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Abstract Objective: To describe the implementation of a multi-step antimicrobial stewardship program in a haemato-oncology and stem cell transplantation program unit. Methods: Pre-post quasi-experimental study with two interrupted time-series analyses, conducted between 01/01/2019 and 31/12/2022 in the Paediatric Haemato-Oncology Unit of the Padua Paediatric Hospital. The interventions were: (1) 02/2020: dissemination of febrile neutropenia clinical pathways, (2) April 2021: provision of the clinical pathways via a customized App (Firstline.org) and implementation of a twice-a-week prospective audit and feedback. The main outcome was antibiotic consumption measured by days of administered therapy (DOTs)/1000 patients’ days for all antibiotics and most used molecules. Results: The first intervention (clinical pathways) resulted in a decrease in the overall antibiotic use by the haemato-oncology unit, with an abrupt reduction of 3-gen cephalosporins in favor of piperacillin-tazobactam, as indicated by the clinical pathways. Meropenem and glycopeptide use did not vary. The second intervention (antimicrobial stewardship) further decreased total antibiotic consumption, and a significant decline in meropenem, amikacin, and glycopeptides was achieved. Conclusions: Multi-step stewardship based on guidelines dissemination, multidisciplinary team intervention and collaboration (“handshake” stewardship) was highly effective in optimizing guidelines adherence and reducing overprescriptions in a fragile patient cohort.

Abstract Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. Blood MX1 expression is superior to IFI27 expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore, MX1 expression offers potential to stratify patients for antiviral therapy or infection control interventions. Blood IFI27 expression is superior to MX1 expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing.

Abstract Fluorescence spectroscopy is a fundamental tool in life sciences and chemistry, with applications in environmental monitoring, food quality control, and biomedical diagnostics. However, analysis of spectroscopic data with deep learning, in particular of fluorescence excitation-emission matrices (EEMs), presents significant challenges due to the typically small and sparse datasets available. Furthermore, the analysis of EEMs is difficult due to their high dimensionality and overlapping spectral features. This study proposes a new approach that exploits domain adaptation with pretrained vision models, along with a novel interpretability algorithm to address these challenges. Thanks to specialised feature engineering of the neural networks described in this work, we are now able to provide deeper insights into the physico-chemical processes underlying the data. The proposed approach is demonstrated through the analysis of the oxidation process in extra virgin olive oil (EVOO), showing its effectiveness in predicting quality indicators and identifying the spectral bands and thus the molecules involved in the process. This work describes a significantly innovative approach to deep learning for spectroscopy, transforming it from a black box into a tool for understanding complex biological and chemical processes.

Abstract This paper analyses how YouTube authenticates engagement metrics and, more specifically, how the platform corrects view counts by removing “fake views” (i.e., views considered artificial or illegitimate by the platform). Working with one and a half years of data extracted from a thousand French YouTube channels, we show the massive extent of the corrections done by YouTube, which concern the large majority of the channels and over 78% of the videos in our corpus. Our analysis shows that corrections are not done continuously as videos collect new views, but instead occur in batches, generally around 5 p.m. every day. More significantly, most corrections occur relatively late in the life of the videos, after they have reached most of their audience, and the delay in correction is not independent of the final popularity of videos: videos corrected later in their life are more popular on average than those corrected earlier. We discuss the probable causes of this phenomenon and its possible negative consequences on content diffusion. By inflating view counts, fake views could make videos appear more popular than they are and unwarrantedly encourage their recommendation, thus potentially altering the public debate on the platform. This could have implications on the spread of online misinformation, but their in-depth exploration requires first-hand information on view corrections, which YouTube does not provide through its API. This paper presents a series of experimental techniques to work around this limitation, offering a practical contribution to the study of online attention cycles (as described in the “Data and methods” section). At the same time, this paper is also a call for greater transparency by YouTube and other online platforms about information with crucial implications for the quality of online debate.

Abstract Colorectal cancer (CRC) tumors are composed of heterogeneous and plastic cell populations, including a pool of cancer stem cells that express LGR5. Whether these distinct cell populations display different mechanical properties, and how these properties might contribute to metastasis is poorly understood. Using CRC patient derived organoids (PDOs), we find that compared to LGR5- cells, LGR5+ cancer stem cells are stiffer, adhere better to the extracellular matrix (ECM), move slower both as single cells and clusters, display higher nuclear YAP, show a higher survival rate in response to mechanical confinement, and form larger transendothelial gaps. These differences are largely explained by the downregulation of the membrane to cortex attachment proteins Ezrin/Radixin/Moesin (ERMs) in the LGR5+ cells. By analyzing single cell RNA-sequencing (scRNA-seq) expression patterns from a patient cohort, we show that this downregulation is a robust signature of colorectal tumors. Our results show that LGR5- cells display a mechanically dynamic phenotype suitable for dissemination from the primary tumor whereas LGR5+ cells display a mechanically stable and resilient phenotype suitable for extravasation and metastatic growth.

This scenario discusses generative AI in light of Bruno Latour’s sociology of technology. It considers why Latour showed little interest in the simulation of intelligence and how connectionist AI fails to meet his condition for scientificity but offers a fascinating writing mediation. AI is most interesting not because it emulates human thinking or writing, but because it differs from them. Drawing on actor-network theory, this scenario argues against the idea of machines becoming detached from their creators and highlights how AIs can only exist through the support of their human assistants. The risks associated with these technologies do not come from an improbable singularity, but from their embedding in the dull and exploitative industry of digital attention economy.

Abstract Collaboration is a key driver of science and innovation. Mainly motivated by the need to leverage different capacities and expertise to solve a scientific problem, collaboration is also an excellent source of information about the future behavior of scholars. In particular, it allows us to infer the likelihood that scientists choose future research directions via the intertwined mechanisms of selection and social influence. Here we thoroughly investigate the interplay between collaboration and topic switches. We find that the probability for a scholar to start working on a new topic increases with the number of previous collaborators, with a pattern showing that the effects of individual collaborators are not independent. The higher the productivity and the impact of authors, the more likely their coworkers will start working on new topics. The average number of coauthors per paper is also inversely related to the topic switch probability, suggesting a dilution of this effect as the number of collaborators increases.

Background: This study aims to evaluate the feasibility, efficacy, and safety of distal transradial access (dRA) for the endovascular management of malfunctioning dialysis fistulas. This study also compares dRA with conventional access techniques, such as proximal radial and transvenous access, focusing on technical success, clinical outcomes, and vascular access site complications (VASCs). Methods: A retrospective multicenter study was conducted across four hospitals, including 292 patients treated between January 2019 and June 2024. Of these, 57 patients underwent dRA, and 235 received proximal radial or transvenous access. Key outcomes included technical success (successful completion of the procedure), clinical success (restoration of functional dialysis access), and complication rates. Data were collected on procedure times and complication profiles. Results: Technical success was achieved in 96.5% of patients undergoing dRA, compared to 98.3% in those receiving conventional access (p = 0.388). Clinical success was similar between groups (96.5% vs. 97%, p = 0.835). The overall complication rate was 10.5% for dRA and 8.5% for conventional access (p = 0.632). Cannulation time was longer for dRA (109.1 vs. 91.9 s, p < 0.001), but total procedure duration was comparable between the groups. No major complications were observed in either cohort, and improved post-procedure access flow rates were recorded in all patients. Conclusions: Distal transradial access is a feasible and effective approach for the endovascular management of malfunctioning dialysis fistulas, with outcomes comparable to conventional access techniques. It provides a safe alternative, particularly for patients with complex fistulas, while maintaining a low complication profile.

Abstract Metastability of many-body quantum states is rare and still poorly understood. An exceptional example is the low-temperature metallic state of the layered dichalcogenide 1T-TaS2 in which electronic order is frozen after external excitation. Here we visualize the microscopic dynamics of injected charges in the metastable state using a multiple-tip scanning tunnelling microscope. We observe non-thermal formation of a metastable network of dislocations interconnected by domain walls, that leads to macroscopic robustness of the state to external thermal perturbations, such as small applied currents. With higher currents, we observe annihilation of dislocations following topological rules, accompanied with a change of macroscopic electrical resistance. Modelling carrier injection into a Wigner crystal reveals the origin of formation of fractionalized, topologically entangled networks, which defines the spatial fabric through which single particle excitations propagate. The possibility of manipulating topological entanglement of such networks suggests the way forward in the search for elusive metastable states in quantum many body systems.

Abstract Mirror symmetry plays a major role in determining the properties of matter and is of particular interest in condensed many-body systems undergoing symmetry breaking transitions under non-equilibrium conditions. Typically, in the aftermath of such transitions, one of the two possible broken symmetry states is emergent. However, synthetic systems and those formed under non-equilibrium conditions may exhibit metastable states comprising of both left (L) and right (R) handed symmetry. Here we explore the formation of chiral charge-density wave (CDW) domains after a laser quench in 1T-TaS2 with scanning tunneling microscopy. Typically, we observed transient domains of both chiralities, separated spatially from each other by domain walls with different structure. In addition, we observe transient density of states modulations consistent with interference of L and R-handed charge density waves within the surface monolayer. Theoretical modeling of the intertwined domain structures using a classical charged lattice gas model reproduces the experimental domain wall structures. The superposition (S) state cannot be understood classically within the correlated electron model but is found to be consistent with interferences of L and R-handed charge-density waves within domains, confined by surrounding domain walls, vividly revealing an interference of Fermi electrons with opposite chirality, which is not a result of inter-layer interference, but due to the interaction between electrons within a single layer, confined by domain wall boundaries.

Abstract Since the late ’80s, CERN has pioneered the development of niobium thin film radio-frequency (RF) cavities deposited on copper substrates for several particle accelerator applications. However, niobium thin film cavities historically feature a progressive performance degradation as the accelerating field increases. In this study, we describe a temperature mapping system based on contact thermometry, specially designed to obtain temperature maps of niobium-coated copper cavities and, consequently, study the mechanisms responsible for performance degradation. The first temperature maps on a niobium/copper 1.3 GHz cavity are reported along with its RF performance. In addition to some hotspots displayed in the temperature maps, we surprisingly observed a temperature decrease in a limited portion of the cavity cell as the accelerating field increased. This may shed new light on understanding the heat dissipation of niobium thin film cavities in liquid helium-I, which might be exploited to improve the RF cavity performance.

Abstract F508del, the most frequent mutation in cystic fibrosis (CF), impairs the stability and folding of the CFTR chloride channel, thus resulting in intracellular retention and CFTR degradation. The F508del defect can be targeted with pharmacological correctors, such as VX-809 and VX-445, that stabilize CFTR and improve its trafficking to plasma membrane. Using a functional test to evaluate a panel of chemical compounds, we have identified tricyclic pyrrolo-quinolines as novel F508del correctors with high efficacy on primary airway epithelial cells from CF patients. The most effective compound, PP028, showed synergy when combined with VX-809 and VX-661 but not with VX-445. By testing the ability of correctors to stabilize CFTR fragments of different length, we found that VX-809 is effective on the amino-terminal portion of the protein that includes the first membrane-spanning domain (amino acids 1–387). Instead, PP028 and VX-445 only show a stabilizing effect when the second membrane-spanning domain is included (amino acids 1–1181). Our results indicate that tricyclic pyrrolo-quinolines are a novel class of CFTR correctors that, similarly to VX-445, interact with CFTR at a site different from that of VX-809. Tricyclic pirrolo-quinolines may represent novel CFTR correctors suitable for combinatorial pharmacological treatments to treat the basic defect in CF.

Abstract Understand the origin, transport, and character of organic matter entering Antarctic fjords is essential as they are major components of the global carbon cycle and budget. Macromolecular pools of particulate organic matter, bulk organic geochemistry, major and trace elements in surface sediments from Collins Bay were analysed as source indicators. Oceanographic conditions, bathymetry (multibeam) and grain size were considered as environmental controlling factors. Sediment samples were taken with a van Veen grab, during the ANTAR XXV Peruvian expedition (February 2018), onboard the R/V “BAP Carrasco” from the Peruvian Navy. Biopolymeric composition revealed the predominance of fresh marine protein-rich organic matter in the seafloor of Collins Bay, denoting high quality food resource for marine benthic heterotrophs. Based on Igeo values (between 0 and 1) Collins Bay can be considered unpolluted with natural levels of As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Distribution of most of these elements with a gradient of decrease from the shallow inner fjord towards the outer deepest fjord, suggest their association with the deposition of detrital material and lithogenic particles supplied by Collins Glacier frontal ablation and runoff. This first comprehensive baseline information would assist in interpreting downcore sedimentary reconstructions and future climate-induce changes.

Abstract Fibromyalgia is a heterogenous primary pain syndrome whose severity has been associated with descending pain modulatory system (DPMS) function and functional connectivity (FC) between pain processing areas. The brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism has been linked to vulnerability to chronic pain. In this cross-sectional imaging genetics study, we investigated fibromyalgia, the relationship between BDNF Val66Met heterozygous genotypes (Val/Met), and the functional connectivity (FC) response pattern to acute pain stimulus in the motor (MC) and prefrontal (PFC) cortex assessed by near-infrared spectroscopy (fNIRS) before and after a cold pressor test utilizing water (0–1 °C). Also, we assessed the relationship between this genotype with the DPMS function and quality of life. We included 42 women (Val/Val = 30; Val/Met = 12) with fibromyalgia, ages 18–65. The MANCOVA comparing Val/Met to Val/Val genotypes showed higher ΔFC between left(l)-PFC—l-MC (β = 0.357, p = 0.048), l-PFC—right(r)-PFC (β = 0.249, p = 0.012), l-PFC—r-MC (β = 0.226, p = 0.022), and l-MC—r-PFC (β = 0.260, p = 0.016). Val/Met genotypes showed higher efficiency of the DPMS and lower disability due to pain. Here we show that fibromyalgia patients carrying the Val/Met BDNF genotype presented an increased ΔFC across MC and PFC in response to acute pain associated with differences in acute pain perception and fibromyalgia symptoms.

Abstract Resistance training with blood flow restriction (RTBFR) allows physically impaired people living with HIV (PWH) to exercise at lower intensities than traditional resistance training (TRT). But the acute and chronic cardiac and metabolic responses of PWH following an RTBFR protocol are unknown. The objective was to compare the safety of acute and chronic effects on hemodynamic and lipid profiles between TRT or RTBFR in PWH. In this randomized control trial, 14 PWH were allocated in RTBFR (GRTBFR; n = 7) or TRT (GTRT; n = 7). Both resistance training protocols had 36 sessions (12 weeks, three times per week). Protocol intensity was 30% (GRTBFR) and 80% (GTRT). Hemodynamic (heart rate, blood pressure) and lipid profile were acutely (rest and post exercise 7th, 22nd, and 35th sessions) and chronically (pre and post-program) recorded. General linear models were applied to determine group * time interaction. In the comparisons between groups, the resistance training program showed acute adaptations: hemodynamic responses were not different (p > 0.05), regardless of the assessment session; and chronicles: changes in lipidic profile favors GRTBFR, which significantly lower level of total cholesterol (p = 0.024), triglycerides (p = 0.002) and LDL (p = 0.030) compared to GTRT. RTBFR and TRT induced a similar hemodynamic adaptation in PWH, with no significant risks of increased cardiovascular stress. Additionally, RTBFR promoted better chronic adequacy of lipid profile than TRT. Therefore, RTBFR presents a safe resistance training alternative for PWH. Trial registration: ClinicalTrials.gov ID: NCT02783417; Date of registration: 26/05/2016.

Abstract Alzheimer’s disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD’s mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.

Barrett’s esophagus is a pre-malignant condition that can progress to esophageal cancer. Here, the authors carry out whole genome sequencing of samples from patients who did or did not progress to cancer and find that mutations in many genes occur regardless of progression status, but also find features associated with progressive disease.

Paracoccidioidomycosis (PCM) is caused by Paracoccidioides spp.; during infection, some host mechanisms limit the availability of iron, thereby reducing its reproduction. However, Paracoccidioides spp. can evade the immune defense and, even under limited iron conditions, use this mineral for growth and dissemination. This study evaluated the iron metabolism of 39 patients who were diagnosed with chronic PCM from 2013 to 2021. The forms of iron before treatment and at the time of clinical cure were evaluated based on the following: serum ferritin levels (storage iron); total iron-binding capacity (TIBC) and transferrin saturation (TSAT) level (transport iron); red blood cell (RBC), hemoglobin (Hb), hematocrit (HCT), and soluble transferrin receptor (sTfR) levels; and sTfR/log ferritin ratio (functional iron). The mean age of the patients was 54.5 years (±6.7 years). Most patients were men (97.4%), rural workers (92.1%), and smokers (84.6%); furthermore, most had moderate disease severity (66.7%). After achieving clinical cure, we observed that serum ferritin levels decreased, and parameters of functional iron increased. The extent of alteration in these parameters were more pronounced in severe cases than in to mild or moderate cases. Furthermore, moderate correlations were observed between C-reactive protein and the Hb (r = -0.500; p = 0.002), RBC (r = -0.461; p = 0.005), HCT (r = -0.514; p = 0.001), and iron levels (r = -0.491; p = 0.002). However, it is possible to infer that PCM interferes with functional and storage iron because improvements in these parameters after treatment as well as associations with disease severity were observed. PCM can lead to anemia of inflammation, which can be differentiated from iron deficiency anemia by a careful investigation of the iron form parameters.

Abstract Cholesterol is a lipid molecule of great biological importance to animal cells. Dysregulation of cholesterol metabolism leads to raised blood total cholesterol levels, a clinical condition called hypercholesterolemia. Evidence has shown that hypercholesterolemia is associated with the development of liver and heart disease. One of the mechanisms underlying heart and liver alterations induced by hypercholesterolemia is oxidative stress. In this regard, in several experimental studies, gold nanoparticles (AuNP) displayed antioxidant properties. We hypothesized that hypercholesterolemia causes redox system imbalance in the liver and cardiac tissues, and AuNP treatment could ameliorate it. Young adult male Swiss mice fed a regular rodent diet or a high cholesterol diet for eight weeks and concomitantly treated with AuNP (2.5 μg/kg) or vehicle by oral gavage. Hypercholesterolemia increased the nitrite concentration and glutathione (GSH) levels and decreased the liver’s superoxide dismutase (SOD) activity. Also, hypercholesterolemia significantly enhanced the reactive oxygen species (ROS) and GSH levels in cardiac tissue. Notably, AuNP promoted the redox system homeostasis, increasing the SOD activity in hepatic tissue and reducing ROS levels in cardiac tissue. Overall, our data showed that hypercholesterolemia triggered oxidative stress in mice’s liver and heart, which was partially prevented by AuNP treatment.

Abstract The photoreceptor-specific nuclear receptor Nr2e3 is not expressed in Nr2e3 rd7/rd7 mice, a mouse model of the recessively inherited retinal degeneration enhanced S-cone sensitivity syndrome (ESCS). We characterized in detail C57BL/6J Nr2e3 rd7/rd7 mice in vivo by fundus photography, optical coherence tomography and fluorescein angiography and, post mortem, by histology and immunohistochemistry. White retinal spots and so-called ‘rosettes’ first appear at postnatal day (P) 12 in the dorsal retina and reach maximal expansion at P21. The highest density in ‘rosettes’ is observed within a region located between 100 and 350 µM from the optic nerve head. ‘Rosettes’ disappear between 9 to 12 months. Non-apoptotic cell death markers are detected during the slow photoreceptor degeneration, at a rate of an approximately 3% reduction of outer nuclear layer thickness per month, as observed from 7 to 31 months of age. In vivo analysis of Nr2e3 rd7/rd7 Cx3cr1 gfp/+ retinas identified microglial cells within ‘rosettes’ from P21 on. Subretinal macrophages were observed in vivo and by confocal microscopy earliest in 12-months-old Nr2e3 rd7/rd7 retinas. At P21, S-opsin expression and the number of S-opsin expressing dorsal cones was increased. The dorso-ventral M-cone gradient was present in Nr2e3 rd7/rd7 retinas, but M-opsin expression and M-opsin expressing cones were decreased. Retinal vasculature was normal.

Abstract Alzheimer’s Disease (AD) is the most common cause of dementia among elderly individuals worldwide, leading to a strong motor-cognitive decline and consequent emotional distress and codependence. It is traditionally characterized by amyloidogenic pathway formation of senile plaques, and recent studies indicate that dysbiosis is also an important factor in AD’s pathology. To overcome dysbiosis, probiotics—as kefir—have shown to be a great therapeutic alternative for Alzheimer’s disease. In this present work, we explored kefir as a probiotic and a metabolite source as a modulator of microbiome and amyloidogenic pathway, using a Drosophila melanogaster model for AD (AD-like flies). Kefir microbiota composition was determined through 16S rRNA sequencing, and the metabolome of each fraction (hexane, dichloromethane, ethyl acetate, and n-butanol) was investigated. After treatment, flies had their survival, climbing ability, and vacuolar lesions accessed. Kefir and fraction treated flies improved their climbing ability survival rate and neurodegeneration index. In conclusion, we show that kefir in natura, as well as its fractions may be promising therapeutic source against AD, modulating amyloidogenic related pathways.

Abstract In bees from genus Melipona, differential feeding is not enough to fully explain female polyphenism. In these bees, there is a hypothesis that in addition to the environmental component (food), a genetic component is also involved in caste differentiation. This mechanism has not yet been fully elucidated and may involve epigenetic and metabolic regulation. Here, we verified that the genes encoding histone deacetylases HDAC1 and HDAC4 and histone acetyltransferase KAT2A were expressed at all stages of Melipona scutellaris, with fluctuations between developmental stages and castes. In larvae, the HDAC genes showed the same profile of Juvenile Hormone titers—previous reported—whereas the HAT gene exhibited the opposite profile. We also investigated the larvae and larval food metabolomes, but we did not identify the putative queen-fate inducing compounds, geraniol and 10-hydroxy-2E-decenoic acid (10HDA). Finally, we demonstrated that the histone deacetylase inhibitor 10HDA—the major lipid component of royal jelly and hence a putative regulator of honeybee caste differentiation—was unable to promote differentiation in queens in Melipona scutellaris. Our results suggest that epigenetic and hormonal regulations may act synergistically to drive caste differentiation in Melipona and that 10HDA is not a caste-differentiation factor in Melipona scutellaris.

Abstract Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a curative treatment for hematologic malignancies. Acute and chronic graft-versus-host disease (GvHD) are the major immune-mediated complications after alloHSCT. However, there is controversy whether neurologic complications after alloHSCT might represent manifestations of GvHD. We report three patients who acquired distinct, severe immune-mediated peripheral or central nervous system diseases after alloHSCT without other, concomitant GvHD manifestations. One patient had been diagnosed with B-cell chronic lymphocytic leukemia and two patients with high risk myelodysplastic syndrome. Patient #1 presented as LGI1- and GAD-IgG positive immune-mediated encephalitis, patient #2 was diagnosed with MOG-IgG positive encephalomyelitis, and patient #3 had chronic inflammatory polyneuropathy associated with SSA(Ro)-IgG positive Sjögren’s syndrome. 100% donor chimerism was detectable in the peripheral blood in all three. The specific antibodies were undetectable in donors’ and patients’ blood before alloHSCT suggesting that the antibodies had arisen from the transplanted donor immune system. Early intensive immunotherapy led to improvement of clinical symptoms and stability of the neurological disease, however, at the cost of losing the graft-versus-malignancy effect in one patient. In conclusion, we provide evidence of isolated, severe allo-immune diseases of the peripheral and central nervous system as complications of alloHSCT (“neuro-GvHD”). Interdisciplinary surveillance and thorough diagnostic work-up are needed for early diagnosis and treatment of neuro-immunologic complications after alloHSCT to improve the otherwise poor outcome.

Abstract Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no β-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.

Pretende-se com este artigo discutir e apresentar definições, benefícios e modificações de cargos provenientes da era da quarta revolução industrial, denominada como indústria 4.0. O conceito da indústria 4.0 está baseado na integração de diversas tecnologias inovadoras revolucionando a forma com que os processos são realizados nas organizações. Como em revoluções industriais ocorridas no decorrer da história, a indústria 4.0 tem provocado impactos e modificações no modelo atual de produção e na dinâmica do trabalho, assim como provocará adaptações nos sistemas trabalhistas. Com o desenvolvimento da quarta revolução industrial, temos uma nova realidade produtiva, onde tudo dentro de uma indústria estará conectado para realizar a melhor tomada de decisão com relação à produção, ao custo e à segurança. Todavia, esta transição do modelo atual de trabalho, em decorrência da era da indústria 4.0, exigirá um grande aprendizado e uma rápida capacitação por parte do trabalhador. Diferentes tipos de empregos serão impactados de maneira específica a sua natureza, sendo que estes impactos dependem de categorias e do setor industrial em si. É imprescindível a realização de uma avaliação sobre os impactos que a indústria 4.0 proporcionará na dinâmica de trabalho.

Different levels of resistance against Rhizopus oryzae infection have been observed between inbred (BALB/c) and outbred (Swiss) mice and are associated with the genetic background of each mouse strain. Considering that macrophages play an important role in host resistance to Rhizopus species, we used different infectious outcomes observed in experimental mucormycosis to identify the most efficient macrophage response pattern against R. oryzae in vitro and in vivo. For this, we compared BALB/c and Swiss macrophage activity before and after intravenous or intratracheal R. oryzae infections. The production of hydrogen peroxide (H2O2) and nitric oxide (NO) was determined in cultures of peritoneal (PMΦ) or alveolar macrophages (AMΦ) challenged with heat-killed spores of R. oryzae. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) were measured to confirm our findings. Naïve PMΦ from female BALB/c mice showed increased production of H2O2, TNF-α, and IL-10 in the presence of heat-killed spores of R. oryzae. Naïve PMΦ from female Swiss mice were less responsive. Naïve AMΦ from the two strains of female mice were less reactive to heat-killed spores of R. oryzae than PMΦ. After 30 days of R. oryzae intravenous infection, lower fungal load in spleen from BALB/c mice was accompanied by higher production of H2O2 by PMΦ compared with Swiss mice. In contrast, AMΦ from BALB/c mice showed higher production of NO, TNF-α, and IL-10 after 7 days of intratracheal infection. The collective findings reveal that, independent of the female mouse strain, PMΦ is more reactive against R. oryzae upon first contact than AMΦ. In addition, increased PMΦ production of H2O2 at the end of disseminated infection is accompanied by better fungal clearance in resistant (BALB/c) mice. Our findings further the understanding of the parasite–host relationship in mucormycosis.

Abstract With approximately 450 species, spiny Solanum species constitute the largest monophyletic group in the Solanaceae family, but a high-quality genome assembly from this group is presently missing. We obtained a chromosome-anchored genome assembly of eggplant (Solanum melongena), containing 34,916 genes, confirming that the diploid gene number in the Solanaceae is around 35,000. Comparative genomic studies with tomato (S. lycopersicum), potato (S. tuberosum) and pepper (Capsicum annuum) highlighted the rapid evolution of miRNA:mRNA regulatory pairs and R-type defense genes in the Solanaceae, and provided a genomic basis for the lack of steroidal glycoalkaloid compounds in the Capsicum genus. Using parsimony methods, we reconstructed the putative chromosomal complements of the key founders of the main Solanaceae clades and the rearrangements that led to the karyotypes of extant species and their ancestors. From 10% to 15% of the genes present in the four genomes were syntenic paralogs (ohnologs) generated by the pre-γ, γ and T paleopolyploidy events, and were enriched in transcription factors. Our data suggest that the basic gene network controlling fruit ripening is conserved in different Solanaceae clades, and that climacteric fruit ripening involves a differential regulation of relatively few components of this network, including CNR and ethylene biosynthetic genes.

Streptococcus pneumoniae is a common coloniser of the human nasopharynx, but it also causes severe diseases. Here, Weight et al. use an experimental human pneumococcal carriage model to show that bacterial colonisation is associated with invasion of the epithelium and enhancement of immune responses.

Loss or over-expression of Grainyhead-like transcription factors (Grhl) prevents closure of the neural tube but the mechanism underlying this is unclear. Here, the authors show that Grhl2 regulates murine posterior-neuropore closure via changes in the identity and biomechanics of the non-neural, surface ectoderm cells.

El presente trabajo tiene el objetivo de compartir con la comunidad científica las reflexiones surgidas al interior de un grupo de trabajo sobre el tema de los Cuidados Paliativos constituido en el Hospital S. Giovanni Calibita de la Isla Tiberina de Roma. Uno se pregunta: ¿cómo se muere en el Hospital? ¿Qué atención existe en relación con el paciente no sanado y destinado al traspaso en términos medianos breves? ¿Los cuidados paliativos pueden ser de ayuda en esta fase de asistencia? ¿Cómo modificar hábitos consagrados de un hospital para enfermos agudos y cómo dirigir los mismos hacia una mayor atención al problema de los cuidados del final de la vida? Y luego: ¿el apoyo paliativo debe quedar destinado a cubrir sólo las últimas fases de la vida o intervenir también antes? El estado del arte médico demuestra cuán lejano está todavía el desarrollo de una correcta mentalidad de acercamiento al tema en discusión en ambiente hospitalario y, salvo algunas virtuosas excepciones, todavía tiende a distinguirse la fase puramente intervencionista de la acción sobre la enfermedad, de aquella más atenta al control de los síntomas postergada a un momento sucesivo y distinto de la intervención causal. Mucho queda por hacer en el ámbito hospitalario y el pensamiento común entre los com- ponentes del grupo, pues es que sólo a través de una adecuada formación se puede orientar la preparación del personal hacia una cultura diversa que permita mirar al paciente en su integridad ampliando la perspectiva que hace que se ocupe sólo de su enfermedad. El artículo refiere las reflexiones de los componentes del grupo de trabajo, representantes de diversas unidades operativas y de varios servicios trasversales, los cuales, con objetividad y transparencia, proponen una lectura crítica de la atención al tema de los cuidados paliativos en sus unidades operativas de pertenencia.

Abstract Hedychium coronarium J. Koening, belonging to Zingiberaceae family, is a perennial herb with fleshly aromatic rhizomes. There are no information about the antiplatelet properties of essential oils (EOs) from rhizomes (HCR) and leaves (HCL) of this herb, additionally, there are reports about the antibacterial activity of the Zingiberaceae species, however, no studies have been carried out in the Colombian Amazon Region. The EOs were characterized by GC-MS, the antiaggregant activity was assessed by ADP and Collagen as platelet agonist and the antibacterial activity against E. faecalis and S. aureus were evidenced by the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). A high content of oxygenated monoterpenes were found in HCL essential oil (EO) and 20 compounds were identified in HCR EO. The HCL EO showed antiaggregant activity when collagen was used and HCR EO showed a concentration-dependent activity against ADP and collagen, meanwhile only the HCR EO showed antibacterial activity against E. faecalis and S. aureus.

Abstract The objective of this study was to estimate variance components for performance and carcass traits in a paternal broiler line. The (co)variance components were estimated by the restricted maximum likelihood method applied to the animal model, including the fixed effect of group (sex and hatch) and additive genetic and residual as random effects. Estimated heritability for performance traits ranged from 0.09 to 0.42. The genetic correlations between traits ranged from -0.50 to 0.97. The heritability estimates of feed intake, weight gain, and feed conversion from 35 to 41 days of age were of low magnitude. The genetic correlations among them were favorable to genetic selection. These results suggest that moderate genetic gain can be obtained to the feed intake and weight gain when the selection criterion is the body weight and prime cuts traits. The feed conversion that had low heritability estimation and low genetic correlation with the body weight and prime cut traits needs to pay greater attention due to the economic importance in the high-meat production lineage breeding programs.

In this paper we suggest a new Bayesian approach to network meta-analysis for the case of discrete multiple outcomes. The joint distribution of the discrete outcomes is modeled through a Gaussian copula with binomial marginals. The remaining elements of the hierarchial random effects model are specified in a standard way, with the logit of the success probabilities given by the sum of a baseline log-odds and random effects comparing the log-odds of each treatment against the reference and having a Gaussian distribution centered at the vector of pooled effects. An adaptive Markov Chain Monte Carlo algorithm is devised for running posterior inference. The model is applied to two datasets from Cochrane reviews, already analysed in two papers so to assess and compare its performance. We implemented the model in a freely available R package called netcopula.

Chronic pulmonary aspergillosis (CPA) is a slow and progressive disease that develops in preexisting lung cavities of patients with tuberculosis sequelae, and it is associated with a high mortality rate. Serological tests such as double agar gel immunodiffusion test (DID) or counterimmunoelectrophoresis (CIE) test have been routinely used for CPA diagnosis in the absence of positive cultures. However, these tests have been replaced with enzyme-linked immunoassay (ELISA) and, a variety of methods. This systematic review compares ELISA accuracy to reference test (DID and/or CIE) accuracy in CPA diagnosis. It was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The study was registered in PROSPERO under the registration number CRD42016046057. We searched the electronic databases MEDLINE (PubMed), EMBASE (Elsevier), LILACS (VHL), Cochrane library, and ISI Web of Science. Gray literature was researched using Google Scholar and conference abstracts. We included articles with patients or serum samples from patients with CPA who underwent two serological tests: ELISA (index test) and IDD and/or CIE (reference test). We used the test accuracy as a result. Original articles were considered without a restriction of date or language. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. We included 14 studies in the review, but only four were included in the meta-analysis. The pooled sensitivities and specificities were 0.93 and 0.97 for the ELISA test. These values were 0.64 and 0.99 for the reference test (DID and/or CIE). Analyses of summary receiver operating characteristic curves yielded 0.99 for ELISA and 0.99 for the reference test (DID and/or CIE). Our meta-analysis suggests that the diagnostic accuracy of ELISA is greater than the reference tests (DID and/or CIE) for early CPA detection.

Nowadays, the study of the upper atmosphere is increasing, mostly because of the need to understand the patterns of Earth's atmosphere. Since studies on global warming have become very important for the development of new technologies, understanding all regions of the atmosphere becomes an unavoidable task. In this paper, we aim to analyze the temperature variability and its trend in the mesosphere and lower thermosphere (MLT) region during a period of 12 years (from 2003 to 2014). For this purpose, three different heights, i.e., 85, 90 and 95 km, were focused on in order to investigate the upper atmosphere, and a geographic region different to other studies was chosen, in the southern region of Brazil, centered in the city of Santa Maria, RS (29°41′02′′ S; 53°48′25′′ W). In order to reach the objectives of this work, temperature data from the SABER instrument (Sounding of the Atmosphere using Broadband Emission Radiometry), aboard NASA's Thermosphere Ionosphere Mesosphere Energetics Dynamics (TIMED) satellite, were used. Finally, two cases were studied related to distinct grids of latitude/longitude used to obtain the mean temperature profiles. The first case considered a grid of 20° × 20° lat/long, centered in Santa Maria, RS, Brazil. In the second case, the region was reduced to a size of 15° × 15° in order to compare the results and discuss the two cases in terms of differences or similarities in temperature trends. Observations show that the size of the geographical area used for the average temperature profiles can influence the results of variability and trend of the temperature. In addition, reducing the time duration of analyses from 24 to 12 h a day also influences the trend significantly. For the smaller geographical region (15° × 15°) and the 12 h daily time window (09:00–21:00 UT) it was found that the main contributions for the temperature variability at the three heights were the annual and semi-annual cycles and the solar flux influence. A smaller trend (−0.02 ± 0.16 % decade−1) was found at 90 km height and small positive trends (0.58 ± 0.26 % and 0.41 ± 0.19 % decade−1) were found at altitudes of 85 and 95 km, respectively.

Individual SNPs have small effects on anthropometric traits, yet the impact of CNVs has remained largely unknown. Here, Kutalik and co-workers perform a large-scale genome-wide meta-analysis of structural variation and find rare CNVs associated with height, weight and BMI with large effect sizes.

Panniculitis and vitiligo-like lesions have been recently identified as rare cutaneous side effects of the combination of BRAF and MEK inhibitors, a standard of care in metastatic and locally advanced BRAF V600 mutated melanoma. An immune-mediated mechanism has been advocated in the pathogenesis of these skin lesions. Herein we retrospectively reviewed our institutional experience with the aim to explore the association between the occurrence of panniculitis and vitiligo-like lesions during combination therapy with dabrafenib (D) and trametinib (T) and outcome of advanced melanoma patients. Among 52 consecutive BRAF V600 mutated melanoma patients submitted to DT in our center, 12 (23%) developed immune related skin lesions (IRSLs): 8 panniculitis and 4 vitiligo. Patients with IRSLs diagnosis obtained a better disease response (83% versus 25%) (p = 0.001) than their counterpart and had a longer progression free survival and overall survival. The association of IRSLs and lower risk of disease progression (HR 0.19; CI 95% 0.04-0.90; p = 0.043) was confirmed after adjusting for major prognostic factors in multivariate analysis. IRSLs might represent an easy predictive surrogate marker for treatment response and favourable outcome in melanoma patients submitted to DT combination therapy.

INTRODUCTION:Studies on metabolomics and CKD have primarily addressed CKD incidence defined as a decline on eGFR or appearance of albuminuria in the general population, with very few evaluating hard outcomes. In the present study, we investigated the association between metabolites and mortality and ESRD in a CKD cohort. SETTING AND METHODS:Data on 454 participants of the Progredir Cohort Study, Sao Paulo, Brazil were used. Metabolomics was performed by GC-MS (Agilent MassHunter) and metabolites were identified using Agilent Fiehn GC/MS and NIST libraries. After excluding metabolites present in

Minerals, such as zinc, copper, and iron are reported to play roles in chronic infectious diseases; however, their role in paracoccidioidomycosis (PCM) remains unknown. This study aimed to examine the micronutrient dynamics and their correlation with serum proteins and thyroid hormones in patients with PCM. In 14 patients with PCM and 10 healthy subjects, we evaluated the body mass index (BMI) along with serum levels of hemoglobin, iron, ferritin, zinc, copper, magnesium, albumin, globulin, thyroid stimulating hormone (TSH), thyroxine (free T4), and triiodothyronine (T3). Evaluations were conducted at the first appointment, before treatment, and at the end of the first, second, fourth, and sixth month of PCM treatment. The control group was only evaluated once. We observed that before treatment, patients with PCM, had higher levels of copper and lower level of iron than those of the control group. After one month of treatment, the iron levels increased, whereas the levels of copper after six months of treatment. Reduction in inflammatory activity, indicated by the normalization of C-reactive protein, ferritin, albumin, and globulin levels, was observed during treatment. However, no correlation was observed between the serum levels of minerals and inflammatory activity or thyroid function in this study. In conclusion, our results showed higher serum copper levels in control group compared to those in pretreatment patients; the clinical importance of this observation should be investigated in further studies. After treatment, serum copper levels showed a tendency to decrease. In addition, serum iron levels were decreased at the stage of active disease, and were increased after treatment. Thus, serum iron levels can be used as a better biomarker for treatment control.

BackgroundRecent studies have begun to identify the molecular determinants of inter-individual variability of cardiorespiratory fitness (CRF) in response to exercise training programs. However, we still have an incomplete picture of the molecular mechanisms underlying trainability in response to exercise training.ObjectiveWe investigated baseline serum and skeletal muscle metabolomics profile and its associations with maximal power output (MPO) gains in response to 8-week of continuous endurance training (ET) and high-intensity interval training (HIIT) programs matched for total units of exercise performed (the TIMES study).MethodsEighty healthy sedentary young adult males were randomized to one of three groups and 70 were defined as completers (> 90% of sessions): ET (n = 30), HIIT (n = 30) and control (CO, n = 10). For the CO, participants were asked to not exercise for 8 weeks. Serum and skeletal muscle samples were analyzed by 1H-NMR spectroscopy. The targeted screens yielded 43 serum and 70 muscle reproducible metabolites (intraclass > 0.75; coefficient of variation < 25%). Associations of baseline metabolites with MPO trainability were explored within each training program via three analytical strategies: (1) correlations with gains in MPO; (2) differences between high and low responders to ET and HIIT; and (3) metabolites contributions to the most significant pathways related to gains in MPO. The significance level was set at P < 0.01 or false discovery rate of 0.1.ResultsThe exercise programs generated similar gains in MPO (ET = 21.4 ± 8.0%; HIIT = 24.3 ± 8.5%). MPO associated baseline metabolites supported by all three levels of evidence were: serum glycerol, muscle alanine, proline, threonine, creatinine, AMP and pyruvate for ET, and serum lysine, phenylalanine, creatine, and muscle glycolate for HIIT. The most common pathways suggested by the metabolite profiles were aminoacyl-tRNA biosynthesis, and carbohydrate and amino acid metabolism.ConclusionWe suggest that MPO gains in both programs are potentially associated with metabolites indicative of baseline amino acid and translation processes with additional evidence for carbohydrate metabolism in ET.

Recent scientific literature has investigated the cardiovascular implications of COVID-19. The mechanisms of cardiovascular damage seem to involve the protein angiotensin-converting enzyme 2 (ACE2), to which severe acute respiratory syndrome (SARS) coronavirus-2 (CoV-2) binds to penetrate cells and other mechanisms, most of which are still under study. Cardiovascular sequelae of COVID-19 include heart failure, cardiomyopathy, acute coronary syndrome, arrhythmias, and venous thromboembolism. This article aims to collect scientific evidence by exploiting PubMed, Scopus, and Pedro databases to highlight the cardiovascular complications of COVID-19 and to define the physiotherapy treatment recommended for these patients. Exercise training (ET), an important part of cardiac rehabilitation, is a powerful tool in physiotherapy, capable of inducing significant changes in the cardiovascular system and functional in the recovery of endothelial dysfunction and for the containment of thromboembolic complications. In conclusion, due to the wide variety of possible exercise programs that can be obtained by combining intensity, duration, and speed in various ways, and by adjusting the program based on continuous patient monitoring, exercise training is well suited to the treatment of post-COVID patients with an impaired cardiovascular system of various degrees.

SARS-CoV-2 infection has spread all over the world in the last year, causing millions of COVID-19 cases among humans with a large variability of symptoms and signs, including those on the skin. Among these, a contemporary cluster of chilblain-like lesions with no certain relationship with the infection has been reported. The aim of this paper is to delineate a profile of chilblain-like lesions and to establish the state-of-the-art knowledge about this new phenomenon.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Metabolic adjustments were studied in channel catfish Ictalurus punctatus exposed to 1.5 mg L-1 of phe nol (10% LC50) for four days and recovered for seven days. Lower triacylglycerol (TGA) stores and increased muscle fat free acids (FFA) suggest fat catabolism in muscle. Remarkable liver FFA decrease (-31%) suggests liver fat catabolism as well. Increased muscular ammonia levels and ASAT (aspartate aminotransferase) and decreased plasma aminoacids suggest higher muscular amino acid uptake. Constant levels of glucose and increased liver glycogen stores, associated with lower amino acids in plasma, indicate gluconeogenesis from amino acids. This is supported by higher hepatic ALAT and ASAT. Higher hepatic LDH followed by lower plasma lactate may indicate that plasma lactate was also used as gluconeogenic substrate. Biochemical alterations were exacerbated during the post-exposure recovery period. Reduction in muscle and plasma protein content indicate proteolysis. A higher rate of liver fat catabolism was resulted from a remarkable decrease in hepatic TGA (-58%). Catabolic preference for lipids was observed in order to supply such elevated energy demand. This study is the first insight about the metabolic profile of I. punctatus to cope with phenol plus its ability to recover, bringing attention to the biological consequences of environmental contamination.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

Iceland is one of the most recognizable and iconic places on Earth, offering an unparalleled chance to admire the most powerful natural phenomena related to the combination of geodynamic, tectonic and magmatic forces, such as active rifting, volcanic eruptions and subvolcanic intrusions. We have identified and selected 25 geosites from the Snæfellsnes Peninsula and the Northern Volcanic Zone, areas where most of the above phenomena can be admired as they unfold before the viewers’ eyes. We have qualitatively assessed the selected volcano−tectonic geosites by applying a set of criteria derived from previous studies and illustrated them through field photographs, unmanned aerial vehicle (UAV)-captured images and 3-D models. Finally, we have discussed and compared the different options and advantages provided by such visualization techniques and proposed a novel, cutting-edge approach to geoheritage promotion and popularization, based on interactive, navigable Virtual Outcrops made available online.

In this study, we aimed to evaluate the immunomodulatory effects of crude leaf extracts from Piper gaudichaudianum Kunth, P. arboreum Aub., P. umbellata L., P. fuligineum Kunth, and Peperomia obtusifolia A. Dietr. on an in vitro model of inflammatory response. The crude extracts were previously obtained by maceration of the leaves. The half-maximal inhibitory concentration was determined by the MTT assay using human peripheral blood mononuclear cells. Human monocytes were simultaneously challenged with each crude extract and lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, to induce a strong inflammatory response. After 24 h of incubation, cell-free supernatants were used for evaluating the mediators involved in inflammation: H2O2, TNF-α, IL-8, IL-6, IL-1β, IL-10, IL-12, FGF-b, and TGF-β1. We also compared the results with the effects of ketoprofen, a well-known anti-inflammatory drug. The P. gaudichaudianum crude extract downmodulated the production of H2O2, IL-1β, IL-6, IL-8, and TGF-β1 by LPS-stimulated monocytes; P. arboreum, IL-1β, IL-6, IL-8, and TNF-α; P. umbellata and P. fuligineum, H2O2, IL-1β, IL-6, IL-8, IL-10, and TNF-α; and P. obtusifolia, H2O2, IL-6, IL-8, IL-10, and TNF-α. In general, the crude leaf extracts amplified the anti-inflammatory response when compared with ketoprofen, particularly reducing the production of IL-8, a mediator involved in neutrophil recruitment during tissue damage. Thus, the crude leaf extracts of P. gaudichaudianum, P. arboreum, P. umbellata, P. fuligineum, and Peperomia obtusifolia elicited an anti-inflammatory response against LPS-challenged monocytes. These findings show the anti-inflammatory properties of these crude leaf extracts and offer new perspectives for their use in the treatment of inflammatory diseases.

Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls.LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p