Attended with and head-turning sign can be clinical markers of cognitive impairment in older adults.

We read the paper by Soysal et al. (2017) with interest as we have experience of both the Attended With (AW) and the Head-Turning Sign (HTS) in a neurology-led cognitive disorders clinic.

Subtherapeutic voriconazole concentrations associated with concomitant dexamethasone: case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Voriconazole has significant drug interactions due to metabolism by CYP enzymes. Subtherapeutic voriconazole concentrations associated with concomitant dexamethasone are not well described. CASE DESCRIPTION: An 84-year-old male was started on voriconazole for a fungal brain abscess. He was readmitted due to clinical failure thought to be the result of subtherapeutic voriconazole concentrations. Dexamethasone was identified as a potential cause due to its induction of CYP enzymes. This interaction was substantiated by sequential troughs that demonstrated a rise in voriconazole concentrations as dexamethasone was tapered off. WHAT IS NEW AND CONCLUSION: Therapeutic drug monitoring for patients on voriconazole and dexamethasone is essential to prevent suboptimal clinical outcomes.

Clinical and microbiological implications of time-to-positivity of blood cultures in patients with Gram-negative bacilli bacteremia.

Time-to-positivity (TTP) is defined as the length of time from the beginning of culture incubation to the detection of bacterial growth by an automated system. The objective of this study was to assess the clinical and microbiological implications of TTP among patients with Gram-negative bacilli (GNB) bacteremia. This was a prospective, single-center, observational study. Patients aged 18 years or older with one or more blood cultures growing GNB were included and followed until hospital discharge or death. Patients were excluded if they were without symptoms of infection, if they had polymicrobial culture, or if the culture was positive with an obligate anaerobe. A multivariate logistic regression analysis was performed to determine the predictors of in-hospital mortality, including TTP (primary endpoint), demographics, disease severity, comorbidities, pathogen type, source of infection, time to symptom resolution, hospital/intensive care unit (ICU) length of stay, adequacy of empiric antibiotics, and presence of an extended-spectrum beta-lactamase (ESBL)-producing bacteria. One hundred consecutive patients with GNB bacteremia were enrolled. TTP was an independent predictor of mortality; for every hour that TTP was shorter, the risk of mortality increased by 10% [odds ratio (OR) 1.10, 95% confidence interval (CI) 1.00-1.21, p = 0.049]. Other predictors of mortality included severity of illness, ESBL-producing GNB, and ICU admission within 24 h before culture. Mortality was highest among patients with inadequate empiric therapy (56% vs. 14%, p < 0.001) and TTP <11 h (23.1% vs. 8.3%, p = 0.18). Lactose-fermenting GNB had a shorter mean TTP than non-lactose fermenters (11.4 vs. 17.9 h, p = 0.001). Among patients with bacteremia due to GNB, TTP values are inversely associated with mortality risk.

Adherence to the 2007 cystic fibrosis pulmonary guidelines: a national survey of CF care centers.

OBJECTIVE: To examine cystic fibrosis (CF) physician adherence to the 2007 CF Foundation (CFF) Pulmonary Guidelines for Chronic Medications. Specifically adherence and barriers to prescribing level A medication recommendations (i.e., inhaled tobramycin and dornase alfa) and level B medication recommendations (i.e., macrolide antibiotics and hypertonic saline) were studied. METHODS: During Spring 2010, the CFF emailed survey invitations to directors of 136 accredited CF care centers treating 50+ CF patients. Directors were asked to forward the invitations to their physician colleagues. One hundred thirty-three surveys were included in the analyses, representing 92 centers. Barriers were conceptualized based on Cabana et al.'s framework for adherence to guidelines. Adherence was assessed via a case vignette. RESULTS: Logistic regression analysis revealed that higher outcome expectancy (OR = 1.099, CI 1.010-1.196) and fewer environmental/system barriers (OR = 1.484, CI 1.158-1.902) were significantly associated with Vignette Adherence. A trend for an association between Familiarity and Vignette Adherence (OR = 1.642, CI 0.953-2.828) was evident, while no demographic variables were significantly associated with Vignette Adherence. CONCLUSION: Targeting outcome expectancy and external barriers with multifaceted, ongoing interventions may improve guideline adherence. Pulmonologists are clearly looking for empirical evidence that these medications benefit their patients over the long-term and offset patient treatment burden with improved health.

Heavy metal fractionation during the co-composting of biosolids, deinking paper fibre and green waste.

Due to the introduction of the European Union Landfill Directive, composting has become a potentially viable disposal route for some organic wastes. As waste-derived compost is frequently added to soil to improve soil quality, it is important to quantify the environmental risk posed by potentially toxic elements contained within it. Here we used a sequential chemical extraction procedure to investigate the temporal dynamics of heavy metals (Cu, Zn, Pb and Ni) during the co-composting of biosolids, deinking paper fibre and green waste. Overall, composting over 26 weeks reduced the availability of Ni, had no effect on Pb and slightly increased the availability of Cu and Zn. We conclude that although the total Cu and Ni concentrations in the compost exceed legislative guidelines for land application, due to their recalcitrant nature within the compost, this compost posed very little threat to soil or plant quality if used in agriculture or land restoration.

Contaminated land clean-up using composted wastes and impacts of VOCs on land.

This paper describes experiments that demonstrate the effects and potential for remediation of a former steelworks site in Wales polluted with polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Under field conditions, PAH-contaminated soil was composted in-vessel, with or without organic feedstocks, receiving forced aeration for 80 days followed by 4 months maturation. Treatments compared PAH removal in contaminated soil to contaminated soil mixed with three different organic waste mixes after composting and after composts were spread to land. After composting, PAH concentrations declined in all treatments, by up to 38%. Sixteen months after the composts were landspread and vegetation was established, only those containing contaminated soil with organic additions exhibited further PAH removal, by up to 29%. Composting resulted in a decline in the relative concentration of small PAHs, whereas the landspreading-vegetation phase saw a decline in the relative concentration of medium PAHs in two of the three composts exhibiting PAH removal. Under controlled glasshouse conditions, vegetated soil columns of differing depths were exposed to VOCs from beneath. VOC vapour affected both shoot and root growth and soil microbial activity; effects varied with distance from the VOC source. This work demonstrated that on-site remediation of aged PAH-contaminated land can be successfully initiated by in-vessel co-composting followed by land spreading and vegetation, within a practical timeframe.

Initial tree establishment on blocky quarry waste ameliorated with hydrogel or slate processing fines.

Pocket planting reclamation techniques developed in the 1970s for revegetating blocky quarrying waste have met with very limited success, often because the low water-holding capacity of the waste and limited root development within a small volume of planting pocket material result in severe drought mortality. We tested pocket planting approaches for waste tip reclamation at Europe's largest slate quarry, and compared materials for enhancing the continuity of water- and nutrient-holding down into the interior of the waste tip. When small compost-filled pocket planting bags were placed above slate processing fines (SPF) or water absorbent cross-linked polyacrylamide gel ("hydrogel"), tree growth rates increased in comparison with pocket planting bags alone. The SPF significantly improved tree survival especially during severe drought, but survival was not enhanced by the use of hydrogel. The sorption characteristics of hydrogel indicated that its presence may help to reduce nutrient leaching, but that it may have a negative effect on nitrogen availability. A more likely explanation for the poor performance of pure hydrogel is that it did not maintain sufficient available water, because of discontinuities caused by shrinkage and movement of the hydrogel, and/or degradation of water-holding capacity with environmental exposure. However, the root growth observed in the hydrogel treatments suggests that this technique, if adapted to reduce the effects of hydrogel shrinkage by using finer-grade hydrogel, mixing it with other soil-forming material, and reducing its exposure to extremes of temperature or sunlight, might have the potential to improve the growth and survival of trees planted on sites where delivery of heavy materials such as SPF is impractical. Fine mineral processing waste is freely available at active quarries and should be seen as a key resource for reclamation schemes.

Oxacillin-resistant Staphylococcus aureus endophthalmitis after ganciclovir intraocular implant.

PURPOSE: To describe a patient who developed oxacillin-resistant Staphylococcus aureus endophthalmitis after insertion of a ganciclovir intraocular implant. METHOD: Case report. RESULTS: A 42-year-old man with acquired immunodeficiency syndrome (AIDS) and a history of cytomegalovirus retinitis was admitted with right-sided eye pain and decreased visual acuity 10 days after receiving a second ganciclovir intraocular implant in the right eye. A therapeutic vitrectomy, right eye, was performed on the day of admission. A vitreal tap produced frank pus and white, fluffy debris. Cultures of the vitreal fluid grew oxacillin-resistant S aureus, sensitive only to vancomycin, rifampin, and trimethoprim/sulfamethoxazole. The patient was successfully treated with removal of both ganciclovir implants in the right eye and a 4-week course of vancomycin and rifampin. However, the infection left the patient blind in the infected eye. CONCLUSION: Bacterial endophthalmitis is an infrequent but serious complication of the ganciclovir intraocular implant.

Stability of cefepime in peritoneal dialysis solution.

OBJECTIVE: To determine the stability of cefepime in peritoneal dialysis solution. DESIGN: Cefepime HCl was added to premade bags of Delflex peritoneal dialysis solution with 1.5% dextrose to produce a cefepime concentration of approximately 100 microg/mL. Peritoneal dialysis solution bags were stored at 4, 25, and 37 degrees C to simulate refrigeration, room temperature, and body temperature, respectively. Samples were drawn at scheduled times up to 336, 168, and 48 hours, respectively, after the addition of cefepime HCl. Cefepime concentrations were measured by HPLC. SETTING: This study was performed at a university-affiliated tertiary care hospital. OUTCOME MEASURE: If the mean concentration of the samples at a given time and condition was >90% of the initial concentration, cefepime was considered stable at that time and condition. RESULTS: The mean HPLC results for samples drawn at each time and condition were all >90%. CONCLUSIONS: Cefepime is stable in peritoneal dialysis solution with dextrose 1.5% for 14 days refrigerated, seven days at room temperature, and 48 hours at 37 degrees C.

Bovine immunodeficiency virus tat gene: cloning of two distinct cDNAs and identification, characterization, and immunolocalization of the tat gene products.

cDNAs encoding the bovine immunodeficiency virus (BIV) transactivator gene (tat) were cloned from virally infected cells and characterized. BIV expresses two distinct tat mRNAs composed of three exons that are derived by alternative splicing. The BIV tat mRNA splice variants encode Tat proteins of 103 (Tat103) and 108 (Tat108) amino acids. The Tat103 coding region is specified only by exon 2, while that of Tat108 is specified by a truncated exon 2 and the first 30 nt of exon 3. Thus, the first 98 amino acids of each Tat are identical, and have amino terminal, cysteine-rich, conserved core, basic, and carboxyl-terminal domains similar to Tats encoded by primate lentiviruses. BIV-infected bovine cells express a 14-kDa phosphorylated Tat protein identical in size to recombinant Tat expressed in bacteria. BIV Tat was shown to localize exclusively in the nucleoli of virally infected and Tat-expressing cells. Reporter gene assays indicated that Tat103 and Tat108 can strongly transactivate the BIV long terminal repeat (LTR) in virally permissive canine Cf2Th and nonpermissive HeLa and mouse NIH 3T3 cells, but not in permissive lapine EREp cells. However, an intact BIV tat gene is required for viral replication in both Cf2Th and EREp cells. Strong LTR activation by BIV Tat requires a TAR (transactivation responsive) element delimited by viral nt +1 to +31 and the Tat basic domain. BIV Tat strongly cross-transactivates the HIV-1 LTR in a TAR-dependent manner in Cf2Th, but not in EREp, HeLa, or NIH 3T3 cells. In contrast, strong, TAR-dependent cross-transactivation of the BIV LTR by HIV-1 Tat could not be demonstrated in any of these cell types. In Cf2Th cells Tat108 effects a moderately stronger transactivation of the BIV LTR than Tat103, indicative of a functional difference in BIV Tat proteins encoded by the mRNA splice variants. The present studies demonstrate that BIV Tat parallels the primate lentiviral Tats in structure and biochemistry but is not interchangeable with the latter.

Synthesis and assembly of chimeric human immunodeficiency virus gag pseudovirions.

Expression of the HIV Gag precursor in insect cells by recombinant baculoviruses results in the assembly and budding of noninfectious pseudovirions that resemble immature virus. Three strategies for packaging additional viral epitopes into pseudovirions were examined: coinfection of insect cells with individual baculoviruses encoding separate Gag and Env structural genes, inframe Gag-Env fusion proteins, and Gag-frameshift-Env fusion proteins. Electron microscopy and Western blot analysis indicated that neither the coinfection nor the inframe fusion strategies reliably produced large quantities of structurally stable chimeric pseudovirions. The frameshift fusion method utilized the retroviral Gag-Pol ribosomal frameshift mechanism for the coexpression of Gag and Gag-frameshift-Env fusion proteins. Large quantities of pseudovirions containing both the Gag and Env epitopes were produced in insect cells. Mice inoculated with the Gag-frameshift-Env pseudovirions developed cytotoxic lymphocyte responses to both HIV Gag and Env epitopes. Vaccine and immunotherapeutic applications of chimeric pseudovirions are discussed.

Acid-base disorders: classification and management strategies.

Acid-base disorders are common in clinical practice. Simple acid-base disturbances include metabolic acidosis, metabolic alkalosis, respiratory acidosis and respiratory alkalosis. Each can be clearly identified using a common clinical approach. Proper understanding of acid-base disorders requires knowledge of normal physiology. Each of the simple acid-base disorders can be diagnosed by obtaining a good history and performing a physical examination, followed by determinations of electrolyte levels, anion gap and pH. The degree and nature of compensation should then be analyzed. Finally, the ratio of the change in anion gap to the change in serum bicarbonate (delta AG/delta HCO3-) should be determined. When this diagnostic process is applied, proper identification of the disorder can be made and management can be undertaken. Mixed acid-base disorders can also be identified and managed using this method.

Diagnostic assay for Helicobacter hepaticus based on nucleotide sequence of its 16S rRNA gene.

Conserved primers were used to PCR amplify 95% of the Helicobacter hepaticus 16S rRNA gene. Its sequence was determined and aligned to those of related bacteria, enabling the selection of primers to highly diverged regions of the 16S rRNA gene and an oligonucleotide probe for the development of a PCR-liquid hybridization assay. This assay was shown to be both sensitive and specific for H. hepaticus 16S rRNA gene sequences.

Characterization of bovine immunodeficiency virus rev cDNAs and identification and subcellular localization of the Rev protein.

One of the six putative accessory genes of bovine immunodeficiency virus (BIV) is similar to those identified as rev in the human immunodeficiency virus and visna virus genomes. To further analyze the BIV rev gene locus, protein, and function, rev cDNAs were cloned and characterized. BIV rev mRNA is derived from the full-length transcript by multiple splicing events and consists of three exons, including the untranslated leader sequence and two coding exons. BIV rev cDNA was expressed in bacteria and in a mammalian in vitro translation expression system. A 23-kDa Rev protein (p23rev) was immunologically detected in lysates from both systems by using an antiserum made to a synthetic Rev peptide. Recombinant p23rev made in bacteria was purified and used to make a polyvalent antiserum. Antisera to Rev peptide and recombinant p23rev immunoprecipitated p23rev from BIV-infected mammalian cells but not from virions. A mammalian expression vector using the BIV rev cDNA was constructed; p23rev was immunoprecipitated with anti-Rev serum from 32P-labeled lysates of monkey cells transfected with this plasmid, demonstrating that BIV Rev is phosphorylated. Immunofluorescence and immunoelectron microscopy with anti-BIV Rev antisera localized Rev in the nucleus and, particularly, in the nucleoli of BIV-infected cells. In functional studies, the expression of BIV Rev was shown to positively regulate the appearance both of Gag protein, which is translated from the unspliced primary viral transcript, and of singly spliced env mRNA but not that of the multiply spliced tat mRNA. These results demonstrate that BIV Rev activity correlates with the known function of lentivirus Rev proteins.

Laboratory monitoring of nutritional status in burn patients.

Most nutrition laboratory testing relies on serum concentrations of ingested nutrients, their coenzymes, proteins, or lipids. Alternatively, functional tests measure a specific physiological process or biochemical reaction. We compared these two approaches to nutritional assessment in intensive-care burn patients, in whom the serum concentrations of transthyretin (prealbumin), albumin, transferrin, carotene, retinol, ascorbic acid, copper, cholesterol, iron, and calcium were all below established reference ranges. In contrast, serum triglyceride concentrations were often above the reference range. Functional tests for thiamin, riboflavin, pyridoxine, and iron (by zinc protoporphyrin/heme ratio) in these patients all showed normal values. Dietary intake, weight trends, and nitrogen balances all indicated that these patients' estimated caloric and protein needs had been met. These findings suggest that static measurements of serum concentrations may be unreliable indicators of nutritional status in burn patients.

Comparison of the adhesion properties of Deleya marina and the exopolysaccharide-defective mutant strain DMR.

Deleya marina 219 (ATCC 25374) produces large quantities of an acidic exopolysaccharide and characteristically forms mucoid colonies and large aggregates of cells. The exopolysaccharide of wild-type D. marina cells appears to occur as both film and fibrils in electron micrographs. The organization of exopolymeric material was indicative of structural heterogeneity. A spontaneous rough-colony mutant defective in exopolysaccharide, D. marina DMR, has been isolated. The absence of exopolymer corresponds to a nonmucoid, nonaggregating, adhesion-altered phenotype. In microplate adhesion assays, wild-type cells grown at 19 or 25 degrees C attached to hydrophilic surfaces but not to a hydrophobic surface. In contrast, mutant cells exhibited a significantly reduced level of attachment to hydrophilic surfaces and increased adhesion to a hydrophobic surface.

Structural femtochemistry: experimental methodology.

The experimental methodology for structural femtochemistry of reactions is considered. With the extension of femtosecond transition-state spectroscopy to the diffraction regime, it is possible to obtain in a general way the trajectories of chemical reactions (change of internuclear separations with time) on the femtosecond time scale. This method, considered here for simple alkali halide dissociation, promises many applications to more complex reactions and to conformational changes. Alignment on the time scale of the experiments is also discussed.