Case Report: Calcified Cerebral Toxoplasmosis Associated with Perilesional Edema in People Living with HIV/AIDS: Case Series of a Presentation Mimicking Neurocysticercosis.

Perilesional edema, associated or not with neurological manifestations, is a well-characterized finding in cases of calcified neurocysticercosis. There are no previous reports of HIV-related calcified toxoplasmosis that mimics this presentation of neurocysticercosis. We report on five patients, four of them with new-onset neurological manifestations, who showed brain calcifications associated with perilesional edema. All cases had a history of HIV-related toxoplasmosis and current virological and immunological control of HIV infection. Similar to neurocysticercosis, brain calcified toxoplasmosis may cause perilesional edema and symptoms in people living with HIV/AIDS.

Water productivity of rainfed maize and wheat: A local to global perspective.

Water productivity (WP) is a robust benchmark for crop production in relation to available water supply across spatial scales. Quantifying water-limited potential (WPw) and actual on-farm (WPa) WP to estimate WP gaps is an essential first step to identify the most sensitive factors influencing production capacity with limited water supply. This study combines local weather, soil, and agronomic data, and crop modeling in a spatial framework to determine WPw and WPa at local and regional levels for rainfed cropping systems in 17 (maize) and 18 (wheat) major grain-producing countries representing a wide range of cropping systems, from intensive, high-yield maize in north America and wheat in west Europe to low-input, low-yield maize systems in sub-Saharan Africa and south Asia. WP was calculated as the quotient of either water-limited yield potential or actual yield, and simulated crop evapotranspiration. Estimated WPw upper limits compared well with maximum WP reported for field-grown crops. However, there was large WPw variation across regions with different climate and soil (CV = 29% for maize and 27% for wheat), which cautions against the use of generic WPw benchmarks and highlights the need for region-specific WPw. Differences in simulated evaporative demand, crop evapotranspiration after flowering, soil evaporation, and intensity of water stress around flowering collectively explained two thirds of the variation in WPw. Average WP gaps were 13 (maize) and 10 (wheat) kg ha-1 mm-1, equivalent to about half of their respective WPw. We found that non-water related factors (i.e., management deficiencies, biotic and abiotic stresses, and their interactions) constrained yield more than water supply in ca. half of the regions. These findings highlight the opportunity to produce more food with same amount of water, provided limiting factors other than water supply can be identified and alleviated with improved management practices. Our study provides a consistent protocol for estimating WP at local to regional scale, which can be used to understand WP gaps and their mitigation.

Manager traits and quality-of-care performance in hospitals.

PURPOSE: This paper aims to assess the impact of the leadership traits of chief executive officers (CEOs) on hospital performance in the USA. The effectiveness and efficiency of the CEO is of critical importance to the performance of any organization, including hospitals. Management systems and manager behaviours (traits) are of crucial importance to any organization because of their connection with organizational performance. To identify key factors associated with the quality of care delivered by hospitals, the authors gathered perceptions of manager traits from chief executive officers (CEOs) and followers in three groups of US hospitals delivering different levels of quality of care performance. DESIGN/METHODOLOGY/APPROACH: Three high- and three low-performing hospitals were selected from the top and bottom 20th percentiles, respectively, using a national hospital ranking system based on standard quality of care performance measures. Three lean hospitals delivering intermediate performance were also selected. A survey was used to gather perceptions of manager traits (providing a modern or lean management system inclination) from CEOs and their followers in the three groups, which were compared. FINDINGS: Four traits were found to be significantly different (alpha < 0.05) between lean (intermediate-) and low-performing hospitals. The different perceptions between these two hospital groups were all held by followers in the low-performing hospitals and not the CEOs, and all had a modern management inclination. No differences were found between lean (intermediate-) and high-performing hospitals, or between high- and low-performing hospitals. ORIGINALITY/VALUE: These findings support a need for hospital managers to acquire appropriate traits to achieve lean transformation, support a benefit of measuring manager traits to assess progress towards lean transformation and lend weight to improved quality of care that can be delivered by hospitals adopting a lean system of management.

Agronomic and environmental consequences of using liquid mineral concentrates on arable farms.

BACKGROUND: In regions with intensive livestock systems, the processing of manure into liquid mineral concentrates is seen as an option to increase the nutrient use efficiency of manures. The agricultural sector anticipates that these products may in future be regarded as regular mineral fertilisers. We assessed the agronomic suitability and impact on greenhouse gas (GHG) and ammonia emissions of using liquid mineral concentrates on arable farms. RESULTS: The phosphate requirements on arable farms were largely met by raw pig slurry, given its large regional availability. After the initial nutrient input by means of pig slurry, the nitrogen/phosphate ratio of the remaining nutrient crop requirements determined the additional amount of liquid mineral concentrates that can be used. For sandy soils, liquid mineral concentrates could supply 50% of the nitrogen requirement, whereas for clay soils the concentrates did not meet the required nitrogen/phosphate ratio. The total GHG emissions per kg of plant available nitrogen ranged from -65 to 33 kg CO2 -equivalents. It increased in the order digestates < mineral fertiliser < raw slurries. CONCLUSIONS: Liquid mineral concentrates had limited added value for arable farms. For an increased suitability it is necessary that liquid mineral concentrates do not contain phosphate and that the nitrogen availability is increased. In the manure-processing chain, anaerobic digestion had a dominant and beneficial effect on GHG emissions.

Diffusion tensor imaging of the cervical spinal cord of patients with Neuromyelitis Optica.

BACKGROUND: Previous studies have demonstrated a correlation between Expanded Disability Status Scale (EDSS) and Diffusion Tensor Imaging (DTI) metrics, but the conclusions were based on evaluations of the entire cervical spinal cord. OBJECTIVES: The purpose of this study was to quantify the FA and MD values in the spinal cord of NMO patients, separating the lesion sites from the preserved sites, which has not been previously preformed. In addition, we attempted to identify a correlation with EDSS. METHODS: DTI was performed in 11 NMO patients and 11 healthy individuals using a 1.5-T MRI scanner. We measured the FA and MD at ROIs positioned along the cervical spinal cord. The mean values of FA and MD at lesion, preserved and spinal cord sites were compared with those of a control group. We tested the correlations between the mean FA and MD with EDSS. RESULTS: FA in NMO patients was significantly reduced in lesion sites (0.44 vs. 0.55, p=0.0046), preserved sites (0.46 vs. 0.55, p=0.0015), and all sites (0.45 vs 0.55, p=0.0013) while MD increased only in lesion sites (1.03×10(-3)mm(2)/s vs. 0.90×10(-3)mm(2)/s, p=0.009). The FA demonstrated the best correlation with EDSS (r=-0.7603, p=0.0086), particularly at lesion sites. CONCLUSIONS: The results reinforce the importance of the FA index and confirm the hypothesis that NMO is a diffuse disease.

Success rates of nuclear short tandem repeat typing from different skeletal elements.

AIM: To evaluate trends in DNA typing success rates of different skeletal elements from mass graves originating from conflicts that occurred in the former Yugoslavia (Bosnia and Herzegovina and Kosovo) during the 1990s, and to establish correlation between skeletal sample age and success of high throughput short tandem repeat (STR) typing in the large data set of the International Commission on Missing Persons. METHOD: DNA extraction and short tandem repeat (STR) typing have been attempted on over 25000 skeletal samples. The skeletal samples originated from different geographical locations where the conflicts occurred and from different time periods from 1992 to 1999. DNA preservation in these samples was highly variable, but was often significantly degraded and of limited quantity. For the purpose of this study, processed samples were categorized according to skeletal sample type, sample age since death, and success rates tabulated. RESULTS: Well-defined general trends in success rates of DNA analyses were observed with respect to the type of bone tested and sample age. The highest success rates were observed with samples from dense cortical bone of weight-bearing leg bones (femur 86.9%), whereas long bones of the arms showed significantly lower success (humerus 46.2%, radius 24.5%, ulna 22.8%). Intact teeth also exhibited high success rates (teeth 82.7%). DNA isolation from other skeletal elements differed considerably in success, making bone sample selection an important factor influencing success. CONCLUSION: The success of DNA typing is related to the type of skeletal sample. By carefully evaluating skeletal material available for forensic DNA testing with regard to sample age and type of skeletal element available, it is possible to increase the success and efficiency of forensic DNA testing.

Variant alleles, triallelic patterns, and point mutations observed in nuclear short tandem repeat typing of populations in Bosnia and Serbia.

AIM: To present a compendium of off-ladder alleles and other genotyping irregularities relating to rare/unexpected population genetic variation, observed in a large short tandem repeat (STR) database from Bosnia and Serbia. METHODS: DNA was extracted from blood stain cards relating to reference samples from a population of 32800 individuals from Bosnia and Serbia, and typed using Promega's PowerPlex16 STR kit. RESULTS: There were 31 distinct off-ladder alleles were observed in 10 of the 15 STR loci amplified from the PowerPlex16 STR kit. Of these 31, 3 have not been previously reported. Furthermore, 16 instances of triallelic patterns were observed in 9 of the 15 loci. Primer binding site mismatches that affected amplification were observed in two loci, D5S818 and D8S1179. CONCLUSION: Instances of deviations from manufacturer's allelic ladders should be expected and caution taken to properly designate the correct alleles in large DNA databases. Particular care should be taken in kinship matching or paternity cases as incorrect designation of any of these deviations from allelic ladders could lead to false exclusions.

Indomethacin lowers the threshold thermal exposure for hyperthermic radiosensitization and heat-shock inhibition of ionizing radiation-induced activation of NF-kappaB.

PURPOSE: It is well established that salicylate and several other non-steroidal anti-inflammatory agents (NSAID), including indomethacin, can activate the heat-shock response, albeit at high concentrations. This is significant since heat shock significantly alters the cellular cytotoxic response to ionizing radiation (IR). It was previously shown that heat shock, as well as NSAIDs, inhibits IR-induced activation of NF-kappaB and that NF-kappaB protects against IR-induced cytotoxicity. Hence, it is hypothesized that pretreatment with indomethacin before heating will lower the temperature and heating times required to inhibit the activation of NF-kappaB and induce significant hyperthermic radiosensitization. MATERIALS AND METHODS: Experiments were performed in HeLa cell lines and the DNA-binding activity was determined by EMSA. Cellular radiosensitivity was determined by clonogenic assay. RESULTS: HeLa cells pretreated with indomethacin showed a decrease in the temperature-time combination necessary to inhibit IR-induction of NF-kappaB DNA binding. In addition, clonogenic cell survival assays using identical conditions showed an indomethacin dose-dependent enhancement of hyperthermic radiosensitization. Thus, similar concentrations of indomethacin both lowered the threshold thermal exposure to inhibit activation of NF-kappaB DNA-binding and increased the sensitivity of tumour cells to hyperthermic radiosensitization-induced cytotoxicity. In HeLa cells treated with N-alpha-tosylphenylalanyl-chloromethyl ketone (TPCK), a serine protease inhibitor that blocks activation of NF-kappaB, an increase in radiosensitivity was observed. Interestingly, no additional cell killing was observed when heat shock was added to cells treated with TPCK before IR, suggesting a possible common cytotoxic pathway. CONCLUSIONS: The results demonstrate that indomethacin lowers the temperature-time conbination necessary to induce several physiological processes associated with the heat-shock response. Furthermore, NSAID may be potential adjuvants in improving the clinical effectiveness of hyperthermia in radiation therapy.

Indomethacin-induced radiosensitization and inhibition of ionizing radiation-induced NF-kappaB activation in HeLa cells occur via a mechanism involving p38 MAP kinase.

Although ionizing radiation (IR) activates multiple cellular factors that vary depending on dose and tissue specificity, the activation of NF-kappaB appears to be a well-conserved response in tumor cells exposed to IR. Recently, it also has been demonstrated that nonsteroidal anti-inflammatory agents inhibit tumor necrosis factor and interleukin-1-induced NF-kappaB activation and act as radiosensitizing agents. These observations reinforce the growing notion that NF-kappaB may be a protective cellular factor responding to the cytotoxicity of IR and other damaging stimuli. As such, we addressed the idea and mechanism that NF-kappaB is a downstream target of the nonsteroidal anti-inflammatory agent indomethacin and is involved in the process of radiosensitization. In this study, we report that indomethacin inhibited IR-induced activation of NF-kappaB and sensitized HeLa cells to IR-induced cytotoxicity at similar concentrations. Pretreatment of HeLa cells with SB 203580, a pyridinyl imidazole compound that specifically inhibits p38 mitogen-activated protein kinase (MAPK), abrogated the ability of indomethacin to inhibit IR-induced activation of NF-kappaB and diminished the indomethacin radiosensitizing effect. In addition, the transient genetic activation of p38(MAPK) inhibited IR induction of NF-kappaB gene expression in the absence of indomethacin. Finally, permanently transfected cell lines genetically unable to activate NF-kappaB, because of expression of a dominant negative I-kappaBalpha gene, demonstrated increased sensitivity to IR-induced cytotoxicity. Taken together, these results suggest that p38 MAPK is a target involved in indomethacin-induced radiosensitization and that NF-kappaB may be one downstream target in this process.

Increased activator protein 1 activity as well as resistance to heat-induced radiosensitization, hydrogen peroxide, and cisplatin are inhibited by indomethacin in oxidative stress-resistant cells.

It has been established that tumor cells develop resistance to a variety of therapeutic agents after multiple exposures to these agents/drugs. Many of these therapeutic agents also appear to increase the activity of transcription factors, such as activator protein 1 (AP-1), believed to be involved in cellular responses to oxidative stress. Therefore, we hypothesized that cellular resistance to cancer therapeutic agents may involve the increased activity of transcription factors that govern resistance to oxidative stress, such as AP-1. To investigate this hypothesis, a previously characterized cisplatin, hyperthermia, and oxidative stress-resistant Chinese hamster fibroblast cell line, OC-14, was compared to the parental HA-1 cell line. Electrophoretic mobility shift and Western blot assays performed on extracts isolated from OC-14 cells demonstrated a 10-fold increase in constitutive AP-1 DNA-binding activity as well as increased constitutive c-Fos and c-Jun immunoreactive protein relative to HA-1 cells. Treatment of OC-14 cells with indomethacin inhibited constitutive increases in AP-1 DNA-binding activity and c-Fos/c-Jun-immunoreactive protein levels. Clonogenic survival assays demonstrated that pretreatment with indomethacin, at concentrations that inhibited AP-1 activity, significantly reduced the resistance of OC-14 cells to heat-induced radiosensitization, hydrogen peroxide, and cisplatin. These results demonstrate a relationship between increases in AP-1 DNA-binding activity and increased cellular resistance to cancer therapeutic agents and oxidative stress that is inhibited by indomethacin. These results support the hypothesis that inhibition of AP-1 activity with nonsteroidal anti-inflammatory drugs, such as indomethacin, may represent a useful adjuvant to cancer therapy.