Health-related quality of life after general surgical intensive care.

BACKGROUND: Impaired mental and physical health are common complications after intensive care that could influence the patient's health-related quality of life (HRQoL). Earlier research has mainly focused on HRQoL in mixed surgical and medical ICU populations. This study aimed to describe and analyze factors associated with HROoL after discharge from a general surgical ICU. METHODS: A prospective cohort study was conducted in a general surgical ICU in Sweden between 2005 and 2012. Adult patients (≥18 years) with an ICU length of stay ≥96 hours were included. HRQoL was measured at 3, 6, and 12 months after discharge from the ICU using a questionnaire (SF-36). A linear mixed model was used to analyze changes over time and Wilcoxon Signed Rank Tests were used to compare the 12-months results to an age and gender matched reference population in Sweden. Linear regression analyses were performed to explore the impact on HRQoL from background variables. RESULTS: Of 447 patients eligible for the study, 276 patients (62%) answered SF-36 at least once at 3, 6 or 12 months after ICU care and were included in the study. HRQoL improved over time but was still significantly lower at 12 months compared to the reference population. Female gender, age <75 years, living single, and ICU-stay of more than 14 days were associated with lower HRQoL. CONCLUSION: General surgical ICU patients reports low HRQoL 1 year after ICU stay. The impaired HRQoL could be a long-lasting problem with major consequences for the individual, family, and society.

Spatial and temporal trends of bat-borne rabies in Chile.

In Chile, while dog rabies has decreased markedly over the last 30 years, bat rabies is still reported frequently. In order to shed new light on the spatiotemporal trends of these reports, we analysed active and passive data from years 1985 and 2012, which included 61 076 samples from 289 counties of Chile. We found that from 1994 to 2012, more than 15 000 bat samples were submitted for diagnostics through passive surveillance, 9·5% of which tested positive for rabies. By contrast, the prevalence of infection was only ~0·4% among the nearly 12 000 bat samples submitted through active surveillance. We found that the prevalence of dog rabies dropped steadily over the same period, with just a single confirmed case since 1998. None of the 928 samples from wild animals, other than bats, were positive for rabies. Although there has been only one confirmed case of human rabies in Chile since 1985, and a single confirmed case in a dog since 1998, bats remain a reservoir for rabies viruses. While active surveillance indicates that rabies prevalence is low in bat colonies, the high proportion of positive bats submitted through passive surveillance is a concern. To prevent human rabies, local public health agencies should increase research on the basic ecology of bats and the role of stray dogs and cats as potential rabies amplifiers.

A calcium prerinse required to form calcium fluoride in plaque from a sodium fluoride rinse.

The purpose of this study is to determine whether a calcium (Ca) prerinse used before a 228 µg/g (ppm) fluoride (F) rinse would induce the formation of 'calcium fluoride-like' (CaF2-like) deposits in human dental plaque. Sixty minutes after the use of the Ca prerinse/F rinse, plaque samples were collected from 10 volunteers, homogenized, and split into 2 aliquots. The plaque mass from one aliquot was then extracted with a 'plaque-like' solution that extracted all the CaF2-like deposits. The total F in both aliquots was then determined and compared. The results demonstrated that, as in previous studies, the Ca prerinse induced large increases in plaque fluid and total plaque F. However, unlike previous results without the Ca prerinse, 30% of the plaque F deposits were CaF2 or CaF2-like. Given that maintaining an elevated F concentration in the vicinity of a developing lesion may play an important role in the cariostatic effect of this ion, and the potential advantages of CaF2-like deposits as an F source, these results suggest that a Ca prerinse may increase the cariostatic effect of topical agents.

Protection from articular damage by passive or active anti-tumour necrosis factor (TNF)-α immunotherapy in human TNF-α transgenic mice depends on anti-TNF-α antibody levels.

Active anti-tumour necrosis factor (TNF)-α immunization with the kinoid of TNF-α (TNF-K) induces polyclonal anti-TNF-α antibodies and ameliorates arthritis in human TNF-α (hTNF-α) transgenic mice (TTg). We compared the efficacy of TNF-K to that of infliximab (IFX) and of TNF-K and IFX co-administration, and evaluated whether the titres of anti-hTNF-α antibodies induced by immunization were a determinant of TNF-K efficacy. Forty-eight TTg mice received one of the following treatments: TNF-K immunization (TNF-K group); weekly IFX throughout the study duration (IFXw0-15); TNF-K plus weekly IFX for 4 weeks (TNF-K + IFX); and weekly IFX for 4 weeks (IFXw0-4); PBS. Animals were killed at week 16. Anti-hTNF-α antibody titres and clinical and histological scores were compared. All TNF-K immunized mice (TNF-K and TNF-K + IFX) produced anti-hTNF-α antibodies. Titres were higher in TNF-K versus TNF-K + IFX (P < 0·001) and correlated inversely with histological inflammation (R = -0·78; P = 0·0001) and destruction (R = -0·67; P = 0·001). TNF-K + IFX had higher histological inflammation and destruction versus TNF-K (P < 0·05). A receiver operating characteristic (ROC) analysis of anti-hTNF-α antibody titres identified the criterion cut-off value to discriminate most effectively between the TNF-K and TNF-K + IFX groups. Mice with high versus low titres had less histological inflammation and destruction (P < 0·05). In a model of TNF-α-dependent arthritis, protection from articular damage by TNF-K correlates with the titres of induced anti-hTNF-α antibodies. The co-administration of TNF-K and a short course of infliximab does not result in less articular damage versus solely TNF-K, due probably to lower anti-hTNF-α antibody production. These results are relevant for future development of active anti-TNF-α immunization in human disease.

Phytophthora capsici: Recent Progress on Fundamental Biology and Disease Management 100 Years After Its Description.

Phytophthora capsici is a destructive oomycete pathogen of vegetable, ornamental, and tropical crops. First described by L.H. Leonian in 1922 as a pathogen of pepper in New Mexico, USA, P. capsici is now widespread in temperate and tropical countries alike. Phytophthora capsici is notorious for its capability to evade disease management strategies. High genetic diversity allows P. capsici populations to overcome fungicides and host resistance, the formation of oospores results in long-term persistence in soils, zoospore differentiation in the presence of water increases epidemic potential, and a broad host range maximizes economic losses and limits the effectiveness of crop rotation. The severity of disease caused by P. capsici and management challenges have led to numerous research efforts in the past 100 years. Here, we discuss recent findings regarding the biology, genetic diversity, disease management, fungicide resistance, host resistance, genomics, and effector biology of P. capsici.

Human skin Langerhans cells are targets of dengue virus infection.

Dengue virus (DV), an arthropod-borne flavivirus, causes a febrile illness for which there is no antiviral treatment and no vaccine. Macrophages are important in dengue pathogenesis; however, the initial target cell for DV infection remains unknown. As DV is introduced into human skin by mosquitoes of the genus Aedes, we undertook experiments to determine whether human dendritic cells (DCs) were permissive for the growth of DV. Initial experiments demonstrated that blood-derived DCs were 10-fold more permissive for DV infection than were monocytes or macrophages. We confirmed this with human skin DCs (Langerhans cells and dermal/interstitial DCs). Using cadaveric human skin explants, we exposed skin DCs to DV ex vivo. Of the human leukocyte antigen DR-positive DCs that migrated from the skin, emigrants from both dermis and epidermis, 60-80% expressed DV antigens. These observations were supported by histologic findings from the skin rash of a human subject who received an attenuated tetravalent dengue vaccine. Immunohistochemistry of the skin showed CD1a-positive DCs double-labeled with an antibody against DV envelope glycoprotein. These data demonstrate that human skin DCs are permissive for DV infection, and provide a potential mechanism for the transmission of DV into human skin.

Detection of adeno- and lentiviral (HIV1) contaminations on laboratory surfaces as a tool for the surveillance of biosafety standards.

AIMS: As a biosafety laboratory, we survey the handling of adenovirus type 5 (Ad5) and HIV1-derived lentivirus in contained-use facilities in Switzerland to identify insufficiencies of the safety precautions taken by the laboratories. METHODS AND RESULTS: In the past 9 years, we took 430 swab samples from various types of surfaces in research laboratories. Samples were examined for Ad5 contaminations by real-time PCR and infectivity assay or for the presence of lentivirus (HIV1) nucleic acids by real-time (RT) PCR. Samples collected from centrifuges did not only contain Ad5 DNA more frequently but also exhibited higher numbers of Ad5 and lentiviral (HIV1) DNA copies than swabs from any other area of sampling. Five of ten samples containing infectious Ad5 particles or lentivirus (HIV1) RNA were found in samples taken from centrifuges. Ad5 contamination rates were higher in the tube holder and lower on the inner wall of the rotor chamber in centrifuges that were fitted with aerosol tight covers compared to centrifuges without covers. CONCLUSIONS: Our results allowed the comparison of hygiene standards of different laboratories and lead to the identification of centrifuges as hotspots for contaminations. SIGNIFICANCE AND IMPACT OF THE STUDY: Based on our results, we propose to use the collected data as a tool for rating future swab results. Furthermore, the amount of Ad5 and HIV1-derived lentivirus DNA could serve as an indicator of the level of good laboratory practice in contained-use laboratories handling these viral vectors.

Contaminations of laboratory surfaces with Staphylococcus aureus are affected by the carrier status of laboratory staff.

AIM: As a biosafety laboratory, we take samples from surfaces in microbiological laboratories to survey the handling of micro-organisms. Whereas contaminations with other micro-organisms were rare, Staphylococcus aureus was found in the working environment of many laboratories. As 20-60% of the healthy population are carriers of S. aureus we wanted to asses the effect of carriers on our sampling results. METHODS AND RESULTS: Nasal swabs of staff members in nonmicrobiological laboratories and offices as well as surface samples from their personal work environment were taken and analysed for S. aureus DNA. In addition S. aureus strains were isolated using S. aureus-specific agar plates and analysed by randomly amplified polymorphic DNA (RAPD)-PCR and multilocus sequence typing (MLST). Our data show that contaminations with S. aureus in nonmicrobiological environments are common with 29% of the surface samples containing S. aureus DNA. In the working environment of carriers, the number of contaminations was significantly increased compared to the environment of noncarriers. CONCLUSION: The carrier status of staff members significantly affects the number of contaminations on laboratory surfaces. Therefore, even in the absence of intentional handling of S. aureus, contaminations can be detected on a substantial amount of surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: Sampling procedures need to be adapted based on these results with respect to the locations where samples are taken and the threshold for significant contaminations. Because of its wide distribution, S. aureus can serve as a marker for hygienic standards in laboratories.

No calcium-fluoride-like deposits detected in plaque shortly after a sodium fluoride mouthrinse.

Plaque 'calcium-fluoride-like' (CaF(2)-like) and fluoride deposits held by biological/bacterial calcium fluoride (Ca-F) bonds appear to be the source of cariostatic concentrations of fluoride in plaque fluid. The aim of this study was to quantify the amounts of plaque fluoride held in these reservoirs after a sodium fluoride rinse. 30 and 60 min after a 228 microg/g fluoride rinse, plaque samples were collected from 11 volunteers. Each sample was homogenized, split into 2 aliquots (aliquots 1 and 2), centrifuged, and the recovered plaque fluid combined and analyzed using microelectrodes. The plaque mass from aliquot 1 was retained. The plaque mass from aliquot 2 was extracted several times with a solution having the same fluoride, calcium and pH as the plaque fluid in order to extract the plaque CaF(2)-like deposits. The total fluoride in both aliquots was then determined. In a second experiment, the extraction completeness was examined by applying the above procedure to in vitro precipitates containing known amounts of CaF(2)-like deposits. Nearly identical fluoride concentrations were found in both plaque aliquots. The extraction of the CaF(2)-like precipitates formed in vitro removed more than 80% of these deposits. The results suggest that either CaF(2)-like deposits were not formed in plaque or, if these deposits had been formed, they were rapidly lost. The inability to form persistent amounts of CaF(2)-like deposits in plaque may account for the relatively rapid loss of plaque fluid fluoride after the use of conventional fluoride dentifrices or rinses.

[Adenovirus keratoconjunctivitis acquired in an ophthalmology clinic]. / Queratoconjuntivitis por adenovirus generadas a partir de una consulta oftalmológica.

INTRODUCTION: Eye infection is a common cause of ophthalmologic consultation. Adenovirus keratoconjunctivitis outbreaks are common worldwide but its impact and clinical characteristic in Chilean population is unknown. OBJECTIVE: To describe a series of adenovirus keratoconjunctivitis cases. PATIENTS AND METHOD: The Index case and contacts received medical care in the Hospital Clínico Universidad de Chile between April and August 2006. A complete ophthalmologic exam and microbiologic evaluation was performed. RESULTS: Nine patients presented a pattern of characteristic epidemic keratoconjunctivitis. In x cases sub-corneal epithelial infiltrates were observed for a period of more than six months. Three affected patients were ophthalmologists, staff at the Hospital. In seven patients ADV was isolated all belonging to type D genus. CONCLUSIONS: Adenovirus type D caused epidemic keratoconjunctivitis in a series of Chilean individuals. Ophthalmologist may have transmitted the virus to patients.

Cytokinesis is defective in Dictyostelium mutants with altered phagocytic recognition, adhesion, and vegetative cell cohesion properties.

Mutants that have been selected for defects in phagocytic recognition, adhesion, and vegetative cell-cell cohesion were found to be larger and more highly multinucleate than their parent strain. This defect is associated with the complex mutant phenotype of these mutants since revertants of the mutants coordinately acquire the wild-type phenotype for all of the defects. The larger size and multinuclearity were due to a high frequency of failure of cytokinesis in cells of wild-type size. This was shown by purifying the small cells in mutant populations and observing their growth and cell division. The mutant phenotype is more penetrant during axenic growth. Most of the mutants are not multinucleate when grown on bacteria. Recently, new mutants have been isolated that are also multinucleate when grown on bacteria by a strong selection procedure for non-adhesion to tissue culture dishes. The pleiotropic mutant phenotype and the greater penetrance of the mutant phenotype in axenic culture can be explained by hypothesizing a deficiency in a membrane component of the actomyosin motor that is involved in all of the processes defective in the mutants.

Mechanism of phagocytosis in Dictyostelium discoideum: phagocytosis is mediated by different recognition sites as disclosed by mutants with altered phagocytotic properties.

The recognition step in the phagocytotic process of the unicellular amoeba dictyostelium discoideum was examined by analysis of mutants defective in phagocytosis, Reliable and simple assays were developed to measure endocytotic uptake. For pinocytosis, FITC-dextran was found to be a suitable fluid-phase marker; FITC-bacteria, latex beads, and erythrocytes were used as phagocytotic substrates. Ingested material was isolated in one step by centrifuging through highly viscous poly(ethyleneglycol) solutions and was analyzed optically. A selection procedure for isolating mutants defective in phagocytosis was devised using tungsten beads as particulate prey. Nonphagocytosing cells were isolated on the basis of their lower density. Three mutant strains were found exhibiting a clear-cut phenotype directly related to the phagocytotic event. In contrast to the situation in wild-type cells, uptake of E. coli B/r by mutant cells is specifically and competitively inhibited by glucose. Mutant amoeba phagocytose latex beads normally but not protein-coated latex, nonglucosylated bacteria, or erythrocytes. Cohesive properties of mutant cells are altered: they do not form EDTA-sensitive aggregates, and adhesiveness to glass or plastic surfaces is greatly reduced. Based upon these findings, a model for recognition in phagocytosis is proposed: (a) A lectin-type receptor specifically mediates binding of particles containing terminal glucose (E. coli B/r). (b) A second class of "nonspecific" receptors mediate binding of a variety of particles by hydrophobic interaction. Nonspecific binding is affected by mutation in such a way that only strongly hydrophobic (latex) but not more hydrophilic particles (e.g., protein-coated latex, bacteria, erythrocytes) can be phagocytosed by mutant amoebae.

NIH guidelines. Researchers get green light for work on stem cells.

The National Institutes of Health (NIH) issued final guidelines last week allowing NIH-funded researchers to derive human pluripotent stem cells from fetal tissue, but not from embryos. Scientists may also work with embryonic stem cells, but may obtain them only from private sources and must ensure that derivation meets certain ethical conditions. The NIH spent nearly a year finalizing the guidelines, which researchers hope will allow work leading to the improved treatment of diabetes, Parkinson's, and other diseases.

Society for Developmental Biology meeting. A mile-high view of development.

BOULDER, COLORADO--Nearly 600 scientists gathered at the base of the Flatirons to discuss the growth and patterning of organisms including plants, worms, fruit flies, fish, and mice at the 59th annual meeting of the Society for Developmental Biology. Among the highlights were clues about how blind cave fish lost their eyes and how a gene that influences cell movement might help cancer spread.

Endangered species. Migrating otters push law to the limit.

Fourteen years ago, Congress declared the Southern California coast an otter-free zone--but the unwitting creatures aren't cooperating. That's no surprise to federal biologists, who this summer issued a report concluding that the otter-free zone harms the already-endangered population. Federal officials are now trying to come up with a better plan, but it's likely to draw from politics as well as science.

Cell biology. Stem cells: new excitement, persistent questions.

On pages 1775 and 1779, independent research teams describe experiments in which bone marrow cells became neuronlike cells in the brain, providing new evidence for the versatility of adult stem cells. But ample uncertainties must be resolved before such results can be translated into therapeutics. The most important next step, say several stem cell researchers, is to identify the molecular processes that underlie the impressive feats of stem cells, as many of the purported breakthroughs are simply observations.

Cell biology. Stem cell scorecard.

As researchers continue to explore the potential uses of stem cells obtained from a variety of sources (see main text), governments around the world are grappling with whether to allow research on stem cells derived from human embryos. Governments are cautious yet increasingly open to the new research, which may eventually yield treatments for a variety of diseases from Parkinson's to diabetes.

Neurobiology. The come-hither, don't-touch-me proteins.

Two newly discovered receptors, Slit and Roundabout (Robo), help determine how far axons in developing fruit flies travel after they cross the line between the fly's left and right sides. In a pair of papers in the December issue of Neuron, two independent teams report that flies have two proteins very similar to Robo, called Robo2 and Robo3. In two more papers in this week's issue of Cell, both teams describe how the Robo proteins on an axon's cell membrane not only keep the axon from recrossing the midline but also help determine the particular path an axon takes.

Neuroscience. New brain cells prompt new theory of depression.

No one knows what causes depression, although many neuroscientists blame an imbalance of brain chemicals, so-called neurotransmitters, especially those that affect the brain's pleasure responses. Now a few neuroscientists are converging on a radical, but complementary, theory: that depression may be caused by a lack of new cell growth in the brain. The recent discovery that the brain keeps producing neurons into adulthood has given this highly speculative theory at least one leg to stand on.

African research. Against all odds, victories from the front lines.

In one of the world's poorest countries, a team of Malian and American researchers who have been monitoring malaria here since 1997 are attacking malaria both in the lab and in the clinic. The Bandiagara Malaria Project is also laying the groundwork for future trials of a hoped-for vaccine. The researchers' presence has already had a measurable effect: In the past few years, malaria deaths have been rare.