For tissue illumination with endomicroscopic low-power laser (488

For tissue illumination with endomicroscopic low-power laser (488-nm blue laser light) application of fluorescence agents are necessary. Most studies in humans have been performed with intravenous fluorescein sodium (5 mL, 10%). Fluorescein quickly distributes within all compartments of the tissue, and CLE is possible within seconds after injection. It contrasts cellular and subcellular details, connective tissue, and vessel architecture at high resolution, but does not stain nuclei.12 Intravenous fluorescein is a nontoxic agent that is safe and mostly well tolerated, and only transient discoloration of the skin has been described.12

CLE with intravenous fluorescein sodium allows analysis of cellular structure, connective tissue, and blood cells of the colonic mucosa in vivo. However, the nuclei of the intestinal epithelium are not readily Dolutegravir visible because of the pharmacokinetic properties of fluorescein. Acriflavine and cresyl violet are alternative dyes that are applied topically and highlight

nuclei, cell membranes, cytoplasm, and to a lesser extent vessels. Acriflavine accumulates in nuclei and therefore carries a potential mutagenic risk. Cresyl violet, which enriches in the cytoplasm and visualizes nuclear morphology negatively, is an alternative. A 2-step study approach made in 2007 by Goetz and colleagues21 evaluated the staining characteristics and optimal concentration of a single topical contrast agent, cresyl violet (Merck, Darmstadt, Germany) for simultaneous chromoendoscopy and CLE for straightforward and reliable recognition of lesions and their immediate characterization Montelukast Sodium selleck chemicals llc in vivo. After establishing the optimal cresyl violet dye concentration of 0.13% with a pH of 3.8 in an animal preclinical study, 67 sites in 36 patients in a prospective clinical study were topically stained and subsurface serial images were generated at different depths using CLE. The results showed a good resolution with chromoendoscopy for pit pattern classification and good fluorescent contrast for endomicroscopy. Imaging at variable

penetration depths permitted high-resolution visualization of tissue architecture and subcellular details, such as mucin in goblet cells, and, more importantly, cell nuclei so that in vivo distinction of low-grade versus high-grade intraepithelial neoplasia was possible for the first time. Endomicroscopic targeting of biopsies to a region of altered nucleus/cytoplasm ratio on intravital staining with cresyl violet has resulted in the diagnosis of 1 additional case of high-grade intraepithelial neoplasia, and the overall prediction rate of neoplastic changes by CLE was excellent, although the small number of sites investigated may limit the significance of this finding.21 Endomicroscopy is a new imaging tool for gastrointestinal endoscopy. In vivo histology becomes possible at subcellular resolution during ongoing colonoscopy.

Nurses have a pivotal role in the early identification and manage

Nurses have a pivotal role in the early identification and management of the patient with ventriculitis. Index 407 “
“Mary Lou Warren and Melissa McLenon Jacqueline B. Broadway-Duren and Hillary Klaassen Anemias continue to present a challenge to the health care profession. Anemia is defined as a reduction in one or more of the RBC indices. Patients presenting with a mild form of anemia may be asymptomatic; however, in

more serious cases the anemia can become life threatening. In many cases the clinical presentation also reflects the underlying cause. Anemia may be attributed to various causes, whereas autoimmune RBC destruction may be attributed to intrinsic and extrinsic factors. Laboratory tests are essential in facilitating early detection and differentiation of anemia. Edythe M. (Lyn) Greenberg and Elizabeth S. (Sue) Kaled Thrombocytopenia is Selleck OSI-906 defined as a platelet count less than 150,000/μL. It can be the result of decreased platelet production, sequestration of the

platelets, or increased destruction of the platelets. The clinical presentation may vary from an incidental finding to obvious bleeding. Causes of thrombocytopenia include infections, malignancy, liver disease, autoimmune disorders, disseminated intravascular coagulation, pregnancy, medications, and coagulation disorders. Treatment is determined by the underlying cause of the thrombocytopenia. This article discusses the evaluation and management of common causes of thrombocytopenia. Carole L. Mackavey and Robert Hanks

Coagulopathy-related bleeding events are a major concern in the management of LGK-974 mouse acute and chronic liver disease. The liver attempts to maintain a balance between procoagulant and anticoagulant factors, and providers struggle with poor prognostic indicators to manage bleeding and critical complications. Subtle changes in patient presentation that may require extensive provider-directed interventions, such as blood transfusions, intravenous fluid management, mitigating possible sepsis, and evaluating appropriate pharmacologic treatment, are discussed. Jennifer K. Johnson and Elizabeth Sorensen Lymphoma presents itself from slow growing and asymptomatic to aggressive and destructive. Suspicion of aggressive lymphoma warrants prompt diagnostic evaluation because the tumor can be extremely fast growing and can cause significant Mannose-binding protein-associated serine protease sequelae including but not limited to tissue damage, immune suppression, organ failure, compromised circulation, and death. The standard evaluation includes laboratory assay, infectious disease panel, radiographic imaging with computed tomography, bone marrow biopsy, and tissue diagnosis. Two cases studies are presented describing the range of different acute issues that may arise with aggressive lymphomas including tumor lysis, HIV, small bowel obstruction, superior vena cava compression, aggressive disease transformation, and acute renal injury. Edythe M.

CO2 emission was always cyclic, sometimes on the verge of continu

CO2 emission was always cyclic, sometimes on the verge of continuous respiration ( Fig. 2D). Fig. 3 shows the duration Bosutinib mouse of cycles, and of open, closed and flutter phases (where present)

as a function of experimental ambient temperature. The course of all components of DGC follows exponential curves. With rising ambient temperature the open phase decreased slower in duration than the flutter and the closed phases at low to medium Ta. Closed phases were only detectable up to Ta ⩽ 26.3 °C. Fig. 4 shows the duration of the respiration cycles and cycle phases in dependence on resting metabolic rate (RMR). However, the courses of data points indicate a higher order of dependence than a simple exponential decrease. Good linear regression in a double logarithmic graph (inset) strengthens this finding. With rising Ta the cycle frequency (f) increased ( Fig. 1, Fig. 2) following an exponential curve ( Fig. 5). Data fitted best with an exponential function of the type f = y0 + A1Ta/t1, with y0 = 0.12716, A1 = 2.18932, t1 = 11.2997 (R2 = 0.51337, P < 0.0001, N = 37). Respiration cycle frequency was 2.55 ± 3.58 mHz at 4.7 °C, 9.33 ± 13.2 mHz at 9.8 °C, 13.0 ± 24.66 mHz at 19.8 °C, 39.92 ± 25.35 mHz at 31.1 °C selleck inhibitor and 73.97 ± 28.85 mHz at 39.7 °C. Data at 42.4 °C were not included in the fitting curve because single CO2 “peaks”

merged to “plateaus”. Comparison of variances of cycle frequency at the same Ta revealed significant differences between individuals (P < 0.05, N = 2–10, ANOVA). Over the entire temperature range these tests indicated significant differences in 69.5% of comparisons. An ANOVA with the means per animal and Ta (of both species) indicated a slight negative temperature dependence of CO2 release per cycle (P < 0.05; R2 = 0.06685, N = 62, F = 5.36977, DF = 60). The correlation was more pronounced in an analysis with all cycles of all animals, which includes the intra-individual variation ( Fig. 6). CO2 release per cycle as estimated from

the regression line changed from 39.51 μl g−1 cycle−1 at 2.9 °C to 25.4 μl g−1 cycle−1 at 42.4 °C, Single individuals compared at the same temperature showed significant differences Selleck Y 27632 in the variances of mean CO2 emission per cycle and animal (P < 0.05, N = 2–8, ANOVA; see large circles in Fig. 6). Over the entire temperature range these within-Ta comparisons showed inter-individual differences in 56.8% of cases. This implies that the other 43.2% of cases indicated no difference. However, measurements where data of only one individual could be evaluated indicate also considerable intra-individual variance ( Fig. 6, Ta = 22.5 and 42.4 °C). In direct comparison, wasps differed from honeybees significantly in slope and intercept (P < 0.0001 in both cases, ANOVA; see Fig. 6). Cycle frequency (f) increased linearly with the mass specific RMR ( Fig. 7, f (mHz) = −2.54647 + 0.65394 * RMR CO2 (μl g−1 min−1), R2 = 0.976, P < 0.0001, N = 37, means per animal).

55 (children, ages 2–12 years and girls ages 13–21 years) and k =

55 (children, ages 2–12 years and girls ages 13–21 years) and k = 0.70 for boys ages 13–21 years) [16]; and 4) creatinine clearance (CCr) = [(uCr mmol/l × uVolume ml/min) / pCr mmol/l]. Renal handling of Ca and P was investigated using urinary excretion expressed

both as mmol per unit time (2 h and 24 h for uCa, and uP) and as mineral clearance (CCa and CP). CCa and CP were calculated using the following equation: [(uCa or uP mmol/l × urine volume l/h) / (plasma TCa or P mmol/l)] [17]. Tubular maximal reabsorption of phosphate (TmP:GFR) (mmol/l) was determined in the following way: Tubular reabsorption of phosphate (TRP) = 1 − (uP/P) × (Cr/uCr), Enzalutamide if TRP < 0.86 then TmP:GFR = TRP × P mmol/l, if TRP > 0.86 then TmP:GFR = (0.3 × TRP / 1 − (0.8 × TRP)) × P mmol/l [18]. Of

the 46 subjects in the original study, 11 were lost to follow-up; one had died, 4 had moved away from the region, and 6 were not traceable. There was no significant difference in age, sex or proportion with active rickets at presentation between children in RFU and those lost to follow-up. There was also no significant difference in plasma www.selleckchem.com/ATM.html FGF23, 25OHD, 1,25(OH)2D, TCa, P, TALP or PTH at presentation between subjects followed-up in RFU and those who were not (data not shown). The median age of the 35 RFU children was 8.5 (IQR 2.6) years; 66% were male and 34% female. Nine of the 13 subjects with active rickets in the original study were followed up. There was a trend for RFU children to be heavier than LC children, although not significantly (SDS-weight = 0.41 (0.79) p = 0.07). There was no significant difference in standing height, sitting height or BSA between RFU and LC children (SDS-standing height = − 0.17 (0.81) p = 0.4; SDS-sitting height = − 0.06

(0.7) p = 0.8; SDS-BSA = 0.28 (0.81) p = 0.22). None of the RFU children had active rickets as determined by raised TALP and/or Thacher radiographic scoring. However, 19 (54%) had visible lower limb deformities; 10 (29%) had knock-knees, 8 (23%) had bow-legs and 1 (3%) had windswept deformity. Of those with leg deformities, 4 (11%) had switched from bow-legs to knock-knees since presentation, 1 (3%) experienced pain while walking and 2 (6%) experienced pain while running. With aminophylline the exception of two RFU children who were siblings, the parents/guardians of RFU children did not report any other cases of rickets-like bone deformities in their family. Table 1 presents the results from the 2-day dietary assessment. Daily calcium intake was significantly lower in RFU than LC children. The mean calcium intake of RFU children was 188 (124, 283) mg/day compared to 305 (167, 556) mg/day in the LC children. 19 (56%) of the RFU children had calcium intakes of ≤ 200 mg/day compared with 7 (29%) of LC children (χ2 = 6.51, p = 0.005). Calcium intake increased with age but was consistently lower in RFU than LC children across the age bands.

In this sense, PriSE attempts at bringing together young and expe

In this sense, PriSE attempts at bringing together young and experienced researchers, teachers, and other stakeholders in the field, trying to answer their questions and suggesting solutions for a sustainable development of science education in and out of school, and deliberately across several countries and language communities. Chères lectrices, chers lecteurs Nous nous réjouissons de pouvoir find more présenter ce numéro spécial de Perspectives in Science (PISC) intitulé Progress in Science Education (PriSE). Avons-nous besoin d’un nouvel organe scientifique en didactique des sciences? Quelles en sont les exigences en terme de qualité, quels en sont les objectifs?

La recherche en éducation des sciences de la nature est particulièrement dynamique, aussi bien dans le domaine de la recherche fondamentale que dans celui de la recherche appliquée. Elle est située à l’interface des questions click here émanantes de la pratique de l’enseignement en classe et de la formation des enseignants, et doit prendre en compte les nombreuses exigences de notre société moderne par rapport à la science, à la culture et à la formation scientifique. Il est notamment question d’un enseignement basé sur une approche scientifique, du niveau primaire au niveau secondaire. Dans ce contexte, de nombreux pays sont confrontés à des besoins similaires:

• Soutien et développement des jeunes générations de chercheurs dans le domaine de la didactique des sciences naturelles. Il n’existe pas vraiment d’organe de publication en didactique des sciences naturelles en mesure de répondre à ces attentes. Les jeunes chercheurs qui désirent publier dans des journaux établis, le plus souvent en langue anglaise, sont très souvent confrontés à des obstacles tels que la durée des processus de

peer-review ou encore la barrière de la langue. Les périodiques qui visent à mettre en avant pratique et Dichloromethane dehalogenase recherche et au-delà le transfert de savoir depuis la recherche en didactique des sciences vers le développement de matériels pédagogiques ne sont malheureusement que difficilement accessibles pour les enseignants. En considération de cette situation, le numéro spécial PriSE du journal PISC offre une nouvelle plateforme en ligne, un espace dynamique permettant la publication rapide d’articles de recherche, dans l’une des langues suivantes: allemand, anglais, français et italien. L’échange entre des pays différents, ayant des objectifs similaires dans le développement de l’éducation en sciences naturelles, profite directement de ce plurilinguisme et contribue ainsi à une vraie communauté multiculturelle dans le domaine. Les articles sont accessibles gratuitement, dans un format Online-Open-Access, à la communauté scientifique internationale. Les jeunes chercheurs sont particulièrement encouragés à publier leurs premiers travaux dans les futures éditions de PriSE.

Moreover, most of the existing models are based on

histor

Moreover, most of the existing models are based on

historical data from past oil spills obtained from the IOPCF statistics, which by definition is passive, for the detailed discussion the reader is referred to Psarros et al. (2011). Furthermore, such models are developed with the use of data about spill sizes falling in a certain range, usually with small median value for a spill, see Kontovas et al. (2010), thus applying such models for extrapolation beyond this range is very questionable. In the scientific literature find more there are only two models allowing for the estimation of oil spill clean-up costs. One has been proposed by Etkin – Etkin, 1999 and Etkin, 2000 – is deterministic but allows rather wide interpretation of the cost factors considered. Another model has been proposed by Shahriari and Frost (2008) it is

also deterministic, but with no room for interpretation. Predictions of both models hold in the context of global oil spill costs, but they have rather low geographical resolution. Therefore, it is not possible to use the models for the purpose of oil-combating fleet optimization or detailed risk management, as the local conditions are not properly reflected. Moreover, the unique nature of the analyzed sea area of the Gulf of Finland, being classified by the IMO as a Particular Sensitive Sea Area (PSSA), makes it possible for the oil to reach the shore

in a very short time with devastating consequences, www.selleckchem.com/products/Perifosine.html see for example Lecklin et al. (2011). This means that once the oil spill at sea has occurred, it is almost impossible to prevent it from reaching the coast, see Hietala and Lampela, 2007 and Aps et al., 2009. What makes the clean-up operations even more demanding is the fact that the coastline is filled with small islands; making it impossible for the clean-up vessels to navigate in some places even though the sea depth would allow it. Another Niclosamide factor that separates the Gulf of Finland from the larger sea areas is that, according to the HELCOM agreement, use of chemical dispersants or in situ burning are not permitted as oil combating techniques, and the clean-up is mainly performed mechanically, see HELCOM (2012). All these show the complexity of the subject and limitations of existing clean-up cost estimation models. Hence, it is desirable to go to the sources of each of the costs, which together make the total cost of oil spill clean-up operation. This paper introduces a probabilistic model for accidental oil spill cleanup-cost estimation for the Finnish response area of the Gulf of Finland – see Fig. 1.

While a simple linear relationship between inflow and (SWWA) rain

While a simple linear relationship between inflow and (SWWA) rainfall is sufficient to describe much of the variability in observed inflows, the most recent data confirms that the relationship appears to have changed after 1976, with less inflow for a given rainfall amount. The role of temperature in this changed relationship has been investigated but we find that any apparent correlations reflect the fact that rainfall and temperature tend to be inversely related and that temperature and inflow data exhibit long-term variability. When these factors are accounted for there

is no evidence that local temperature changes have any direct effect on inflows. This suggests that other explanations for the changed relationship between rainfall and inflows are more likely. For selleck chemicals llc AZD6244 ic50 example, the combined effects of changes in timing of rainfall events throughout the year, the absence of very heavy rainfall events and long-term changes in the physical character of the catchments – most likely changes to ground water levels. As was found in analyses of previous climate model experiments, the latest set of climate model results (CMIP5, RCP8.5) all project a decline in annual rainfall by the end of the century accompanied

by relatively large uncertainty. Some models (ACCESS1-3, BNU-ESM, CMCC-CESM, IPSL-CM5B-MR, IPSL-CM5B-LR, MPI-ESM-LR and NORESM1-M) exhibit time series that exhibit similarities to the observed SWWA time series in terms of a late 20th century decline. This confirms early interpretations that suggested that both natural variability and the enhanced greenhouse effect have contributed to the rainfall decrease. The climate change projections Acesulfame Potassium continue to indicate a pessimistic outlook for rainfall – a finding consistent with those presented in previously published studies. Despite the consensus amongst the models, there

is still a relatively wide range in the magnitude of the projected decline by the end of the century. Given this range, plus the fact that we have only considered the results associated with a single emissions scenario, we have made no attempt to deal with this uncertainty. The fact that the CMIP5 projections do not differ substantially from previous model projections suggests that further modeling experiments will not yield much more extra information. However, some climate-related questions still deserve attention. For example, are the projected rainfall decreases accompanied by similar changes to mean sea level pressure patterns and the frequency of rain-bearing systems? Is it possible to narrow the uncertainty in the projections by discriminating between models and/or downscaling the result? Otherwise it is apparent that changes in the rainfall/inflow relationship could be just as important, if not more so, than changes to rainfall.

The comparison of the average time spent in obtaining results fro

The comparison of the average time spent in obtaining results from HLAMatchmaker using the conventional and automated methods revealed that the EpHLA find more software was almost 6 times faster when used by manual analysis experts (experienced group) and over 10 times faster when used by users with low analysis experience (Table 3, t-test, p < 0.0001). The class II HLA analysis required a longer average time to perform for both conventional ( Table 3; t-test, p < 0.002) and automated ( Table 3; Mann–Whitney, p < 0.0001) programs when compared to the class I HLA analysis. No difference in the number of non-self eplets was reported by users after both types of analyses: it was counted a total of 72,908 non-self

eplets in HLA class I and 58,762 non-self eplets in HLA class II. However, disagreements were observed with respect to the categorization (colors) given to some eplets between the conventional and automated methods. In fact, there was one disagreement for HLA class I and eleven disagreements for HLA class II eplets. These twelve eplets were classified as reactive (black) in the conventional analysis and as non-reactive (blue) in the automated analysis. As a consequence of such eplet categorization, twenty-one HLA alleles were considered

UMMs, when using the conventional analysis, whereas they were classified as AMMs when using the automated analysis. Due to these 21 AMMs’ disagreements, the number of HLA alleles considered AMMs in the conventional approach Meloxicam was 10,737, however check details in the automated approach 10,758

HLA alleles were considered AMMs. A closer examination of the above reported results revealed that there were errors in eplets’ categorization when using the conventional HLAMatchmaker analysis. In particular, Fig. 1 shows a case with disagreements due to human error in conventional analysis. The revised analysis permitted the correct categorization of eplets as non-reactive and the respective HLA molecules as AMMs. Fig. 1 shows screenshots of categorization eplets’ disagreements between conventional and automated HLAMatchmaker analysis. The assigned cutoff was 500, alleles in bold were assigned was AMMs. The eplets 57PS and 125SH should be blue in conventional analysis (panel 1A), because they are present on bead 47 with negative reaction of MFI = 67 as shown by automated analysis (panel 1B). Also, the allele DQB1*05:02 in conventional analysis should be in bold (panel 1A), because it is an AMM with blue non-self eplets as shown in automated analysis (panel 1B). All disagreements identified in this study occurred due to human errors made by the non-experienced group during the conventional HLAMatchmaker analysis. However, the comparison between two methods showed no statistically significant difference for these variables (class I eplets, p = 0.99; class I AMMs, p = 0.85; class II eplets, p = 0.42 and class II AMMs, p = 0.14).

The current paper has expanded on this approach The current find

The current paper has expanded on this approach. The current findings support Priskin’s (2003b) original conclusion that the public do distinguish between different activities; however Priskin also found that they generally underestimate the negative impacts on the environment compared to that of the marine expert. However, within the current

samples, there were only few differences, with the coastal user sample generally in agreement with the coastal LY294002 molecular weight experts. This may be due to methodological differences such as country, type of shoreline (sandy versus rocky) and the time of data collection (data collected in 1999 for Priskin, and 11 years later for this current work). It could also be because of the reliability of the expert ratings. For this current study, we used 25 coastal experts from around the UK and a further Selleck Ponatinib 44 international academics, whilst Priskin relied purely on her own expertise. Overall, the views between experts and coastal users were remarkably similar which can increase our confidence in these perception-based findings. We developed the questionnaire further in Study 2 and can therefore not make direct statistical comparisons between the two data sets. However, the pattern of findings was very similar between the two studies and no differences were

found between coastal experts from the UK as opposed to elsewhere. This seems to indicate that the findings can be seen as more global issues than only relevant to the United Kingdom. However, the exact level of detrimental impact on the environment may be different in other countries and would be interesting to explore further with a more cross-cultural study. In addition to the perceived impacts different activities

have on rocky shores, the open-ended questions offered in-depth insights. As mentioned above, participants used this opportunity to explain the depreciative behaviours linked with foraging activities, including turning rocks over and lack of knowledge Histidine ammonia-lyase or awareness. Another frequently mentioned theme, especially for the coastal user sample, was littering. Crucially, littering was mentioned spontaneously without a researcher prompt (as this study focussed on purposive recreational activities) yet it turned out to be a consistent key theme. Littering is known to be an important environmental issue, with roughly 2 000 litter items found per kilometre on the UK coastline alone (MCS, 2012). Litter can have numerous effects, including entanglement, ingestion and damage to the environment and its residents (Hall, 2000 and Laist, 1997). Interestingly, however, many of the responses did not only emphasise those detrimental effects of litter on the environment and organisms, but also highlighted the effect it has on visitors’ experiences. This is in line with the finding that marine litter can be a key deterrent for visiting specific beaches (Tudor and Williams, 2006).

1%) and 526 (19 5%) [25] Eight of the 14 different mutations obs

1%) and 526 (19.5%) [25]. Eight of the 14 different mutations observed in that study (57%) were present in our patient pool. The present study also emphasizes the frequency of codon changes at position 533. In clear contrast to previous reports [26] and [27], the majority of isolates in this study exhibited more

than one codon change (2–5). Many codon changes involved more than one base pair change. A significant portion appeared to involve a two-base pair inversion, while others were likely to involve multiple base pair substitutions through point mutations. The selleck chemicals high GC/AT ratio may contribute mechanistically to the mutability of this hot spot region. Noticeably, codon changes at 533 were accompanied by other codon changes in almost all of the isolates (with one exception). Changes at this position are reported to result in variable resistance; therefore, additive resistance could be a significant resistance mechanism in these strains. Some rpoB codon changes have been shown to cause cross-resistance to antibiotics other than rifampicin in M. tuberculosis isolates. Codon changes at 513, 526, and 531 are associated with high-level resistance to rifampicin and rifabutin. Codon changes at 514, 515, 516, 522, and 533 have been reported

to cause rifampicin resistance concomitant with susceptibility Palbociclib or low resistance to rifabutin [28]. Thus, depending on the genotype, the use and disuse of other antibiotics (e.g., in second-line Tb drug treatment) can be suggested

[28]. However, this conclusion depends on the assessment of the novel codon changes and the additive effects of multiple codon changes. Despite the dominance of isolates with the genotype S531 L, the diversity of the isolate HAS1 genotypes is striking. With respect to the 18 isolates obtained from Aleppo, 6 had the S531 L genotype, while the rest (12) had 9 different genotypes. This diversity is consistent with the lower exogenous transmission of resistant strains in Syria, which was suggested by a previous strain genotyping study [21]. One drawback of this study is the small number of Lebanese samples, which cannot be considered representative of the rpo B pool of mutations in Lebanon. Future comparisons with other neighboring countries await more extensive local studies of the rpoB sequence. The authors have no competing interests to declare. This research was funded by the Lebanese University and the Syrian Ministry of Higher Education. “
“GAS TSS is an uncommon form of septicemia caused by Streptococcus pyogenes (Lancefield group A), which is also the pathogen responsible for scarlet fever and other Streptococcal soft tissue infections. As with Staphylococcal TSS, invasive Streptococcal diseases are also caused by biologically potent exotoxins that mediate fever, shock, and tissue injury [1].