Cancer and suicidal ideation and behaviours: Protocol for a systematic review and meta-analysis

Introduction Prevalence of suicidal ideation (SI) and behaviours are higher among patients with cancer than general population. No systematic review/meta-analysis investigated this topic; therefore, our aim will be to assess the relationship between cancer and SI and behaviours. Methods We will search PubMed/MEDLINE, EMBASE, SCOPUS, Web of Science, PsycINFO and Cochrane Library databases from their inception until 30 June 2018. Case-control and cohort studies focused on the association between cancer (any type) and suicidal outcomes (suicide, suicide attempt and SI) will be included. Two team members will independently: (A) perform the selection of the included studies and data extraction, with the supervision of a third member in case of discrepancies and (B) assess each study with: (1) Newcastle-Ottawa Scale (NOS); (2) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement; (3) Grading of Recommendations Assessment, Development and Evaluation (GRADE). We will conduct a random-effects meta-analysis. Individual and pooled ORs and associated 95% CIs will be calculated as well as between-study heterogeneity. We will examine the potential for publication bias. If possible, we will explore reasons for potential between-study heterogeneity. Ethics and dissemination This study does not require ethical approval. The study will be submitted to a peer-reviewed journal, will be publicly disseminated and will be the topic of research presentations.This work is partly supported by the Swedish Cancer Society (grant no: CAN 2014/417), Swedish Research Council for Health, Working Life, and Welfare (grant no: 2017-00531), Karolinska Institutet (Senior Researcher Award and Strategic Research Area in Epidemiology Award)

Multiple subglacial water bodies below the south pole of Mars unveiled by new MARSIS data

The detection of liquid water by the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS) at the base of the south polar layered deposits in Ultimi Scopuli has reinvigorated the debate about the origin and stability of liquid water under present-day Martian conditions. To establish the extent of subglacial water in this region, we acquired new data, achieving extended radar coverage over the study area. Here, we present and discuss the results obtained by a new method of analysis of the complete MARSIS dataset, based on signal processing procedures usually applied to terrestrial polar ice sheets. Our results strengthen the claim of the detection of a liquid water body at Ultimi Scopuli and indicate the presence of other wet areas nearby. We suggest that the waters are hypersaline perchlorate brines, known to form at Martian polar regions and thought to survive for an extended period of time on a geological scale at below-eutectic temperatures

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

Effect of electrode distance in grid electrode: Numerical models and in vitro tests

Electrochemotherapy is an emerging local treatment for the management of superficial tumors and, among these, also chest wall recurrences from breast cancer. Generally, the treatment of this peculiar type of tumor requires the coverage of large skin areas. In these cases, electrochemotherapy treatment by means of standard small size needle electrodes (an array of 0.73 cm spaced needles, which covers an area of 1.5 cm2) is time-consuming and can allow an inhomogeneous coverage of the target area. We have previously designed grid devices suitable for treating an area ranging from 12 to 200 cm2. In this study, we propose different approaches to study advantages and drawbacks of a grid device with needles positioned 2 cm apart. The described approach includes a numerical evaluation to estimate electric field intensity, followed by an experimental quantification of electroporation on a cell culture. The electric field generated in a conductive medium has been studied by means of 3-dimensional numerical models with varying needle pair distance from 1 to 2 cm. In particular, the electric field evaluation shows that the electric field intensity with varying needle distance is comparable in the area in the middle of the 2 electrodes. Differently, near needles, the electric field intensity increases with the increasing electrode distance and supply voltage. The computational results have been correlated with experimental ones obtained in vitro on cell culture. In particular, electroporation effect has been assessed on human breast cancer cell line MCF7, cultured in monolayer. The use of 2-cm distant needles, supplied by 2000 V, produced an electroporation effect in the whole area comprised between the electrodes. Areas of cell culture where reversible and irreversible electroporation occurred were identified under microscope by using fluorescent dyes. The coupling of computation and experimental results could be helpful to evaluate the effect of the needle distance on the electric field intensity in cell cultures in terms of reversible or irreversible electroporation

Liquid Water Detection under the South Polar Layered Deposits of Mars—a Probabilistic Inversion Approach

Liquid water was present on the surface of Mars in the distant past; part of that water is now in the ground in the form of permafrost and heat from the molten interior of the planet could cause it to melt at depth. MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) has surveyed the Martian subsurface for more than fifteen years in search for evidence of such water buried at depth. Radar detection of liquid water can be stated as an inverse electromagnetic scattering problem, starting from the echo intensity collected by the antenna. In principle, the electromagnetic problem can be modelled as a normal plane wave that propagates through a three-layered medium made of air, ice and basal material, with the final goal of determining the dielectric permittivity of the basal material. In practice, however, two fundamental aspects make the inversion procedure of this apparent simple model rather challenging: (i) the impossibility to use the absolute value of the echo intensity in the inversion procedure; (ii) the impossibility to use a deterministic approach to retrieve the basal permittivity. In this paper, these issues are faced by assuming a priori information on the ice electromagnetic properties and adopting an inversion probabilistic approach. All the aspects that can affect the estimation of the basal permittivity below the Martian South polar cap are discussed and how detection of the presence of basal liquid water was done is described

Assessing the role of clay and salts on the origin of MARSIS basal bright reflections

Anomalously bright basal reflections detected by MARSIS at Ultimi Scopuli have been interpreted to indicate the presence of water-saturated materials or ponded liquid water at the base of the South Polar Layered Deposits (SPLD). Because conventional models assume basal temperatures (≤200 K) much lower than the melting point of water, this interpretation has been questioned and other explanations for the source of the bright basal reflections have been proposed, involving clay, hydrated salts, and saline ices. Combining previous published data, simulations, and new laboratory measurements, we demonstrate that the dielectric properties of these materials do not generate strong basal reflections at MARSIS frequencies and Martian temperatures. Plausible candidates remain perchlorates and chlorides brines that exhibit a strong dielectric response at much lower temperatures than other materials. This explanation might require that metastability could be maintained for a long period of time on a geological scale

Monitoring the last Apennine glacier: recent in situ campaigns and modelling of Calderone glacial apparatus

The Calderone glacier is at present the most southern glacier in Europe (42° 28' 15’’ N). The little apparatus (about 20.000 m2 in surface area) has been giving an interesting response both to short- and long-term climatic variations which resulted in a considerable reduction in surface area and volume. The glacial apparatus is split into two ice bodies (glacierets) since 2000. The two glacierets are located in a deep northward valley below the top of the Corno Grande (2912 m asl) in the centre of the Gran Sasso d’Italia mountain range (Central Italy). Such glacial apparatus has been subjected to a strong reduction, with a loss of total surface area of about 50% and thickness of about 65%with respect to the hypothetical size (about 105.00 m2 and 55 m at the Little Ice Age). Since early 90s the Calderone glacier has been subjected to several multidisciplinary field campaigns to monitor and evaluate its role as an environmental indicator in the framework of global warming. Starting from historical series related to more than a century of records, the variability of the different glacier properties has been estimated by using classical geomorphologic methods as well as in situ and remote sensing techniques. In particular, the last field campaigns, in 2015, 2016 and 2019, have been carried out using Ground Penetrating Radar equipped with different antenna frequencies, drone-based survey, snow pit measurements and chemical-physical sampling. The measurement campaigns have been complemented by a regional climate analysis, spanning the last fifty years, and snowpack modelling initialized with microphysical snow data (e.g., snow density, crystal shape and size, hardness). The snowpack chemical analyses include the main and trace elements, soluble inorganic and organic ions, EC/OC and PAH, with different spatial resolution depending on the analytes. We present here the methodological approach used and some preliminary results

Trichphyton violaceum and T. soudanese: re-emerging pathogens in Italy, 2005-2013

Dermatomycoses due to Trichophyton violaceum are described in Mediterranean Countries, North Africa and in the Horn of Africa where T. soudanense is present too, but it was rare until few years ago in Italy. Aim of the present study was to evaluate an Italian multicenter 9 year (2005-2013) experience concerning these re-emerging pathogens. Fifty three fungal strains were sent from clinical laboratories to the Medical Mycology Committee (CoSM) - Italian Association of Clinical Microbiology (AMCLI) for mycological confirmation. Strains were identified as T. violaceum (23) and T. soudanense (30) by phenotypic and genotypic methods. These dermatophytes present epidemiological (high rate of inter-human transmission, high risk among adopted children coming from countries of either the Horn of Africa or Sub-Saharan Africa also in outbreaks of tinea capitis) and clinical peculiarities (reduced alopecia, presence of exudative lesions) confirming the originality of these \u201cimported\u201d dermatophyte infection

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement