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Immune cells need to sustain a state of constant alertness over a lifetime. Yet, little is known about the regulatory processes that control the fluent and fragile balance that is called homeostasis. Here we demonstrate that JAK-STAT signaling, beyond its role in immune responses, is a major regulator of immune cell homeostasis. We investigated JAK-STAT-mediated transcription and chromatin accessibility across 12 mouse models, including knockouts of all STAT transcription factors and of the TYK2 kinase. Baseline JAK-STAT signaling was detected in CD8+T cells and macrophages of unperturbed mice—but abrogated in the knockouts and in unstimulated immune cells deprived of their normal tissue context. We observed diverse gene-regulatory programs, including effects of STAT2 and IRF9 that were independent of STAT1. In summary, our large-scale dataset and integrative analysis of JAK-STAT mutant and wild-type mice uncovered a crucial role of JAK-STAT signaling in unstimulated immune cells, where it contributes to a poised epigenetic and transcriptional state and helps prepare these cells for rapid response to immune stimuli.

Aim In the United Kingdom (UK), 600 deaths per annum are attributable to drowning. Despite this there is scarce critical care data on drowning patients globally. We describe drowning cases admitted to critical care units with a focus on functional outcomes.Materials and Methods Medical records for critical care admissions following a drowning event were retrospectively reviewed across six hospitals in Southwest England for cases presenting in the period between 2009 and 2020. Data was collected according to the Utstein international consensus guidelines on drowning.Results Forty-nine patients were included, 36 males and 13 females, including seven children. Median submersion duration was 2.5 min 20 cases were in cardiac arrest when rescued. At discharge 22 patients had preserved functional status, 10 patients had a reduced functional status. 17 patients died in hospital.Conclusion Admission to critical care following drowning is uncommon and associated with high rates of mortality and poor functional outcomes. We find that 31% of those who survived a drowning event subsequently required an increased level of assistance with their activities of daily living.

Molecular identification of pollen carried by insects informs about their history of visited plants. For migratory butterflies, it can be used to trace long-range movements enduring days of flight over thousands of kilometers. Here, we present a protocol to (1) isolate pollen grains from butterfly bodies and (2) prepare metabarcoding libraries for their identification using the internal transcribed spacer 2 fragment, a common barcode used to identify plants. This protocol would be applicable to other insect groups and metabarcoding markers.

Environmental microbial triggers shape the development and functionality of the immune system. Alveolar macrophages (AMs), tissue-resident macrophages of the lungs, are in constant and direct contact with inhaled particles and microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred to as trained immunity. Here, we investigated whether a ubiquitous microbial compound has the potential to induce AM training in vivo. We discovered that intranasal exposure to ambient amounts of lipopolysaccharide (LPS) induced a pronounced AM memory response, characterized by enhanced reactivity upon pneumococcal challenge. Exploring the mechanistic basis of AM training, we identified a critical role of type 1 interferon signaling and found that inhibition of fatty acid oxidation and glutaminolysis significantly attenuated the training effect. Notably, adoptive transfer of trained AMs resulted in increased bacterial loads and tissue damage upon subsequent pneumococcal infection. In contrast, intranasal pre-exposure to LPS promoted bacterial clearance, highlighting the complexity of stimulus-induced immune responses, which likely involve multiple cell types and may depend on the local immunological and metabolic environment. Collectively, our findings demonstrate the profound impact of ambient microbial exposure on pulmonary immune memory and reveal tissue-specific features of trained immunity.

ABSTRACTBackgroundLumefantrine (LMF) is first-line antimalarial drug, possesses activity against almost all human malarial parasites, but the in vivoactivity of this molecule gets thwarted due to its low and inconsistent oral bioavailability (i.e. 4–12%) owing to poor biopharmaceutical attributes.MethodsLumefantrine phospholipid complex (LMF-PC) was prepared by rota-evaporation method following job’s plot technique for the selection of apt stoichiometric ratios. Docking studies were carried out to determine the possible interaction(s) of LMF with phosphatidylcholine analogue. Comparative in vitrophysiochemical, solid-state characterization, MTT assay, dose-response on P. falciparum, in vivoefficacy studies including pharmacokinetic and chemosuppression on NK-65 P. bergheiinfected mice were carried out.ResultsAqueous solubility was distinctly improved (i.e. 345 times) with phospholipid complex of LMF. Cytotoxicity studies on Hela and fibroblast cell lines demonstrated safety of LMF-PC with selectivity indices of 4395 and 5139, respectively. IC50value was reduced almost 2.5 folds. Significant enhancement in Cmax(3.3-folds) and AUC (2.7-folds) of rat plasma levels indicated notable pharmacokinetic superiority of LMF-PC over LMF suspension. Differential leukocytic count and cytokine assay delineated plausible immunoregulatory role of LMF-PC with nearly 98% chemosuppression and over 30 days of post-survival.ConclusionSuperior antimalarial efficacy and survival time with full recovery of infected mice revealed through histopathological studies.

Postoperative delirium (POD) is a transient neurocognitive disorder in which the patient's awareness, attention and cognitive performance are acutely impaired.

This article investigates the efficiency of using ethanol as the extracting solvent for the desalination of pre-treated mine wastewater. The wastewater, concentrated through reverse osmosis (RO), had a salinity of 47,115.60 ppm before solvent extraction. Results showed that 13.31% of the salt was extracted via ethanol extraction using a ratio of 85:15 (v/v) ethanol to RO concentrate at 55 °C. An average salinity reduction of 46.04% was achieved. Ethanol was effective in reducing scaling ions such as calcium and sulfate and, to a lesser extent, magnesium. The highest removal efficiencies were achieved for the arsenic and manganese elements, despite their low inlet concentrations (0.299 ppm and 0.181 ppm, respectively). The removal efficiencies of monovalent ions were moderate. However, the results revealed concerning levels of iron, lithium, and boron, showing a high concentration of the two last elements in the product water. This study shows the significance of ethanol extraction desalination as a viable alternative to thermal desalination processes, especially for generating water that meets specific end-use needs.

Objective At present, minimal invasive direct coronary artery grafting is the least invasive nonrobotic surgical approach to revascularize the left anterior descending artery with the left internal mammary artery. Total endoscopic coronary bypass grafting is performed with the help of a telemanipulator (“robot”). A prospective proof-of-concept study was initiated to investigate a nonrobotic total endoscopic coronary bypass grafting approach.Methods Twenty patients with significant left anterior descending artery or left main stem lesion were operated on via three or four left thoracic access ports. Under exclusive endoscopic vision, the left internal mammary artery was harvested and anastomosed to the left anterior descending artery manually. Cardiopulmonary bypass and cardioplegic arrest were planned in all cases.Results In 10 patients, the operation was completed successfully as nonrobotic total endoscopic coronary bypass grafting. Reasons for conversions to minimal invasive direct coronary artery grafting or conventional sternotomy were dense pleural adhesions (3 patients), bleeding of the anastomosis (3), diffuse bleeding during left internal mammary artery harvesting (2), identification problems of the target artery (1), or left internal mammary artery failure (1). Postoperative angiography in five primarily successful nonrobotic total endoscopic coronary bypass grafting patients showed patent anastomoses in four cases. One patient was reoperated on for early anastomotic failure in a 1.0-mm target vessel. Until now, a percutaneous coronary intervention of remaining lesions as staged hybrid procedure was performed in three patients (2 nonrobotic total endoscopic coronary bypass grafting, 1 minimal invasive direct coronary artery grafting).Conclusions With a thoroughly surveyed learning curve, nonrobotic total endoscopic coronary bypass grafting procedure could become an alternative to other available treatment options; however, the value of the procedure has to be further investigated.

From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day of life, closely followed by a wave of IL-13-producing type 2 innate lymphoid cells (ILC2s), which coincided with the appearance of alveolar macrophages (AMs) and their early polarization to an IL-13-dependent anti-inflammatory M2 phenotype. ILC2s contributed to lung quiescence in homeostasis by polarizing tissue resident AMs and induced an M2 phenotype in transplanted macrophage progenitors. ILC2s continued to maintain the M2 AM phenotype during adult life at the cost of a delayed response to Streptococcus pneumoniaeinfection in mice. These data highlight the homeostatic role of ILC2s in setting the activation threshold in the lung and underline their implications in anti-bacterial defenses.

Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.

This article presents the author's experience with a man named Stephan Prokhorov who was successful in every aspect of life but was worried about his successfulness. According to Prokhorov, he has performed every kind of labor, even descending to the most menial services. In the last he came to work in a bathhouse. he is being working there since last seventeen years. In conclusion he said that there is little wisdom in all human agitations, and none at all when one looks life very seriously. He lives without God and he is sorry for people because of there helplessness against God.

Phosphatidylinositol 3-kinase catalytic subunit p110β is involved in tumorigenesis and hemostasis. However, it remains unclear if p110β also regulates platelet-mediated immune responses, which could have important consequences for immune modulation during anti-cancer treatment with p110β inhibitors. Thus, we investigate how platelet p110β affects inflammation and infection. Using a mouse model of Streptococcus pneumoniae-induced pneumonia, we find that both platelet-specific p110β deficiency and pharmacologic inhibition of p110β with TGX-221 exacerbate disease pathogenesis by preventing platelet-monocyte and neutrophil interactions, diminishing their infiltration and enhancing bacterial dissemination. Platelet p110β mediates neutrophil phagocytosis of S. pneumoniae in vitroand curtails bacteremia in vivo. Genetic deficiency or inhibition of platelet p110β also impairs macrophage recruitment in an independent model of sterile peritonitis. Our results demonstrate that platelet p110β dysfunction exacerbates pulmonary infection by impeding leukocyte functions. Thereby, our findings provide important insights into the immunomodulatory potential of PI3K inhibitors in bacterial infection.

Individualized heparin management (IHM) uses heparin dose–response curves to improve hemostasis management during cardiac surgery as compared with activated clotting time‐based methods.

Macrophages are dynamic immune cells that can adopt several activation states. Fundamental to these functional activation states is the regulation of cellular metabolic processes. Especially in mice, metabolic alterations underlying pro-inflammatory or homeostatic phenotypes have been assessed using various techniques. However, researchers new to the field may encounter ambiguity in choosing which combination of techniques is best suited to profile immunometabolism. To address this need, we have developed a toolbox to assess cellular metabolism in a semi-high-throughput 96-well-plate-based format. Application of the toolbox to activated mouse and human macrophages enables fast metabolic pre-screening and robust measurement of extracellular fluxes, mitochondrial mass and membrane potential, and glucose and lipid uptake. Moreover, we propose an application of SCENITH technology for ex vivometabolic profiling. We validate established activation-induced metabolic rewiring in mouse macrophages and report new insights into human macrophage metabolism. By thoroughly discussing each technique, we hope to guide readers with practical workflows for investigating immunometabolism.

Objective Nonrobotic total endoscopic coronary bypass grafting is commonly considered as technically too difficult. After endoscopic practicing in a simple box model, we questioned this statement in a more sophisticated training model.Methods In a handmade chest model containing a mechanically actuated porcine heart, anastomoses between homologous vein and shunted anterior coronary artery were performed using Prolene 7–0 sutures or U-clips in 20 anastomoses each. Commercially available endoscopic instruments and exclusive two-dimensional endoscopic vision were used. As quality control, the procedures were recorded, flow was measured, indocyanine green dye angiograms were performed, vinylpolysiloxane endocasts were produced, and finally the anastomoses were assessed from the endothelial side. Three-dimensional computed tomographic reconstruction was explored for cast measuring.Results All anastomoses were completed successfully in a time of 51 ± 14 minutes (Prolene) and 48 ± 10 minutes (U-clips). Despite suboptimal equipment, a reproducible sequence of the procedure was established and documented. Improving surgical performance was reflected in a reduction in anastomotic leakage and time requirement. The quality assessment protocol showed a learning curve and problems itself, which are briefly discussed.Conclusions A beating heart model is an adamant requirement of training for the technically demanding procedure of nonrobotic total endoscopic coronary bypass grafting. Refinement of the model and quality assessment as well as expansion of training to other regions of the heart should prepare for a cost-effective, broad-based clinical application of nonrobotic endoscopic techniques in coronary surgery. Available high-definition three-dimensional vision systems and the development of appropriate (articulating) instruments will make the procedure safer and quicker and will cut the learning curve.

Objective The long-term survival after minimal invasive direct coronary artery bypass (MIDCAB) surgery to any coronary territory in patients with ejection fraction of ≤30% was investigated for the first time in literature.Methods Seventy-three patients with primary MIDCAB and 89 patients with reoperative MIDCAB were studied including preoperative risk factors, operative details, early postoperative complications, and survival up to 10 years postoperatively.Results Despite the high-risk profile of the patients, the MIDCAB approach for targeted revascularization resulted in excellent short-term results. Ventricular arrhythmia contributed to four of six early deaths. Survival at 5 years postoperatively was 62.5% for primary MIDCAB and 43.2% for reoperative MIDCAB and at 10 years was 36.9% and 29.5%, respectively. Functionally complete vascularization correlates with significantly better long-term survival particularly in primary MIDCAB procedures.Conclusions MIDCAB is a valuable option for targeted revascularization in high-risk patients with low ejection fraction and reoperation.

Objective Conventional reoperative coronary artery bypass grafting is associated with risk of sternal re-entry, injury to patent grafts, and embolization from diseased grafts. Sternal sparing minimally invasive direct coronary artery bypass (MIDCAB) avoids such risks in cases where it is technically feasible. We sought to examine in-hospital outcomes of reoperative MIDCAB surgery.Methods We recorded prospective standardized data from the New York Cardiac Surgical Reporting System database of 369 reoperative MIDCAB cases from 1996 to 2006 and compared with 822 primary MIDCAB patients in the same time period. We compared the preoperative risk profile and postoperative in-hospital outcomes and length of stay for both groups.Results There was a significantly higher risk profile typical of the reoperative patient population (P < 0.001 for stroke, peripheral/cerebrovascular disease, extensive aortic calcification, renal failure, and left ventricular ejection fraction <40%) compared with the primary MIDCAB group. Despite this fact, there was no difference in the in-hospital outcomes and length of hospital stay between the two groups.Conclusions Reoperative MIDCAB provides targeted coronary revascularization and avoids hazards of sternal re-entry, graft injury and manipulation, and deleterious effects of cardiopulmonary bypass. This hastens recovery and provides excellent early outcomes equivalent to primary MIDCAB procedures.

Objective Long-term survival after off-pump surgery in patients with low ejection fraction was investigated.Methods Three hundred forty-six patients with ejection fraction 30% or less with isolated off-pump coronary artery bypass surgery (OPCAB) were compared with a propensity matched historical group operated on-pump (ONCAB) and with data from literature after percutaneous coronary intervention and OPCAB surgery.Results The lower invasiveness of OPCAB contributed to a significantly better 30-day survival, shorter postoperative length of stay, and fewer in-hospital complications. Incomplete revascularization of the posterior and lateral territories of the heart correlated with higher 1-year mortality. The probability of survival for 8 years after OPCAB was 50.1% (n = 76) versus 49.7% (n = 82) for ONCAB without comparable data from literature for OPCAB or percutaneous coronary intervention in these high-risk patients.Conclusions OPCAB surgery in patients with low ejection fraction is a viable alternative but so far without demonstrable long-term survival advantage to ONCAB.

Rhinoviruses (RVs) and coronaviruses (CoVs) upregulate host cell metabolic pathways such as glycolysis to meet their bioenergetic demands for rapid multiplication. Using the glycolysis inhibitor 2-deoxy-D-glucose (2-DG), we assessed the dose-dependent inhibition of viral replication of minor- and major-receptor group RVs in epithelial cells. 2-DG disrupted RV infection cycle by inhibiting template negative-strand as well as genomic positive-strand RNA synthesis, resulting in less progeny virus and RV-mediated cell death. Assessment of 2-DG´s intracellular kinetics revealed that after a short-exposure to 2-DG, the active intermediate, 2-DG6P, is stored intracellularly for several hours. Finally, we confirmed the antiviral effect of 2-DG on pandemic SARS-CoV-2 and showed for the first time that 2-DG also reduces replication of endemic human coronaviruses (HCoVs). These results provide further evidence that 2-DG could be utilized as a broad-spectrum antiviral.

Recent structural, petrological and geochronological work on plutons in eastern Borborema Province (NE Brazil) has helped to constrain its tectonic evolution during the Brasiliano/Pan-African Orogeny. 645-630 Ma-old plutons have been intensely affected by solid-state deformation. They show an early, shallowly to moderately-dipping foliation conformable with the regional fabric of country rocks, which is overprinted by a steeply-dipping foliation related to strike-slip shearing. Two compositional groups are recognized: (i) medium-K, epidote-bearing granodiorites, and (ii) coarse-grained granites and associated diorites. 590-580 Ma-plutons were emplaced before or at the very early stage of movement along large transcurrent shear zones, and include high-K calc-alkaline plutons and metaluminous syenites. The 590-580 Ma-old plutons underpin the change from a low-angle tectonic event to transpressive deformation. Once emplaced, these plutons in turn favored the localization of strain needed to promote nucleation of the spatially associated shear zones. Finally, two-mica leucogranites and dike swarms of widely varying compositions were emplaced around 570 Ma at the advanced stages of motion along transcurrent shear zones.

Collisional and accretionary processes have been recognized in several Precambrian orogens, but the formation of intracontinental (ensialic) orogens has remained elusive. The recognition that modern orogenic belts (as, for example, the mountain belts of central Asia) may form in response to far-field stresses transmitted to the interior of continental plates removed much of the objection against Proterozoic intracontinental deformation. However, the causes responsible for the localization of contractional deformation are still uncertain. Due to the strong dependence of lithosphere rheology on temperature, lithospheric thermal weakening prior to contraction must be a required condition. Studies of dioritic rocks from Borborema Province, northeastern Brazil, and Damara belt, southern Africa, indicate that they are derived from ancient, incompatible elements-enriched subcontinental lithosphere. The concentrations of the heat-producing elements K (0.6 wt %), U (0.02–0.2 ppm) and Th (0.15–1.5 ppm) estimated for this source allow calculations of heat production between 0.09 and 0.25 mW m−3. These high values of heat generation may cause increases in temperature of several tens to three hundred degrees Celsius with respect to cratonic mantle lithosphere, leading to great reductions in lithosphere strength. Consequently, continental domains underlain by hot and weak continental mantle may thicken under the action of relatively feeble tectonic forces. High rheological contrasts between these domains and adjacent stiff and cold blocks provide an explanation for formation of intracontinental orogens.

Accretion of exotic terranes during the Cariris Velhos (late Mesoproterozoic to early Neoproterozoic) and Brasiliano (late Neoproterozoic) events has been proposed as an important process of continental growth in Borborema province, northeastern Brazil. If this hypothesis holds true, it is reasonable to assume that the roots of these accreted blocks have variable chemical and isotopic compositions. Here, we investigate this possibility using lithospheric-derived high-K calc-alkalic diorites. These rocks are widespread throughout the province and occur in areas proposed to represent distinct tectonic terranes. The similar geochemical and Sm-Nd isotopic signatures of the diorites (TDM from 1.7 to 2.0 Ga), except for one pluton, impose serious limitations to the terrane accretion model in Borborema province. On the contrary, these data strongly suggest that a large portion of the province is underlain by a LILE-enriched metasomatized lithospheric mantle formed around 2.0 Ga.

This work presents geochemical data for granitic plutons that intruded the Alto Pajeu terrane, Borborema Province, northeastern Brazil, during several distinct tectonic cycles. The Alto Pajeu terrane is represented in the study area by metasedimentary (Sao Caetano Formation) and metavolcanosedimentary (Irajai Formation) sequences overlying a gneissic-migmatitic basement. Several granitic plutons of different ages, mineralogical proportions, and chemical compositions have invaded the supracrustal and basement rocks. Two deformational events, one tangential (older) and the other transcurrent (younger), were identified. The metamorphic grade determined for the metasedimentary rocks varies from amphibolite to high amphibolite facies, with temperatures ranging from 600 to 680°C and pressures from 6.0 to 7.5 kbar. Three magmatic events with distinct ages were identified for the tectonic evolution of the Alto Pajeu terrane in the study area. The older magmatic event is related to the Transamazonico orogenic cycle (∼ 2.0 Ga), the intermediary magmatic event to the Cariris Velhos cycle (∼0.97 Ga), and the younger magmatic event to the Brasiliano orogenic cycle (∼0.55 Ga). The Cariris Velhos- and Brasiliano-age granites are geochemically classified as peraluminous, subalkalic granites of the calc-alkalic series, whereas the Transamazonico-age granite is metaluminous and alkaline. Geochemical data presented and discussed here suggest that the magmatism related to the three tectonic events had distinctly different sources and petrogenetic evolutions.

Numerous transcurrent NE-SW, mainly sinistral, and E-W dextral-trending shear zones transect Borborema Province, northeastern Brazil. The most important kinematic event involving those shear zones reflects deformation related to the Brasiliano (Pan-African) tectonic cycle. The Afogados da Ingazeira shear zone (AISZ) is probably the most important of the NE-SW-trending lineaments, having continuity for over 250 km. Field work associated with petrographic studies (including quartz c-axis patterns), conducted in an area encompassing the north-central part of this shear zone, indicate that sinistral transcurrent deformation was responsible for the main banding/foliation (C-S) observed in the rocks. Mineral assemblages and microstructural features are suggestive of a deformational history starting under low- to medium-amphibolite facies (thermal peak conditions) and decreasing until greenschist facies.

The influence of temperature and applied stress on creep in single crystals of lead has been investigated. Between 20 and 180 K a thermally activated “logarithmic” creep is observed that is easily interpreted in terms of theory based on a work hardening concept. In case recovery processes are absent the weakening of the “logarithmic” creep is determined by hardening of the crystal during the creep process and the level of effective stresses. The creep vanishes when the effective stresses become zero. The disappearance of creep at the point T0 has been shown experimentally. The temperature T0 is that at which critical shear stresses reach the temperature-independent branch of the yield-point curve ?T(T). At temperatures higher than T0 a steady-state creep is observed. At a fixed stress the creep rate is determined by the rate of recovery processes. The results obtained are described in terms of thermally activated dislocation motion.

High-K calc-alkalic plutons represent a significant proportion of the abundant magmatic bodies that intruded Borborema province (BP) of northeastern Brazil during the Neoproterozoic Brasiliano (Pan-African) orogeny. They consist of an association of mafic to intermediate (diorites to granodiorites) and felsic rocks (coarse-grained to porphyritic quartz monzonites to granites). Field and petrographic evidence indicates that the felsic and mafic rocks coexisted as contemporaneous melts, and major- and trace-element data favor magma mixing over fractional crystallization as the main petrogenetic process responsible for the petrographic and geochemical variability of these rocks. Major- and trace-element, oxygen-isotope, and radiogenic-isotope (Sr and Nd) data suggest that (1) the main source rocks of the granitoids are lower-crustal amphibolites having rare-earth-element (REE) and isotopie characteristics similar to the associated mafic rocks and (2) the source region of the diorites is the metasomatized subcontinental lithospheric mantle. These inferences imply that crustal growth occurred during the Brasiliano orogeny. Dewatering of the mantle and lower crust and addition of consolidated mafic rocks and I-type granitoids to the middle crust certainly strengthened the entire lithosphere, thus contributing to the final cratonization of the BP.Field evidence indicates that the BP high-K calc-alkalic plutons were emplaced in an intracontinental setting, implying that this magmatism was not subduction-zone related. Although the plutons are spatially associated with transcurrent shear zones, the scale of magmatism is too broad to be assigned to shear heating. 40Ar/39Ar data indicate that large areas of the BP underwent slow cooling, unlike orogenic belts where delamination or convective removal of the lithosphere occurred. Therefore, only large convective instabilities in the sublithospheric mantle may explain the thermal anomaly responsible for melting in the BP. It is proposed that a mantle plume impinging the base of the continental lithosphere under the BP may represent such a laterally extensive and long-lived heat source.

The Itaporanga batholith (state of Paraiba, northeastern Brazil) is composed of an intimate association of potassic, calc-alkalic, porphyritic quartz monzonitic to granitic rocks and biotite diorites. Net-veined structures demonstrate that the main petrogenetic process during evolution of this batholith involved coexistence and local mixing of magmas. In this work, mineral chemistry and oxygen-isotope data are discussed as an attempt to establish the origin of these magmas. Temperatures obtained through mineral chemistry vary from 690° to 730° C for felsic and mafic rocks, suggesting control by the processes of mingling and mixing of magmas. Chemistries of amphibole and biotite are controlled by the bulk chemistry of K-dioritic to quartz monzodioritic and porphyritic quartz monzonitic rocks, which were influenced by coexistence and local mixing of magmas. A biotite diorite enclave that did not equilibrate with the host quartz monzonite has amphibole and biotite compositions that differ from those diorites and quartz diorites that more intimately interacted with the porphyritic quartz monzonites. Oxygen-isotope data for quartz show that the K-diorite is enriched in 18O relative to the porphyritic quartz monzonite, suggesting that these rocks were not related through crystal fractionation processes and that their magmas had different isotopic signatures. This information, combined with mineral chemistry data, strongly suggests that K-dioritic and porphyritic quartz monzonitic magmas were not consanguineous.

Cerebral malaria is a serious plasmodial infection that calls for immediate treatment for parasitic clearance from brain. Oral regimen of cerebral malaria is an impracticable option, it being often associated with problems like impaired consciousness, nausea and anorexia. The current research studies were, accordingly, undertaken to develop a patient-friendly non-invasive and rapid therapy via intranasal delivery of artemether (AM) and lumefantrine (LMF) employing their surface-modified lipidic nanocarriers (LNCs) using N, N, N trimethyl chitosan (TMC) as the polymer. Systematically developed employing Quality-by-Design (QbD) principles, LNCs and TMC-LNCs exhibited particle size of 63.7 and 80.8 nm, polydispersity of 0.19 and 0.28, respectively, along with modulated drug release profile for a period of 48 h. TMC-LNCs indicated nearly 2- and 7-folds enhancement in the mucoadhesive strength and nasal mucosal permeation vis-à-visconventional LNCs and pure drug(s) suspension, respectively. In vitro nitric oxide assay unraveled the potential of both TMC-LNCs and LNCs to trigger macrophages for stimulating innate immune response against the parasites. Brain biodistribution studies in female C57BL/6 mice indicated higher drug concentrations in mice brain with intranasally delivered TMC-LNCs over intranasal and peroral AM-LMF suspension. Further, the speed and effectiveness of TMC-LNCs and LNCs in eradicating Plasmodium bergheiANKA strain in the murine model was also evaluated. Intranasal TMC-LNC demonstrated considerable in vivoanti-plasmodial efficacy with over 95% parasite suppression on day 7, followed by intranasal LNCs (82.5%), intranasal AM-LMF (79.1%) and peroral AM-LMF (46.3%). Overall, the surface-modified formulation, i.e.,intranasal TMC-LNCs demonstrated markedly superior efficacy and parasitic suppression in brain.

In Russian cruelty one feels a diabolic ingenuity, as if it were a question of something exquisite and delicate. One cannot explain it by the words psychic abnormality and sadism, which really explain nothing at all. Hundreds of such aphorisms containing the fine flower of centuries of popular wisdom are current in Russian villages. Young girls are brought up on them, these proverbs are their school. And the young girls, too, are beaten with equal ardor. The author once studied the records of the Moscow courts for the decade 1901-1910, he was struck by the enormous number of outrages upon young girls and of all sorts of other crimes with minors. Beating is a favorite pastime in Soviet Union and it matters little whom one beats.

The article is from a series of reminiscences of Nikolai Lenin published in the Neue Rundschau. The author states that to him Lenin is the hero of a legend, a man who had torn the burning heart out of his breast in order to light up for mankind the path which shall lead it out of the shameful chaos of the present, out of the rotting bog of stupid current politics. His hero-character has almost no outward adornment. His heroism is of a type not rare in Soviet Union--the modest, ascetic martyrdom of an honorable, intellectual revolutionary who honestly believes in the possibility of justice on earth; the heroism of a man who has renounced all the pleasures of life to do hard work for the happiness of mankind.

Zusammenfassung: Intraabdominale oder -thorakale Fehllagen nach Einführen einer Thoraxdrainage können vorkommen, eine Perforation des linken Ventrikels ist bisher selten beschrieben. Wir berichten von einer 57-jährigen Patientin, die nach Anlage einer Pleuradrainage wegen eines postpneumonischen Pleuraergusses akut kreislaufinsuffizient und bei kardiogenem sowie hämorrhagischem Schock prolongiert reanimationspflichtig wurde. Intraoperativ fand sich eine Perforation des linken Ventrikels mit Hämoperikard. Trotz initial infauster Ausgangssituation resultierte funktionell ein gutes Outcome.

No relevant conflicts of interest to declare.

During low-temperature (550°C) impregnation with nitrogen, thin intercrystalline films (precipitates) form in transformer steel (Fe+3% Si).

Presents letters to the editor on different topics. Comments of the U.S. policy towards smaller European nations; Effects of actions of radical Americans; Manifestations produced by the war in the Soviet Union.

Summary: Cystic fibrosis (CF) patients (n = 157) from the GDR were analysed for the occurrence of the recently discovered 3bp deletion causing CF. About 50% of all investigated patients were homozygotes and about 30% heterozygotes for this deletion. Of the analysed CF chromosomes from these patients, 62% carry the deletion, which is in strong linkage disequilibrium with the KM19 restriction fragment length polymorphism allele 2 and the 1/2 XV2c/KM19 haplotype.

Objectives. To measure device-associated infection (DAI) rates, microbiological profiles, bacterial resistance, extra length of stay, and attributable mortality in intensive care units (ICUs) in three Brazilian hospitals that are members of the International Nosocomial Infection Control Consortium (INICC). Methods. Prospective cohort surveillance of DAIs was conducted in five ICUs in three city hospitals in Brazil by applying the definitions of the U.S. Centers for Disease Control and Prevention National Nosocomial Infections Surveillance System (CDC-NNIS). Results. Between April 2003 and February 2006, 1 031 patients hospitalized in five ICUs for an aggregate 10 293 days acquired 307 DAIs, a rate of 29.8% or 29.8 DAIs per 1 000 ICUdays. The ventilator-associated pneumonia (VAP) rate was 20.9 per 1 000 ventilator-days; the rate for central venous catheter-associated bloodstream infections (CVC-BSI) was 9.1 per 1 000 catheter-days; and the rate for catheter-associated urinary tract infections (CAUTI) was 9.6 per 1 000 catheter-days. Ninety-five percent of all Staphylococcus aureus DAIs were caused by methicillin-resistant strains. Infections caused by Enterobacteriaceae were resistant to ceftriaxone in 96.7% of cases, resistant to ceftazidime in 79.3% of cases, and resistant to piperacillintazobactam in 85.7% of cases. Pseudomonas aeruginosa DAIs were resistant to ciprofloxacin in 71.3% of cases, resistant to ceftazidime in 75.5% of cases, and resistant to imipenem in 27.7% of cases. Patients with DAIs in the ICUs of the hospitals included in this study presented extra mortality rates of 15.3% (RR 1.79, P = 0.0149) for VAP, 27.8% (RR 2.44, P = 0.0004) for CVC-BSI, and 10.7% (RR 1.56, P = 0.2875) for CAUTI. Conclusion. The DAI rates were high in the ICUs of the Brazilian hospitals included in this study. Patient safety can be improved through the implementation of an active infection control program comprising surveillance of DAIs and infection prevention guidelines. These actions should become a priority in every country. [ABSTRACT FROM AUTHOR]