment of SARS-CoV-2 infection.


Effect of a urine culture stewardship initiative on urine culture utilization and catheter-associated urinary tract infections in intensive care units.
Urine cultures have poor specificity for catheter-associated urinary tract infections (CAUTIs). We evaluated the effect of a urine-culture stewardship program on urine culture utilization and CAUTI in adult intensive care units (ICUs). A quasi-interventional study was performed from 2015 to 2017. The study cohort comprised 21,367 patients admitted to the ICU at a teaching hospital. The urine culture stewardship program included monthly 1-hour discussions with ICU house staff emphasizing avoidance of "pan-culture" for sepsis workup and obtaining urine culture only if a urinary source of sepsis is suspected. The urine culture utilization rate metric (UCUR; ie, no. urine cultueres/catheter days ×100) was utilized to measure the effect. Monthly UCUR, catheter utilization ratio (CUR), and CAUTI rate were reported on an interactive quality dashboard. To ensure safety, catheterized ICU patients (2015-2016) were evaluated for 30-day readmission for UTI. Time-series data and relationships were analyzed using Spearman correlation coefficients and regression analysis. Urine culture utilization decreased from 3,081 in 2015 to 2,158 in 2016 to 1,218 in 2017. CAUTIs decreased from 78 in 2015 to 60 in 2016 and 28 in 2017. Regression analysis over time showed significant decreases in UCUR (r, 0.917; P < .0001) and CAUTI rate (r, 0.657; P < .0001). The co-correlation between UCUR and CAUTI rate was (r, 0.625; P < .0001) compared to CUR and CAUTI rate (r, 0.523; P = .004). None of these patients was readmitted with a CAUTI. Urine culture stewardship program was effective and safe in reducing UC overutilization and was correlated with a decrease in CAUTIs. Addition of urine-culture stewardship to standard best practices could reduce CAUTI in ICUs.


Observational studies of infections in rheumatoid arthritis: a metaanalysis of tumor necrosis factor antagonists.
Published metaanalyses of tumor necrosis factor (TNF) antagonists and infection have focused on randomized controlled trials, which tend to have short duration, relatively small size, and stringent inclusion/exclusion criteria that may limit enrollment to patients at low risk of infection. We performed a systematic review and synthesis of observational studies of TNF antagonists and infection risk. We conducted a systematic literature search of studies estimating overall risk of serious infection after anti-TNF exposure in rheumatoid arthritis (RA). We estimated a pooled relative risk (RR) for the relevant observational studies, using a random-effects model. Five cohort studies and 2 nested case-control studies were included in the metaanalysis. Anti-TNF therapy appeared to significantly increase risk of serious infection (pooled adjusted RR 1.37, 95% CI 1.18, 1.60). Our metaanalysis of observational data demonstrated an increased risk of serious infection in subjects with RA receiving anti-TNF therapy, versus those not receiving these agents.


Successful Prolonged Desensitization to Epoetin-Alfa Hypersensitivity in an Adult Patient With Advanced Chronic Kidney Disease.
The use of erythropoiesis-stimulating agents (ESAs) reduces the need for recurrent blood transfusions in patients with advanced kidney disease. Rarely, allergic reactions to recombinant human erythropoietin can develop, complicating anemia management due to cross-reactivity between these agents. We report the use of an outpatient desensitization protocol, which was successfully completed in an adult patient who developed a maculopapular rash as a form of delayed-type hypersensitivity reaction (DTH) to epoetin-alfa (EPO) use, followed by successful re-introduction of EPO and continued tolerance.


Sestrin 2 induces autophagy and attenuates insulin resistance by regulating AMPK signaling in C2C12 myotubes.
Impaired insulin-stimulated glucose uptake in skeletal muscle serves a critical role in the development of insulin resistance (IR), whereas the precise mechanism of the process remains unknown. Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes. Activation of Sesn2 may activate AMP-activated protein kinase (AMPK) accompanied by suppression of mammalian target of rapamycin (mTOR), which may ultimately lead to autophagy induction. In view of the potential protective effects of autophagy on the physiological and the pathological regulatory processes via the regulation of energy homeostasis and metabolism, we investigated the effects of Sesn2 on the components of the insulin signaling pathway and insulin-stimulated glucose uptake in palmitate-induced insulin-resistant C2C12 myotubes. We showed that Sesn2 effectively restored the impaired insulin signaling. Moreover, autophagic activity decreased in response to palmitate, whereas Sesn2 significantly reversed the palmitate-suppressed autophagic signaling in this context. Our findings further revealed that Sesn2-induced autophagy contributed to restore the impaired insulin signaling through the activation of AMPK signal. Even in the presence of palmitate, Sesn2 up-regulation maintained insulin sensitivity and glucose metabolism via AMPK-dependent autophagic activation.


Early Onset Neonatal Sepsis Due to Salmonella enterica Serovar 4,5,12:i:-: A Case Report with Literature Review.
The authors report a case of a 36-week male infant born via spontaneous vaginal delivery who developed Salmonella sepsis at HRH Princess Maha Chakri Sirindhorn Medical Center Srinakharinwirot University, Nakhon Nayok, Thailand. He was born to a mother without identifiable risk factors. On day 3, he developed fever tachycardia, lethargy, poor feeding and diarrhea prompting a sepsis evaluation. Blood and stool cultures were positive for S. enterica serovar 4,5,12:i:-. Therefore, Salmonella infection should be considered in the differential diagnosis of early onset neonatal sepsis (EOS) particularly in endemic areas.


Random Lasing via Plasmon-Induced Cavitation of Microbubbles.
Numerous laboratories have observed random lasing from optically pumped solutions of plasmonic nanoparticles (NPs) suspended with organic dye molecules. The underlying mechanism is typically attributed to the formation of closed-loop optical cavities enabled by the large local field and scattering enhancements in the vicinity of plasmonic NPs. In this manuscript, we propose an alternative mechanism that does not directly require the plasmon resonance. We used high-speed confocal microspectroscopy to observe the photophysical dynamics of NPs in solution. Laser pulses induce the formation of microbubbles that surround and encapsulate the NPs, then sharp peaks <1.0 nm are observed that match the spectral signature of random lasing. Electromagnetic simulations indicate that ensembles of microbubbles may form optical corral containing standing wave patterns that are sufficient to sustain coherent optical feedback in a gain medium. Collectively, these results show that ensembles of plasmonic-induced bubbles can generate optical feedback and random lasing.


Targeting Mitochondrial Network Architecture in Down Syndrome and Aging.
Mitochondria are organelles that mainly control energy conversion in the cell. In addition, they also participate in many relevant activities, such as the regulation of apoptosis and calcium levels, and other metabolic tasks, all closely linked to cell viability. Functionality of mitochondria appears to depend upon their network architecture that may dynamically pass from an interconnected structure with long tubular units, to a fragmented one with short separate fragments. A decline in mitochondrial quality, which presents itself as an altered structural organization and a function of mitochondria, has been observed in Down syndrome (DS), as well as in aging and in age-related pathologies. This review provides a basic overview of mitochondrial dynamics, from fission/fusion mechanisms to mitochondrial homeostasis. Molecular mechanisms determining the disruption of the mitochondrial phenotype in DS and aging are discussed. The impaired activity of the transcriptional co-activator PGC-1α/PPARGC1A and the hyperactivation of the mammalian target of rapamycin (mTOR) kinase are emerging as molecular underlying causes of these mitochondrial alterations. It is, therefore, likely that either stimulating the PGC-1α activity or inhibiting mTOR signaling could reverse mitochondrial dysfunction. Evidence is summarized suggesting that drugs targeting either these pathways or other factors affecting the mitochondrial network may represent therapeutic approaches to improve and/or prevent the effects of altered mitochondrial function. Overall, from all these studies it emerges that the implementation of such strategies may exert protective effects in DS and age-related diseases.


[Use of various methods to isolate exopolysaccharide of eltor cholera Vibrios and its immunochemical characteristics].
Isolation of Vibrio eltor exopolysaccharide and study of its immunochemical properties. Rugose variants of strains V. eltor 18895 and V. eltor 18843 obtained by us by selection in M9 medium were used in the study. Exopolysaccharides (EPS) were isolated by K. Kierek (2003), S.P. Zadnova (2004), N.P. Elinova (1984) methods and analyzed for carbohydrate, protein, nucleic acid content and lipopolysaccharide impurity. EPS, LPS, R-LPS structure was compared by high-pressure chromatography. Neutral sugars and amino sugars were identified by thin layer chromatography. Polyclonal antibodies were produced against EPS preparation isolated by N.P. Elinova (1984) method. Specific activity of obtained mice sera was tested by DIA method. EPS isolated by N.P. Elinova method (1984) was shown not to contain extraneous impurities. V. eltor EPS structure differs from LPS and R-LPS. Monosaccharide composition of EPS from ctx+ V. eltor 18895 strain is presented by a wider specter of carbohydrates including glucose, mannose, rhamnose, galacturonic acid. Use in DIA of specific sera produced against EPS from toxigenic strain did not reveal general epitopes with capsule polysaccharides of V. cholerae O139, V. parahaemolyticus and V. vulnificus. Use of EPS as an immunogen promoted production of sera that are specific against EPS and rugose variants of Vibrio cholerae eltor that can be used for their detection or characterization.


Plasminogen plays a crucial role in bone repair.
The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen-deficient (Plg⁻/⁻) mice. Bone repair of the femur is delayed in Plg⁻/⁻ mice, unlike that in the wild-type (Plg⁺/⁺) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg⁻/⁻ mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were decreased at the site of bone damage in Plg⁻/⁻ mice. Conversely, heterotopic ossification was not significantly different between Plg⁺/⁺ and Plg⁻/⁻ mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF-β were comparable between Plg⁺/⁺ and Plg⁻/⁻ mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-β, and VEGF, thereby leading to the enhancement of bone repair.


Clustering of cardiovascular risk factors. time trends during 28 years.
To assess the development in frequency and clustering of hypertension, hypercholesterolaemia, high body mass index (BMI), physical inactivity and tobacco smoking in the period 1964-1992, and to evaluate any sex and age differences. Five cross-sectional investigations on cardiovascular risk factors performed in 1964, 1978, 1982-1984, 1986-1987 and 1991-1992 comprising random samples in a suburban area of Copenhagen, Denmark. Physical activity during leisure time and smoking habits were assessed by self-administered questionnaire. Blood pressure, weight, height and serum total cholesterol were measured according to WHO standards. A total of 8644 persons aged 30, 40, 50 and 60 years participated with an equal number of men and women. Women had fewer risk factors than men and younger persons had fewer risk factors than older persons. In the period 1964-1992 there was a decreasing number of risk factors. The 50 year olds show a sex difference in the period 1982-1992, whereas there was no sex difference among the 60 year olds. Tobacco smoking was the most common risk factor. BMI > 27.5 has become more and more frequent throughout the period, especially in men. The BMI has conquered third place in all age groups. The association of BMI > 27.5 and sedentary leisure time physical activity has become the most frequent. Clustering among risk factors decreased over time in both sexes. The association of elevated BMI and sedentary leisure time activity may contribute to the rising frequency of chronic disease such as diabetes mellitus and cardiovascular disease.


Treatment of Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause, occurring in adults and limited to the lungs. In the past, treatment was aimed at minimizing inflammation and slowing the progression of inflammation to fibrosis. However, the underlying lesion in IPF may be more fibrotic than inflammatory, explaining why few patients respond to anti-inflammatory therapies and the prognosis remains poor. In this review of literature, we will be focusing on main lines of treatment including current medications, supportive care, lung transplantation evaluation, and potential future strategies of treatment.


MEASUREMENTS OF THE PARASITIC NEUTRON DOSE AT ORGANS FROM MEDICAL LINACS AT DIFFERENT ENERGIES BY USING BUBBLE DETECTORS.
Conventional linear accelerators (LINACs) for radiotherapy produce fast secondary neutrons due to photonuclear processes. The neutron presence is considered as an extra undesired dose during the radiotherapy treatment, which could cause secondary radio-induced tumors and malfunctions to cardiological implantable devices. It is thus important to measure the neutron dose contribution to patients during radiotherapy, not only at high-energy LINACs, but also at lower energies, near the giant dipole resonance reaction threshold. In this work, the full body neutron dose equivalent has been measured during single-field radiotherapy sessions carried out at different LINAC energies (15, 10 and 6 MV) by using a tissue equivalent (for neutrons) anthropomorphic phantom together with bubble dosemeters. Results have shown that some neutron photoproduction is still present also at lower energies. As a consequence, emitted photoneutrons cannot be ignored and represent a risk contribution for patients undergoing radiotherapy.


Impact of high-grade obstruction on outcomes in patients with appendiceal inflammatory masses managed by nonoperative treatment.
To retrospectively assess the impact of high-grade obstructions identified on initial CT on outcomes of patients with appendiceal inflammatory masses managed by nonoperative treatment. Institutional Review Boards approved this retrospective study and informed consent was waived. Included were 52 consecutive patients diagnosed with appendiceal inflammatory masses by CT scan and managed by nonoperative treatment. The main outcome measure was treatment failure and secondary outcomes were complications and initial and total hospital stay. Patient demographics, inflammatory markers, and CT findings for presence of an appendiceal inflammatory mass and high-grade obstruction were assessed. Patients with and without high-grade obstruction were compared for patient characteristics and outcomes using Fisher exact test and Student t-test. Among 52 patients, 14 (27%) had high-grade obstruction on CT examination at presentation. No significant differences were observed in patient characteristics (P > 0.05), treatment failure (P = 0.33), complications (P = 0.29), or initial (P = 0.73) or total (P = 0.72) hospitalization between patients with and without high-grade obstruction. For patients who were managed by nonoperative treatment for appendiceal inflammatory masses, the presence of high-grade obstruction identified on initial CT scan did not significantly affect outcomes of treatment failure, complications, and initial and total hospitalization.


A molecular dynamics simulation study decodes the early stage of the disassembly process abolishing the human SAMHD1 function.
The human sterile alpha motif SAM and HD domain-containing protein 1 (SAMHD1) restricts in non-cycling cells type the infection of a large range of retroviruses including HIV-1, reducing the intracellular pool concentration of deoxynucleoside triphosphates (dNTPs) required for the reverse transcription of the viral genome. The enzyme is in equilibrium between different forms depending on bound cofactors and substrate. In this work, two SAMHD1 three-dimensional models have been investigated through classical molecular dynamics simulation, to define the role of cofactors and metal ions in the association of the tetrameric active form. A detailed analysis of the inter-subunit interactions, taking place at the level of helix 13, indicates that removal of metal ions and cofactors induces an asymmetric loosening of the monomer-monomer interface leading to the formation of a loose tetramer where the two dimeric interfaces are weakened in different way.


The effect of diet on fecal moisture, osmolarity of fecal extracts, products of bacterial fermentation and loss of minerals in feces of weaned pigs.
Litters of pigs were allotted to one of three dietary treatments. Treatment 1 (T1) consisted of a corn-soybean meal starter diet. Pigs fed treatment 2 (T2) received a steamed, rolled oat groats-casein diet and pigs in treatment 3 (T3) remained with the sow. Four pigs/treatment were used to investigate the difference in performance and the cause of post-weaning diarrhea associated with early weaning of pigs at 4 wk of age to a starter diet. Fecal moisture, osmolarity, acetic acid, lactic acid and glucose contents were all good indicators of dietary differences because of treatment X age interactions. These variables increased faster in fecal extracts from pigs fed the corn-soybean meal diet. Lactic acid, volatile fatty acid (VFA) levels, glucose and pH values were indicative of a more active bacterial fermentation in pigs receiving T1 than in those receiving T2 or pigs remaining with the sow (T3). Excess minerals appear to contribute significantly to the osmolarity of fecal material. Of the anions, lactate was the main contributor to the osmolarity of feces of T1 pigs, followed by P, VFA, of which acetic acid contributed 70%, and Cl. The main cations were K, Na and Ca. In T2, P was the main anion, followed by lactate, VFA and Cl, while the main cations were Na, K and Ca. Minerals seemed to be the major osmotic particles in fecal extracts of pigs remaining with the sow. Phosphorus was the major anionic contributor to osmolarity, followed by VFA, Cl and lactic acid. Potassium was the major cation, followed by Na and Ca.(ABSTRACT TRUNCATED AT 250 WORDS)


Identifying predictors of interferon-γ release assay results in pediatric latent tuberculosis: a protective role of bacillus Calmette-Guerin?: a pTB-NET collaborative study.
Interferon-γ (IFN-γ) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date. To investigate factors influencing results of IFN-γ release assays in children using a large European data set. The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-γ release assay. Multivariate analyses examined age, bacillus Calmette-Guérin (BCG) vaccination status, and sex as predictor variables of results. Subgroup analyses included children who were household contacts. A total of 1,093 children had a QuantiFERON-TB Gold In-Tube assay and 382 had a T-SPOT.TB IFN-γ release assay. Age was positively correlated with a positive blood result (QuantiFERON-TB Gold In-Tube: odds ratio [OR], 1.08 per year increasing age [P < 0.0001]; T-SPOT.TB: OR, 1.14 per year increasing age [P < 0.001]). A positive QuantiFERON-TB Gold In-Tube result was shown by 5.5% of children with a tuberculin skin test result less than 5 mm, by 14.8% if less than 10 mm, and by 20.2% if less than 15 mm. Prior BCG vaccination was associated with a negative IFN-γ release assay result (QuantiFERON-TB Gold In-Tube: OR, 0.41 [P < 0.001]; T-SPOT.TB: OR, 0.41 [P < 0.001]). Young age was a predictor of indeterminate IFN-γ release assay results, but indeterminate rates were low (3.6% in children < 5 yr, 1% in children > 5 yr). Our data show that BCG vaccination may be effective in protecting children against Mycobacterium tuberculosis infection. To restrict use of IFN-γ release assays to children with positive skin tests risks underestimating latent infection.


Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy.
Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean +/- SEM) 0.8 +/- 0.2 pmol/l in the first trimester to 2.7 +/- 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 +/- 8 U/l (first trimester) to 347 +/- 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 +/- 0.2 pmol/l (first trimester) to 3.1 +/- 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 +/- 0.05 nmol/l from 0.19 +/- 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 +/- 0.11 (first trimester) to a nadir of 0.19 +/- 0.04 6 weeks postpartum (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)


A novel type II secretion system in Pseudomonas aeruginosa.
The genome sequence of Pseudomonas aeruginosa strain PAO1 has been determined to facilitate postgenomic studies aimed at understanding the capacity of adaptation of this ubiquitous opportunistic pathogen. P. aeruginosa produces toxins and hydrolytic enzymes that are secreted via the type II secretory pathway using the Xcp machinery or 'secreton'. In this study, we characterized a novel gene cluster, called hxc for homologous to xcp. Characterization of an hxcR mutant, grown in phosphate-limiting medium, revealed the absence of a 40 kDa protein found in the culture supernatant of wild-type or xcp derivative mutant strains. The protein corresponded to the alkaline phosphatase L-AP, renamed LapA, which is secreted in an xcp-independent but hxc-dependent manner. Finally, we showed that expression of the hxc gene cluster is under phosphate regulation. This is the first report of the existence of two functional type II secretory pathways within the same organism, which could be related to the high adaptation potential of P. aeruginosa.


Comparative studies on growth and physiological responses of unicellular and colonial Microcystis aeruginosa to Acorus calamus.
In order to explore the growth inhibition and physiological responses of unicellular and colonial Microcystis aeruginosa during coexistence with Acorus calamus, algal densities, chlorophyll a contents, exopolysaccharide (EPS) concentrations, malondialdehyde (MDA) contents, catalase (CAT) activities, and peroxidase (POD) activities of the two algae strains were analyzed. Although the unicellular and colonial strains of M. aeruginosa were both inhibited by A. calamus, unicellular algae were more sensitive than the colonial algae. The measurement results for EPS, MDA, CAT, and POD showed that unicellular M. aeruginosa had higher levels of stress related damage than colonial strains when they were exposed to the same density of A. calamus, and the cellular defense system of colonial M. aeruginosa was stronger than that of unicellular M. aeruginosa. Natural blooms of Microcystis are typically composed of colonial forms of M. aeruginosa, therefore future efforts to control such blooms, possibly through the development of new algicides, should focus on the unique characteristics of colonial M. aeruginosa strains.