Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-dose oritavancin in the treatment of acute bacterial skin infections.

BACKGROUND Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment. METHODS We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin. RESULTS The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, -1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, -5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, -0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin. CONCLUSIONS A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.).
SlmA Antagonism of FtsZ Assembly Employs a Two-pronged Mechanism like MinCD

Assembly of the Z-ring over unsegregated nucleoids is prevented by a process called nucleoid occlusion (NO), which in Escherichia coli is partially mediated by SlmA. SlmA is a Z ring antagonist that is spatially regulated and activated by binding to specific DNA sequences (SlmA binding sites, SBSs) more abundant in the origin proximal region of the chromosome. However, the mechanism by which SBS bound SlmA (activated form) antagonizes Z ring assembly is controversial. Here, we report the isolation and characterization of two FtsZ mutants, FtsZ-K190V and FtsZ-D86N that confer resistance to activated SlmA. In trying to understand the basis of resistance of these mutants, we confirmed that activated SlmA antagonizes FtsZ polymerization and determined these mutants were resistant, even though they still bind SlmA. Investigation of SlmA binding to FtsZ revealed activated SlmA binds to the conserved C-terminal tail of FtsZ and that the ability of activated SlmA to antagonize FtsZ assembly required the presence of the tail. Together, these results lead to a model in which SlmA binding to an SBS is activated to bind the tail of FtsZ resulting in further interaction with FtsZ leading to depolymerization of FtsZ polymers. This model is strikingly similar to the model for the inhibitory mechanism of the spatial inhibitor MinCD.
Reproduction in Men with Klinefelter Syndrome: The Past, the Present, and the Future

Klinefelter syndrome (KS) is the most common chromosomal aberration in men. There are approximately 250,000 men with KS in the United States, and the prevalence of KS in male reproductive practices is 3 to 4%; however, most men are never diagnosed. KS has an effect on normal development, growth, social interactions, bone structure, and sexual and reproductive function, thus a multidisciplinary approach to men with KS is important in providing state of the art care to children and men with KS. Over the last 10 years, with advancements in artificial reproductive techniques and the successful delivery of healthy children from men with KS, the involvement of reproductive endocrinologists and urologists in the care of patients with KS is becoming commonplace. The new areas of intense research investigate optimal methods of hormonal manipulations, preservation of fertility in adolescents, and development of universal early screening programs for KS. This review provides the latest update in our understanding of the pathophysiology, natural history, and evolving paradigms of therapy in adolescents and men with KS.
Age-related decline in central serotonin transporter availability with [ 123 I ] bCIT SPECT <

Postmortem studies have provided limited and conflicting data regarding aging effects on the central serotonin transporter (SERT). The present study investigated the effect of age on SERT availability in the human brainstem and diencephalon with single photon emission computed tomography (SPECT) using the ligand [ I]2b-carbomethoxy-3 b-(4-iodophenyl)tropane ([ I]b-CIT). Healthy control subjects (n 5 126) who ranged in age from 18 to 88 were injected with 6.0. 8 (mean6 SD) mCi [I]b-CIT and imaged 23.16 1.9 h later under equilibrium conditions. A ratio of specific to nondisplaceable brain uptake (i.e., V 30 5 [brainstem-diencephalon –occipital]/occipital), a measure proportional to the binding potential ( Bmax/KD), was derived. SERT availability (V 30) showed a significant inverse correlation with age (r 5 20.40, P , 0.0001). Linear regression analysis revealed that V 30 declined by 29.5% over the age range 18 to 88, or approximately 4.2% per decade. These results demonstrate reductions in the availability of central SERT binding sites with age in living human subjects. © 2000 Elsevier Science Inc. All rights reserved.
Is there a family profile of addictive behaviors? Family functioning in anorexia nervosa and drug dependence disorder.

OBJECTIVES The objective of the study was to determine whether family profiles differ between patients with anorexia nervosa or drug dependence disorder. METHOD 25 families of patients with anorexia nervosa and 26 families of patients with drug dependence disorder responded to a battery of self-reports (Interpersonal Dependence Inventory, Family Adaptability and Cohesion Evaluation Scales, and Family Questionnaire). RESULTS A lack of social self-confidence was observed in patients with anorexia nervosa or drug dependence disorder and their parents. Family disturbances characterized by low cohesion and emotional reliance on another person were observed in the families of patients with anorexia nervosa or drug dependence disorder. CONCLUSIONS The present study suggests that there are differing levels of severity of family disturbances among fathers, mothers, and patients in both anorexia nervosa and drug dependence disorder.
Source (or Part of the following Source): Type Article Title Pyroglutamate Abeta Pathology in App/ps1ki Mice, Sporadic and Familial Alzheimer's Disease Cases Author(s) Pyroglutamate Abeta Pathology in App/ps1ki Mice, Sporadic and Familial Alzheimer's Disease Cases

Copyright It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content licence (like Creative Commons). UvA-DARE is a service provided by the library of the University of Amsterdam (http://dare.uva.nl) Abstract The presence of Ab pE3 (N-terminal truncated Ab starting with pyroglutamate) in Alzheimer's disease (AD) has received considerable attention since the discovery that this peptide represents a dominant fraction of Ab peptides in senile plaques of AD brains. This was later confirmed by other reports investigating AD and Down's syndrome postmortem brain tissue. Importantly, Ab pE3 has a higher aggregation propensity, and stability, and shows an increased toxicity compared to full-length Ab. We have recently shown that intraneuronal accumulation of Ab pE3 peptides induces a severe neuron loss and an associated neurological phenotype in the TBA2 mouse model for AD. Given the increasing interest in Ab pE3 , we have generated two novel monoclonal antibodies which were characterized as highly specific for Ab pE3 peptides and herein used to analyze plaque deposition in APP/PS1KI mice, an AD model with severe neuron loss and learning deficits. This was compared with the plaque pattern present in brain tissue from sporadic and familial AD cases. Abundant plaques positive for Ab pE3 were present in patients with sporadic AD and familial AD including those carrying mutations in APP (arctic and Swedish) and PS1. Interestingly , in APP/PS1KI mice we observed a continuous increase in Ab pE3 plaque load with increasing age, while the density for Ab 1-x plaques declined with aging. We therefore assume that, in particular, the peptides starting with position 1 of Ab are N-truncated as disease progresses , and that, Ab pE3 positive plaques are resistant to age-dependent degradation likely due to their high stability and propensity to aggregate.
Bronchial carcinoid tumours

Some features of 22 cases of carcinoid tumour are described. The histology of the tumour was the criterion for inclusion in the series. The histology was reviewed by an observer unfamiliar with the clinical features. Six patients, each with an entirely endobronchial tumour of typical histology treated satisfactorily by surgery, are excluded from further consideration; the remaining 16 are considered for factors which may be significant in assessing the long-term prognosis, in addition to a histological assessment. The experience in this series is compared with a number of considerably larger series from the literature. The conclusion is reached that no single feature, histological or clinical, can be a basis for reaching a reliable prognosis. Lobectomy is regarded as the operation of choice in treatment.
Visual Attention to the Periphery Is Enhanced in Congenitally Deaf Individuals

We compared normally hearing individuals and congenitally deaf individuals as they monitored moving stimuli either in the periphery or in the center of the visual field. When participants monitored the peripheral visual field, greater recruitment (as measured by functional magnetic resonance imaging) of the motion-selective area MT/MST was observed in deaf than in hearing individuals, whereas the two groups were comparable when attending to the central visual field. This finding indicates an enhancement of visual attention to peripheral visual space in deaf individuals. Structural equation modeling was used to further characterize the nature of this plastic change in the deaf. The effective connectivity between MT/MST and the posterior parietal cortex was stronger in deaf than in hearing individuals during peripheral but not central attention. Thus, enhanced peripheral attention to moving stimuli in the deaf may be mediated by alterations of the connectivity between MT/MST and the parietal cortex, one of the primary centers for spatial representation and attention.
Is Replication Important for HCI?

Replication is emerging as a key concern within subsections of the HCI community. In this paper, we explore the relevance of science and technology studies (STS), which has addressed replication in various ways. Informed by this literature, we examine HCI’s current relationship to replication and provide a set of recommendations and points of clarification that a replication agenda in HCI should concern itself with.
Using In situ Dynamic Cultures to Rapidly Biofabricate Fabric-Reinforced Composites of Chitosan/Bacterial Nanocellulose for Antibacterial Wound Dressings

Bacterial nano-cellulose (BNC) is considered to possess incredible potential in biomedical applications due to its innate unrivaled nano-fibrillar structure and versatile properties. However, its use is largely restricted by inefficient production and by insufficient strength when it is in a highly swollen state. In this study, a fabric skeleton reinforced chitosan (CS)/BNC hydrogel with high mechanical reliability and antibacterial activity was fabricated by using an efficient dynamic culture that could reserve the nano-fibrillar structure. By adding CS in culture media to 0.25–0.75% (w/v) during bacterial cultivation, the CS/BNC composite hydrogel was biosynthesized in situ on a rotating drum composed of fabrics. With the proposed method, BNC biosynthesis became less sensitive to the adverse antibacterial effects of CS and the production time of the composite hydrogel with desirable thickness could be halved from 10 to 5 days as compared to the conventional static cultures. Although, its concentration was low in the medium, CS accounted for more than 38% of the CS/BNC dry weight. FE-SEM observation confirmed conservation of the nano-fibrillar networks and covering of CS on BNC. ATR-FTIR showed a decrease in the degree of intra-molecular hydrogen bonding and water absorption capacity was improved after compositing with CS. The fabric-reinforced CS/BNC composite exhibited bacteriostatic properties against Escherichia coli and Staphylococcus aureus and significantly improved mechanical properties as compared to the BNC sheets from static culture. In summary, the fabric-reinforced CS/BNC composite constitutes a desired candidate for advanced wound dressings. From another perspective, coating of BNC or CS/BNC could upgrade the conventional wound dressings made of cotton gauze to reduce pain during wound healing, especially for burn patients.
Activity in the Fusiform Gyrus Predicts Conscious Perception of Rubin's Vase–Face Illusion

We localized regions in the fusiform gyrus and superior temporal sulcus that were more active when subjects viewed photographs of real faces than when they viewed complex inanimate objects and other areas in the parahippocampal gyrus and the lateral occipital lobe that showed more activity during the presentation of nonface objects. Event-related functional magnetic resonance imaging was then used to monitor activity in these extrastriate visual areas while subjects viewed Rubin's vase-face stimulus and indicated switches in perception. Since the spontaneous shifts in interpretation were too rapid for direct correlation with hemodynamic responses, each reported percept (faces or vase) was prolonged by suddenly adding subtle local contrast gradients (embossing) to one side or the other of the figure-ground boundary, stabilizing the percept. Under these conditions, only face-selective areas in the fusiform gyrus responded more strongly during the perception of faces. To control for effects of the physical change to Rubin's stimulus (i.e., addition of embossing), we compared activity when the face contours were embossed after the subject had just reported the onset of perception of either faces or vase. Activity in the fusiform face area responded more strongly under the first condition, despite the fact that the physical stimulus sequences were identical. Moreover, on a trial-to-trial basis, the activity was statistically predictive of the subjects' responses, suggesting that the conscious perception of faces could be made explicit in this extrastriate visual area.
Cell cycle arrest induced by the bacterial adenylate cyclase toxins from Bacillus anthracis and Bordetella pertussis

Bacillus anthracis oedema toxin (ET) and Bordetella pertussis adenylate cyclase toxin (ACT) enter host cells and produce cAMP. To understand the cellular consequences, we exposed J774 cells to these toxins at ng ml−1 (pM) concentrations, then followed cell number and changes in cell signalling pathways. Under these conditions, both toxins produce a concentration‐dependent inhibition of cell proliferation without cytotoxicity. ET and ACT increase the proportion of cells in G1/G0 and reduce S phase, such that a single addition of ET or ACT inhibits cell division for 3–6 days. Treatment with ET or ACT produces striking changes in proteins controlling cell cycle, including virtual elimination of phosphorylated ERK 1/2 and Cyclin D1 and increases in phospho‐CREB and p27Kip1. Importantly, PD98059, a MEK inhibitor, elicits a comparable reduction in Cyclin D1 to that produced by the toxins and blocks proliferation. These data show that non‐lethal concentrations of ET and ACT impose a prolonged block on the proliferation of J774 cells by impairment of the progression from G1/G0 to S phase in a process involving cAMP‐mediated increases in phospho‐CREB and p27Kip1 and reductions in phospho‐ERK 1/2 and Cyclin D1. This phenomenon represents a new mechanism by which these toxins affect host cells.
Virus-mediated swapping of zolpidem-insensitive with zolpidem-sensitive GABAA receptors in cortical pyramidal cells

• We generated lenti‐ and adeno‐associated viruses which were used to replace the zolpidem‐insensitive GABAA receptors of a transgenic mouse line with wild‐type, zolpidem‐sensitive ones. • The virally expressed wild‐type, zolpidem‐sensitive GABAA receptor γ2 subunits were tagged with a small immunotag (AU1). • Light microscopic fluorescent and electron microscopic freeze‐fracture immunogold labelling revealed that the virally introduced AU1‐tagged γ2 subunit‐containing receptors had a normal synaptic distribution on cortical pyramidal cells. • In vitro patch‐clamp recordings demonstrated that the insertion of this immunotag did not alter the kinetic and pharmacological properties of the virally inserted γ2 subunits. • Our results demonstrate a novel transgenic–viral pharmacogenetic approach, which allows the selective silencing of well‐defined neuronal populations in the brain.
Comparison of Two Molecular Assays for Detection and Characterization of Aspergillus fumigatus Triazole Resistance and Cyp51A Mutations in Clinical Isolates and Primary Clinical Samples of Immunocompromised Patients

In hematological patients, the incidence of invasive aspergillosis (IA) caused by azole resistant Aspergillus fumigatus (ARAf) is rising. As the diagnosis of IA is rarely based on positive culture in this group of patients, molecular detection of resistance mutations directly from clinical samples is crucial. In addition to the in-house azole resistance ARAf polymerase chain reaction (PCR) assays detecting the frequent mutation combinations TR34/L98H, TR46/Y121F/T289A, and M220 in the Aspergillus fumigatus (A. fumigatus) Cyp51A gene by subsequent DNA sequence analysis, we investigated in parallel the commercially available AsperGenius® real time PCR system in detecting the Cyp51A alterations TR34/L98H and Y121F/T289A directly from 52 clinical samples (15 biopsies, 22 bronchoalveolar lavage (BAL), 15 cerebrospinal fluid (CSF) samples) and ARAf isolates (n = 3) of immunocompromised patients. We analyzed DNA aliquots and compared both methods concerning amplification and detection of Aspergillus DNA and Cyp51A alterations. As positive control for the feasibility of our novel Y121F and T289A PCR assays, we used two A. fumigatus isolates with the TR46/Y121F/T289A mutation combination isolated from hematological patients with known Cyp51A alterations and a lung biopsy sample of a patient with acute myeloid leukemia (AML). The rate of positive ARAf PCR results plus successful sequencing using the ARAf PCR assays was 61% in biopsies, 29% in CSF, 67% in BAL samples and 100% in isolates. In comparison the amount of positive PCRs using the AsperGenius® assays was 47% in biopsies, 42% in CSF, 59% in BAL samples and 100% in isolates. Altogether 17 Cyp51A alterations were detected using our ARAf PCRs plus DNA sequencing and therefrom 10 alterations also by the AsperGenius® system. The comparative evaluation of our data revealed that our conventional PCR assays are more sensitive in detecting ARAf in BAL and biopsy samples, whereby differences were not significant. The advantage of the AsperGenius® system is the time saving aspect. We consider non-culture based molecular detection of Aspergillus triazole resistance to be of high epidemiological and clinical relevance in patients with hematological malignancies.
Association Between Pregnancy Induced Hypertension and Low Birth Weight; A Population Based Case-Control Study

The purpose of this study was to investigate the association between pregnancy-induced hypertension and low birth weight. A population-based case control study was conducted. Antenatal mothers who attended the government health centers in the district of Kuala Muda, Kedah, Malaysia from June 2003 to May 2004 were recruited. Cases were 312 mothers who delivered low birth weight babies, and controls were 312 mothers who delivered normal birth weight babies. Face-to-face interviews using a structured questionnaire and a review of medical records were carried out. After controlling for important confounders such as gestational age at delivery, maternal age, ethnicity, education, parity, and previous history of abortion, pregnancy-induced hypertension was found to be an independent risk factor (adjusted odds ratio = 5.06; 95% confidence interval: 2.63, 9.71) for low birth weight. There was a significant association of pregnancy-induced hypertension with low birth weight. Women who delivered low birth weight babies were 5 times more likely to have had pregnancy-induced hypertension.
The living-room: browsing, organizing and presenting digital image collections in interactive environments

We present the living-room, an interactive application for browsing, organizing and sharing digital photos. The application runs in an instrumented environment on a wall display and an interactive tabletop, which is meant to simulate a future living room. We discuss the design rationale as well as the interaction techniques and the technical implementation. To asses how well our design goals were met, we evaluated the application in a study with 10 participants with mostly good results.
Development of a Myoelectric Controller based on Knee Angle Estimation

This paper presents the development of a bioinstrumentation system for the acquisition and pre-processing of surface electromyographic (SEMG) signals, as well as the proposal of a myoelectric controller for leg prostheses, using algorithms for feature extraction and classification of myoelectric patterns. The implemented microcontrolled bioinstrumentation system is capable of recording up to four SEMG channels, and one electrogoniometer channel. The proposed neural myoelectric controller is capable of predicting the intended knee joint angle from the measured SEMG singals. The controller is designed in three stages: feature extraction, using auto-regressive model and amplitude histogram; feature projection, using self organizing maps; and pattern classification, using a Levenberg-Marquadt neural network. The use of SEMG signals and additional mechanical information such as that provided by the electrogoniometer may improve precision in the control of leg prostheses. Preliminary results are presented.
Portal branch ligation induces efficient retrovirus‐mediated gene delivery in rat liver

The in vivo transduction of hepatocytes with conventional retrovirus vectors requires the induction of cell division and this can currently only be achieved by invasive surgery or by inducing severe liver damage. We hypothesised that partial portal branch ligation (PBL) could induce hepatocyte proliferation and efficient gene transfer in the rat.