Analisi in vivo e in vitro dell’attività del doppio carbapenemico nelle infezioni da Klebsiella pneumoniae produttrice di carbapenemasi

Negli ultimi anni si è assistito ad un incremento delle Enterobacteriaceae che producono carbapenemasi (CPE) in tutto il mondo; in Italia nell'ultima decade si è osservato un trend in drammatico aumento dei ceppi di Klebsiella pneumoniae resistente ai carbapenemi (CR-Kp). La presente tesi dimostra l’efficacia in vivo e l’attività in vitro della terapia con il doppio carbapenemico (meropenem + ertapenem) nei pazienti con infezione da Klebsiella pneumoniae produttrice di carbapenemasi, nei quali l’utilizzo della colistina era controindicato per tossicità o resistenza. I dati clinici sono stati supportati dalle analisi in vitro, che hanno evidenziato come questa associazione risulti sinergica e battericida. Siamo inoltre stati in grado di dimostrare che il regime con doppio carbapenemico associato alla colistina risulta efficace anche a concentrazioni sub-inibitorie dei farmaci. Il doppio carbapenemico da solo può essere una valida opzione terapeutica nei casi in cui la colistina risulta poco indicata, mentre la combinazione meropenem + ertapenem + colistina può essere particolarmente utile nei soggetti in condizioni cliniche gravi, quando una precoce risposta clinica è fondamentale. Il nostro case report dimostra invece l’efficacia della terapia con doppio carbapenemico in una paziente sottoposta a trapianto renale e con una grave infezione batteriemica da Escherichia coli produttrice di carbapenemasi. Questo approccio non convenzionale potrebbe essere considerato come terapia di salvataggio in quei soggetti in cui altre combinazioni antibiotiche falliscono o quando si preferisce non utilizzare la colistina. Infine questo caso evidenzia che fare test di sinergia in vitro rappresenta un’utile strategia per selezionare la migliore combinazione antibiotica, specialmente nei casi di infezioni in individui ad alto rischio come i soggetti trapiantati

Reproduction, Growth and Biomineralization of Calcifying Marine Organisms and their Relationships with Environmental Parameters

Global climate changes, driven by increasing temperature and pCO2, negatively affect marine ecosystem and mainly calcifying organisms. The reproduction of the zooxanthellate coral, Balanophyllia europaea, varied significantly along a latitudinal gradient of temperature and solar radiation. The warmer populations showed a lower reproductive efficiency due to the inhibition of the zooxanthellae photosynthesis, leading less available energy for reproduction. On the contrary, the B. europaea population, naturally living along a pCO2 gradient, did not show differences in oocytes development, production and morphology, probably by reallocating additional energy due to increasing of photosynthetic efficiency of zooxanthellae under pCO2 conditions. Increasing pCO2 negatively influenced spermaries production and development in L. pruvoti, causing a delayed in fertilization process, probably due to the lack of zooxanthellae involving in a lack of additional energy available for coral. The effects of high temperature, pCO2 and their interaction were tested on two symbiotic tropical corals, Fungia granulosa (solitary) and Pocillopora verrucosa (colonial). F. granulosa showed negative effects only in interaction treatment, while P. verrucosa showed decreased photosynthetic efficiency, increased bleaching tissue and mortality in all treatments. The more sensitivity of P. verrucosa could be explained by lower tissue thickness, making it more exposed and vulnerable to external environmental conditions. To investigate the role of intra-skeletal organic matrix in coral biomineralization, four Mediterranean species with different trophic strategy and growth form were selected. B. europaea organic matrix presented stronger control and higher independence from the crystallization environment than the other corals. Shell features of clam Chamelea gallina varied along a latitudinal gradient of temperature and solar radiation. Shells from the warmest and the most irradiated population were ~30% lighter due to thinner and more porous shells. No variation was observed in shell polymorphism at the nanoscale level, indicating no effects of environmental parameters on its composition and crystallography

Pesca de pequeñas embarcaciones en Madeira: recreativa frente artesanal

Small-scale recreational and artisanal fisheries are popular activities in the Autonomous Region of Madeira, and to date no information is available on their impact on regional coastal ecosystems. Through fishers’ surveys and official registers of fish landings, we described and characterized these fisheries in Madeira, comparing artisanal and recreational fisheries. In 2017, artisanal boats landed 91 species in fishing ports, while recreational catches landed 58 species. The most frequent catches were Dentex gibbosus, Phycis phycis and Pagrus pagrus for artisanal fishery and P. pagrus, Serranus atricauda and Diplodus spp. for recreational fishery. Comparing the same techniques, artisanal fishery always showed higher catch per unit effort values than recreational boat fishery. Nevertheless, the low number of artisanal fishery boats in comparison with the recreational ones reflected the lower total landings of the artisanal fishery, which in 2017 were 62.3 t, compared with the 509.8 t estimated catches for the recreational fishery. Though the estimated recreational fishing data were based on surveys and thus subject to various biases, this activity seems to negatively affect coastal ecosystems and, together with artisanal fishing, exerts a combined pressure on targeted species. Improved legislation for both fisheries is essential for an appropriate management of resources.La pesca recreativa y artesanal a pequeña escala (small-scale fisheries - SSF) es una actividad común en la Región Autónoma de Madeira de la que hasta la fecha, no se dispone de información sobre su impacto en los ecosistemas costeros regionales. A través de encuestas a pescadores y los registros oficiales de descargas de las especies capturadas, fue posible describir y caracterizar esta modalidad de pesca en la región y comparando la pesca artesanal con la recreativa. En 2017, las embarcaciones artesanales registraron descargas de 91 especies diferentes, mientras que en las capturas recreativas se contabilizaron 58 especies. Las capturas más frecuentes fueron Dentex gibbosus, Phycis phycis y Pagrus pagrus para la pesca artesanal, y P. pagrus, Serranus atricauda y Diplodus spp. para la recreativa. Al comparar las mismas técnicas coincidentes en las dos modalidades de pesca, se observó que en la pesca artesanal siempre presentó valores de CPUE más altos que la recreativa embarcada. Aún así, debido al bajo número de embarcaciones artesanales, se observó que los valores anuales de descargas totales para esta pesquería, son mucho menores que los estimados para la pesca recreativa embarcada (en 2017 fueron de 62,3 t en pesca artesanal, mientras que lo estimado para la pesca recreativa fueron 509,8 t). A pesar de que los datos estimados de pesca recreativa se basaron en encuestas y, por lo tanto, están sujetos a varios sesgos, esta actividad parece que puede afectar a los ecosistemas costeros, que junto con la pesca artesanal, puede ejercer una presión importante sobre las especies objetivo. Adecuar la legislación en ambas pesquerías es fundamental para poder realizar una gestión adecuada de los recursos

Severe bloodstream infection due to KPC-producer e coli in a renal transplant recipient treated with the double-carbapenem regimen and analysis of in vitro synergy testing a case report

Transplant recipients are at high risk of infections caused by multidrug resistant microorganisms. Due to the limited thera- peutic options, innovative antimicrobial combinations against carbape- nem-resistant Enterobacteriaceae causing severe infections are necessary. A 61-year-old woman with a history of congenital solitary kidney underwent renal transplantation. The postoperative course was compli- cated by nosocomial pneumonia due to Stenotrophomonas maltophilia and pan-sensitive Escherichia coli, successfully treated with antimicrobial therapy. On postoperative day 22, diagnosis of surgical site infection and nosocomial pneumonia with concomitant bacteremia due to a Kle- bisella pneumoniae carbapenemase-producer E coli was made. The patient was treated with the double-carbapenem regimen (high dose of merope- nem plus ertapenem) and a potent synergistic and bactericidal activity of this un-conventional therapeutic strategy was observed in vitro. Despite a microbiological response with prompt negativity of blood cultures, the patient faced a worse outcome because of severe hemorrhagic shock. The double-carbapenem regimen might be considered as a rescue therapy in those subjects, including transplant recipients, in whom previous antimicrobial combinations failed or when colistin use might be discouraged. Performing in vitro synergy testing should be strongly encouraged in cases of infections caused by pan-drug resistant strains, especially in high-risk patients

Citizen science and expert judgement: A cost-efficient combination to monitor and assess the invasiveness of non-indigenous fish escapees

Mapping the distribution and evaluating the impacts of marine non-indigenous species (NIS) are two fundamental tasks for management purposes, yet they are often time consuming and expensive. This case study focuses on the NIS gilthead seabream Sparus aurata escaped from offshore farms in Madeira Island in order to test an innovative, cost-efficient combined approach to risk assessment and georeferenced dispersal data collection. Species invasiveness was screened using the Aquatic Species Invasiveness Screening Kit (AS-ISK), and revealed a high invasion risk. Occurrences of S. aurata were assessed involving citizens in GIS participatory mapping and data from recreational fishing contests. A probability map showed that S. aurata is well dispersed around Madeira Island. This assessment proved to be a cost-efficient early warning method for detecting NIS dispersal, highlighting the urgent need for additional surveys that should search for sexually mature individuals and assess the direct and indirect impacts in the native ecosystemFundação para a Ciência e Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Diversity and patterns of marine non-native species in the archipelagos of Macaronesia

Tiago Marques and Carolina Marques thank partial support by CEAUL (funded by FCT through the project UIDB/00006/2020).Aims The present study is the first attempt to grasp the scale and richness of marine biological invasions in Macaronesia. We pioneered a comprehensive non-native species (NNS), inventory in the region to determine their diversity patterns and native distribution origins. NNS were defined here as the result of both introductions and range expansions. We also used statistical modelling to examine relationships among NNS richness, anthropogenic activities, demographic and geographical variables across Macaronesia. Location Macaronesia. Methods A comprehensive literature search was conducted for marine NNS records in Macaronesia, registering the first record's location and year from 1884 to 2020. We used univariate and multivariate analyses to evaluate differences and similarities in community composition. By applying a Generalized Linear Model (GLM), we tested hypotheses regarding NNS richness as a function of anthropogenic activities, demographic and geographical variables. Results A total of 144 marine non-native species (NNS) were recorded for the whole of Macaronesia. The highest NNS richness was registered in the Canary Islands (76 NNS), followed by the Azores (66 NNS), Madeira (59 NNS) and finally Cabo Verde (18 NNS). Some differences amongst archipelagos were observed, such as the high number of non-native macroalgae in the Azores, fishes in the Canary Islands and tunicates in Cabo Verde. Overall, macroalgae, tunicates and bryozoans were the predominant taxonomic groups in the Macaronesian archipelagos. Madeira and Canary Islands were the archipelagos with more similarity in marine NNS, and Cabo Verde the most divergent. Finally, GLM suggested that non-native richness patterns across Macaronesia were dependent on the considered archipelago and strongly affected by (1) minimum distance to the mainland, (2) the total number of ports and marinas and (3) total marinas area (km2). Conclusions The model results and NNS listing in the present study will likely raise the awareness and response regarding marine NNS in the whole Macaronesia region, serving as a baseline for future research as well as implementing and enforcing regulations related to the introduction of marine NNS in oceanic islands.Publisher PDFPeer reviewe

Security Messages: Or, How I Learned to Stop Disregarding and Heed the Warning

Attacks on information security continue to be reported in the media, and result in large losses for organizations. While some attacks are the result of sophisticated threats, others can be traced to failures by organizational insiders to observe basic security policies such as using caution when opening unsolicited email attachments. Faced with the challenges and time demands of everyday stressors, security policy compliance can be costly for individuals; security actions require time and distract attention from other primary tasks. This costliness can lead individuals to ignore prompts to perform security updates, scan their computers for threats, or reboot their computers to apply security updates. This dissertation contains three studies that address the following overarching research question: How can end-user adherence to security messages be better understood and improved, and how can theory inform security-message design? First, two complementary studies are presented that examine the integration of media naturalness theory into a security message context using field study and fMRI designs. Study 1, the field study, unobtrusively captures objective measures of attention from Amazon Mechanical Turk users (N=510) as they perform a between-subjects deception protocol. Study 2, the fMRI study, examines neural activations from a within-subjects participant design (N=23) in response to different security message designs with integrated emotive human facial expressions. Data from studies 1 and 2 show that warnings with integrated facial expressions of threat (fear, disgust) generally elicited greater adherence rates and higher evidence of cognition and elaboration than did warnings with integrated neutral facial expressions or than did warnings with no integrated facial expressions, supporting our hypotheses. Study 3 explores the pattern of risk taking and analysis that users engage in when interacting with interruptive security messages. The corroboration of multiple behavioral dependent variables suggests that users predominantly use a bimodal risk tradeoff paradigm when interacting with interruptive security messages. All three studies address the overarching research question of understanding and improving end user adherence to security messages

Disease Outbreak in a Keystone Grazer Population Brings Hope to the Recovery of Macroalgal Forests in a Barren Dominated Island

Macroalgal forests play a key role in shallow temperate rocky reefs worldwide, supporting communities with high productivity and providing several ecosystem services. Sea urchin grazing has been increasingly influencing spatial and temporal variation in algae distributions and it has become the main cause for the loss of these habitats in many coastal areas, causing a phase shift from macroalgae habitats to barren grounds. The low productive barrens often establish as alternative stable states and only a major reduction in sea urchin density can trigger the recovery of macroalgal forests. The present study aims to assess if the 2018 disease outbreak, responsible for a strong reduction in the sea urchin Diadema africanum densities in Madeira Island, was able to trigger a reverse shift from barren grounds into macroalgae-dominated state. By assessing the diversity and abundance of benthic sessile organisms, macroinvertebrates and fishes before, during and after that particular mass mortality event, we evaluate changes in benthic assemblages and relate them to variations in grazer and herbivore densities. Our results revealed a clear shift from barren state to a macroalgae habitat, with barrens characterized by bare substrate, sessile invertebrate and Crustose Coralline Algae (CCA) disappearing after the mortality event. Overall variations in benthic assemblages was best explained by four taxa (among grazers and herbivores species). However, it was the 2018 demise of D. africanum and its density reduction that most contributed to the reverse shift from a long stable barren state to a richer benthic assemblage with higher abundance of macroalgae. Despite this recent increase in macroalgae dominated habitats, their stability and persistence in Madeira Island is fragile, since it was triggered by an unpredictable disease outbreak and depends on how D. africanum populations will recover. With no control mechanisms, local urchin populations can easily reach the tipping point needed to promote a new shift into barren states. New conservation measures and active restoration are likely required to maintain and promote the local stability of macroalgal forests

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015