Sepsis-Associated Disseminated Intravascular Coagulation and Thromboembolic Disease

Sepsis is almost invariably associated with haemostatic abnormalities ranging from subclinical activation of blood coagulation (hypercoagulability), which may contribute to localized venous thromboembolism, to acute disseminated intravascular coagulation (DIC), characterized by massive thrombin formation and widespread microvascular thrombosis, partly responsible of the multiple organ dysfunction syndrome (MODS), and subsequent consumption of platelets and coagulation proteins causing, in most severe cases, bleeding manifestations. There is general agreement that the key event underlying this life-threatening sepsis complication is the overwhelming inflammatory host response to the infectious agent leading to the overexpression of inflammatory mediators. Mechanistically, the latter, together with the micro-organism and its derivatives, causes DIC by 1) up-regulation of procoagulant molecules, primarily tissue factor (TF), which is produced mainly by stimulated monocytes-macrophages and by specific cells in target tissues; 2) impairment of physiological anticoagulant pathways (antithrombin, protein C pathway, tissue factor pathway inhibitor), which is orchestrated mainly by dysfunctional endothelial cells (ECs); and 3) suppression of fibrinolysis due to increased plasminogen activator inhibitor-1 (PAI-1) by ECs and likely also to thrombin-mediated activation of thrombin-activatable fibrinolysis inhibitor (TAFI). Notably, clotting enzymes non only lead to microvascular thrombosis but can also elicit cellular responses that amplify the inflammatory reactions. Inflammatory mediators can also cause, directly or indirectly, cell apoptosis or necrosis and recent evidence indicates that products released from dead cells, such as nuclear proteins (particularly extracellular histones), are able to propagate further inflammation, coagulation, cell death and MODS. These insights into the pathogenetic mechanisms of DIC and MODS may have important implications for the development of new therapeutic agents that could be potentially useful particularly for the management of severe sepsis

Application of vegetation index time series to value fire effect on primary production in a Southern European rare wetland

Fire disturbance is an intrinsic component of the Mediterranean biome playing an important role in ecosystem dynamics and processes. However, frequent and severe anthropogenic wildfires can be detrimental to natural ecosystems, particularly in small natural protected areas, where they may hamper the flow of ecosystem services (ES). While post-fire dynamics of individual ES are heavily context-dependent, the primary productivity of the ecosystem can be regarded as a generic driver of several provisioning and regulating ES, as it represents the amount of energy available to plants for storage, growth, and reproduction, which drives future ecosystem structure and functions. The aim of this study was to evaluate the effect of anthropogenic wildfire on the primary productivity of a rare wetland ecosystem in the Natura 2000 site \u201cTorre Guaceto\u201d in Southern Europe. Productivity was estimated by calculating a 15-year time series of vegetation indices (EVI and NDWI)from remotely sensed MODIS imagery. Our results in terms of PP trends may be relevant to assess the change in ecosystems services provided by wetlands. Interactions between wildfire, ecosystem productivity and climate were then analyzed. During the selected period, climate did not play a significant effect on primary productivity, which was mainly driven by post-fire vegetation recovery. Findings of the present study demonstrate that the wildfire affecting the Natural Protected Area of Torre Guaceto in summer 2007 had a major effect on primary productivity, inducing the regeneration of Phragmites australis and the replacement of old individuals by structurally and functionally better ones

In vivo analysis of the Escherichia coli ultrastructure by small-angle scattering

The flagellated Gram-negative bacterium Escherichia coli is one of the most studied microorganisms. Despite extensive studies as a model prokaryotic cell, the ultrastructure of the cell envelope at the nanometre scale has not been fully elucidated. Here, a detailed structural analysis of the bacterium using a combination of small-angle X-ray and neutron scattering (SAXS and SANS, respectively) and ultra-SAXS (USAXS) methods is presented. A multiscale structural model has been derived by incorporating well established concepts in soft-matter science such as a core-shell colloid for the cell body, a multilayer membrane for the cell wall and self-avoiding polymer chains for the flagella. The structure of the cell envelope was resolved by constraining the model by five different contrasts from SAXS, and SANS at three contrast match points and full contrast. This allowed the determination of the membrane electron-density profile and the inter-membrane distances on a quantitative scale. The combination of USAXS and SAXS covers size scales from micrometres down to nanometres, enabling the structural elucidation of cells from the overall geometry down to organelles, thereby providing a powerful method for a noninvasive investigation of the ultrastructure. This approach may be applied for probing in vivo the effect of detergents, antibiotics and antimicrobial peptides on the bacterial cell wall

Ethical issues associated with in-hospital emergency from the medical emergency team's perspective: a national survey

Medical Emergency Teams (METs) are frequently involved in ethical issues associated to in-hospital emergencies, like decisions about end-of-life care and intensive care unit (ICU) admission. MET involvement offers both advantages and disadvantages, especially when an immediate decision must be made. We performed a survey among Italian intensivists/anesthesiologists evaluating MET's perspective on the most relevant ethical aspects faced in daily practice

Molecular interactions, characterization and photoactivity of Chlorophyll a/chitosan/2-HP-β-cyclodextrin composite films as functional and active surfaces for ROS production

Novel photosensitizing film based on the natural hybrid polymer Chitosan/2-hydroxy-propyl-β-Cyclodextrin (CH/CD) is synthesized introducing Chlorophyll a (CH/CD/Chla) as a photoactive agent for possible application in antimicrobial photodynamic therapy (PDT). The polymer absorbs visible light, in turn able to generate reactive oxygen species (ROS) and, therefore it can be used as environmental friendly and biodegradable polymeric photosensitizer (PS). The modified film is characterized by means of different spectroscopic, calorimetric, diffraction techniques and microscopic imaging methods including time-resolved absorption spectroscopy. UV–Vis, FTIR-ATR and X-ray Photoelectron Spectroscopy (XPS) analyses suggest that Chla shows a strong affinity toward Chitosan introducing interactions with amino groups present on the polymer chains. Nanosecond laser flash photolysis technique provides evidence for the population of the excited triplet state of Chla. Photogeneration of singlet oxygen is demonstrated by both direct detection by using infrared luminescence spectroscopy and chemical methods based on the use of suitable traps. Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM) and Differential Scanning Calorimetry (DSC) analyses confirm also the occurrence of structural changes both on the film surface and within the film layer induced by the insertion of the pigment. Moreover, X-ray Diffraction data (XRD) shows the existence of an amorphous phase for the chitosan films in all the compared conditions

Key fundamental aspects for mapping and assessing ecosystem services: Predictability of ecosystem service providers at scales from local to global

How an apparent static and ordered landscape condition in social ecological landscapes (SELs), can be made sustainable in terms of maintenance and improvement of the provision of ecosystem services (ESs) in face of unpredictable disturbance and change? Our contribution to the Mapping and Assessment of Ecosystem Services (MAES) working group is to advance some recommendations on how to approach the dynamic analysis of complex adaptive systems to improve ecosystem resilience, habitat connectivity and the delivery of ESs. We show exemplary cases where we utilize the NDVI provided by remote sensing to evaluate land cover transformations and processes and ES provisioning. We focus on NDVI because it allows the supply of information on net primary production, i.e., the energetic foundation of nearly all ecosystems and that provides the basis of most of ESs. The use of spectral entropy, and nonlinear analysis of spatial temporal dynamics to investigate trajectory predictability of SELs provide very useful insight into the dynamics of SELs and can assist in the characterization of the links between land cover patterns with ecological processes to support more reliable assessments and accountings of ESs

Nanocellulose/fullerene hybrid films assembled at the air/water interface as promising functional materials for photo-electrocatalysis

Cellulose nanomaterials have been widely investigated in the last decade, unveiling attractive properties for emerging applications. The ability of sulfated cellulose nanocrystals (CNCs) to guide the supramolecular organization of amphiphilic fullerene derivatives at the air/water interface has been recently highlighted. Here, we further investigated the assembly of Langmuir hybrid films that are based on the electrostatic interaction between cationic fulleropyrrolidines deposited at the air/water interface and anionic CNCs dispersed in the subphase, assessing the influence of additional negatively charged species that are dissolved in the water phase. By means of isotherm acquisition and spectroscopic measurements, we demonstrated that a tetra-sulfonated porphyrin, which was introduced in the subphase as anionic competitor, strongly inhibited the binding of CNCs to the floating fullerene layer. Nevertheless, despite the strong inhibition by anionic molecules, the mutual interaction between fulleropyrrolidines at the interface and the CNCs led to the assembly of robust hybrid films, which could be efficiently transferred onto solid substrates. Interestingly, ITO-electrodes that were modified with five-layer hybrid films exhibited enhanced electrical capacitance and produced anodic photocurrents at 0.4 V vs Ag/AgCl, whose intensity (230 nA/cm2) proved to be four times higher than the one that was observed with the sole fullerene derivative (60 nA/cm2)

PIK3CA-Related Overgrowth Spectrum From Diagnosis to Targeted Therapy: A Case of CLOVES Syndrome Treated With Alpelisib

PIK3CA-related overgrowth spectrum (PROS) is an umbrella term referring to various clinical entities, which share the same pathogenetic mechanism. These conditions are caused by somatic gain-of-function mutations in PIK3CA, which encodes the 110-kD catalytic α subunit of PI3K (p110α). These PIK3CA mutations occur as post-zygotic events and lead to a gain of function of PI3K, with consequent constitutional activation of the downstream cascades (e.g., AKT/mTOR pathway), involved in cellular proliferation, survival and growth, as well as in vascular development in the embryonic stage. PIK3CA-related cancers and PROS share almost the same PIK3CA mutational profile, with about 80% of mutations occurring at three hotspots, E542, E545, and H1047. These hotspot mutations show the most potent effect on enzymatic activation of PI3K and consequent downstream biological responses. If present at the germinal level, these gain-of-function mutations would be lethal to the embryo, therefore we only see them in the mosaic state. The common clinical denominator of PROS disorders is that they are sporadic conditions, presenting with congenital or early childhood onset overgrowth with a typical mosaic distribution. However, the severity of PROS is highly variable, ranging from localized and apparently isolate overgrowth to progressive and extensive lipomatous overgrowth associated with life-threatening vascular malformations, as seen in CLOVES syndrome. Traditional therapeutic approaches, such as sclerotherapy and surgical debulking, are often not curative in PROS patients, leading to a recrudescence of the overgrowth in the treated area. Specific attention has been recently paid to molecules that are used and studied in the oncogenic setting and that are targeted on specific alterations of the pathway PI3K/AKT/mTOR. In June 2018, Venot et al. showed the effect of Alpelisib (BYL719), a specific inhibitor for the p110α subunit of PI3K, in patients with PROS disorders who had severe or life-threatening complications and were not sensitive to any other treatment. In these cases, dramatic anatomical and functional improvements occurred in all patients across many types of affected organ. Molecular testing in PROS patients is a crucial step in providing the conclusive diagnosis and then the opportunity for tailored therapy. The somatic nature of this group of diseases makes challenging to reach a molecular diagnosis, requiring deep sequencing methods that have to be performed on DNA extracted from affected tissue. Moreover, even analyzing the DNA extracted from affected tissue there is no guarantee to succeed in detection of the casual somatic mutation, since the affected tissue itself is highly heterogeneous and biopsy approaches can be burdened by incorrect sampling or inadequate tissue sample. We present an 8-year-old girl with CLOVES syndrome, born with a large cystic lymphangioma involving the left hemithorax and flank, multiple lipomas, and hypertrophy of the left foot and leg. She developed severe scoliosis. Many therapeutic approaches have been attempted, including Sildenafil treatment, scleroembolization, laser therapy, and multiple debulking surgeries, but none of these were of benefit to our patient's clinical status. She then started treatment with Rapamycin from May 2019, without significant improvement in both vascular malformation and leg hypertrophy. A high-coverage Whole Exome Sequencing analysis performed on DNA extracted from a skin sample showed a mosaic gain-of-function variant in the PIK3CA gene (p.H1047R, 11% of variant allele frequency). Once molecular confirmation of our clinical suspicion was obtained, after a multidisciplinary evaluation, we decided to discontinue Sirolimus and start targeted therapy with Alpelisib (50 mg/day). We noticed a decrease in fibroadipose overgrowth at the dorsal level, an improvement in in posture and excellent tolerability. The treatment is still ongoing

Perceived barriers to infection prevention and control for nursing home certified nursing assistants: a qualitative study.

Healthcare-associated infections, while preventable, result in increased morbidity and mortality in nursing home (NH) residents. Frontline personnel, such as certified nursing assistants (CNAs), are crucial to successful implementation of infection prevention and control (IPC) practices. The purpose of this study was to explore barriers to implementing and maintaining IPC practices for NH CNAs as well as to describe strategies used to overcome these barriers. We conducted a multi-site qualitative study of NH personnel important to infection control. Audio-recorded interviews were transcribed verbatim and transcripts were analyzed using conventional content analysis. Five key themes emerged as perceived barriers to effective IPC for CNAs: 1) language/culture; 2) knowledge/training; 3) per-diem/part-time staff; 4) workload; and 5) accountability. Strategies used to overcome these barriers included: translating in-services, hands on training, on-the-spot training for per-diem/part-time staff, increased staffing ratios, and inclusion/empowerment of CNAs. Understanding IPC barriers and strategies to overcome these barriers may better enable NHs to achieve infection reduction goals