Current knowledge and practice of Candida auris screening in France: A nationwide survey from the French Society of Medical Mycology (SFMM).

Due to large outbreaks observed worldwide, Candida auris has emerged as a major threat to healthcare facilities. To prevent these phenomena, a systematic screening should be performed in patients transferred from regions where the pathogen is highly endemic. In this study, we recorded and analyzed French mycologists' current knowledge and practice regarding C. auris screening and diagnosis. Thirty-six centers answered an online questionnaire. Only 11 (30.6 %) participants were aware of any systematic screening for C. auris for patients admitted to their hospital. In the case of post-admission screening, axillae/groins (n = 21), nares (n = 7), rectum (n = 9), and mouth (n = 6) alone or various combinations were the body sites the most frequently sampled. Only six centers (8.3 %) reported using a commercially available plate allowing the differentiation of C. auris colonies from that of other Candida species, while five laboratories (13.8 %) had implemented a C. auris-specific qPCR. Considering the potential impact on infected patients and the risk of disorganization in the care of patients, it is crucial to remember to biologists and clinicians the utmost importance of systematic screening on admission.

RNA-Seq mapping and detection of gene fusions with a suffix array algorithm.

High-throughput RNA sequencing enables quantification of transcripts (both known and novel), exon/exon junctions and fusions of exons from different genes. Discovery of gene fusions-particularly those expressed with low abundance- is a challenge with short- and medium-length sequencing reads. To address this challenge, we implemented an RNA-Seq mapping pipeline within the LifeScope software. We introduced new features including filter and junction mapping, annotation-aided pairing rescue and accurate mapping quality values. We combined this pipeline with a Suffix Array Spliced Read (SASR) aligner to detect chimeric transcripts. Performing paired-end RNA-Seq of the breast cancer cell line MCF-7 using the SOLiD system, we called 40 gene fusions among over 120,000 splicing junctions. We validated 36 of these 40 fusions with TaqMan assays, of which 25 were expressed in MCF-7 but not the Human Brain Reference. An intra-chromosomal gene fusion involving the estrogen receptor alpha gene ESR1, and another involving the RPS6KB1 (Ribosomal protein S6 kinase beta-1) were recurrently expressed in a number of breast tumor cell lines and a clinical tumor sample.

Virtual enriched environments in paediatric neuropsychological rehabilitation following traumatic brain injury: Feasibility, benefits and challenges.

A frequent consequence of traumatic brain injury (TBI) is a significant reduction in patients' cerebral activation/arousal, which clinicians agree is not conducive to optimal rehabilitation outcomes. In the context of paediatric rehabilitation, sustained periods of inactivity are particularly undesirable, as contemporary research has increasingly called into question the Kennard principle that youth inherently promotes greater neural plasticity and functional recovery following TBI. Therefore, the onus to create rehabilitation conditions most conducive to harnessing plasticity falls squarely on the shoulders of clinicians. Having noted the efficacy of environmental enrichment in promoting neural plasticity and positive functional outcomes in the animal literature, some researchers have suggested that the emerging technology of Virtual Reality (VR) could provide the means to increase patients' cerebral activation levels via the use of enriched Virtual Environments (VEs). However, 10 years on, this intuitively appealing concept has received almost no attention from researchers and clinicians alike. This paper overviews recent research on the benefits of enriched environments in the injured brain and identifies the potential and challenges associated with implementing VR-based enrichment in paediatric neuropsychological rehabilitation.

[Non-aggressive diagnostic approach to invasive pulmonary aspergillosis in a hematology unit. Retrospective analysis of a series of 16 cases]. / Approche diagnostique non agressive de l'aspergillose pulmonaire invasive en hématologie. Analyse rétrospective d'une série de 16 cas.

PURPOSE: Among neutropenic patients, diagnosis of invasive pulmonary aspergillosis is difficult. Computed tomographic scan, bronchoalveolar lavage and histology are considered invasive procedures, because they represent an infectious risk for these immunocompromised patients. METHODS: We describe the clinical and noninvasive paraclinical (X-rays, serology) signs of invasive pulmonary aspergillosis, from a retrospective study of 16 cases in a haematology unit. RESULTS: Outside of fever and chills, cough and polypnea are the earliest signs, followed by chest pain, dyspnea, lung auscultation changes, and haemoptysis. The sensitivity of each sign is higher than 56%. Before the onset of lung auscultation changes, the chest X-ray shows mainly unilateral alveolar infiltrates. Sensitivity of serology is weak (25%), but contributed to early diagnosis in 16.6% of cases. CONCLUSION: A better knowledge of the invasive pulmonary aspergillosis clinical, radiological and serological signs could help the practician to prescribe an 'invasive' investigation (computed tomographic scan, bronchoalveolar lavage) to confirm the diagnosis of this fungal infection.

Age-related telomere shortening occurs in lens epithelium from old rats and is slowed by caloric restriction.

We have investigated whether the average relative telomere length of lens epithelial cells (LECs) from brown Norway rats decreases with the age of the donor animal, and whether chronic caloric restriction (CR) of the rats delays the telomere shortening. Our previous studies have demonstrated that clonal proliferative potential of rodent LECs as well as the in vivo rate of DNA synthesis decreases with age and that this decrease is slowed by chronic lifelong caloric restriction (CR). In order to determine if telomeric shortening might be involved in this loss of proliferative potential, we examined relative telomeric lengths in young, old ad lib fed (AL), and old calorically restricted (CR) brown Norway rats. We used fluorescence in situ hybridization with a peptide nucleic acid probe (PNA) complementary to the telomeric repeat sequence to quantitate relative telomere lengths in LECs in lens sections (TELO-FISH). Control experiments demonstrated that the PNA probe binding was restricted almost entirely to the terminal portions of the rat chromosomes with less than 5% bound at interstitial sites in typical metaphase spreads. The relative telomere lengths of interphase human fibroblast standards, as determined by TELO-FISH, were in good agreement with terminal restriction fragment analyses of the same standards and with literature values for rat cells. The average telomere lengths of interphase nuclei in the old AL rat LECs were found to be 21% shorter than paired young AL controls (P < 0.01 by Wilcoxian signed rank test). The calorically restricted old rats had less telomere erosion (12%) than the old AL group (P < 0.05). Although it is not clear whether such moderate telomeric erosion can limit cell division in rodent LECs, the telomeric shortening correlated well with previous studies demonstrating reduced clonal, replicative potential, and reduced rates of in vivo DNA replication in LECs from old rodents and a delay in this attenuation in animals on chronic CR.

The effect of high and very low fluorescent light exposure levels on age-related cataract in a pigmented mouse strain.

This study examined the effect of fluorescent light on the timing and severity of age-related cataracts in a fully pigmented mouse strain, the (C57BL/6 x C3H)F1, that normally develops slowly progressing age-related cataracts only beyond middle age. Two groups of 56 animals each were exposed, respectively, either to a daily range of 66-222 foot candles (FC) or to 1 FC of standard fluorescent lighting for a period beginning at 5 weeks of age and ending at 33.5 months (by which time approximately 65% of the colony had died). Contrary to previous reports involving albino rats or mice and a strain of pigmented but cataract-prone transgenic mice, the two groups of animals in this experiment did not differ for cataract development in time of first occurrence, rate of advancement, or degree of severity. It was concluded that genetic predisposition, based on levels of oxidative free radical production vs antioxidant enzyme and repair enzyme protection in the lens, was probably the major factor governing the rate and degree of age-related cataract development in these animals. The effect of relatively intense life-long fluorescent light exposure was so minimal as not to be manifested in this strain of mice under the conditions of this experiment. Remarkably, maintaining the one group of mice in semi-darkness from 5 weeks of age to beyond their mean lifespans did nothing to delay or reduce the incidence or severity of their age-related cataracts.

Chronic illness: trauma, language, and writing: breaking the silence.

In our work with families that struggle with a chronic illness, we have relied on three ideas. First, we regard illness as a relationally traumatizing experience, not just for the person with the illness, but for other members of the family as well. We use the phrase "relational trauma" because of its effects on members of a wider system who also show signs of physical stress, isolation, and helplessness (Sheinberg & Fraenkel, 2000). Our second concern is how the conversation that leads to new stories is expanded through the development of voice and the use of writing. Looking at language, we are particularly attentive to the social prevalence of negative metaphors that surround and engulf the ill person and her family: dependence, poor genes, repressed personalities, weak constitutions, et cetera (Sontag, 1984). These negative metaphors, or outside voices, join with the inner voices of the ill person and result in a silence that disconnects people at a time when connections must be relied on and above question. Our third emphasis is on the use of writing as the means to create new voices, metaphors, and multiple descriptions that can reinvigorate the conversations silenced by the illness. Once the family's voices are reconstituted through writing, the emotions that have been displaced by the illness are restored to their conversation. I have included new research from JAMA detailing the treatment of patients with chronic illness through their use of writing.

Training in virtual environments: transfer to real world tasks and equivalence to real task training.

Virtual environments (VEs) are extensively used in training but there have been few rigorous scientific investigations of whether and how skills learned in a VE are transferred to the real world. This research aimed to measure and evaluate what is transferring from training a simple sensorimotor task in a VE to real world performance. In experiment 1, real world performances after virtual training, real training and no training were compared. Virtual and real training resulted in equivalent levels of post-training performance, both of which significantly exceeded task performance without training. Experiments 2 and 3 investigated whether virtual and real trained real world performances differed in their susceptibility to cognitive and motor interfering tasks (experiment 2) and in terms of spare attentional capacity to respond to stimuli and instructions which were not directly related to the task (experiment 3). The only significant difference found was that real task performance after training in a VE was less affected by concurrently performed interference tasks than was real task performance after training on the real task. This finding is discussed in terms of the cognitive load characteristics of virtual training. Virtual training therefore resulted in equivalent or even better real world performance than real training in this simple sensorimotor task, but this finding may not apply to other training tasks. Future research should be directed towards establishing a comprehensive knowledge of what is being transferred to real world performance in other tasks currently being trained in VEs and investigating the equivalence of virtual and real trained performances in these situations.

Neovascularization in aged mice: delayed angiogenesis is coincident with decreased levels of transforming growth factor beta1 and type I collagen.

Angiogenesis, the growth of new vessels from existing microvasculature, is delayed in aged animals. In this study we asked whether this impairment might be due, in part, to changes in the expression of a growth factor, transforming growth factor-beta1 (TGF-beta1), and a matrix protein, type I collagen, which have been shown to regulate angiogenesis in vivo. We implanted polyvinyl alcohol sponges subcutaneously in the dorsa of young and aged mice and examined the sponges 7 to 21 days later for the presence of invasive fibrovascular bundles. Blood vessel ingrowth and proliferative activity were assessed by immunostain for von Willebrand factor and Ki-67, respectively. The fibrovascular bundles were also analyzed for TGF-beta1 and type I collagen. Relative to young mice, angiogenic invasion of sponges in aged mice was similar at 7 days, was diminished significantly (70%) at 14 days, but was again similar by 21 days after implantation. The expression of TGF-beta1 and type I collagen mRNA and protein in fibrovascular bundles was coincident but was also delayed (42 to 47%) at 14 days in the aged mice. Moreover, levels of active TGF-beta1 were decreased (48%) in the sera of aged relative to young mice. The delay in angiogenesis in aged mice was thus associated with decreased expression of TGF-beta1 and type I collagen by neovascular bundles. We conclude that changes in the levels of growth factors and proteins in the extracellular matrix contribute to impaired angiogenesis in aging.

Rape flashbacks: constructing a new narrative.

This article offers an approach to the dissolution of rape flashbacks when the usual treatment of talk and group support doesn't work. The client, with her family, constructs a new rape scenario to replace her abusive story. In the new story, the client introduces a chosen protective figure into the flashback, which has the effect of interrupting the old scenario so that it cannot take place in the same way again. This approach relies on the client finding a new or freed voice in the treatment conversations in order to tell her story differently. The new, repopulated story eventually has the effect of altering her memory and renewing her life direction and belief in herself.

Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice.

Aged mice that have undergone long-term caloric-restriction (CR) have improved health and enhanced longevity in comparison to aged mice that are ad libitum-fed (AL). However, caloric-restriction does not benefit the impaired wound healing of aged mice. To test the hypothesis that CR mice have the capacity for enhanced wound repair, but require a short-term period of additional nutrient intake to show this advantage, we assessed wound healing in CR mice that had been refed (RF) an ad libitum diet for 4 weeks prior to wounding. Two strains of AL young (Y AL) (4-6 months), AL middle-aged (M AL) (15-17 months), and three different, matched cohorts of old mice (O) (30-33 months): O AL, O CR, and O RF were studied. Two full-thickness 4 mm diameter punch biopsy skin wounds were created on the dorsum of each mouse. Animals were sacrificed and wounds were harvested at 1,2,3,5, and 7 days post-wounding. Repair of wounds was slower in O AL and O CR mice compared to Y AL and M AL animals. In contrast, the O RF mice healed similarly to that of the Y AL and M AL mice, as assessed by measures of wound area and histologic criteria. O RF mice demonstrated enhanced synthesis of type I collagen mRNA in comparison to O AL and O CR mice. A greater number of endothelial cells and fibroblasts at the wound edge of the O RF mice exhibited replication in vivo as measured by uptake of BrdU. O RF mice had higher levels of insulin-like binding protein 3 (IGFBP-3). Furthermore, fibroblasts derived from the explant of the punch biopsy of O CR mouse skin revealed enhanced proliferation and contraction in vitro, in comparison to fibroblasts from the O AL mice. In conclusion, O RF mice demonstrate an enhanced capacity to undergo wound repair in comparison to O AL mice. This effect appears to be mediated, in part, by enhanced cell proliferation, contraction, and collagen biosynthesis. In addition, short-term refeeding induced an increase in the serum level of IGFBP-3, the major binding protein for IGF-1. These data confirm that cells from O CR animals have a preserved proliferative, biosynthetic, and contractile capacity, but that an adequate source of nutrients is necessary to demonstrate this advantage in wound healing.

Caloric restriction: conservation of in vivo cellular replicative capacity accompanies life-span extension in mice.

In male mice of a long-lived hybrid strain (B6D2F1), long-term 40% caloric restriction (CR) extended both mean and maximum life spans by 36 and 20%, respectively, over that of ad libitum fed (AL) controls. Measurements of entry into S-phase were made in vivo of six different cell types in five different organs using 2-week exposures to BrdU. The labeling index (L.I.) in all organs studied was lower in young CR mice than in young AL fed mice. In most cases, the L.I. in AL mice fell to the levels of that in the CR mice by 13 months of age, and the two groups then remained so through old age. However, when the L.I. was measured in old CR mice which had been placed on the AL diet for a period of 4 weeks (this was termed refeeding (RF), it was found to be above that of similar age AL or CR mice and almost at the level of young AL mice. This was still true, but to a lesser degree, in a repeat study using an 8-week period of RF. In a separate but parallel in vitro study (companion paper, this volume), the superiority of CR over AL for retention of cellular replication capacity was confirmed by clone size distribution measurements made in several cell types in mice of several age groups. These results indicate that: (1) the rate of cell replication in AL diet mice diminishes greatly by early middle age in all organ sites studied and then plateaus or declines much more slowly; (2) CR broadly preserves in vivo cellular replicative capacity but often requires the energy levels provided by a switch to AL feeding to demonstrate this late in life; (3) accordingly, the replicative deficit in AL fed mice appears to be cumulative and is significant only in old age. The mechanism(s) involved is yet to be discovered but may be related to, or even the same as, that which extends life spans in CR animals. Correspondingly, and with corroborative data from our in vitro companion study, (W. R. Pendergrass et al., 1995. Exp. Cell. Res. 217, 309-316), we suggest that cell populations sustain an accrual of biochemical damage or physiological alterations which increasingly limit their replicative capacity as the animal ages, and that CR reduces the accrual of this damage.

Creating a participant text: writing, multiple voices, narrative multiplicity.

This article uses the ideas of social constructionism to explore how families change by investigating the way our perceptions of ourselves in relation to others are formed through language. The idea that language has the inherent potential to generate a reply has strongly influenced our thinking. We propose that the reply to others is shaped by our initial reply to ourselves in inner conversation. Interaction moves back and forth from inner conversation to conversation with others, from monologue to dialogue, becoming the "stuff" of new narratives. The particular focus on language in this article is on how adding writing to the session conversation produces a "participant text," a therapeutic narrative that is composed of the voices of the family and the therapists. These voices, often newly discovered or invented, allow our narrative discourse to expand and multiply. Using this approach with individuals, couples, and families from different socioeconomic levels, we have worked with mourning, divorcing couples, recovery from abuse, marital conflict, parenting dilemmas, and physical illness.

Extracellular fibrinogenolytic enzyme of Aspergillus fumigatus: substrate-dependent variations in the proteinase synthesis and characterization of the enzyme.

To get a better understanding of the role of the previously reported fibrinogenolytic enzyme of Aspergillus fumigatus, we investigated the in vitro conditions of enzyme synthesis and attempted to characterize it. Modification of the nitrogen source did not influence the extracellular serine-proteinase profile, but resulted in important quantitative differences in the yields in batch cultures. The enzyme synthesis appeared to be an inducible phenomenon in A. fumigatus since it was initiated exclusively in the presence of proteins or protein hydrolysate. Free amino acids or inorganic nitrogen compounds could not promote significant enzyme production. Moreover, peptone at a concentration of 0.1% appeared to be the best inducer of enzyme synthesis. Conversely, modification of the carbon source did not affect fungal growth or enzyme synthesis. However, the production of chymotrypsin was highly sensitive to the carbohydrate level in the culture medium and, with peptone as nitrogen source, highest yields were obtained in the presence of 0.3 or 0.5% glucose. Culture filtrates of A. fumigatus CBS 113.26 grown with peptone or nitrate as nitrogen source were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Comparison of the protein patterns suggested for the proteinase a molecular mass of 33 kDa which was confirmed by chromatographic purification of the enzyme through (N alpha-CBZ)-D-phenylalanine agarose.

Dissecting the hematopoietic microenvironment. IX. Further characterization of murine bone marrow stromal cells.

We have previously shown the adherent nontransformed, nonimmortalized murine bone marrow stromal cell (BMSC) population to consist of phagocytic macrophage and endothelial-like cells and nonphagocytic fibroblasts. Both colonial and near confluent growth of each cell type was obtained following magnetic bead separation, subsequent passaging, and sustained culture with fetal bovine serum and cytokines. Monoclonal antibody staining of antigenic determinants was used to characterize the phenotype of the stromal cell population in primary platings of murine colony-forming unit fibroblast and long-term bone marrow cultures. The antibodies MECA-99, MECA-32, and MJ7-18, raised against murine vascular endothelial antigenic determinants, and von Willebrand's factor all stained selectively for the rounded endothelial-like cells. Endothelial-like cells as well as macrophages expressed the myeloid surface antigens F4/80, 7/4, and Mac-1 under our culture conditions. The cytoskeleton of the stromal fibroblasts in culture was shown to express smooth muscle-specific actin isoforms, as evidenced by positive staining of stress fibers for alpha smooth muscle-1, CGA-7 (alpha/gamma isoforms), and HHF-35 (recognizes all muscle-specific actins). Under culture conditions, stromal fibroblasts were also found to be positive for a polyclonal smooth muscle myosin. It was found that these fibroblasts stained for collagens type I, III, and IV in our cultures. Although collagen type IV is considered a by-product of endothelial cells, endothelial-like cells in our cultures did not stain for any of the collagen types. We propose a classification listing for murine BMSCs as macrophages, endothelial-like cells, and fibroblasts that display smooth muscle-like characteristics in culture.

Simultaneous concept analysis of spiritual perspective, hope, acceptance and self-transcendence.

This paper seeks to clarify four previously elusive concepts of concern to nurses: spiritual perspective, hope, acceptance and self-transcendence. Simultaneous concept analysis (SCA), a method developed by the authors, was used to generate a process model of antecedents, critical attributes and outcomes of all four concepts. This resulted in refined theoretical definitions for each concept. Interrelationships that became apparent among the concepts are discussed and implications of these interrelationships for theory and measurement are presented.

Love and violence: gender paradoxes in volatile attachments.

This article presents a multidimensional, theoretical model for the understanding of relationships in which men are violent toward women. It argues that abusive relationships exemplify, in extremis, the stereotypical gender arrangements that structure intimacy between men and women generally. Moreover, it proposes that paradoxical gender injunctions create insoluble relationship dilemmas that can explode in violence. A multifaceted approach to treatment, which incorporates feminist and systemic ideas and techniques, is described.

A method to establish pure fibroblast and endothelial cell colony cultures from murine bone marrow.

Studies on the effect of the microenvironment on hematopoiesis would benefit from the availability of pure populations of nontransformed cells of each of the stromal cell types. The adherent murine bone marrow stromal cell population in this study consisted of fibroblasts, endothelial cells, and macrophages. Fibroblasts were segregated from the phagocytic endothelial cells and macrophages by allowing the phagocytic cells to ingest magnetic beads, with subsequent exposure to a magnetic field, effecting cell separation. Pure colony cultures of fibroblasts and endothelial cells were formed by varying the bead-to-cell ratio and incubation period of the cells. For complete purification of the fibroblasts, subsequent passaging was also necessary. Near confluent growth of each type was obtained with subsequent passages and sustained culture. The cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was used to enhance endothelial cell growth. We were not able to obtain pure populations of bone marrow macrophages in near confluent culture. The three cell types were identified by cellular morphology, acid and alkaline phosphatase staining, binding with the lectins Ulex europaeus and Bandeiraea simplicifolia, and the capacity to stain for the factor VIII-related antigen (von Willebrand's Factor).

Intervention factors for promoting adjustment to nightwork and shiftwork.

This chapter reviews a broad range of factors that, if controlled, might promote adaptation to nightwork, shiftwork, and extended workshifts. Systematic study has begun in four of the areas reported here: work schedule design, napping, bright light stimulation, and drugs. Physical activity, ambient temperature, diet, and individual behaviors have been studied only superficially.