Unexpected silicon localization in calcium carbonate exoskeleton of cultured and fossil coccolithophores.

Coccolithophores, marine calcifying phytoplankton, are important primary producers impacting the global carbon cycle at different timescales. Their biomineral structures, the calcite containing coccoliths, are among the most elaborate hard parts of any organism. Understanding the morphogenesis of coccoliths is not only relevant in the context of coccolithophore eco-physiology but will also inform biomineralization and crystal design research more generally. The recent discovery of a silicon (Si) requirement for crystal shaping in some coccolithophores has opened up a new avenue of biomineralization research. In order to develop a mechanistic understanding of the role of Si, the presence and localization of this chemical element in coccoliths needs to be known. Here, we document for the first time the uneven Si distribution in Helicosphaera carteri coccoliths through three synchrotron-based techniques employing X-ray Fluorescence and Infrared Spectromicroscopy. The enrichment of Si in specific areas of the coccoliths point to a targeted role of this element in the coccolith formation. Our findings mark a key step in biomineralization research because it opens the door for a detailed mechanistic understanding of the role Si plays in shaping coccolith crystals.

Italian midwives in Europe: a qualitative study on the experiences of professional migration.

Aim: To explore the reasons for Italian midwives' decision to migrate, and their lived professional and emotional experiences. Methods: A descriptive phenomenological study was conducted recruiting Italian midwives who were working abroad in European countries. We offered a telephone or web interview. Two researchers conducted, audio-recorded, and fully transcribed the interviews and other two researchers, independently, performed a content analysis. Results: Thirty-two midwives having professional experiences in the UK, Ireland, Germany, Switzerland, and Spain were interviewed. Five themes emerged: 1) Education, 2) Migration decision-making, 3) Professional experience abroad, 4) Midwives' perceptions of their role, 5) Satisfaction versus desire to return. Our findings show a general dissatisfaction with Italian job opportunities in terms both of access to employment and work conditions. This scenario is complicated by the status of the professional midwifery in Italy. Conclusion: Stakeholders should ensure that the migration of Italian midwives is not synonymous with dispersion but is a channel of professional growth and mutual exchange.

Poor patient awareness and frequent misdiagnosis of migraine: findings from a large transcontinental cohort.

BACKGROUND AND PURPOSE: Although migraine is the second most disabling condition worldwide, there is poor awareness of it. The objective was to assess the awareness of migraine and previous diagnostic and therapeutic consultations and treatments in a large international population of migraineurs. METHODS: This was a multicentre study conducted in 12 headache centres in seven countries. Each centre recruited up to 100 patients referred for a first visit and diagnosed with migraine. Subjects were given a structured clinical questionnaire-based interview about the perceptions of the type of headache they suffered from, its cause, previous diagnoses, investigations and treatments. RESULTS: In all, 1161 patients completed the study. Twenty-eight per cent of participants were aware that they suffered from migraine. Sixty-four per cent called their migraine 'headache'; less commonly they used terms such as 'cervical pain' (4%), tension headache (3%) and sinusitis (1%). Eight per cent of general practitioners and 35% of specialists (of whom 51% were neurologists and/or headache specialists) consulted for migraine formulated the correct diagnosis. Before participating in the study, 50% of patients had undergone X-ray, computed tomography and/or magnetic resonance imaging of the cervical spine and 76% underwent brain and/or cervical spine imaging for migraine. Twenty-eight per cent of patients had received symptomatic migraine-specific medications and 29% at least one migraine preventive medication. CONCLUSIONS: Although migraine is a very common disease, poor awareness of it amongst patients and physicians is still an issue in several countries. This highlights the importance of the promotion of migraine awareness to reduce its burden and limit direct and indirect costs and the risk of exposure to useless investigations.

Quality indicators in headache care: an implementation study in six Italian specialist-care centres.

BACKGROUND: Headache disorders are highly prevalent, and have a substantial and negative impact on health worldwide. They are largely treatable, but differences in structure, objectives, organization and delivery affect the quality of headache care. In order to recognize and remedy deficiencies in care, the Global Campaign against Headache, in collaboration with the European Headache Federation, recently developed a set of quality indicators for headache services. These require further assessment to demonstrate fitness for purpose. This is their first implementation to evaluate quality in headache care as a multicentre national study. METHODS: Between September and December 2016, we applied the quality indicators in six Italian specialist headache centres (Bologna, Firenze, Modena, Padova, Roma Campus Bio-Medico and Roma Sapienza). We used five previously developed assessment instruments, translated into Italian according to Lifting The Burden's translation protocol for hybrid documents. We took data from 360 consecutive patients (60 per centre) by questionnaire and from their medical records, and by different questionnaires from their health-care providers (HCPs), including physicians, nurses, psychologists and nursing assistants. RESULTS: The findings, comparable between centres, confirmed the feasibility and practicability of using the quality indicators in Italian specialist headache centres. The questionnaires were easily understood by HCPs and patients, and were not unduly time-consuming. Diagnoses were almost all (> 97%) according to ICHD criteria, and routinely (100%) reviewed during follow-up. Diagnostic diaries were regularly used by 96% of physicians. Referral pathways from primary to specialist care existed in five of the six clinics, as did urgent referral pathways. Instruments to assess disability and quality of life were not used regularly, a deficiency that needs to be addressed. CONCLUSION: This Italy-wide survey confirmed in six specialist centres that the headache service quality indicators are fit for purpose. By establishing majority practice, identifying commonalities and detecting deficits as a guide to quality improvement, the quality indicators may be used to set benchmarks for quality assessment. The next step is extend use and evaluation of the indicators into non-specialist care.

BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection.

BACKGROUND: Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed. METHODS: To assess the prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS). RESULTS: In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses. CONCLUSIONS: BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.

Histo-cytological diagnostic accuracy in lung cancer.

OBJECTIVE: The majority of patients with lung cancer are treated on the basis of a diagnosis made from the analysis of a small tumour biopsy or a cytological sample and histotype is becoming a critical variable in clinical workup as it has led to the introduction of newer biologically targeted therapies. Consequently, simply classifying cancers as small cell lung cancers or non-small cell lung cancers is no longer sufficient. METHODS: From 2009 to 2011, a review of the histo-cytological database was conducted to identify all small biopsy and cytology specimens collected for diagnostic purposes in patients with a thoracic lesion. In total, 941 patients were studied by examining exfoliative and/or aspirative cytological samples. To establish the accuracy of these methods, cytological and biopsy diagnoses were compared with each other and with subsequent resection specimens when available. Moreover, during the diagnostic workup, we examined a validated panel of immunohistochemical markers. RESULTS: The diagnostic concordance of pre-operative diagnoses with surgical samples was high in both cytology and biopsy samples [κ = 0.71, confidence interval (CI) = 0.6-0.81; P < 0.0001 and κ = 0.61, CI = 0.41-0.82; P < 0.0001 respectively; good agreement] but concordance between cytology and biopsy was moderate (κ = 0.5, CI = 0.43-0.54; P < 0.0001). Immunohistochemistry-aided diagnoses were definitive for histotype in 92.8% of both cytology (206/222) and biopsy (155/167) specimens. CONCLUSION: We found that lung cancer diagnosis and subtyping of cytology and biopsy samples are highly feasible and concordant; thus, the diagnostic approach to lung cancer does not require more invasive procedures.

Assessment of xylem phenology: a first attempt to verify its accuracy and precision.

This manuscript aims to evaluate the precision and accuracy of current methodology for estimating xylem phenology and tracheid production in trees. Through a simple approach, sampling at two positions on the stem of co-dominant black spruce trees in two sites of the boreal forest of Quebec, we were able to quantify variability among sites, between trees and within a tree for different variables. We demonstrated that current methodology is accurate for the estimation of the onset of xylogenesis, while the accuracy for the evaluation of the ending of xylogenesis may be improved by sampling at multiple positions on the stem. The pattern of variability in different phenological variables and cell production allowed us to advance a novel hypothesis on the shift in the importance of various drivers of xylogenesis, from factors mainly varying at the level of site (e.g., climate) at the beginning of the growing season to factors varying at the level of individual trees (e.g., possibly genetic variability) at the end of the growing season.

FOLFOXIRI plus bevacizumab as first-line treatment in BRAF mutant metastatic colorectal cancer.

BACKGROUND: BRAF V600E mutation plays a negative prognostic role in metastatic colorectal cancer (mCRC), leading to a median Progression Free Survival (PFS) of 4-6months with first-line conventional treatments. Our group recently reported in a retrospective exploratory analysis of a phase II trial that FOLFOXIRI (5-FU/LV+Oxaliplatin+Irinotecan) plus bevacizumab might allow to achieve remarkable results in terms of PFS and Overall Survival (OS) also in this poor-prognosis subgroup. The aim of this work was to prospectively validate our retrospective finding. PATIENTS AND METHODS: This phase II trial was designed to detect an increase in 6month-Progression Free Rate (6m-PFR) from 45% to 80% in a population of BRAF mutant mCRC patients treated with first-line FOLFOXIRI plus bevacizumab. Secondary end-points were PFS, OS, response rate (RR) and the analysis of outcome parameters in the pooled population consisting of both retrospectively and prospectively included patients. This trial is registered with ClinicalTrials.gov, number NCT01437618. RESULTS: Two-hundred-fourteen potentially eligible mCRC patients were screened for BRAF mutational status. Fifteen BRAF mutant patients (7%) were included in the validation cohort. At a median follow up of 25.7months, 6m-PFR was 73%. Median PFS and OS were 9.2 and 24.1months, respectively. In the pooled population, at a median follow up of 40.4months, 6m-PFR was 84%. Median PFS and OS were 11.8 and 24.1months, respectively. Overall RR and disease control rate were 72% and 88%, respectively. CONCLUSION: Lacking randomised trials in this specific molecular subgroup, FOLFOXIRI plus bevacizumab might be a reasonable option for the first-line treatment of BRAF mutant mCRC patients.

FOLFOXIRI in combination with panitumumab as first-line treatment in quadruple wild-type (KRAS, NRAS, HRAS, BRAF) metastatic colorectal cancer patients: a phase II trial by the Gruppo Oncologico Nord Ovest (GONO).

BACKGROUND: The FOLFOXIRI regimen developed by the Gruppo Oncologico Nord Ovest (GONO) demonstrated higher activity and efficacy compared with FOLFIRI in metastatic colorectal cancer (mCRC). Panitumumab is effective in some patients with KRAS codon 12-13 wild-type mCRC. KRAS codon 61, HRAS, NRAS, and BRAF V600E mutations might predict resistance to anti-epidermal growth factor receptor antibodies. PATIENTS AND METHODS: We conducted a phase II study evaluating the combination of panitumumab (6 mg/kg on day 1) with a slightly modified GONO-FOLFOXIRI (irinotecan 150 mg/m², oxaliplatin 85 mg/m², and folinate 200 mg/m² on day 1, followed by fluorouracil 3000 mg/m² as a 48-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of wild-type KRAS, HRAS, NRAS (codon 12-13-61), and BRAF unresectable mCRC patients. Fluorouracil dose was reduced to 2400 mg/m² after two of the first three patients reported grade 3-4 diarrhoea (in one case with febrile neutropenia). Induction treatment was scheduled for a maximum of 12 cycles, followed by panitumumab ± fluorouracil/folinate maintenance until progression. Primary end point was overall response rate (ORR). RESULTS: Eighty-seven patients were screened and 37 were enrolled. Thirty-three patients achieved an objective response (ORR: 89%; 95% CI 75% to 96%). Sixteen patients (43%) underwent secondary surgery of metastases, and R0 resection was achieved in 13 cases (35%). At a median follow-up of 17.7 months, median progression-free survival was 11.3 months (95% CI 9.7-12.9 months). After amendment, most common grade 3-4 adverse events reported during induction treatment were neutropenia (48%; febrile neutropenia: 5%), diarrhoea (35%), asthenia (27%), stomatitis (14%), and skin toxic effect (14%). One treatment-related death was registered. CONCLUSIONS: Adding panitumumab to FOLFOXIRI is feasible decreasing the dose of fluorouracil and irinotecan to reduce the risk of diarrhoea. Activity and secondary resectability of metastases among Ras-BRAF wild-type patients are promising.

Nickel and cobalt recycling from lithium-ion batteries by electrochemical processes.

The presence of LiCoO(2) and LiCo(x)Ni((1-x))O(2) in the cathodic material of Li-ion and Li-polymer batteries has stimulated the recovery of Co and Ni by hydrometallurgical processes. In particular, the two metals were separated by SX method and then recovered by electrochemical (galvanostatic and potentiostatic) processes. The metallic Ni has been electrowon at 250 A/m(2), pH 3-3.2 and 50 degrees C, with 87% current efficiency and 2.96 kWh/kg specific energy consumption. Potentiostatic electrolysis produces a very poor Ni powder in about 1 h with current efficiency changing from 70% to 45% depending on Ni concentration in the electrolyte. Current efficiency of 96% and specific energy consumption of 2.8 kWh/kg were obtained for Co at 250 A/m(2), pH 4-4.2 and 50 degrees C, by using a solution containing manganese and (NH(4))(2)SO(4). The Co powder, produced in potentiostatic conditions (-0.9 V vs. SCE, pH 4, room temperature) appears particularly suitable for Co recycling as cobaltite in new batteries.

Encephalitis without meningitis due to sandfly fever virus serotype toscana.

The role of Toscana (TOS) virus in producing encephalitis without meningitis is uncertain. We studied 2 cases of TOS virus encephalitis without meningitis by means of nested polymerase chain reaction assay and DNA sequencing. Findings confirm that TOS virus may directly cause encephalitis and suggest the usefulness of DNA sequencing in investigating relationships between TOS virus molecular patterns and the spectrum of neurological involvement.

Soluble CD30 antigen in human colostrum.

It is now well established that the CD30 glycoprotein is a surface antigen expressed by activated T cells producing T-helper (Th)-2-type lymphokines. Mounting laboratory evidence, however, suggests that CD30 expression is not confined to a functionally restricted subset of T cells, but also identifies activated cells with a Th-1 and Th-0 pattern of cytokine secretion. CD30-bearing T lymphocytes release a soluble form of the molecule (sCD30), which can be detected both in vitro and in vivo. In the present study, very high levels of sCD30 were found in colostrum from 20 puerperal women, but not in autologous and heterologous (nonpregnant women) blood samples. These data strongly support an involvement of CD30+ T cells in the immune processes which take place at the level of the mammary gland during pregnancy and lactation. Passively transferred immune components such as immunoglobulins, cytokines, macrophages, natural killer cells, granulocytes and memory/activated T cells, all of which may help the baby to fight off infections, have been revealed in human breast milk. However, how Th-2-type cytokine-secreting T cells or other T-cell types help to endow the congenitally immunocompromised newborn infant with extrinsic immunological support remains an open question.

Two-Dimensional Gel Electrophoresis Analysis of the Response of Pseudomonas putida KT2442 to 2-Chlorophenol.

The effects of exposure of Pseudomonas putida KT2442 to 2-chlorophenol as a model for the chemical stress response were examined by two-dimensional polyacrylamide gel electrophoresis. Individual protein concentrations were determined at 45, 65, and 95 min following the addition of 2-chlorophenol at a concentration of 1.63 mM to exponentially growing cultures of P. putida KT2442 by silver staining the separated proteins. The changes in the protein concentrations could be classified into four categories, namely those which increased continuously during exposure, those which decreased in concentration, those which showed a concentration peak at some point following exposure, and those which were essentially unaffected. Thirty proteins with isoelectric points between pH 4 and 6 increased in concentration, 27 decreased, and 90 had a concentration maximum or minimum between 45 and 95 min. Of those proteins with isoelectric points between 5.5 and 10, 68 increased in concentration, 39 decreased in concentration, and 47 showed a concentration peak in the middle of the sampling period. Thus, in the evaluation of the stress response, a functional description requires an understanding both of proteins which are required at higher concentrations and of those whose presence appears to be no longer essential.

Neurobrucellosis complicating pregnancy: a case report.

BACKGROUND: Brucellosis in humans is an infectious disease which may occur following contact with infected domestic animals or the ingestion of unpasteurized dairy products. It has rarely been described in pregnancy. The diagnosis, neuropsychiatric manifestations, and management of brucellosis in a 3rd-trimester pregnant woman are discussed. CASE: A 24-year-old Mexican female, G(3)P(2002), at 30 weeks gestation presented with fever, shaking chills, night sweats, a non-productive cough, weakness, nausea, vomiting, anorexia, and vague, dull, upper abdominal pain as well as neuropsychiatric findings. Extensive evaluation revealed serologic and culture evidence of Brucella infection. Her worsening neuropsychiatric condition necessitated preterm delivery with satisfactory neonatal and improved maternal outcomes. CONCLUSION: Bacteriologic infection of pregnant women with neuropsychiatric manifestations should prompt a careful investigation, and brucellosis should be considered if there is a travel history possibly compatible with contact with domestic animals or the ingestion of unpasteurized dairy products.

The environmental behavior of chemicals in soil: atrazine as an example.

In this work a mathematical model has been developed and used to estimate the soil vertical distribution of Atrazine dispersed in the environment. Water transport, rise due to capillarity, and partition among soil-contained water, air, and organic matter, as well as degradation processes, are considered. As far as the vertical mobility in soil is concerned, the model has been derived from that proposed by P. H. Nichols, A. Walker, and R. J. Baker [1982). Pestic. Sci. 12, 484-494). Such a model has been extended to include a procedure which takes into account the Atrazine mobility due to gravitational water flow. The organic carbon (O.C.) concentration gradient in soil was also considered in the evaluation when assessing partition processes, according to models by P. J. McCall et al. [1983). Residue Rev. 13, 231-241) and D. McKay and S. Paterson [1982). Environ. Sci. Technol. 16, 12, 654). The degradation processes are assumed to be first order, linearly related with O.C. content in soil. The application of this model to two sets of soil data demonstrated that Atrazine requires a long time (2 years or more, depending on soil features) in order to percolate at a depth comparable with those of a groundwater source.

Reproducibility of low-dose extrapolation procedure: comparison of estimates obtained using different rodent species and strains.

Carcinogenic risk assessment based on low-dose extrapolation of dose-response relationships is characterized by a significant level of uncertainty. The aim of this study was to investigate the reproducibility of risk estimates carried out using different animal species and strains. The Weibull and multistage mathematical modes, as well as the "linearized multistage" model (EPA "conservative" procedure), have been used for dose-response relationship fitting. Whenever necessary, the Michaelis-Menten function was introduced in the models to account for a possible metabolic process. The analysis was directed to dietary sodium saccharin and vinyl chloride inhalation carcinogenicity (nine total dose-response relationships). Data from different strains, species, and researchers were available for these substances. The general pattern of two sodium saccharin curves was an upward curve in both cases with a high consistency among parameters and risk estimates (the latter ranging within a factor 3). For vinyl chloride the trend was clearly downward for six carcinogenic dose-response relationships from different species; low-dose risk estimates, based on the upper confidence limits of the linear component, range within a factor 3. The study has indicated the reproducibility of the low-dose extrapolation process using different strains and species.

Dose-response relationships in rodents of promoter carcinogens: a tentative interpretation of some downward trends.

This study analyzes a set of dose-response curves relative to promoter carcinogens administered to experimental animals with or without initiator pretreatment. In the case of initiator plus promoter treatment, as well as for low experimental doses, the experimental data and their mathematical fitting indicate a downward shape of the dose-response curves as a general feature. In this study, the following hypothesis, according to the two-stage carcinogenic action of initiator plus promoter treatment, is presented to interpret this downward shape: (i) an initiating action, involving a subset of available "targets" (the number of "initiated" targets is assumed to depend on initiating treatment level), and (ii) a subsequent dose-dependent promoting process, mainly involving the initiated targets. This process reaches a saturation level when all the initiated targets have been promoted. This kind of process may be quantitatively described by a saturated exponential model: P(d) = K(1 - exp(-K0 + K1d)] which fits the experimental data fairly well. No indication supporting the hypothesis of a threshold for the chemicals examined resulted from the analysis. In the specific case of sodium saccharin, experimental dose-response relationships were available with or without initiator pretreatment (BBN and MNU). While in the first case the shape of the dose-response curve is downward, in the second case, it is upward and significantly different.