Advanced mapping of inorganic treatments on porous carbonate stones by combined synchrotron radiation high lateral µXRPD and µXRF.

Understanding the effects of consolidating inorganic mineral treatments on carbonate stones of cultural heritage, and on the nature and distribution of newly formed products within the matrix, poses a significant challenge in Heritage Science and Conservation Science. Existing analytical methods often fail to deliver spatial and compositional insights into the newly formed crystalline phases with the appropriate high lateral resolution. In this study, we explore the capabilities and limitations of synchrotron radiation (SR) micro-X-ray powder diffraction (µXRPD) mapping combined with micro-X-ray fluorescence (µXRF) to give insight into compounds formed following the application of ammonium oxalate (AmOx) and diammonium phosphate-based (DAP) solutions on porous carbonate stone. Ultimately, the integration of µXRPD mapping and µXRF analysis proved itself a powerful asset in providing precise qualitative and quantitative data on the newly formed phases, in the case of both calcium oxalates (CaOxs) and calcium phosphates (CaPs), and their complex stratigraphic distribution, thus opening a new route for applications to a more comprehensive study of inorganic treatments applied to carbonate substrates.

Chemical analysis of marine microdebris pollution in macroalgae from the coastal areas of Argentina.

Marine microdebris (MDs, <5 mm) and mesodebris (MesDs, 5-25 mm), consist of various components, including microplastics (MPs), antifouling or anticorrosive paint particles (APPs), and metallic particles (Mmps), among others. The accumulation of these anthropogenic particles in macroalgae could have significant implications within coastal ecosystems because of the role of macroalgae as primary producers and their subsequent transfer within the trophic chain. Therefore, the objectives of this study were to determine the abundance of MDs and MesDs pollution in different species of macroalgae (P. morrowii, C. rubrum, Ulva spp., and B. minima) and in surface waters from the Southwest Atlantic coast of Argentina to evaluate the ecological damage. MDs and MesDs were chemically characterized using µ-FTIR and SEM/EDX to identify, and assess their environmental impact based on their composition and degree of pollution by MPs, calculating the Polymer Hazard Index (PHI). The prevalence of MDs was higher in foliose species, followed by filamentous and tubular ones, ranging from 0 to 1.22 items/g w.w. for MPs and 0 to 0.85 items/g w.w. for APPs. It was found that macroalgae accumulate a higher proportion of high-density polymers like PAN and PES, as well as APPs based on alkyd, PMMA, and PE resins, whereas a predominance of CE was observed in surrounding waters. Potentially toxic elements, such as Cr, Cu, and Ti, were detected in APPs and MPs, along with the presence of epiplastic communities on the surface of APPs. According to PHI, the presence of high hazard score polymers, such as PAN and PA, increased the overall risk of MP pollution in macroalgae compared to surrounding waters. This study provided a baseline for MDs and MesDs abundance in macroalgae as well as understanding the environmental impact of this debris and their bioaccumulation in the primary link of the coastal trophic chain.

Assessment of meso- and microplastics distribution in coastal sediments and waters at the middle estuary of the Rio De La Plata, Argentina (SW Atlantic Ocean).

Estuarine coastal water and sediments collected from multiple locations within the middle Río de la Plata (RDLP) estuary were analyzed in order to identify the presence of microplastics (MPs, <5 mm) and mesoplastics (MePs, 5-25 mm) in one of the most significant estuaries in the Southwestern Atlantic. The present study represents one of the first researches to survey MPs and MePs contamination in key stations at RDLP estuary. Average concentrations of 14.17 ± 5.50 MPs/L and 10.00 MePs/L were detected in water samples, while 547.83 ± 620.06 MPs/kg (dry weight) and 74.23 ± 47.29 MePs/kg d.w. were recorded in sediments. The greatest abundances were observed in the more anthropized areas, near urban settlements. Fibers were the most conspicuous plastic items in water and sediments, followed by fragments. On the other hand, surface sediments, and 50 cm and 100 cm-depth sediments also presented MPs and MePs indicating they could serve as a stratigraphic indicator for recently formed sediments. The main polymer type identified were acrylic fibers, followed by polypropylene (PP) and polyethylene terephthalate (PET). Besides, SEM-EDX detected the presence of Si, Fe, Ti, Al and Cl onto the plastics' surface. These elements may serve as additives to enhance the plastics' properties, such as in the case of Ti, or they could originate from the environment, like biogenic Si or Fe, and Al possibly as a component of the suspended particles or sediments adhered to the micro or meso plastics. Finally, the results of the present study showed that MPs and MePs are commonly found in waters and also tend to be trapped in sediments of the RDLP estuary supporting the assertion that these areas play a substantial role in influencing the transport, dispersion, and buildup of MPs in estuarine regions.

Marine microdebris pollution in sediments from three environmental coastal areas in the southwestern Argentine Atlantic.

Microplastics (MPs) and antifouling paint particles (APPs) are important components of marine microdebris (MDs), which constitute a potential environmental risk. This study analyzed baseline contamination levels of MDs and mesodebris (MesDs) in intertidal sediments at different depths, exploring the geomorphological influence in three Argentine coastal environments: Bahía Blanca Estuary (BBE), Los Pocitos (LP) and Puerto Madryn (PM). The MDs and MesDs samples were characterized by µ-FTIR, SEM/EDX and XRD. The abundance of MPs and APPs in sediments, range between 19.78 and 1087.19 and between 0 and 172.93 items/kg d.w., respectively. Despite variations in population and industrial developments in these areas, MPs abundance shows no significant differences in low and high intertidal zones. However, mean MPs concentrations were higher in the surface layer (0-5 cm) compared to the deeper sediments (5-10 cm), indicating recent MPs deposition. Chemical characterization evidenced the presence of cellulose (CE) and denser polymers as acrylonitrile butadiene styrene (ABS) and polyacrylics (PAN), APPs, metallic and black MDs. Surface degradation and heavy metals (Zn, Cr, and Ba) were also detected in APPs and other MDs, either as additives or adhered to their surfaces. Changes in crystallinity were also observed on the MesDs due to weathering. The calculated polymer hazard index (PHI) and the presence of hazardous polymers such as ABS and PAN indicated an increased risk of MPs pollution on the BBE and PM coasts. The pollution load index (PLI) values (from 4.63 to 5.34) suggested unpolluted to moderately polluted levels. These findings offer insights into potential risks associated with MDs in Argentine intertidal sediments, underscoring the critical need to comprehend the geomorphology and the influence of coastal dynamics. This is crucial for effectively addressing challenges linked to MDs pollution guiding the development of robust management and mitigation strategies.

Chemical-analytical characterization and leaching of heavy metals associated with nanoparticles and microplastics from commercial face masks and the abundance of personal protective equipment (PPE) waste in three metropolitan cities of South America.

In this study, we surveyed the presence of personal protective equipment (PPE) waste on the streets of Bogotá-Colombia, Lima-Perú, and Mar del Plata-Argentina. Furthermore, this work is also focused on the release capacity of Ag, Cu, and Zn metals associated with nanoparticles, and microplastics (MPs) from textile face masks (TFMs) and disposable face masks. According to our results, an association between low-income areas and PPE waste was found, which may be related to the periodicity of waste collection and economic activity. Polymers, like polypropylene, cotton-polyester, and additives, such as CaCO3, MgO, and Ag/Cu as nanoparticles, were identified. TFMs released high levels of Cu (35,900-60,200 µg·L-1), Zn (2340-2380 µg·L-1), and MPs (4528-10,640 particles/piece). Metals associated with nanoparticles leached by face masks did not present any antimicrobial activity against P. aeruginosa. Our study suggests that TFMs may leach large amounts of polluting nano/micromaterials in aquatic environments with potential toxicological effects on organisms.

Sleep changes during a spontaneous manic episode: PSG assessment in a clinical context.

Sleep plays a key role in the pathogenesis and clinical presentation of mood disorders. However, only a few studies have investigated sleep architecture during the manic episodes of Bipolar Disorder (BD) and changes in sleep parameters that follow clinical variations. Twenty-one patients (8 males, 13 females) affected by BD, manic phase, underwent polysomnographic recordings (PSG) at the beginning of the admission in our ward (T0) and after three weeks of hospital treatment (T1). All participants were clinically evaluated using Young Mania Rating Scale (YMRS), Pittsburgh Sleep Quality Index (PSQI) and Morningness-Eveningness Questionnaire (MEQ). During the admission, we observed an increase in both quantity (Total Sleep Time - TST) and quality (Sleep Efficiency - SE) of sleep. In addition, clinical improvement, evaluated with YMRS and PSQI scales, was accompanied by a significant increase in the percentage of REM sleep. According to our findings, the improvement of manic symptoms is accompanied by an increase in "REM pressure" (increase in REM% and REM density, reduction of REM latency). Overall, changes in sleep architecture appear to be markers sensitive to clinical variations during manic phases of Bipolar Disorder.

Influence of phytoestrogens on endometrial thickness: a systematic review and meta-analysis.

The objective of this systematic review was to evaluate the influence of the use of phytoestrogens on variations in endometrial thickness in postmenopausal women. Randomized controlled trials were searched in the following electronic databases until March 2020: MEDLINE, Embase, Cochrane Library, Web of Science and LILACS. We used the terms 'phytoestrogens' and 'endometrium' or 'endometrial hyperplasia' to search for relevant trials. The data were analyzed using RevMan 5.3 software. A total of 10 studies involving 1476 patients were included. The difference in endometrial thickness was evaluated in 10 studies, with a total of 805 participants in the phytoestrogen group and 761 in the control group. Such a difference was not significant between groups after 3 months (standardized mean difference [SMD] 0.00, 95% confidence interval [CI] - 0.37 to 0.37; I2 = 63%), 6 months (SMD -0.30, 95% CI -0.79 to 0.19; I2 = 70%), 12 months (SMD -0.02, 95% CI 0.22 to -0.18; I2 = 0%) and 24 months (SMD -0.09, 95% CI -0.25, 0.08; I2 = 0%) of use. Our meta-analysis shows no changes in endometrial thickness in women using phytoestrogens. Evidence is still uncertain owing to the presence of heterogeneity among the studies currently available, whose reported outcomes cover a period between 3 and 6 months.

Occurrence, distribution, and characterization of suspended microplastics in a highly impacted estuarine wetland in Argentina.

Microplastics have been a global concern due to their potential and widespread risks to organisms and environments. In this study, we investigated the abundance, distribution, and characteristics of microplastics (MPs) in the surface waters of the Bahía Blanca Estuary (BBE), specifically in its inner and middle zone. The results showed the dominant shape of MPs were fibers, being black, transparent, and blue the main colors. The concentrations of MPs ranged from 182 to 33,373 items m-3 with a mean value of 6162 items m-3. The highest concentrations of MPs were detected in the middle zone of the estuary, a site that receives untreated sewage effluents from the city. The most abundant size ranges were from 0.5 to 1.5 mm (44.21%) and ˂0.5 mm (40.21%) and were predominant at all the sampling sites. The concentration of mesoplastics in the inner zone (16 items m-3) presented larger values than in the middle zone (5 items m-3). A wide variety of polymeric materials with predominance of microfibers such as cellulose-based, polyacrylonitrile, polyethylene terephthalate, and polypropylene were identified. Polyester/alkyd resins and poli(vinyl chloride) were also found. The analysis of MPs surface through SEM/EDX detected a variety of elements such as C, O, Si, Al, K, Ca, Cl, Ti, Fe, S, and P, indicating potential contaminant carriers in the water column. Some plastic particles presented a high degree of degradation on their surface morphology. Untreated sewage discharges appear to be a significant input of MPs. Therefore, the results provided in the present study should be considered by stakeholders interested in the management and conservation of this large coastal wetland with significant ecological and economic value.

Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion.

PURPOSE: The question whether the new cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs aimed at restoring CFTR protein function might improve glucose metabolism is gaining attention, but data on the effect of lumacaftor/ivacaftor treatment (LUMA/IVA) on glucose tolerance are limited. We evaluated the variation in glucose metabolism and insulin secretion in CF patients homozygous for Phe508del CFTR mutation after one-year treatment with LUMA/IVA in comparison to patients with the same genotype who did not receive such treatment. METHODS: We performed a retrospective case-control study on 13 patients with a confirmed diagnosis of CF, homozygous for the Phe508del CFTR mutation, who received LUMA/IVA for one year (cases) and 13 patients with identical genotype who did not receive this treatment (controls). At the beginning and conclusion of the follow-up, all subjects received a modified 3 h OGTT, sampling at baseline, and at 30 min intervals for plasma glucose, serum insulin, and c-peptide concentrations to evaluate glucose tolerance, and quantify by modeling beta-cell insulin secretion responsiveness to glucose, insulin clearance and insulin sensitivity. RESULTS: LUMA/IVA did not produce differences in glucose tolerance, insulin secretory parameters, clearance and sensitivity with respect to matched controls over one-year follow-up. CONCLUSION: We found no evidence of improvements in glucose tolerance mechanisms in patients with CF after one-year treatment with LUMA/IVA.

Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment.

PURPOSE: Reliable cut-offs for basal (bCT) and calcium stimulated calcitonin (casCT) are needed for an early and accurate diagnosis of medullary thyroid cancer (MTC). PATIENTS AND METHODS: Fifty-four new patients with nodular goiter were enrolled and analysed together with those previously published by our group for a total of 135 cases. bCT and casCT were measured by a highly sensitive method and the results compared with histological findings. In a subgroup of patients, cardiac rhythm was recorded before and during the calcium test. RESULTS: In both females (F) and males (M), there was a significant correlation between tumor size and bCT levels (P < 0.001). The receiver operating characteristic plot analyses showed that, for bCT, the new cut-off points able to separate non-MTC from MTC patients were > 30 (F) and > 34 pg/mL (M), whereas the best casCT thresholds were > 79 (F) and > 466 pg/mL (M). bCT was shown to harbour a high accuracy, though some cases were diagnosed only upon stimulation test. Importantly, combining bCT, below or above the cut-offs, with casCT above the cut-offs, all the MTC cases were correctly identified. A reversible sinus bradycardia was observed in 9% of cases during the test. CONCLUSIONS: Refined cut-offs for bCT and casCT in patients with nodular goiter are reported. Sensitive bCT was shown to have a high accuracy, but the combination with casCT data was needed to identify all MTC cases. The reliability and safety of calcium test strongly favour the routine use of CT determination in nodular thyroid disease.

Chemical composition and abundance of microplastics in the muscle of commercial shrimp Pleoticus muelleri at an impacted coastal environment (Southwestern Atlantic).

Microplastics (plastics <5 mm) contamination is of worldwide concern and represents a threat to the environment, biota, and humans. Also, they are potential carriers of other contaminants, increasing their adverse effects. In this study, it was analyzed for the first time the chemical composition and abundance of microplastics (MPs) in the commercial shrimp Pleoticus muelleri. Fibers were the predominant plastics (mean: 1.31 fibers g-1 wet weight) in the abdominal muscle of the shrimps being black, the dominant colour. µ-Raman showed that fibers were composed of polyethylene (PE), polypropylene (PP), and cellulose. Also, weathering and topography of the fibers were analyzed through wide-field confocal microscopy. C, O, Si, Al, K, as well as Fe, Zn, S, Ba, Br, and Ti on the plastic surface were detected with SEM/EDS, indicating potential carriers of contaminants. CAPSULE: The shrimp Pleoticusmuelleri ingests fibers with different chemical elements adsorbed on the plastic surface.

Non-invasive characterisation of molecular diffusion of agent into turbid matrix using micro-SORS.

This study proposes a non-invasive analytical method to study the molecular diffusion of a chemical agent into a turbid matrix with an emerging analytical technique, micro-Spatially Offset Raman Spectroscopy (micro-SORS). Here, the micro-SORS concept has been extended from the analysis of chemically distinct stratified layers to the studies and monitoring of the absorption and diffusion processes, addressing a key analytical need in a number of areas including polymer, pharmaceutical, forensic and biomedical sciences. In Cultural Heritage the knowledge of the penetration depth of a polymer used to consolidate or to protect an object, or the absorption depth of solvents used during a cleaning procedure is crucial for the performance evaluation of restoration methods and their safety towards the work of art. To date the most common protocol for obtaining this type of information comprises the application of stratigraphical analysis on cross-sections prepared after taking a small amount of sample from the work of art. This approach is destructive and may lack of statistical meaning, since the analytical information is limited to the micro area of sampling. To overcome these drawbacks, in this study micro-SORS was successfully used, for the first time, to non-invasively characterise the penetration of a polymer and of a viscous solvent into a gypsum substrate, permitting the reconstruction of the diffusion trends of the products into the matrix and the evaluation of their performances.

Isolated limb perfusion for soft tissue sarcoma: Current practices and future directions. A survey of experts and a review of literature.

Soft tissue sarcomas constitute 1% of adult malignant tumors. They are a heterogeneous group of more than 50 different histologic types. Isolated limb perfusion is an established treatment strategy for locally advanced sarcomas. Since its adoption for sarcomas in 1992, after the addition of TNFα, few modifications have been done and although indications for the procedure are essentially the same across centers, technical details vary widely. The procedures mainly involves a 60 min perfusion with melphalan and TNFα under mild hyperthermia, achieving a limb preservation rate of 72-96%; with an overall response rates from 72 to 82.5% and an acceptable toxicity according to the Wieberdink scale. The local failure rate is 27% after a median follow up of 14-31 months compared to 40% of distant recurrences after a follow up of 12-22 months. Currently there is no consensus regarding the benefit of ILP per histotype, and the value of addition of radiotherapy or systemic treatment. Further developments towards individualized treatments will provide a better understanding of the population that can derive maximum benefit of ILP with the least morbidity.

Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.

Molecular markers for the classification of cytologically indeterminate thyroid nodules.

BACKGROUND: The diagnosis of indeterminate lesions of the thyroid is a challenge in cytopathology practice. Indeed, up to 30% of cases lack the morphological features needed to provide definitive classification. Molecular tests have been developed to assist in the diagnosis of these indeterminate cases. The first studies dealing with the preoperative molecular evaluation of FNA samples focused on the analysis of BRAFV600E or on the combined evaluation of two or three genetic alterations. The sensitivity of molecular testing was then improved through the introduction of gene panels, which became available for clinical use in the late 2000s. Two different categories of molecular tests have been developed, the 'rule-out' methods, which aim to reduce the avoidable treatment of benign nodules, and the 'rule-in' tests that have the purpose to optimize surgical management. The genetic evaluation of indeterminate thyroid nodules is predicted to improve patient care, particularly if molecular tests are used appropriately and with the awareness of their advantages and weaknesses. The main disadvantage of these tests is the cost, which makes them rarely used in Europe. To overcome this limitation, customized panels have been set up, which are able to detect the most frequent genetic alterations of thyroid cancer. CONCLUSIONS: In the present review, the most recent available versions of commercial molecular tests and of custom, non-commercial panels are described. Their characteristics and accuracy in the differential diagnosis of indeterminate nodules, namely Bethesda classes III (Atypical follicular lesion of undetermined significance, AUS/FLUS) and IV (Suspicious for follicular neoplasm, FN/SFN) are fully analyzed and discussed.

Clinical and personality profile of depressed suicide attempters: A preliminary study at the open-door policy Mood Disorder Unit of San Raffaele Hospital.

Suicidal behavior is a complex phenomenon with high rates among psychiatric inpatients. Mood disorders and personality dysfunctions represent relevant risk factors for suicides attempts and suicidal ideation. Our study aims to investigate the role of the co-occurrence of clinical variables (duration of depressive state, previous suicide attempts), socio-demographic variables (gender, employment and civil status) and narcissistic personality features in the suicide risk of admitted psychiatric patients affected by a mood disorder. The sample was composed of 93 patients consecutively admitted in an open ward psychiatric Unit. Forty-eight participants had a positive history of previous suicide attempts: the suicide attempters (SA) were mostly female, unemployed and married. The SA group were observed to have suffered from a depressive episode with a longer duration; moreover in the SA group, the presence of active suicidal ideation was significantly related to a higher number of previous suicide attempts. In the whole sample, suicidal ideation was significantly related to narcissistic vulnerability personality features. Using a multidimensional approach, the present study allows a preliminary profiling of patients at risk for suicidal behavior during hospitalization.

Long-term Follow-up and Post-relapse Outcome of Patients with Localized Retroperitoneal Sarcoma Treated in the Italian Sarcoma Group-Soft Tissue Sarcoma (ISG-STS) Protocol 0303.

BACKGROUND: This study was designed to assess patterns of recurrence and long-term outcomes of patients undergoing surgery for localized retroperitoneal sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and radiotherapy (RT). METHODS: Patients received three cycles of HLI (14 g/m2). RT was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. The primary endpoint was relapse-free survival (RFS) after surgery. Secondary endpoints were overall survival (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS) and post-relapse OS were estimated. The trial was registered with ITASARC_*II_2004_003. RESULTS: Between 2003 and 2010, 83 patients were recruited. At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was 46.6% [95% confidence interval (CI) 29.6-52.4]. Thirty-two patients died. Seven-year OS rate was 63.2% (95% CI 42.7-66.0). The corresponding CCI of LR and DM were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The only factor significantly associated with LR was FNCLCC grading, whereas histological subtype resulted associated with DM. At recurrence, 24 patients (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. CONCLUSIONS: LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one half of relapsed patients underwent further surgery, prognosis was poor.

Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis.

Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens.

High genetic diversity of Jatropha curcas assessed by ISSR.

Jatropha curcas L. is a highly promising oilseed for sustainable production of biofuels and bio-kerosene due to its high oil content and excellent quality. However, it is a perennial and incipiently domesticated species with none stable cultivar created until now despite genetic breeding programs in progress in several countries. Knowledge of the genetic structure and diversity of the species is a necessary step for breeding programs. The molecular marker can be used as a tool for speed up the process. This study was carried out to assess genetic diversity of a germplasm bank represented by J. curcas accessions from different provenance beside interspecific hybrid and backcrosses generated by IAC breeding programs using inter-simple sequence repeat markers. The molecular study revealed 271 bands of which 98.9% were polymorphic with an average of 22.7 polymorphic bands per primer. Genetic diversity of the germplasm evaluated was slightly higher than other germplasm around the world and ranged from 0.55 to 0.86 with an average of 0.59 (Jaccard index). Cluster analysis (UPGMA) revealed no clear grouping as to the geographical origin of accessions, consistent with genetic structure analysis using the Structure software. For diversity analysis between groups, accessions were divided into eight groups by origin. Nei's genetic distance between groups was 0.14. The results showed the importance of Mexican accessions, congeneric wild species, and interspecific hybrids for conservation and development of new genotypes in breeding programs.

Patient-derived solitary fibrous tumour xenografts predict high sensitivity to doxorubicin/dacarbazine combination confirmed in the clinic and highlight the potential effectiveness of trabectedin or eribulin against this tumour.

BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. RESULTS: Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. CONCLUSION: Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients.