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This article explores the use of artificial intelligence (AI) in the development of vaccines against pathogens. AI has shown promise in predicting and forecasting potential vaccines based on genetic and proteomic data, which can help expedite the vaccine creation process. The article also discusses the use of AI in developing vaccines for viral, bacterial, and parasitic diseases. However, there are challenges in using AI for parasite vaccines due to limited data on nematodes. The article emphasizes that while AI can enhance vaccine development, it should not replace traditional laboratory testing and regulatory processes for ensuring safety and effectiveness. [Extracted from the article]

Pyrin is a cytosolic immune sensor that nucleates an inflammasome in response to inhibition of RhoA by bacterial virulence factors, triggering the release of inflammatory cytokines, including IL-1β. Gain-of-function mutations in the MEFV gene encoding Pyrin cause autoinflammatory disorders, such as familial Mediterranean fever (FMF) and Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). To precisely define the role of Pyrin in pathogen detection in human immune cells, we compared initiation and regulation of the Pyrin inflammasome response in monocyte-derived macrophages (hMDM). Unlike human monocytes and murine macrophages, we determined that hMDM failed to activate Pyrin in response to known Pyrin activators Clostridioides difficile (C. difficile) toxins A or B (TcdA or TcdB), as well as the bile acid analogue BAA-473. The Pyrin inflammasome response was enabled in hMDM by prolonged priming with either LPS or type I or II interferons and required an increase in Pyrin expression. Notably, FMF mutations lifted the requirement for prolonged priming for Pyrin activation in hMDM, enabling Pyrin activation in the absence of additional inflammatory signals. Unexpectedly, in the absence of a Pyrin response, we found that TcdB activated the NLRP3 inflammasome in hMDM These data demonstrate that regulation of Pyrin activation in hMDM diverges from monocytes and highlights its dysregulation in FMF. Pyrin inflammasome activation in human macrophages normally requires licensing by lipopolysaccharide or interferons, which increase pyrin expression. This study shows that MEFV mutations that cause familial Mediterranean fever enable pyrin activation in the absence of prior licensing. [ABSTRACT FROM AUTHOR]

The investigation was carried out during the COVID19 pandemic in 2021, maintaining relevance and investigative relevance. The objective is to know the socio-educational conditions generated by the educational community at the national level, in order to train mothers, fathers, and teachers, with technical-pedagogical strategies that reactivate and improve the sectoral teaching-learning process, using the methodology of scientific research for case studies, with a qualitative-quantitative approach from binding action with virtual activity design, carrying out a national situational diagnosis, taking an intentional stratified sample of 13,921 people from 24 provinces, through data collection tools; with community intervention methodology of linkage with society, managing to train 1,566 direct beneficiaries and 4,698 indirect. Taking as a unit of work and analysis a segmented focal structure of the educational community belonging to 40 educational institutions distributed nationwide. [ABSTRACT FROM AUTHOR]

Migratory insects may move in large numbers, even surpassing migratory vertebrates in biomass. Long-distance migratory insects complete annual cycles through multiple generations, with each generation's reproductive success linked to the resources available at different breeding grounds. Climatic anomalies in these grounds are presumed to trigger rapid population outbreaks. Here, we infer the origin and track the multigenerational path of a remarkable outbreak of painted lady (Vanessa cardui) butterflies that took place at an intercontinental scale in Europe, the Middle East, and Africa from March 2019 to November 2019. Using metabarcoding, we identified pollen transported by 264 butterflies captured in 10 countries over 7 months and modeled the distribution of the 398 plants detected. The analysis showed that swarms collected in Eastern Europe in early spring originated in Arabia and the Middle East, coinciding with a positive anomaly in vegetation growth in the region from November 2018 to April 2019. From there, the swarms advanced to Northern Europe during late spring, followed by an early reversal toward southwestern Europe in summer. The pollen-based evidence matched spatiotemporal abundance peaks revealed by citizen science, which also suggested an echo effect of the outbreak in West Africa during September–November. Our results show that population outbreaks in a part of species' migratory ranges may disseminate demographic effects across multiple generations in a wide geographic area. This study represents an unprecedented effort to track a continuous multigenerational insect migration on an intercontinental scale. [Display omitted] • Citizen science reports explosions of the butterfly Vanessa cardui in 2019 • Metabarcoding of butterfly-transferred pollen identifies non-native plant species • Plant distribution modeling infers butterfly migration and the outbreak's origin • Middle Eastern outbreak impacts Europe and Africa demographics Gorki et al. trace the migrations of painted lady butterfly (Vanessa cardui) population explosions during 2019. Anomalous vegetation growth and citizen science pinpoint the Middle East as the outbreak origin. DNA sequencing of transported pollen grains reveals long-distance movements across generations over the Middle East, Europe, and Africa. [ABSTRACT FROM AUTHOR]

Traditional medicinal plants are cardinal sources of new drug molecules for malaria treatment. The present study evaluates the antiplasmodial potential of erucic acid (EA) isolated from ethanolic whole plant extract of Thlaspi arvense (EWETA) and its synthetic methyl ester derivative (EA-OMe) and also confirms the in vivo efficacy of the crude extract. EA and EA-OMe exhibited considerable in vitro activity against chloroquine (CQ)-sensitive (IC 50 5.80 μg/ml and 6.25 μg/ml) and CQ-resistant (IC 50 6.07 µg/ml and 8.58 µg/ml) strains of P. falciparum , respectively. Both compounds were non-toxic to HeLa cells and normal dermal fibroblasts with high selectivity index. However, EA and EA-OMe exhibited moderate suppressive activity in vivo. Further, EWETA illustrated ED 50 <50 mg/kg in the suppressive test and prolonged the survival of treated mice in comparison to infected control. It also showed considerable preventive (500 mg/kg) and curative (100 mg/kg) activity with 91.75% and 91.93% chemo-suppression, respectively. Biochemical analysis also highlights the safety of EWETA to the liver and kidney function of the rodent host. It can be concluded that EA and EA-OMe are contributing to the activity of EWETA besides other components, which are being characterized. [Display omitted] • Erucic acid (EA) and its synthetic methyl ester derivative (EA-O-Me) were isolated from EWETA. • EA and EA-O-Me exhibited considerable in vitro activity against 3D7 and RKL-9 strains of P. falciparum. • Both compounds were non-toxic to HeLa cells and normal dermal fibroblasts with high selectivity index (SI >10). • The compounds exhibited moderate in vivo antimalarial activity, however, EWETA illustrated considerable efficacy. • Biochemical analysis also highlights the safety of EWETA to the liver and kidney function of the rodent host.. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum multi-drug resistant (MDR) strains are a great challenge to global health care. This predicament implies the urgent need to discover novel antimalarial drugs candidate from alternative natural sources. The Himalaya constitute a rich repository of medicinal plants which have been used traditionally in the folklore medicine since ages and having no scientific evidence for their activity. Crambe kotschyana Boiss. and Eremurus himalaicus Baker are used for their antipyretic and hepatoprotective properties in Kinnaur district of Himachal Pradesh, India. This study would investigate the antiplasmodial efficacy of C. kotschyana and E. himalaicus extracts, their fractions and active components using in vitro, in vivo and in silico approaches to provide a scientific insight into their activity. The methanol extracts of C. kotschyana (CKME) and E. himalaicus (EHME) were prepared by maceration followed by fractionation using ethyl acetate. The isolation of flavonoid glycosides isorhamnetin-3, 7-di-O-glucoside from C. kotschyana and luteolin-6-C-glucoside (isoorientin) from E. himalaicus was carried out by antiplasmodial activity-guided isolation. In vitro antimalarial activity was assessed by WHO method while in vitro cytotoxicity was ascertained employing the MTT assay. Molecular docking and molecular dynamics simulation were performed using the Glide module of Schrödinger Software and Gromacs-2022 software package respectively. In vivo curative activity was assessed by Ryley and Peters method. The methanol extracts of both the plants illustrated the best antiplasmodial activity followed by the ethyl acetate fractions. Iso-orientin (IC 50 6.49 μg/ml) and Isorhamnetin-3,7-di-O-glucoside (IC 50 9.22 μg/ml) illustrated considerable in vitro activity even against P. falciparum resistant strain. Extracts/fractions as well as the isolated compounds were found to be non-toxic with CC 50 > 640 μg/ml. Molecular docking studies were performed with these 2 O-glucosides against four malaria targets to understand the binding pose of these molecules and the results suggested that these molecules have selectivity for lactate dehydrogenase enzyme. CKME and EHME exhibited curative activity in vivo along with increase in Mean Survival Time of mice. The research delineated the scientific evidence that both the therapeutic herbs possessed antimalarial activity and notably, bioactive compounds responsible to exhibit the antimalarial activity have been isolated, identified and characterized. Further studies are underway to assess the antiplasmodial efficacy of isolated compounds alone and in combination with standard antimalarials. [Display omitted] • Isorhamnetin-3, 7-di-O-glucoside was isolated from C. kotschyana. • Luteolin-6-C-glucoside (isoorientin) was isolated from E. himalaicus. • Extracts/fractions & isolated compounds exhibited promising antimalarial activity with no toxicity. • Molecular docking showed selectivity of O-glucosides for lactate dehydrogenase and FP3. • Methanol extract of both plants exhibited promising in vivo curative activity. [ABSTRACT FROM AUTHOR]

Background From the results of a previous study, it remained to be investigated if a perioperative rise of few tested coagulation and inflammation markers is caused by conventional cardiopulmonary bypass (CPB) itself or rather by direct recirculation of pericardial fluids. Methods Forty-eight patients operated on with conventional CPB for myocardial revascularization were randomized either for direct recirculation of pericardial suction fluids or for cell saving (CS). Results Thrombin–antithrombin complexes showed lower values intraoperatively in the CS group (p < 0.0001), and D-dimers tended to remain lower at intensive care unit arrival (p = 0.095). Tests of inflammation markers were less meaningful. Conclusion Direct recirculation of pericardial fluids rather than conventional CPB itself causes major intraoperative changes of some coagulation markers. Pericardial blood loss with direct recirculation should be kept to a minimum to avoid unnecessary activation of coagulation. Inflammation markers need further investigations. [ABSTRACT FROM AUTHOR]

In the present publication, the topic of educational innovation is analyzed, relating it to the academic performance of the students from San Martin de Porras University, with the perspective of improving their performance in an integral manner. Likewise, the best resources of modern pedagogy are developed thanks to the rational incorporation into university teaching, of innovative means and processes, and also to the use of new technologies, which tend to improve knowledge in their methodological and conceptual strategies and models that lead to institutional changes. It is good to point out that the application of innovative experiences is related to the use of audiovisual and computational resources. As a conclusion, it is important to point out that the strategic educational innovation that has been developed, which is nourished by science and technology, has as a great objective to improve the academic performance of students in the academic, cognitive and motivational fields. [ABSTRACT FROM AUTHOR]

Background Total endoscopic coronary artery bypass grafting (TECAB) is currently performed exclusively with the help of a telemanipulator. After extensive practice in a biomechanical model, the operation was performed as a nonrobotic approach in an animal study. Methods Six large domestic pigs were anesthetized and intubated. Port access and endoscopic vision were used exclusively during the intrathoracic procedure. In five animals, an internal mammary artery was harvested, extracorporeal circulation was established via peripheral vessel access, and the ascending aorta occluded with an intraluminal balloon. In cardioplegic arrest, an anastomosis of internal mammary artery and left anterior descending coronary artery was performed with shortened 7-0 monofil thread running suture. As a terminal study, the animals were humanely killed and the quality of the anastomoses was checked. Results After a steady learning curve, the fifth animal was operated on successfully and a satisfactory anastomosis was documented. Conclusion Despite demanding differences to humans as shape of thoracic cavity and size of peripheral access vessels, the viability of the nonrobotic TECAB concept was documented in a living animal model. [ABSTRACT FROM AUTHOR]

Background: Supposedly, minimized extracorporeal circulation or off-pump revascularization as alternatives to conventional extracorporeal circulation (ONCAB) reduce inflammation and coagulation disturbances. Methods: One hundred and twenty coronary artery bypass graft (CABG) patients were prospectively randomized for three surgical techniques. Coagulation and inflammation markers were measured up to 72 hours postoperatively. Results: Coagulation factors I, II, V, X, antithrombin III and C-reactive protein did not differ perioperatively between the groups and increased, as did several other markers, 12 to 72 hours postoperatively. Compared to its alternatives, ONCAB showed the most obvious transient increase in thrombin-antithrombin complexes (p<0.0001), D-dimers (p=0.0059), tissue factor pathway inhibitor (p=0.0005), factor VIII (p=0.0041) and tumor necrosis factor α (p=0.0300) during the operation and up to 12 hours postoperatively. Furthermore, ONCAB generated lower leukocyte and platelet counts and higher values of soluble P-selectin and soluble intercellular adhesion molecule 1 at some time points. Conclusions: With similarity in pivot coagulation factors, a specific detrimental influence of ONCAB on common coagulation pathways was excluded. Higher perioperative concentrations of products from the coagulation cascade most likely indicate activation of pericardial blood – recirculated only in ONCAB. Furthermore, with only temporary differences in markers of inflammation, the alternatives to ONCAB altogether were without advantage at 72 hours postoperatively. In the general answer to surgical trauma, the part of modern extracorporeal circulation is possibly overestimated. The study is registered at the German Clinical Trial Registry. Registration number DRKS00007580. URL: https://drks-neu.uniklinik-freiburg.de/drks_web/ URL: http://apps.who.int/trialsearch/ [ABSTRACT FROM AUTHOR]

The rice (Oryzaesativa L.) is the main food source in Ecuador. It is mainly a part of the staple diet of people from coast region. The disease called blast or burning rice caused by Pyricularia oryzae Cav., is among adverse biotic factors to the culture. It can cause damage from 59.6% to 100%. The objective of this research was to quantify the severity (numbers of lesions per leaf) in 39 materials (lines and varieties) in small and medium size of rice. Both of them were divided into two experiments established in central zone on ecuadorian region. The severity of rice blast was assessed on leaves of the lower, middle and superior strata in plants of rice, once by week, totaling eight times. It was used an experimental design at random complete blocks (RCB) with 3 replications. The values obtained were joined in the Area under progress curve on rice blast (AUPCRB). It was used "T" test at 5% probability of error for comparison between treatments means. There was differential health behavior between genotypes assessed in both experiments. Outstanding materials in the first experiment were the variety INIAP-16 (9.9) and the lines INIAP-14-7 (11.2) while in the second experiment were the variety Caluma (17.4) and the line CC-05-27 (18.8) for having obtained a least AUPCRB. [ABSTRACT FROM AUTHOR]

Abstract: Repeated ash fall events have occurred during the 1999-ongoing eruption of Tungurahua volcano, Ecuador, notably during the late 1999 and August 2001 eruptive phases. While the eruptive styles were similar, these two phases had different impacts on nearby rural and urban Andean populations: ash falls in late 1999 had limited effects on human health and farming, whereas the 2001 phase resulted in medical problems, death of animals in livestock, and damages to houses and crops. Here we investigate the origin of this difference by estimating the size of the August 2001 event (VEI, magnitude, intensity), and by comparing monitoring information of the 1999 and 2001 phases (duration, explosion rate, column height, SO2 output rate). The results show that both phases ranked at VEI 3, although the longer 1999 phase was likely larger than the 2001 phase. Mass magnitude (M) and intensity (I) indexes calculated for the 2001 phase reach M ≈2.7 and I ≈6.5 when based on ash fall layer data, but increase to M ≈3.2 and I ≈7.0 when ballistic products are included. We investigated the influence of rain fall and wind flow regimes on ash dispersion, sedimentation and remobilization. The analysis indicates that the harmful effect of the 2001 phase resulted from unfavorable conditions that combined volcanological and seasonal origins, including: a) a low elevation of the ash plume above rural regions owed to a usually bent-over column, b) ash sedimentation in a narrow area west of the volcano under sub-steady wind directions, c) anticipated ash settling by frequent rain flushing of low intensity, and d) formation of a wet cohesive ash coating on buildings and harvests. Conversely, the stronger 1999 phase injected a large amount of ash at higher elevation in the dry season; the ash was widely disseminated across the whole Ecuadorian territory and beyond, and was frequently removed by rain and winds. In summary, our study illustrates the influences of eruption size and weather conditions on the impact of volcanic activity in a tropical setting and puts emphasis on the necessity to merge volcanological and meteorological monitoring duties for hazard assessment and alert level definition, in order to mitigate the effect of ash falls in the Andes and elsewhere. [Copyright &y& Elsevier]

Background: Adequate perfusion of the right ventricle with retrograde cardioplegia has always been questioned. However, clinical studies suggested sufficient protection and, up to now, intraoperative assessment of cardioplegia distribution has been difficult.Methods: As a pilot study in 14 patients, we used indocyanine green laser fluorescence angiography (ICGLA) to assess vascular and myocardial perfusion of different areas of the right anterior ventricular wall. Regions of interest were analyzed quantitatively using a new software package.Results: ICGLA allowed rapid and reliable visualization of cardioplegic flow and distribution. Retrograde cardioplegia revealed perfusion defects in the territory of the right anterior cardiac veins when compared to antegrade delivery and to areas close to the left anterior descending vein(s), confirmed by quantitative analyses of maximal fluorescence intensity. Five patients were excluded from quantitative analyses. The learning curve, pitfalls, limitations and special image details are described.Conclusion: A larger study is necessary to examine the relevance of perfusion defects to metabolic changes in affected myocytes and to global right ventricular function. [ABSTRACT FROM PUBLISHER]

The objective was to study agronomic development and yield of two bean varieties "Ecuavegetal-2" (EVG-2) and "Pata de paloma", under intercropped system with "INIAP H-552" hybrid corn through three seed intervals: 16 and 8 days before corn seeding (dbcs) and seeding of beans simultaneously with corn and also to measure productivity using the Land Equivalent Ratio (LER) and economic LER of the intercropped systems along with single crops. "Pata de paloma" showed less incidence of diseases, higher number of legumes and number of seeds per plant, although better weight of 100 grains was for "EVG-2". About seeding dates, better number of legumes was obtained at 8 and 16 dbcs. Intercropped bean recorded better yield components averages than single crops. The yield (kg ha-1) at 16 and 8 dbcs, did not present significant differences. Intercropped corn was not affected either by bean varieties or seeding dates. LER and economic LER analyses show higher coefficients for intercropped systems especially when bean was planted at 16 y 8 dbcs, higher LER coefficients were found when "Pata de paloma" was intercropped with "INIAP H-552" at 16 and 8 dbcs and higher REI coefficients were registered when "EVG-2" was intercropped with "INIAP H-552" at 8 and 16 dbcs. [ABSTRACT FROM AUTHOR]

Many investors and producers of teak wood in Ecuador without supplies from seedlings produced by small plant nurseries no modern technology, and they have the largest supply of seedlings, the technification can be a limiting factor in normal development of commercial plantations which does not guarantee obtaining vigorous plantations, healthy and high-timber production. From this point of view is necessary to know the entire process of production of seedlings as well as the origin and seed management, production costs and marketing systems. The study was realized in the influence area of the Los Rios province, Ecuador, because in this province there are established most of teak plant nurseries that supply the demand on the ecuadorian. Coast and Amazon. It was found that small nursery owners occupy their own property, carry out field activities, supervisory or marketing, although not in large nurseries where the technician oversees the work. The large plant nursers use certified seed and nursers small plant use seeds harvested trees from in the locality. The costs of seedlings of small plant nursers and producer of stumps was 0.07 USD, and tech producer level and in vitro plantlets 0.19 USD. The best value is obtained at the level of stumps (36%) followed by the production of plantlets in vitro (31%). The demand for the coming years requires an amount of approximately three to four million of seedlings, while supply does not exceed two million and a half, there is an unsatisfied demand which must be satisfied by small producers, which becomes a challenge because must build strategic alliances to achieve competitive production costs. [ABSTRACT FROM AUTHOR]

The effect of the density was evaluated in the development of trees of Tectona grandis L.F., Cordia megalantha S.F. Blake, Cybistax donnell smithii Rose and Triplaris cumingiana Fisch. & Mey. in permanent parcels established in 1997, in "La Represa" farm. The major growth in diameter was obtained to the density of 123 trees ha-1 (spacing: 9 x 9 m). The species that reached major diametric growth in this spacing was the Teak with 36.53 cm, continued by Guayacan with 33.80 cm. The trees registered a major volume average (m3) in the spacing 9 x 9 m. However, in the four studied species there is a major volume for hectare at the spacing of 6 x 6 m, due to the major number of trees for hectare. The species that presented major volume average was the Teak with 1.076 m3 and the minor volume average registered in Laurel with 0.316 m3. [ABSTRACT FROM AUTHOR]

We document Lepidoblepharis conolepis from El Cielito, Carchi province, northern Ecuador. This record, the first record for Carchi province, represents a northward range extension of 90 km from the previously known occurences. All known occurrences of L. conolepis, including our new record, are restricted to the western slopes of the Ecuadorian Andes at sites within fragmented natural forest habitats. [ABSTRACT FROM AUTHOR]

The Alagoinhas pluton is a member of the widespread high-K calc-alkaline association of northeastern Brazil. Some authors suggest that this region represents an amalgamation of distinct tectonic terranes assembled during the Brasiliano (Pan-African) orogeny. Our work compares geochemical data (major, trace and REE) of the Alagoinhas with other plutons of same petrotectonic association (Caruaru-Arcoverde batholith). These plutons apparently intrude several distinct tectonic terranes, separated by a major E-W dextral transcurrent system, the East Pernambuco shear zone (EPSZ). Anisotropy of magnetic susceptibility and structural data for the Alagoinhas pluton are used to compare tectonic regimes across the EPSZ. The results indicate that the Caruaru-Arcoverde batholith and the Alagoinhas pluton evolved from similar sources and were subjected to the same tectonic regime during emplacement, placing severe restrictions on use of the EPSZ as a suture zone between distinct tectonic terranes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sinigrin illustrated promising activity against P. falciparum (3D7, RKL-9 strains). • The compound exhibited no toxicity with high selectivity index (SI > 10). • It enhanced nitric oxide (NO) production from RAW 264.7 macrophages in vitro. • The compound illustrated high binding affinity with falcipain-3. • Sinigrin in combination with artesunate exhibited good activity in vivo with enhanced immune response and no toxicity to the vital organs of host. Plant-derived antimalarials are indispensable for malaria treatment and a platform for new drugs. The present study explores sinigrin, for malaria using in vitro, in silico and in vivo strategies and the immune response generated after administration. The compound exhibited promising activity against chloroquine (CQ)-resistant (RKL-9) IC 50 5.14 μg/mL and CQ-sensitive (3D7) IC 50 5.47 μg/mL strains of P. falciparum and was safe in both in vitro (CC 50 > 640 μg/mL) and in vivo (LD 50 > 2 g/kg) toxicity studies. In addition, virtual screening showed hydrogen bonding, hydrophobic and van der Waals interactions with amino acid residues of 3BPM (falcipain-3). In vivo studies revealed promising antimalarial activity of sinigrin (200 mg/kg) with 87.44% chemo-suppression on day 5 and significantly (p < 0.0001) enhanced the mean survival time (21 ± 4.74 days) in contrast to the infected control (5.4 ± 1.14 days). In combination therapy, sinigrin (100 mg/kg and 200 mg/kg) augmented the efficacy of artesunate (AS 50 mg/kg) with 100% survival and no recrudescence. These observations are further corresponded and supported by DLC, NO production, cytokine analysis, biochemical and histopathological studies. Treatment with the combination resulted in a regulated interplay of immune cells and cytokines aiding in parasite clearance in addition to its specific inhibitory activity. We report the antimalarial activity of sinigrin first time with best D-score against falcipain-3. These findings highlight sinigrin as a HIT molecule, which may potentially be used in drug and vaccine development approaches. [ABSTRACT FROM AUTHOR]

The increasing resistant cases even against artemisinin-based combination therapy have necessitated the need to develop new antimalarials. Phytomedicinal therapy is a benchmark for malaria in the Himalayan region. As the dialect and traditional variations have been seen along with this, usage of medicinal plant, its portion (shoot and root system) and mode of preparation also varies. There is no scientific evidence available for illustrating the antiplasmodial activity of the rhizomes of Bergenia ciliata (Saxifragaceae), which is known to be an antipyretic (fever akin to malaria), hepato-protective, and also for spleen enlargement. The present study evaluates the antimalarial activity of ethanol extract of B. ciliata rhizomes (EREBC). HPTLC was performed to identify and quantify three marker compounds in EREBC. The in vitro antimalarial activity was evaluated by schizont maturation inhibition assay. MTT assay was employed to test the cytotoxicity of EREBC. Peter's 4-day test and Peters method was employed to discern the suppressive and preventive activity of the extract respectively. HPTLC analysis revealed the presence of bergenin, epicatechin and gallic acid in the extract. EREBC exhibited considerable inhibition (IC 50 < 5 μg/mL) of schizont maturation of both RKL-9 and MRC-2 strains of P. falciparum. EREBC was non-toxic to both HeLa cells and normal dermal fibroblasts (CC 50 > 1000 μg/mL). The selectivity index was > 200 for both strains. Acute toxicity of EREBC was > 4 g/kg. EREBC exhibited considerable in vivo suppressive activity with 96.48% inhibition at 500 mg/kg in comparison to chloroquine (96.08%). The ED 50 of the extract was < 50 mg/kg. No mortality was evident in mice administered with different doses of EREBC (50–500 mg/kg) throughout the follow up period of 28 days. EREBC exhibited safety to liver and kidney function of mice as observed from biochemical analysis. Overall, the study illustrates the marked efficacy and potential of EREBC as an antimalarial agent with bergenin, epicatechin and gallic acid its major constituents, which played a pivotal role in the generation of the immune response. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: The antiphospholipid syndrome (APLS) is a complex autoimmune disease often connected to systemic lupus erythematodes. Main features are thromboses, fetal loss and specific antibodies. The involved autoantibodies are directed against plasma proteins such as beta2glycoprotein1 (β2GPI) or prothrombin which depend on negatively charged phospholipids. Direct antibodies against phospholipids are of no importance for APLS. Clotting tests such as activated partial thromboplastin time or diluted Russell''s viper venom test (dRVVT) can show a prolonged time for coagulation despite a prothrombotic state in vivo but the investigator needs awareness about disturbing phospholipid sources and other influential factors. Enzyme linked immuno sorbent assay tests for antibodies against cardiolipin, β2GPI and prothrombin are valuable solid phase tests with different specificity. Antiphospholipid, anticardiolipin or lupus anticoagulant are misnomers in connection with APLS. They are preserved as a reminiscence of the pioneering work on the way to the still not exactly revealed basics of APLS. Valve operations in APLS patients seem to be rare; a meta-analysis of 57 cases proves that the perioperative management is, at the moment, an empirical approach with high morbidity and mortality in these young patients. [Copyright &y& Elsevier]

The article presents a speech by Gorki Gonzales Mantilla delivered at a ceremony in which law professor Alessandro Pizzorusso was awarded an honoris causa degree by the Pontificia Universidad Católica del Perú in Lima, Peru. The speaker mentions Pizzorusso's role in the shift toward constitutionalism after fascism in Italy, presents an overview of his academic career at the University of Pisa in Italy, and notes several of his works, including "Valorizzazione délia Costituzione."

Abstract: The East Pernambuco shear zone system (EPSZ) conventionally has been taken as the limit between the central and southern domains of the oriental sector of the Neoproterozoic Borborema province (NE Brazil). To constrain the tectonic evolution of the southern domain during the Brasiliano orogeny, the authors undertake a structural and anisotropy of magnetic susceptibility study of the 580Ma Cachoeirinha pluton, located 10km south of the EPSZ. The results suggest a model for its emplacement and deformation in which (1) successive magma batches accumulated at the gently dipping interface between orthogneisses and overlying schists and paragneisses and (2) homogeneous NNE–SSW stretching of the pluton was followed by strain localization along conjugate subvertical corridors of noncoaxial shear during the last stages of crystallization. Outcrop-scale, magmatic to solid-state dextral and sinistral shear zones that affect the pluton have similar orientations to the large transcurrent mylonitic belts that characterize the central domain of the Borborema province. Thus, at the time of intrusion of the Cachoeirinha pluton, the central and southern domains of the Borborema province were undergoing deformation related to the same far-field stresses, and the EPSZ is not a major suture zone between domains with distinct geological histories. Instead, the present-day separation of the eastern Borborema province into central and southern domains resulted from progressive deformation that led to the development of the EPSZ. The absence of large shear zones in the southern domain can be explained by the faster regional cooling than in the central domain, where the longer magmatism duration resulted in persistent elevated crustal temperatures, which in turn allowed a greater amount of finite strain to accumulate. [Copyright &y& Elsevier]

Studies the intralithospheric differentiation and crustal growth at the Borborema province in northeastern Brazil. Granitoid bodies of the high-K calc-alkalic association in northeastern Brazil; Origin of the high compatible element contents of the quartz diorites; Indication of the high contents of compatible elements in quartz diorites and granitoids.

The pulmonary microbiome after lung transplantation has recently come into the focus of research. Especially, host-microbiome interactions are thought to be an important factor in graft-related immunological processes. In lung transplantation, temporal changes of the pulmonary microbiome have not yet been elucidated. In a total cohort of 80 patients receiving standard double lung transplantation, 50 bronchioalveolar lavage (BAL) samples from donors were collected prior to cold ischemia. After transplantation, 128 BAL samples were collected at various time points of routine follow-up bronchoscopies between 0 and 400 days post-transplant. Bacterial 16S rRNA gene sequencing was conducted to analyze the composition of the pulmonary microbiome in these samples. The lung microbiome showed significant temporal dynamics after lung transplantation. Recipient-donor similarity between matched samples decreased after the first week post transplantation. Underlying transplant indications were significantly associated with microbial profiles even after transplantation. Shannon diversity and Chao1 richness at the species level showed an increasing diversity of the microbiome over time. Our data provides new insights into the dynamics of microbial profiles after transplantation. We observed that recipient-associated factors, rather than the donor microbiome, shape the lung microbiome after transplantation. [ABSTRACT FROM AUTHOR]

Spirometric lung function is one of the central clinical parameters to assess allograft function after lung transplantation (LTX). Reduction in FEV1 can be the result of infections, rejections episodes and most importantly development of CLAD. Currently, there is no means to predict short-term changes in lung function after LTX. Bronchoalveolar samples of patients after standard double LTX were taken during follow-up bronchoscopy at multiple different time points. Lipidomic, metabolomic, flow cytometric and bacterial 16S rRNA gene sequencing (microbiome) data were analyzed. We then used a machine learning approach to predict future changes in FEV1 from these sample data to characterize patient lung function trajectories. We trained support vector machine (SVM) regressors on the collected lipidomic, metabolomic, microbiome and flow cytometry datasets. Changes in FEV1 within 30, 60 or 90 days after lavage sample collection were used as response variables. To train hyper-parameters and evaluate model accuracy, a nested leave-one-out cross validation scheme was used. Model accuracy was benchmarked against a model trained on clinical metadata. At a prediction timeframe of 30 days, lipidomic data were available from 34 samples of 20 patients. Lipidomics showed the highest predictive power for short-term changes 30 and 60 days after sample collection. Prediction accuracy (R2) of intra-alveolar lipid composition for a 30-day projection was 0.24, meaning that BAL lipid profiles could explain more than 20 percent of total variation in relative change in FEV1 for this time span. R² for clinical metadata alone was only 0.1, and metabolomics, microbiome and FACS analysis of BAL showed no predictive accuracy at this time point. Our results suggest that the intra-alveolar lipid composition is a powerful predictor of short-term changes in lung allograft function. This could potentially facilitate pre-emptive therapeutic interventions. [ABSTRACT FROM AUTHOR]

Naturally occurring pentacyclic triterpenoids and their semisynthetic analogues have engrossed increasing attention for their anticancer potential and exhibiting promising role in discovery of new anticancer agents. Present study include the semi synthetic modifications of Lantadenes from the weed Lantana carama and their structures delineation by FT-IR, 1H-NMR, 13C-NMR & mass spectroscopy. All the compounds were scrutinized for in vitro cytotoxicity, ligand receptor interaction and in vivo anticancer studies. Most of the novel analogues displayed potent antiproliferative activity against A375 & A431 cancer cell lines and found superior to parent Lantadenes. In particular, 3β-(4-Methoxybenzoyloxy)-22β-senecioyloxy-olean-12-en-28-oic acid was found to be most suitable compound, with IC 50 value of 3.027 μM aganist A375 cell line having least docking score (−69.40 kcal/mol). Promising anticancer potential of the lead was further indicated by significant reduction in tumor volume and burden in two stage carcinoma model. These findings suggests that the Lantadene derivatives may hold promising potential for the intervention of skin cancers. Anticancer potential of Lantadene esters against skin malignancy. [Display omitted] • Naturally existing Lantadenes were isolated from the weed Lantana camara and followed by semi-synthetic modifications at C-3 position. • Structural confirmation of newly synthesized molecules were delineated by IR, NMR and mass spectroscopic methods. • Pre-clinical Investigations were performed to evaluate anticancer activity of Lantadene derivatives. • An outcome of this study suggests promising anticancer potential of lead analogue. • Semi-synthetic modifications of naturally existing Lantadenes were made at C-3 position. • Structural confirmation was delineated by various spectroscopic methods followed by determination of anticancer potential. • An outcome suggests promising anticancer potential of lead analogue. [ABSTRACT FROM AUTHOR]

Macrophages undergo extensive metabolic rewiring upon activation which assist the cell in roles beyond energy production and synthesis of anabolic building blocks. So-called immunometabolites that accumulate upon immune activation can serve as co-factors for enzymes and can act as signaling molecules to modulate cellular processes. As such, the Krebs-cycle-associated metabolites succinate, itaconate and alpha-ketoglutarate (αKG) have emerged as key regulators of macrophage function. Here, we describe that 2-hydroxyglutarate (2HG), which is structurally similar to αKG and exists as two enantiomers, accumulates during later stages of LPS-induced inflammatory responses in mouse and human macrophages. D-2HG was the most abundant enantiomer in macrophages and its LPS-induced accumulation followed the induction of Hydroxyacid-Oxoacid Transhydrogenase (HOT). HOT interconverts αKG and gamma-hydroxybutyrate into D-2HG and succinic semialdehyde, and we here identified this enzyme as being immune-responsive and regulated during the course of macrophage activation. The buildup of D-2HG may be further explained by reduced expression of D-2HG Dehydrogenase (D2HGDH), which converts D-2HG back into αKG, and showed inverse kinetics with HOT and D-2HG levels. We tested the immunomodulatory effects of D-2HG during LPS-induced inflammatory responses by transcriptomic analyses and functional profiling of D-2HG-pre-treated macrophages in vitro and mice in vivo. Together, these data suggest a role for D-2HG in the negative feedback regulation of inflammatory signaling during late-stage LPS-responses in vitro and as a regulator of local and systemic inflammatory responses in vivo. Finally, we show that D-2HG likely exerts distinct anti-inflammatory effects, which are in part independent of αKG-dependent dioxygenase inhibition. Together, this study reveals an immunometabolic circuit resulting in the accumulation of the immunomodulatory metabolite D-2HG that can inhibit inflammatory macrophage responses. • 2HG is among the top induced immunometabolites in inflammatory macrophages. • D-2HG builds up when the initial inflammatory response begins to resolve. • HOT and D2HGDH are immune-responsive and could mediate D-2HG induction. • Octyl-D-2HG is anti-inflammatory in vitro and in vivo. • D-2HG can serve as a negative feedback loop to stop inflammation. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition characterized by uncontrolled systemic inflammation and coagulation, leading to multiorgan failure. Therapeutic options to prevent sepsis-associated immunopathology remain scarce. Here, we established a mouse model of long-lasting disease tolerance during severe sepsis, manifested by diminished immunothrombosis and organ damage in spite of a high pathogen burden. We found that both neutrophils and B cells emerged as key regulators of tissue integrity. Enduring changes in the transcriptional profile of neutrophils include upregulated Cxcr4 expression in protected, tolerant hosts. Neutrophil Cxcr4 upregulation required the presence of B cells, suggesting that B cells promoted disease tolerance by improving tissue damage control via the suppression of neutrophils' tissue-damaging properties. Finally, therapeutic administration of a Cxcr4 agonist successfully promoted tissue damage control and prevented liver damage during sepsis. Our findings highlight the importance of a critical B-cell/neutrophil interaction during sepsis and establish neutrophil Cxcr4 activation as a potential means to promote disease tolerance during sepsis. [ABSTRACT FROM AUTHOR]

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 ICU-days. 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]

Abstract: Detailed structural work conducted at the eastern area of the Neoproterozoic Brasiliano (=Pan-African) Borborema Province (northeastern Brazil) has shown two orientations of stretching lineations with ESE trend in supracrustal rocks and NE trend in underlying orthogneisses. In the metasedimentary sequence, numerous kinematic indicators showing a top-to-the-northwest sense of shear denote a well-developed non-coaxial deformation. In the orthogneisses, lineations formed dominantly during coaxial deformation, although a component of NE-directed shear is locally observed. The two lineations were produced under similar high-temperature metamorphic conditions and are interpreted as the result of a protracted NW–SE contractional strain regime where (i) subhorizontal non-coaxial shear with superimposed flattening led to an initial phase of NW-directed thrusting, (ii) flattening strains mainly accumulated in the orthogneisses with progressive deformation, leading to a lineation oblique to the transport direction, (iii) the subhorizontal fabric in basement and cover rocks was refolded by overturned folds, and, then (iv) cross-cut by conjugate ENE-striking dextral and NNE-striking sinistral shear zones contemporaneous with NE-trending upright folds. It is proposed that vertical partitioning of strain between basement and cover may explain the presence of oblique lineations in this orogenic belt that did not go through a final stage of extensional collapse. [Copyright &y& Elsevier]

The laminated limestones of the Crato Formation, Araripe Basin (NE of Brazil) have been investigated, as they are analogous to facies of the carbonate reservoirs of the pre-salt sequence of the Brazilian marginal basins. The Early Cretaceous Crato laminites comprise a complex range of structures that may play an important role in the porosity and permeability distribution in carbonate reservoirs. This work aims to (1) understand the control of a boundary fault zone (the Triunfo Fault, Lower Cretaceous) on the development in carbonate breccia pipes of the Crato Formation, and (2) constrain the timing of brittle deformation, based on field observations, microstructural investigation and U–Pb carbonate geochronology. The breccia pipes are observed surrounding both normal and strike-slip faults. The brittle deformation superimposed on the pipes is characterized by brecciation and veining that show multiples phases of mineralization. Our results propose the circulation of fluid along the pre-existing faults and pipes, these fluids are responsible for polyphasic deformation in the pipes. We report two U–Pb ages from carbonate-vein mineralization of 94.9 ± 3.8 Ma (Cenomanian to Turonian) and 80.2 ± 3.0 Ma (2σ) (Campanian), which provide time constraints on the brittle reactivations of the Triunfo Fault Zone, during the post-rift phase of the Araripe Basin. • Polyphase formation of breccia pipes in Aptian carbonates strongly controlled by a fault zone of the Araripe Basin. • Two reactivation episodes of the Fault Triunfo zone dated at 94.9 ± 3.8 Ma (Cenomanian to Turonian) and 80.2 ± 3 Ma (Campanian). • Vein fills register fluids of different chemical composition during the post-rift phase of the Araripe Basin. • Multiple fluid circulation events through pre-existing faults and pipes are responsible by deformations in the breccia pipes. [ABSTRACT FROM AUTHOR]

Obesity-induced white adipose tissue (WAT) hypertrophy is associated with elevated adipose tissue macrophage (ATM) content. Overexpression of the triggering receptor expressed on myeloid cells 2 (TREM2) reportedly increases adiposity, worsening health. Paradoxically, using insulin resistance, elevated fat mass, and hypercholesterolemia as hallmarks of unhealthy obesity, a recent report demonstrated that ATM-expressed TREM2 promoted health. Here, we identified that in mice, TREM2 deficiency aggravated diet-induced insulin resistance and hepatic steatosis independently of fat and cholesterol levels. Metabolomics linked TREM2 deficiency with elevated obesity-instigated serum ceramides that correlated with impaired insulin sensitivity. Remarkably, while inhibiting ceramide synthesis exerted no influences on TREM2-dependent ATM remodeling, inflammation, or lipid load, it restored insulin tolerance, reversing adipose hypertrophy and secondary hepatic steatosis of TREM2-deficient animals. Bone marrow transplantation experiments revealed unremarkable influences of immune cell-expressed TREM2 on health, instead demonstrating that WAT-intrinsic mechanisms impinging on sphingolipid metabolism dominate in the systemic protective effects of TREM2 on metabolic health. [ABSTRACT FROM AUTHOR]

Lipocalin 2 (LCN2) is a secreted glycoprotein with roles in multiple biological processes. It contributes to host defense by interference with bacterial iron uptake and exerts immunomodulatory functions in various diseases. Here, we aimed to characterize the function of LCN2 in lung macrophages and dendritic cells (DCs) using Lcn2-/- mice. Transcriptome analysis revealed strong LCN2-related effects in CD103+ DCs during homeostasis, with differential regulation of antigen processing and presentation and antiviral immunity pathways. We next validated the relevance of LCN2 in a mouse model of influenza infection, wherein LCN2 protected from excessive weight loss and improved survival. LCN2-deficiency was associated with enlarged mediastinal lymph nodes and increased lung T cell numbers, indicating a dysregulated immune response to influenza infection. Depletion of CD8+ T cells equalized weight loss between WT and Lcn2-/- mice, proving that LCN2 protects from excessive disease morbidity by dampening CD8+ T cell responses. In vivo T cell chimerism and in vitro T cell proliferation assays indicated that improved antigen processing by CD103+ DCs, rather than T cell intrinsic effects of LCN2, contribute to the exacerbated T cell response. Considering the antibacterial potential of LCN2 and that commensal microbes can modulate antiviral immune responses, we speculated that LCN2 might cause the observed influenza phenotype via the microbiome. Comparing the lung and gut microbiome of WT and Lcn2-/- mice by 16S rRNA gene sequencing, we observed profound effects of LCN2 on gut microbial composition. Interestingly, antibiotic treatment or co-housing of WT and Lcn2-/- mice prior to influenza infection equalized lung CD8+ T cell counts, suggesting that the LCN2-related effects are mediated by the microbiome. In summary, our results highlight a novel regulatory function of LCN2 in the modulation of antiviral immunity. Author summary: Outcome from infectious diseases is determined by the adequacy of the immune response, with efficient clearance of the causative pathogen, while keeping the inflammatory response in check to avoid excessive inflammation, tissue damage and resulting mortality. The regulation of immunity is shaped by multiple players. As such lipocalin (LCN) 2 exhibits immune-modulatory properties and for instance deactivates alveolar macrophages, but the precise mode of action remains unclear. Here, we explored the precise effects of LCN2 on cellular lung immunity, and discovered that LCN2 markedly impacted homeostatic expression of pulmonary dendritic cell (DC) genes related to anti-influenza immunity. In agreement with this finding, LCN2-deficient mice infected with influenza virus showed a higher mortality and more pronounced immune response, despite an unaltered viral clearance. Mechanistically, we found the presence of LCN2 associated with dampened DC functions, ultimately preventing exuberant T cell activation during influenza infection. Considering LCN2's antibacterial effects as a siderophore-binding protein, we speculated that an indirect, microbiome-dependent effect might explain these findings. In fact, LCN2 remarkably shaped the microbiome composition, and interference via antibiotics or cohousing erased the protective effects of LCN2 on the anti-viral immune response. [ABSTRACT FROM AUTHOR]

Background: Incidence of pulmonary aspergillosis is rising worldwide, owing to an increased population of immunocompromised patients. Notable potential of the pulmonary route has been witnessed in antifungal delivery due to distinct advantages of direct lung targeting and first-pass evasion. The current research reports biomimetic surface-active lipid-polymer hybrid (LPH) nanoparticles (NPs) of voriconazole, employing lung-specific lipid, i.e., dipalmitoylphosphatidylcholine and natural biodegradable polymer, i.e., chitosan, to augment its pulmonary deposition and retention, following nebulization. Results: The developed nanosystem exhibited a particle size in the range of 228–255 nm and drug entrapment of 45–54.8%. Nebulized microdroplet characterization of NPs dispersion revealed a mean diameter of ≤ 5 μm, corroborating its deep lung deposition potential as determined by next-generation impactor studies. Biophysical interaction of LPH NPs with lipid-monolayers indicated their surface-active potential and ease of intercalation into the pulmonary surfactant membrane at the air-lung interface. Cellular viability and uptake studies demonstrated their cytocompatibility and time-and concentration-dependent uptake in lung-epithelial A549 and Calu-3 cells with clathrin-mediated internalization. Transepithelial electrical resistance experiments established their ability to penetrate tight airway Calu-3 monolayers. Antifungal studies on laboratory strains and clinical isolates depicted their superior efficacy against Aspergillus species. Pharmacokinetic studies revealed nearly 5-, 4- and threefolds enhancement in lung AUC, Tmax, and MRT values, construing significant drug access and retention in lungs. Conclusions: Nebulized LPH NPs were observed as a promising solution to provide effective and safe therapy for the management of pulmonary aspergillosis infection with improved patient compliance and avoidance of systemic side-effects. [ABSTRACT FROM AUTHOR]

Fault zones commonly have spatially variable fault rocks and brittle structures. Differing fault-rock attributes may retard or increase cross- and along-fault permeability. Our work analyzed brittle deformation of a segment of the Patos shear zone, Triunfo Fault, which is located in the northern border of the Araripe Basin, NE Brazil. We investigated the structural evolution and tectonic implications of the Triunfo Fault by mapping damage zone width patterns and the types and distributions of breccia and brittle structure arrays within the fault zone using scanline fracture analysis techniques and topographic and aeromagnetometric data. Fractured rocks of the damage zone mainly comprise: mylonitic orthogneiss (footwall); and sandstone and carbonate rocks (hangingwall). The fault core is composed of tectonic breccia and cataclasites occurring as lenses, with calcite-filled veins. Due to fault sinuosity and rheology heterogeneities, the width of the damage zone ranges from 240 to 290m (footwall), and 372–610m (hangingwall). Our analysis obtained from the topographic and gravimetric data combined with field data indicate the following sequential deformation phases: a) Dn, Brasiliano Orogeny, dextral shear zone; b) Dn+1, Paleozoic time, brittle-ductile deformation; and c) Dn+2, Lower Cretaceous time, brittle deformation. • Brittle deformation of Patos shear zone and its influence on the tectonic evolution of the northern border of Araripe Basin. • Asymmetry of damage zones due to the fault sinuosity and rheology heterogeneities of host rocks. • Overlap of the deformational phases and its tectonic impact in the width of damage zones. • Tectonic evolution of the Araripe Basin under a strike-slip regime. [ABSTRACT FROM AUTHOR]

Introduction: The increasing prevalence and impact of pelvic floor disorders (PFD) on women's quality of life highlights the importance of improving awareness and knowledge of these conditions. To date, several studies have examined knowledge of PFDs among women. All studies showed that there is a lack of knowledge among women and that education programs are necessary to fill this gap. According to the nICE guidelines on best practice in healthcare, public awareness of pelvic floor health should be increased by promoting throughout life. Aim: The hypothesis assumes that health and medical science students have some knowledge of pelvic floor disorders, including urinary incontinence (UI) and pelvic organ prolapse (POP). The study aims to accurately evaluate this knowledge to identify potential gaps and areas that require educational improvement in their degree programs. Material and methods: In a cross-sectional survey, the Prolapse and Incontinence Knowledge Questionnaire (PIKQ) was used to assess students' knowledge of pelvic floor disorders, focusing on UI and POP. The PIKQ, which is divided into a UI and a POP scale, contains 12 questions each on etiology, diagnosis, and treatment, scored with correct (one point) or incorrect/unknown (zero points) answers. Competence was defined as a score of ≥80% on the PIKQ-UI (≥10 correct answers) and ≥50% on the PIKQPOP (≥6 correct answers). Results: A total of 179 respondents returned the questionnaire. Among them, 46 respondents reported their gender as male, 131 as female and 1 as non-binary; age (18-22 65%, 23-26 34%, 27-30 1%). Respondents overall showed a good knowledge of PFD in general, with a PIKQ overall score of 18,22±3,44. UI knowledge was deemed proficient in 78,78% (mean 10,51; median 11; SD 1,38) of participants (n=141), while POP knowledge was deemed proficient in 83,8% (mean 7,71; median 8; SD 2,45) of participants (n=150). Conclusions: The majority of health and medical science students have a good knowledge of pelvic floor disorders. This supports the hypothesis that these students have a solid understanding of PFDs and emphasizes their preparedness in this aspect of healthcare. [ABSTRACT FROM AUTHOR]

Summary Lung development and function arises from the interactions between diverse cell types and lineages. Using single-cell RNA sequencing (RNA-seq), we characterize the cellular composition of the lung during development and identify vast dynamics in cell composition and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, innate lymphocytes (ILCs), and basophils. Using interleukin (IL)-33 receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and granulocyte-macrophage colony-stimulating factor (GM-CSF), characterized by unique signaling of cytokines and growth factors important for stromal, epithelial, and myeloid cell fates. Antibody-depletion strategies, diphtheria toxin-mediated selective depletion of basophils, and co-culture studies show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole-tissue signaling interaction map on the single-cell level can broaden our understanding of cellular networks in health and disease. Graphical Abstract Highlights • Single-cell signaling map of lung development identifies inter-lineage crosstalk • Lung-resident basophils are broadly interacting cells located near alveoli • Lung environment imprints the gene signature of basophils via IL33 and GM-CSF • Basophils regulate alveolar macrophage maturation and immunomodulation functions A population of resident basophils regulates the development and function of alveolar macrophages to control lung homeostasis. [ABSTRACT FROM AUTHOR]