Diverse reductive dehalogenases are associated with Clostridiales-enriched microcosms dechlorinating 1,2-dichloroethane

The achievement of successful biostimulation of active microbiomes for the cleanup of a polluted site is strictly dependent on the knowledge of the key microorganisms equipped with the relevant catabolic genes responsible for the degradation process. In this work, we present the characterization of the bacterial community developed in anaerobic microcosms after biostimulation with the electron donor lactate of groundwater polluted with 1,2-dichloroethane (1,2-DCA). Through a multilevel analysis, we have assessed (i) the structural analysis of the bacterial community; (ii) the identification of putative dehalorespiring bacteria; (iii) the characterization of functional genes encoding for putative 1,2-DCA reductive dehalogenases (RDs). Following the biostimulation treatment, the structure of the bacterial community underwent a notable change of the main phylotypes, with the enrichment of representatives of the order Clostridiales. Through PCR targeting conserved regions within known RD genes, four novel variants of RDs previously associated with the reductive dechlorination of 1,2-DCA were identified in the metagenome of the Clostridiales-dominated bacterial community

Adherence With Antihypertensive Drug Therapy and the Risk of Heart Failure in Clinical Practice

Randomized clinical trials have shown that antihypertensive treatment reduces the risk of heart failure (HF). Limited evidence exists, however, on whether and to what extent this benefit is translated into real-life practice. A nested case–control study was carried out by including the cohort of 76 017 patients from Lombardy (Italy), aged 40 to 80 years, who were newly treated with antihypertensive drugs during 2005. Cases were the 622 patients who experienced hospitalization for HF from initial prescription until 2012. Up to 5 controls were randomly selected for each case. Logistic regression was used to model the HF risk associated with adherence to antihypertensive drugs, which was measured by the proportion of days covered by treatment (PDC). Data were adjusted for several covariates. Sensitivity analyses were performed to account for possible sources of systematic uncertainty. Compared with patients with very low adherence (PDC, ≤25%), low, intermediate, and high adherences were associated with progressively lower risk of HF, reduction in the high-adherence group (>75%) being 34% (95% confidence interval, 17%–48%). Similar effects were observed in younger (40–70 years) and older (71–80 years) patients and between patients treated with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. There was no evidence that adherence with calcium-channel blockers reduced the HF risk. Antihypertensive treatment lowers the HF risk in real-life practice, but adherence to treatment is necessary for a substantial benefit to take place. This is the case with a variety of antihypertensive drugs

Sociodemographic determinants of knowledge on the figure of radiologist: results of a survey in large university hospital

Introduction Despite overlaying an irreplaceable role as a key diagnostic tool in modern medicine, the role of radiologist still appears to be unclear to patients. Methods We conducted a survey in outpatient clinic of Radiological Sciences Department of the University Hospital “A. Gemelli” in Rome, aiming to assess how correct patients identify the figure of the radiologist. The patients were interviewed by the trained physician using structured questionnaire. Results We included the number of 259 patients. Majority were female 63.3%, most were 60-69 years old (24.3%), have finished second grade secondary school (35.1%) and were subjected to magnetic resonance (28.6%) while the least were subjected to chest X-ray (8.1%). Only 38.7% answered correctly to question No 1 “Who performed your examination?”, and only 30.9% correctly identified the radiologist as a person interpreting the exam (question No 2 “Who is going to interpret your radiological examination?”). Overall, 16.8% responded correctly to the both questions. Significantly less patients with primary school (OR: 0.18, CI 95% 0.06-0.49) and first grade secondary school (OR: 0.37, CI 95% 0.18-0.75) correctly addressed the question No 1 in compare to those with second grade secondary school. The first grade secondary education (OR: 0.43, CI 95% 0.20-0.92) was inversely associated with correct answer to question No 2.  Patients with primary education were significantly less prone to give both correct answers (OR: 0.12, CI 95% 0.02-0.60). Conclusion We report insufficient knowledge among patients on radiologist’s role in healthcare system. The level of knowledge is associated with level of education

The occurrence of paraffin and other petroleum waxes in the marine environment: A review of the current legislative framework and shipping operational practices

Among the various materials that make up marine debris, lumps of petroleum waxes such as paraffin and microcrystalline wax, are regularly found on beaches worldwide, although not included in the current definition of marine litter. Ingestion by marine organisms is occasionally documented in the scientific literature and mass beaching events are frequently reported along the European coasts, with obvious detrimental consequences to the local communities that have to manage the clean-up and disposal of this substance. According to Annex II of the MARPOL regulation, petroleum waxes are classified as "high viscosity, solidifying, and persistent floating products," whose discharge at sea of tank-washing residues is strictly regulated, but currently permitted within certain limits. Starting from the description of a large stranding event occurred along the Italian coasts in 2017, we review the existing knowledge and regulatory framework and urge the relevant authorities to address this issue, showing that wax pollution is creating evident damages to the European coastal municipalities. Pending further investigations on the potential hazard that this kind of pollution is posing to marine ecosystems, we suggest a careful and more stringent revision of the policies regulating discharges of these products at sea

Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer

PI3K inhibitor; PIK3CA mutations; Trastuzumab resistanceInhibidor de PI3K; Mutacions PIK3CA; Resistència al trastuzumabInhibidor de PI3K; Mutaciones PIK3CA; Resistencia a trastuzumabPurpose Dysregulation of the PI3K pathway is one of the most common events in breast cancer. Here we investigate the activity of the PI3K inhibitor MEN1611 at both molecular and phenotypic levels by dissecting and comparing its profile and efficacy in HER2 + breast cancer models with other PI3K inhibitors. Methods Models with different genetic backgrounds were used to investigate the pharmacological profile of MEN1611 against other PI3K inhibitors. In vitro studies evaluated cell viability, PI3K signaling, and cell death upon treatment with MEN1611. In vivo efficacy of the compound was investigated in cell line- and patient-derived xenografts models. Results Consistent with its biochemical selectivity, MEN1611 demonstrated lower cytotoxic activity in a p110δ-driven cellular model when compared to taselisib, and higher cytotoxic activity in the p110β-driven cellular model when compared to alpelisib. Moreover, MEN1611 selectively decreased the p110α protein levels in PIK3CA mutated breast cancer cells in a concentration- and proteasome-dependent manner. In vivo, MEN1611 monotherapy showed significant and durable antitumor activity in several trastuzumab-resistant PIK3CA-mutant HER2 + PDX models. The combination of trastuzumab and MEN1611 significantly improved the efficacy compared to single agent treatment. Conclusions The profile of MEN1611 and its antitumoral activity suggest an improved profile as compared to pan-inhibitors, which are limited by a less than ideal safety profile, and isoform selective molecules, which may potentially promote development of resistance mechanisms. The compelling antitumor activity in combination with trastuzumab in HER2 + trastuzumab-resistant, PIK3CA mutated breast cancer models is at the basis of the ongoing B-Precise clinical trial (NCT03767335).This work was supported by Regione Lazio, POR FESR 2014–2020 Bando “Life 2020_Progetti. integrati” for the project “PISTA (PI3K for Solid Tumor therApy)” (CUP F57H18000070007)

Optimal Selection Techniques for Cloud Service Providers

Nowadays Cloud computing permeates almost every domain in Information and Communications Technology (ICT) and, increasingly, most of the action is shifting from large, dominant players toward independent, heterogeneous, private/hybrid deployments, in line with an ever wider range of business models and stakeholders. The rapid growth in the numbers and diversity of small and medium Cloud providers is bringing new challenges in the as-a-Services space. Indeed, significant hurdles for smaller Cloud service providers in being competitive with the incumbent market leaders induce some innovative players to "federate" deployments in order to pool a larger, virtually limitless, set of resources across the federation, and stand to gain in terms of economies of scale and resource usage efficiency. Several are the challenges that need to be addressed in building and managing a federated environment, that may go under the "Security", "Interoperability", "Versatility", "Automatic Selection" and "Scalability" labels. The aim of this paper is to present a survey about the approaches and challenges belonging to the "Automatic Selection" category. This work provides a literature review of different approaches adopted in the "Automatic and Optimal Cloud Service Provider Selection", also covering "Federated and Multi-Cloud" environments

The role of fungi in heterogeneous sediment microbial networks

While prokaryote community diversity and function have been extensively studied in soils and sediments, the functional role of fungi, despite their huge diversity, is widely unexplored. several studies have, nonetheless, revealed the importance of fungi in provisioning services to prokaryote communities. Here, we hypothesise that the fungal community plays a key role in coordinating entire microbial communities by controlling the structure of functional networks in sediment. We selected a sediment environment with high niche diversity due to prevalent macrofaunal bioturbation, namely intertidal mangrove sediment, and explored the assembly of bacteria, archaea and fungi in different sediment niches, which we characterised by biogeochemical analysis, around the burrow of a herbivorous crab. We detected a high level of heterogeneity in sediment biogeochemical conditions, and diverse niches harboured distinct communities of bacteria, fungi and archaea. saprotrophic fungi were a pivotal component of microbial networks throughout and we invariably found fungi to act as keystone species in all the examined niches and possibly acting synergistically with other environmental variables to determine the overall microbial community structure. In consideration of the importance of microbial-based nutrient cycling on overall sediment ecosystem functioning, we underline that the fungal microbiome and its role in the functional interactome cannot be overlooked

Consistent bacterial selection by date palm root system across heterogeneous desert oasis agroecosystems

Highly productive conventional agroecosystems are spatially embedded in resource-homogeneous systems and count on generally nutrient-rich soils. On the contrary, desert oases are isolated, the soil is relatively poor, but yet productivity is similar to conventional agroecosystems. Soil dominates over plant as the main factor shaping root-associated microbiomes in conventional agroecosystems. We hypothesize that in desert oasis, the environmental discontinuity, the resource paucity and limited microbial diversity of the soil make the plant a prevailing factor. We have examined the bacterial communities in the root system of date palm (Phoenix dactylifera), the iconic keystone species of the oases, grown in heterogeneous soils across a broad geographic range (22,200 km2 surface area) of the Sahara Desert in Tunisia. We showed that, regardless of the edaphic conditions and geographic location, the plant invariably selects similar Gammaproteobacteria- and Alphaproteobacteria-dominated bacterial communities. The phylogeny, networking properties and predicted functionalities of the bacterial communities indicate that these two phyla are performing the ecological services of biopromotion and biofertilization. We conclude that in a desert agroecosystem, regardless of the soil microbial diversity baseline, the plant, rather than soil type, is responsible of the bacterial community assembly in its root systems, reversing the pattern observed in conventional agroecosystem

The CRACK programme: a scientific alliance for bridging healthcare research and public health policies in Italy

Healthcare utilisation databases, and other secondary data sources, have been used with growing frequency to assess health outcomes and healthcare interventions worldwide. Their increased popularity as a research tool is due to their timely availability, the large patient populations covered, low cost, and applicability for studying real-world clinical practice. Despite the need to measure Italian National Health Service performance both at regional and national levels, the wealth of good quality electronic data and the high standards of scientific research in this field, healthcare research and public health policies seem to progress along orthogonal dimensions in Italy. The main barriers to the development of evidence-based public health include the lack of understanding of evidence-based methodologies by policy makers, and of involvement of researchers in the policy process. The CRACK programme was launched by some academics from the Lombardy Region. By extensively using electronically stored data, epidemiologists, biostatisticians, pharmacologists and clinicians applied methods and evidence to several issues of healthcare research. The CRACK programme was based on their intention to remove barriers that thwart the process of bridging methods and findings from scientific journals to public health practice. This paper briefly describes aim, articulation and management of the CRACK programme, and discusses why it might find articulated application in Italy