Increased D-dimer value and occult cancer in the absence of detectable thrombosis.

Fibrin formation and removal occurs continuously during the development of malignancy. Accordingly, hemostatic disorders in cancer patients are a rather frequent observation and range from asymptomatic laboratory changes to massive thromboembolism or haemorrhage. We document the case of an asymptomatic women, who was enrolled as a healthy control in a study and showed up with a substantially increased D- dimer value. After ruling out the most probable sources of D-dimer elevation, such as thrombosis, inflammation and trauma, she underwent laboratory and radiological investigations for malignancy, which were consistent with a colorectal metastatic adenocarcinoma. This case allow us to hypothesize that screening for occult malignancy in the presence of apparently inexplicable elevated D-dimer values may be taken into consideration

Anti-biofilm inhibitory synergistic effects of combinations of essential oils and antibiotics

In recent years, the increase of bacteria antibiotic-resistance has been a severe problem for public health. A useful solution could be to join some phytochemicals naturally present in essential oils (EOs) to the existing antibiotics, with the aim to increase their efficacy in therapies. According to in vitro studies, EOs and their components could show such effects. Among them, we studied the activity of Cinnammonum zeylanicum, Mentha piperita, Origanum vulgare, and Thymus vulgaris EOs on bacterial biofilm and their synergism when used in association with some common antibiotics such as norfloxacin, oxacillin, and gentamicin. The chemical composition of EOs was determined using gas chromatography (GC) coupled with mass spectrometry (MS) techniques. The EOs drug efficacy was evaluated on four different strains of Gram-positive bacteria forming biofilms. The synergistic effects were tested through the chequerboard microdilution method. The association EOs-antibiotics showed a strong destruction of the biofilm growth of the four bacterial species considered. The interaction of norfloxacin with EOs was the most effective in all the tested combinations against the strains object of this study. These preliminary results suggest the formulation of a new generation of antimicrobial agents based on a combination of antimicrobial compounds with different origin

Synergistic activity of new diclofenac and essential oils combinations against different candida spp

According to recent studies, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have shown a good antimicrobial and antifungal activity. Their association with essential oils (EOs) could be useful for the treatment of infections caused by Candida spp. The aim of this studyis to evaluate the synergistic antifungal activity of new combinations between Diclofenac Sodium Salt (DSS), a widely used NSAID, with EOs of Mentha × piperita, Pelargonium graveolens and Melaleuca alternifolia. The in-vitro antifungal activity was determined on different Candida strains. The determination of the chemical composition of EOs was carried out by gaschromatography-massspectrometry (GC-MS). Susceptibility testing of planktonic cells was performed by using the broth microdilution assay and checkerboard methods. Minimum Inhibitory Concentrations (MIC) of DSS was in a range from 1.02 to 2.05 µg/mL reaching a MIC value of 0.05 µg/mL when combined with Pelargonium graveolens (FICI = 0.23–0.35) or Menthapiperita (FICI = 0.22–0.30) EOs. These preliminary results show thatthe combination of the EOs with DSS improves the antifungal activity on all the tested Candida strains

Increased Gene Expression of RUNX2 and SOX9 in Mesenchymal Circulating Progenitors Is Associated with Autophagy during Physical Activity

Lack of physical exercise is considered an important risk factor for chronic diseases. On the contrary, physical exercise reduces the morbidity rates of obesity, diabetes, bone disease, and hypertension. In order to gain novel molecular and cellular clues, we analyzed the effects of physical exercise on differentiation of mesenchymal circulating progenitor cells (M-CPCs) obtained from runners. We also investigated autophagy and telomerase-related gene expression to evaluate the involvement of specific cellular functions in the differentiation process. We performed cellular and molecular analyses in M-CPCs, obtained by a depletion method, of 22 subjects before (PRE RUN) and after (POST RUN) a half marathon performance. In order to prove our findings, we performed also in vitro analyses by testing the effects of runners' sera on a human bone marrow-derived mesenchymal stem (hBM-MSC) cell line. PCR array analyses of PRE RUN versus POST RUN M-CPC total RNAs put in evidence several genes which appeared to be modulated by physical activity. Our results showed that physical exercise promotes differentiation. Osteogenesis-related genes as RUNX2, MSX1, and SPP1 appeared to be upregulated after the run; data showed also increased levels of BMP2 and BMP6 expressions. SOX9, COL2A1, and COMP gene enhanced expression suggested the induction of chondrocytic differentiation as well. The expression of telomerase-associated genes and of two autophagy-related genes, ATG3 and ULK1, was also affected and correlated positively with MSC differentiation. These data highlight an attractive cellular scenario, outlining the role of autophagic response to physical exercise and suggesting new insights into the benefits of physical exercise in counteracting chronic degenerative conditions

Dark chocolate modulates platelet function with a mechanism mediated by flavan-3-ol metabolites

Cocoa is a rich source bioactive compounds, i.e., flavan-3-ols, and its consumption has been associated with several beneficial effects, such as the positive modulation of the hemostasis targeted by the platelet function. However, these phenolic compounds have a very low bioavailability and extensively undergo phase I and II metabolism, with the appearing into the bloodstream of (epi) catechin conjugates and phenyl-g-valerolactones and their conjugates, at different times. The aims of this study were to explore the effect of dark chocolate on platelet function and to investigate the relationship between this interplay and flavan-3-ol derived metabolites. Eighteen healthy male volunteers ingested 50 g of 90% cocoa chocolate within 5 minutes. Blood samples were collected immediately before chocolate ingestion (T0) and 4 hours afterwards (T1). Platelet function analyzer (PFA)-100 closure time was assessed using collagen/adenosine-50-diphosphate (COL/ADP) and collagen/epinephrine (COL/EPI) cartridges. Plasma flavan-3-ol metabolites were identified and quantified by means of liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-ESI-MS/MS). Results evidenced a significant increase of COL/ADP-induced PFA-100 closure time, but not COL/EPI, 4 hours after ingestion of dark chocolate. Total plasma structurally-related (epi)catechin metabolite (SREM) concentration significantly increased at T1, together with 4 out of the 6 detected metabolites. Total phenyl-g-valerolactone concentrations remained unchanged. Spearman correlations evidenced a strong correlation between COL/ADP closure time and SREMs, mainly led by (epi)catechin-sulfate isomers. These data confirm that the potential beneficial effect of dark chocolate on primary hemostasis may be mediated by flavan-3-ol circulating metabolites

Molecular simplification of natural products: Synthesis, antibacterial activity, and molecular docking studies of berberine open models

Berberine, the main bioactive component of many medicinal plants belonging to various genera such as Berberis, Coptis, and Hydrastis is a multifunctional compound. Among the numerous interesting biological properties of berberine is broad antimicrobial activity including a range of Gram-positive and Gram-negative bacteria. With the aim of identifying berberine analogues possibly endowed with higher lead-likeness and easier synthetic access, the molecular simplification approach was applied to the secondary metabolite and a series of analogues were prepared and screened for their antimicrobial activity against Gram-positive and Gram-negative bacterial test species. Rewardingly, the berberine simplified analogues displayed 2–20-fold higher potency with respect to berberine. Since our berberine simplified analogues may be easily synthesized and are characterized by lower molecular weight than the parent compound, they are further functionalizable and should be more suitable for oral administration. Molecular docking simulations suggested FtsZ, a well-known protein involved in bacterial cell division, as a possible target

Zooarchaeological evidence of functional and social differentiation in northern Italy between the Neolithic and Bronze ages

Many sites dating from the Neolithic to the Bronze Age have been investigated in northern Italy and have provided important zooarchaeological data. These sites are mostly settlements, but also places of worship and necropoli. While there are few zooarchaeological studies for the north-western part of Italy, the north-east and the Po Valley have been better investigated. Particularly important are the pile-dwellings and the Terramare sites of the Po Valley as they have a long chronological span, the animal bone assemblages are large and, therefore, highly statistically reliable, and have been excavated relatively recently. There is evidence of functional and social differentiation in the Bronze Age which coincided with the evolution of more complex societies. The most common type of functional differentiation began when human communities started to settle and is visible in the zooarchaeological record. Until the end of the Copper Age, animal bone assemblages are characterized by the presence of both domestic animals and a relatively important proportion of wild animals. In the early Bronze Age, domestic animals dominated, if not entirely, the assemblages, and a growing interest in secondary products is evident. From the Middle Bronze Age, the foundation of semi-permanent settlements multiplied in the Alpine area, in the internal areas (secondary valleys and areas far from the main watercourses) and at medium-high altitudes. This was coupled with the seasonal occupation of sites at a high altitude, used for the practice of vertical transhumance (alpine pasture). This phenomenon implies the existence of a settlement hierarchy and, therefore, of forms of social stratification within the framework of the settlement system. Unfortunately, the few zooarchaeological studies of sites located in the Emilia Apennines do not currently allow us to confirm the existence of such links between the mountain sites and those on the plain. Nevertheless, other evidence, such as the introduction of the horse, which is attested from the late Early Bronze Age onwards, can be interpreted as proof of social differentiation; the horse was, in fact, considered a status symbol of the emerging warrior elite. Very few animal burials, dated to the period studied, show the link between animal species (such as dog, cattle, deer) and cultural practices, although a number of examples of such a relationship are provided by the terramare necropoli. In conclusion, in light of current knowledge, it seems that zooarchaeology cannot confirm the existence of important forms of social stratification. This does not mean that they cannot necessarily be postulated: the complex use of territory and the evidently communal nature of funerary and cult ceremonies (which often involved animals) that characterize the Bronze Age make it difficult to exclude the existence of such stratification

Reference miRNAs for colorectal cancer: analysis and verification of current data

MicroRNAs (miRNAs) hold great promise in cancer research. The use of appropriate reference miRNAs for normalization of qPCR data is crucial for accurate expression analysis. We present here analysis and verification of current data, proposing a workflow strategy for identification of reference miRNAs in colorectal cancer (CRC). We performed a systematic review of studies aimed to identify stable reference miRNAs in CRC through high-throughput screening. Among the candidate miRNAs selected from the literature we excluded those predicted to target oncogenes or tumor suppressor gene. We then assessed the expression levels of the remaining candidates in exosomes, plasma and tissue samples from CRC patients and healthy controls. The expression stability was evaluated by box-plot, 06Cq analysis, NormFinder and BestKeeper statistical algorithms. The effects of normalisers on the relative quantification of the oncogenic miR-1290 was also assessed. Our results consistently showed that different combinations of miR-520d, miR-1228 and miR-345 provided the most stably expressed reference miRNAs in the three biological matrices. We identified suitable reference miRNAs for future miRNA expression studies in exosomes plasma and tissues CRC samples. We also provided a novel conceptual framework that overcome the need of performing ex novo identification of suitable reference genes in single experimental systems

Proposta di una “checklist” per il prelievo di sangue venoso

The collection of venous blood is central in clinical laboratory activity. Although there is widespread perception that this practice is simple and free of complications and side effects, it is undeniable that the vast majority of laboratory errors arises from ignorance, incompetence or negligence during venipuncture. It has hence become advisable to prepare a document in simplified form of checklist, consisting of a concise but comprehensive list of activities to be completed or verified in order to prevent errors during venous blood collection. In the intention of authors, this synthetic checklist is a modular tool, adaptable to different local contexts, it can be easily and gradually implemented, it is supported by scientific evidence and consensus of experts and created with the support of different healthcare professionals and it is adherent to the best practices and requires minimal resources for implementation. It is reasonable to assume that this checklist may be able to withstand system and individual changes, strengthening the standards for safety of both operators and patients, limiting potential failure patterns. We hope that the checklist may be implemented in all healthcare facilities where routine venous blood collection is performed, after adaptation to suit characteristics of local organization

Raccomandazioni per l’identificazione e la gestione dei risultati critici nei laboratori clinici

Critical results (also known as panic or alarm results) identify a laboratory test result associated with a serious risk for the patient's health, requiring immediate communication to the physician to establish appropriate therapeutic interventions. The adoption of an efficient procedure for the communication of critical values/results is crucial for clinical, ethical, organizational reasons, because it is a requirement for laboratory accreditiation and because of potential legal consequences related to the lack of notification of harmful laboratory results. In 2008, the Italian Society of Clinical Biochemistry and Laboratory Medicine (SIBioC) published its first consensus-based recommendation for the detection and management of critical values in clinical laboratories, with the aim to improve the implementation of standardized and universally accepted procedures, promoting an essential policy toward rational and efficient solutions to this issue. These new recommendations represent a complete review of the first document. Using the same consensus conference method between experts of scientific societies, the main aspects of clinical risk, patient safety and legal liability of health care workers were re-considered. The SIBioC and the Italian Society of Laboratory Medicine (SIPMeL), Intersociety Study Group on Standardization of extra-analytical variability of laboratory results, together with the Italian Society of Ergonomics and Human Factors (SIE) collaboration, issued the present join document