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In 2017, the WHO classification of tumours of the endocrine organs established the criteria for a NIFTP diagnosis. The present paper considers some aspects that are still debated or unresolved: the real incidence and clinical meaning of multifocal/multinodular lesions, the biological behaviour of micro-NIFTP, the sprinkling phenomenon and the corresponding modifications to the FNA reporting systems based on changes to the ROM. Moreover, the paper suggests possible scenarios for the clinical-pathological management of this entity. From the initial 1470 cases, a group of 68 NIFTPs was recruited in a 9 year-long period. The average age at diagnosis was 55 years. The average diameter of the lesion was 1.7 cm (0.1 cm–10 cm). In 41 cases (60.1%), the lesion was inserted in the context of a multinodular background. In 12 cases, the diagnosis was incidental and the pre- operative FNA was performed on a different target. In 10 out of 68 cases, there was a multifocal NIFTP; in 14.7% of patients, PTC-like nuclear features showed sprinkling phenomenon. The cytological revision allocated 21 cases (49%) to the SIAPEC TIR3 indeterminate class and a nuclear score 2 or 3 were identified in 25 smears. Multifocality is part of the spectrum of NIFTPs, that can arise in a multinodular background with variable sizes from microscopic lesions to very large ones. Cytopathological criteria such as an evaluation of the nuclear score may help the pathologists in promoting a NIFTP diagnosis in the preoperative setting.

In the field of thyroid neoplasms, the most interesting recent change regards the introduction of a new terminology for follicular-patterned thyroid tumors, named Noninvasive Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP). This pre-malignant tumor is considered to be the putative precursor of invasive carcinomas. However, given that several issues are still unresolved, the application of ancillary tools, based on omics-techniques, may improve the clinical management of these challenging cases. The present paper highlights the proteomic profiles of a series of NIFTPs submitted to Fine Needle Aspirations (FNAs) and analysed by MALDI-imaging in order to confirm the heterogeneous phenotype of nodules included in the present NIFTP terminology and to underline the necessity of more accurate biomarkers that can be used for their characterization. Ethical and economic implications in terms of healthcare costs, operative risks, morbidity, as well as the potential need for lifelong hormone replacement therapy, seem to be significant reasons to approach the characterization of NIFTPs using alternative tools such as MALDI-MSI.

INTRODUCTION An accurate diagnostic classification of thyroid lesions remains an important clinical aspect that needs to be addressed in order to avoid 'diagnostic' thyroidectomies. Among the several 'omics' techniques, proteomics is playing a pivotal role in the search for diagnostic markers. In recent years, different approaches have been used, taking advantage of the technical improvements related to mass spectrometry that have occurred. Areas covered: The review provides an update of the recent findings in diagnostic classification, in genetic definition and in the investigation of thyroid lesions based on different proteomics approaches and on different type of specimens: cytological, surgical and biofluid samples. A brief section will discuss how these findings can be integrated with those obtained by metabolomics investigations. Expert commentary: Among the several proteomics approaches able to deepen our knowledge of the molecular alterations of the different thyroid lesions, MALDI-MSI is strongly emerging above all. In fact, MS-imaging has also been demonstrated to be capable of distinguishing thyroid lesions, based on their different molecular signatures, using cytological specimens. The possibility to use the material obtained by the fine needle aspiration makes MALDI-MSI a highly promising technology that could be implemented into the clinical and pathological units.

Several proteomic strategies are used extensively for the purpose of biomarker discovery and in order to obtain insights into the molecular aspects of cancers, using either body fluids or tissue as samples. Among them, MALDI-imaging can be applied to cytological thyroid specimens to investigate the molecular signatures of different pathological conditions and highlight differences in the proteome that are of relevance for diagnostic and pathogenetic research. In this study, 26 ex-vivo fine needle aspirations from benign thyroid nodules (n = 13) and papillary thyroid carcinomas (n = 13) were analyzed by MALDI-imaging. Based on the specific protein signatures capable of distinguishing the aforementioned patients, MALDI-imaging was able to correctly assign, in blind, the specimens from ten additional FNABs to a malignant or benign class, as later confirmed by the morphological classification. Moreover, some proteins presented a progressive overexpression in malignant phenotypes when compared with Hashimoto's thyroiditis and hyperplastic/follicular adenoma. This data not only suggests that a MALDI-imaging based approach can be a valuable tool in the diagnosis of thyroid lesions but also in the detection of proteins that have a possible role in the promotion of tumorigenic activity.

A central tenant of the World Health Organisation Framework on Integrated People-Centred Health Services (2017) is reframing from health systems being designed around diseases and health institutions, towards health systems designed for and with people. South Eastern Sydney Local Health District (SESLHD) vision for Integrated Care is to develop a primary care-based system of person-centred care planning and coordination underpinned by client-care professional interactions that emphasises involvement, supported by multidisciplinary team care and appropriate care logistics (Stewart et al 2017). The SESLHD Integrated Care Action Plan (2015-18) has enabled progress in the ‘middle-out’ approach, focusing on building a shared narrative for Integrated Care and enhancing access to technical and functional enablers. In 2018, the focus for Integrated Care is evolving to meso-level activities, such as building stronger partnerships and encouraging innovation across SESLHD and Central and Eastern Sydney Primary Health Network (CESPHN). Neighbourhoods for Wellbeing (N4W) is a novel small-scale test of change, drawing on the principles of codesign. A partnership between SESLHD & CESPHN, it aims to better understand the environment, skills and mindsets for supporting the new and different relationships and conversations that are critical for ensuring health and social needs of the person are the key determinants and focus for 1. planned service improvement and innovation within local primary care services, and 2. empowering communities and generating momentum for broader social change. Adopting complexity science perspective for planning change within the dynamic and change repellent health and social systems (Braithwaite 2014), N4W will start by working locally and engaging in iterative cycles of appreciative inquiry and participative collective action. Participants will include a change-ready general practice, enrolled patients (the community members who regularly access the practice) and other local primary care services identified as stakeholders. Complementing CESPHN Person Centred Medical Neighbourhood program based on Bodenheimer’s ten building blocks of high performing primary care (Bodenheimer, et al, 2014), N4W will advise and coach participants in working with person-centred improvement approaches and building capability for leading change together. N4W is framed within a salutogenic orientation, whereby it is proposed that each person has ability and access to internal and external resources to live well, and when supported by an enabling environment can use them in a way that promotes health and well-being (Antonovsky, 1996). A person’s orientation is influenced by how they see and experience the world around them, this is unique to each person and their life. With the intent of encouraging people to consider the benefits of reframing or shifting their sense-making towards salutogenesis, requires a combination of cognitive, behavioural and motivational factors. Normalisation Process Theory (NPT) will ensure N4W evaluation rigorously explores each of these factors and their impact at an individual and collective level. This poster will illustrate the scope of the project, the methodology, the anticipated risks, knowledge capture strategies and the expected outcomes. As a place-based program of work, it is anticipated that the principles will be transferrable to other contexts and cultures.

In 2018, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued their increase. The annual global average carbon dioxide concentration at Earth's surface was 407.4 ± 0.1 ppm, the highest in the modern instrumental record and in ice core records dating back 800 000 years. Combined, greenhouse gases and several halogenated gases contribute just over 3 W m−2 to radiative forcing and represent a nearly 43% increase since 1990. Carbon dioxide is responsible for about 65% of this radiative forcing. With a weak La Niña in early 2018 transitioning to a weak El Niño by the year's end, the global surface (land and ocean) temperature was the fourth highest on record, with only 2015 through 2017 being warmer. Several European countries reported record high annual temperatures. There were also more high, and fewer low, temperature extremes than in nearly all of the 68-year extremes record. Madagascar recorded a record daily temperature of 40.5°C in Morondava in March, while South Korea set its record high of 41.0°C in August in Hongcheon. Nawabshah, Pakistan, recorded its highest temperature of 50.2°C, which may be a new daily world record for April. Globally, the annual lower troposphere temperature was third to seventh highest, depending on the dataset analyzed. The lower stratospheric temperature was approximately fifth lowest. The 2018 Arctic land surface temperature was 1.2°C above the 1981-2010 average, tying for third highest in the 118-year record, following 2016 and 2017. June's Arctic snow cover extent was almost half of what it was 35 years ago. Across Greenland, however, regional summer temperatures were generally below or near average. Additionally, a satellite survey of 47 glaciers in Greenland indicated a net increase in area for the first time since records began in 1999. Increasing permafrost temperatures were reported at most observation sites in the Arctic, with the overall increase of 0.1°-0.2°C between 2017 and 2018 being comparable to the highest rate of warming ever observed in the region. On 17 March, Arctic sea ice extent marked the second smallest annual maximum in the 38-year record, larger than only 2017. The minimum extent in 2018 was reached on 19 September and again on 23 September, tying 2008 and 2010 for the sixth lowest extent on record. The 23 September date tied 1997 as the latest sea ice minimum date on record. First-year ice now dominates the ice cover, comprising 77% of the March 2018 ice pack compared to 55% during the 1980s. Because thinner, younger ice is more vulnerable to melting out in summer, this shift in sea ice age has contributed to the decreasing trend in minimum ice extent. Regionally, Bering Sea ice extent was at record lows for almost the entire 2017/18 ice season. For the Antarctic continent as a whole, 2018 was warmer than average. On the highest points of the Antarctic Plateau, the automatic weather station Relay (74°S) broke or tied six monthly temperature records throughout the year, with August breaking its record by nearly 8°C. However, cool conditions in the western Bellingshausen Sea and Amundsen Sea sector contributed to a low melt season overall for 2017/18. High SSTs contributed to low summer sea ice extent in the Ross and Weddell Seas in 2018, underpinning the second lowest Antarctic summer minimum sea ice extent on record. Despite conducive conditions for its formation, the ozone hole at its maximum extent in September was near the 2000-18 mean, likely due to an ongoing slow decline in stratospheric chlorine monoxide concentration. Across the oceans, globally averaged SST decreased slightly since the record El Niño year of 2016 but was still far above the climatological mean. On average, SST is increasing at a rate of 0.10° ± 0.01°C decade−1 since 1950. The warming appeared largest in the tropical Indian Ocean and smallest in the North Pacific. The deeper ocean continues to warm year after year. For the seventh consecutive year, global annual mean sea level became the highest in the 26-year record, rising to 81 mm above the 1993 average. As anticipated in a warming climate, the hydrological cycle over the ocean is accelerating: dry regions are becoming drier and wet regions rainier. Closer to the equator, 95 named tropical storms were observed during 2018, well above the 1981-2010 average of 82. Eleven tropical cyclones reached Saffir-Simpson scale Category 5 intensity. North Atlantic Major Hurricane Michael's landfall intensity of 140 kt was the fourth strongest for any continental U.S. hurricane landfall in the 168-year record. Michael caused more than 30 fatalities and $25 billion (U.S. dollars) in damages. In the western North Pacific, Super Typhoon Mangkhut led to 160 fatalities and $6 billion (U.S. dollars) in damages across the Philippines, Hong Kong, Macau, mainland China, Guam, and the Northern Mariana Islands. Tropical Storm Son-Tinh was responsible for 170 fatalities in Vietnam and Laos. Nearly all the islands of Micronesia experienced at least moderate impacts from various tropical cyclones. Across land, many areas around the globe received copious precipitation, notable at different time scales. Rodrigues and Réunion Island near southern Africa each reported their third wettest year on record. In Hawaii, 1262 mm precipitation at Waipā Gardens (Kauai) on 14-15 April set a new U.S. record for 24-h precipitation. In Brazil, the city of Belo Horizonte received nearly 75 mm of rain in just 20 minutes, nearly half its monthly average. Globally, fire activity during 2018 was the lowest since the start of the record in 1997, with a combined burned area of about 500 million hectares. This reinforced the long-term downward trend in fire emissions driven by changes in land use in frequently burning savannas. However, wildfires burned 3.5 million hectares across the United States, well above the 2000-10 average of 2.7 million hectares. Combined, U.S. wildfire damages for the 2017 and 2018 wildfire seasons exceeded $40 billion (U.S. dollars).

The aim of this study was to determine the presence and the level of contamination of the most important mycotoxins (deoxynivalenol, fumonisin B1 and B2, aflatoxin B1, B2, G1 and G2, ochratoxin A and zearalenone) in 48 samples of extruded dry dog food found in the Italian market (24 samples from standard economy lines, 24 of premium lines). Analyses were performed using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Although the concentrations of the mycotoxins in all samples proved to respect the European legislation with regards to animal feed, the analyses revealed a substantial presence of deoxynivalenol, fumonisins and ochratoxin A, with values above the limit of quantification (5 µg/kg) in 100%, 88% and 81% of the samples, respectively. In contrast, aflatoxins and zearalenone contamination proved to be very modest, with 88% and 75% of the samples, respectively, showing concentrations below the corresponding limit of quantification (5 µg/kg for aflatoxins and 10 µg/kg for zearalenone). Moreover, despite a very heterogeneous contamination, the concentration of fumonisins and ochratoxin A was significantly higher in standard foods than in premium ones (491 vs. 80.2 µg/kg dry matter for fumonisin B1; 113 vs. 38.5 µg/kg dry matter for fumonisin B2; 599 vs. 103 µg/kg dry matter for total fumonisins; 23.8 vs. 13.0 µg/kg dry matter for ochratoxin A; P < 0.001). Furthermore, a simultaneous presence of different mycotoxins (at concentrations higher than their limit of quantification) was observed in most of the pet foods analyzed; in particular, 19% of the samples were contaminated by no fewer than two different types of mycotoxins, 52% by three, 25% by four and 2% by all the mycotoxins evaluated. These results revealed the need for further investigation into the potential risk deriving from chronic exposure to low doses of the different types of mycotoxins that pet species are subject to today.

Background Due to the recent proposal of the non-invasive follicular thyroid neoplasm with papillary-like nuclear feature (NIFTP) category, the authors analyse the state of the art in the challenging diagnosis of follicular thyroid neoplasms in routine practice. Methods and results A consecutive series of 200 histological diagnoses, with complete cytological correlation, was analysed following the introduction of the NIFTP definition. The study was conducted in a general hospital with a high prevalence of thyroid benign nodules that accounted for approximately 60% of surgically-treated nodules. The significant incidence of the new NIFTP category was 7%. Concurrently, a gradual decrease of the follicular variant of papillary thyroid carcinoma (fvPTC) was observed (3.5%). When evaluating the FNA biopsies within the NIFTP group, despite the systematic evaluation of nuclear crowding, enlargement, irregularities and clearing, the final cytological class was often indeterminate for malignancy (Thy3/III-IV, 71%). At histology, the application of the semiquantitative NIFTP score for the evaluation of the PTC-like nuclear features was able to discriminate benign lesions (score 0/1) from fvPTC (score 2/3). A certain degree of overlapping still persisted between NIFTP and fvPTC (score 2) or between NIFTP and benign lesions (score 1). Conclusions In the routine evaluation of FNA biopsies, the presence of subtle and questionable PTC-like nuclear features still remains a controversial aspect of the diagnostic workflow. Given that the NIFTP category was introduced to stratify the low-risk group of thyroid tumours more precisely, pathologists should force themselves to apply the nuclear score rigorously and to classify cases assigned a score of 1 as benign proliferations.

Background: The British system (Thy1-5), the Bethesda system for reporting thyroid cytopathology (BSRTC) and the Italian Society of Anatomic Pathology and Cytology (SIAPEC) classification represent the most important international classifications for thyroid cytopathology. Irrespective of the system used, the 'indeterminate' categories are still debated among cytopathologists, particularly with regard to diagnostic criteria, clinical impact of subclassification and role of molecular techniques. Aim: We aimed to find answers to the following questions: Are there shared criteria in cytological preparations that allow the division of indeterminate follicular lesions into subcategories? What is the true clinical impact of this possible subclassification? Methods: Among 1150 consecutive thyroid fine needle aspiration (FNA) specimens, 80 patients had nodules with a final cytological report of Tir3 (SIAPEC)/Thy3. These 80 cases were re-evaluated and subclassified according to morphological criteria into three groups: pure follicular proliferations, Hürthle cell follicular lesions and atypical proliferations. Results: Sixteen (20%) cases were categorized as pure follicular proliferations, 40 (50%) as Hürthle cell follicular lesions and 24 (30%) as atypical proliferations. Surgery was performed in 57 cases (71%). Cyto-histological correlation showed that follicular adenoma was the most frequent final diagnosis in the cases treated by surgery (24/57, 42%). The overall malignancy rate in the Tir3 category was 28% (16/57). Atypical proliferations were more often malignant than either of the follicular groups (53% versus 19%, P = 0.019). Conclusions: A five-tiered classification, subdividing the 'indeterminate for malignancy' class into 'follicular proliferations' and 'atypical lesions' could be adopted. As a result of their higher risk of malignancy, surgical management of the atypical lesions would be justified. In future, the introduction of a genetic panel might contribute to their stratification, to the determination of a more accurate risk of malignancy of the atypical lesions and to the verification of follicular proliferations that are benign. © 2013 John Wiley & Sons Ltd.

BackgroundIntraperitoneal local anaesthetic nebulization is a relatively novel approach to pain management after laparoscopic surgery. This randomized, double-blind, placebo-controlled trial evaluated the effects of intraperitoneal ropivacaine nebulization on pain control after laparoscopic cholecystectomy. MethodsPatients undergoing laparoscopic cholecystectomy were randomized to receive intraperitoneal nebulization of ropivacaine 1% (3 ml) before surgical dissection and normal saline 3 ml at the end of surgery (preoperative nebulization group); intraperitoneal nebulization of normal saline 3 ml before surgical dissection and ropivacaine 1% (3 ml) at the end of surgery (postoperative nebulization group); or intraperitoneal nebulization of normal saline 3 ml before surgical dissection and at the end of surgery (placebo group). Intraperitoneal nebulization of ropivacaine or saline was performed using the Aeroneb Pro® device. Anaesthetic and surgical techniques were standardized. The degree of pain on deep breath or movement, incidence of shoulder pain, morphine consumption, and postoperative nausea and vomiting were collected in the post-anaesthesia care unit and at 6, 24, and 48 h after surgery.ResultsCompared with placebo, ropivacaine nebulization significantly reduced postoperative pain (-33%; Cohen's d 0.64), referred shoulder pain (absolute reduction -98%), morphine requirements (-41% to -56% Cohen's d 1.16), and time to unassisted walking (up to -44% Cohen's d 0.9) (P

Different rainfall parameters are analysed in the present work in order to describe precipitation in three Argentine reference stations. These locations represent their precipitation climate region through a centenary data record. The selected parameters are annual accumulated precipitation, number of days with precipitation and precipitation intensity. All three stations indicate a positive trend in the first two variables over the studied period; moreover, because of a proportional increase, the precipitation intensity parameter has no significant variability. From the analysis of these variables and applying statistical methods, a climatic jump is found in each station, around the 1950s. A second focus of this work is the analysis of rain spells. To this end, a cutoff value for each station is found and used so as to establish the relationship between the accumulated precipitation and the frequency of rain spells per year. The total number of rain spells follows an exponential decay function for their relative frequency, considering the number of days that constitutes them. Rain spell characterisation allows for the understanding of their contribution to precipitation, according with its duration.

Background: Integrated Care in Australia has mostly been implemented as micro-level initiatives rather than systemically, which has challenged its sustainability [1]. South Eastern Sydney Local Health District (SESLHD) and the Central and Eastern Sydney Primary Health Network (CESPHN) have sought to scale the benefits of existing micro-level strategies, such as inter-disciplinary coordination, coordination, and person-centred care, in order to increase population-level impacts and enhance sustainability. The focus of their joint Integrated Care Strategy has shifted towards implementation of meso- and macro-level integrated care programs [2]. This paper presents an overview of the evolution, implementation and evaluation of this novel program. About the IC Program: The centrepiece of the revamped Strategy is three interlinked programs, based on Bodenheimer’s 10 building blocks [3]: 1) General Practice 2020:a quality improvement activity in general practice involving practice teams. 2) Care Coordination: a model of service involving Clinical Nurse Consultants and a social worker. 3) Talking Wellbeing:a co-produced salutogenic initiative based in general practice. Th objectives of these programs are to: Strengthen partnerships and integration. Support general practice to transition towards a person-centred medical neighbourhood (PCMN) model. Establish a sustainable, localised care coordination model. Build connections and experiences that enhance individual and collective wellbeing. The PCMN model is an Australian federal government initiative, similar to the health care home concept [4]. Desired outcomes of the PCMN are aligned with the quadruple aim [5]. Evaluation: The three programs will be evaluated at: (i) consumer, (ii) provider, and (iii) service levels. The overall analytic approach is informed by Normalisation Process Theory [6], with emphasis on the impact, acceptability, feasibility, sustainability, and scalability of the Strategy. Data will be collected at 6, 12 and 18 months points following implementation. Implications for Integrated Care: Lessons learnt from the evolution and and implementation of the three programs that make up the Strategy will have relevant to integrated care in other settings. References: 1- Angus L and Valentijn PP (2018). From micro to macro: assessing implementation of integrated care in Australia. Australian Journal of Primary Health. 24;59-65. 2- Stewart G, Bradd P, Bruce T, et al (2017). Integrated care in practice – the South Eastern Sydney experience. Journal of Integrated Care. Vol.25;No.1:49-60. 3- Bodenheimer T, Ghorob A, Willard-Grace R and Grumbach K (2014). The 10 building blocks of high-performing primary care. Annals of Family Medicine. Vol.12;No.2;166-171. 4- Grant R and Greene D (2012). The Health Care Home Model: Primary Health Care Meeting Public Health Goals. American Journal of Public Health. Vol.102;No.6:1096-1103. 5- Bodenheimer T and Sinsky C (2014). From Triple to Quadruple Aim: Care of the Patient Requires Care of the Provider. Annals of Family Medicine. Vol.12;No.6;573-576. 6- May CR, et al (2018). Using Normalization Process Theory in feasibility studies and process evaluations of complex healthcare interventions: a systematic review. Implementation Science. 13(1):80.

Objective Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique proteomic technology that explores the spatial distribution of biomolecules directly in situ, thus integrating molecular and morphological information. The possibility of correlating distribution maps of multiple analyses with cytological features makes it an ideal research tool for discovering new diagnostic markers. A previous study showed that MALDI-IMS could help discrimination between different types of thyroid lesions, especially papillary thyroid carcinoma (PTC); the present feasibility study on ex vivo fine needle aspiration (FNA) smears describes its potential in detecting new proteomic targets of other thyroid lesions (follicular lesions, medullary carcinoma). Methods MALDI-IMS was conducted on ex vivo FNAs obtained from surgical specimens and corresponding in vivo samples. Differences between proteomic profiles of different thyroid lesions were compared. Results Comparing the protein profiles of hyperplastic nodules obtained from three different patients with each other, and with a new PTC, showed a high degree of concordance, indicating good reproducibility of the IMS technology on cytological samples, suggesting its potential as a tool for biomarker discovery. Furthermore, comparison of the average proteomic profiles of hyperplastic nodules with a Hurthle cell adenoma revealed significant differences, underlying the capability of MALDI-IMS to distinguish between different thyroid lesions. Finally, the proteomic profile of medullary thyroid carcinoma was also characterized. Conclusions Our results confirmed the possible role of MALDI-IMS in the search for diagnostic targets of PTC and follicular lesions, which could be applied in larger trials aimed at the identification of proteins, convertible to cost-effective diagnostic tools such as immunohistochemistry. These tests could be used to analyse in vivo cytological smears, improving the preoperative diagnosis of indeterminate thyroid nodules.

L'esposizione umana ai PFC avviene principalmente attraverso la dieta ed in particolar modo il pesce è risultato tra i prodotti alimentari più inquinati. Il perfluorottano sulfonato (PFOS) e l’acido perfluorottanoico (PFOA) sono i composti più importanti e studiati. Lo scopo del presente lavoro è stato quello di effettuare un monitoraggio preliminare sulla presenza di queste due molecole in 50 campioni di muscolo di branzini, di cui 30 allevati e 20 pescati, prelevati in diverse località italiane del mar Mediterraneo. Il metodo utilizzato prevede un’estrazione con solvente seguita da due passaggi di purificazione: uno con sali ed uno con fase solida dispersiva. L’estratto è stato poi analizzato mediante un sistema UPLC-MS/MS. I dati mostrano ampia contaminazione di questa specie ed evidenziano una netta prevalenza di PFC nei branzini pescati (PFOS da 112,4 ng/L a >2000 ng/L e PFOA da 3,3 ng/L a 487,0 ng/L) rispetto a quelli allevati (PFOS da 11,1 ng/L a 104,5 ng/L e PFOA da

The term perfluorinated (PFCs) defines synthetic fully-fluorinated compounds; since the ‘50s they have been largely employed in a wide range of industrial and consumer applications, due to their chemical and physical properties. Only recently researches on their potential adverse effects on both the environment and human health have been conducted, highlighting carcinogenic activity, toxic effects on reproduction, liver and kidney. Human exposure to PFCs is mainly through diet, and in particular fishery products are one of the most contaminated food. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two most important and investigated compounds of this group. The aim of this work was to carry out a preliminary monitoring on the presence of these two molecules in 50 bass muscle samples, of which 30 reared and 20 fished, collected from different Italian areas of the Mediterranean Sea. The method used was based on an extraction with organic solvent followed by two purification steps: one with salts and one with dispersive solid phase. The extract was finally analysed by means of a UPLC-MS/MS system. Data showed a relevant contamination of this species and evidenced a significant difference of concentrations between fished (PFOS from 112.4 ng/L to >2000 ng/L and PFOA from 3.3 ng/L to 487.0 ng/L) and reared basses (PFOS from 11.1 ng/L to 104.5 ng/L and PFOA from

A method using ultra performance liquid chromatography coupled with tandem mass spectrometry was developed to measure cobalamins in naturally enriched raw milk and to evaluate their fate during thermal treatments and along the process of cheese making. After addition of methotrexate as internal standard, samples were submitted to heat treatment in the presence of cyanide, which converts all the less-stable cobalamins into cyanocobalamin; then, purification was performed by a solid-phase extraction step. Reverse-phase ultra performance liquid chromatography separation coupled with tandem mass spectrometry provided a fast and reliable determination. Mass spectrometric analysis was carried out in multiple reaction monitoring mode. The monitored transitions were m/z 678.36 → 147.10 and 678.36 → 359.30 for vitamin B 12 and m/z 455.22 → 175.13 and 455.22 → 308.22 for methotrexate (internal standard). The limit of quantification was 2ng/g. The method showed good linearity from 2 to 20ng/g (R 2 ≥0.98) and intra- and interday precisions were always less than 19%.

I composti perfluorurati (PFC) sono sostanze completamente fluorurate di origine antropica e presentano svariate applicazioni industriali e domestiche, quali imballaggi per alimenti, rivestimenti antiaderenti per tegami, schiume antiincendio, detergenti, cosmetici etc. Anche se i loro primi impieghi risalgono agli anni ’50, scarsa attenzione è stata data ai loro potenziali effetti nocivi sia sull’ambiente che sull’uomo fino a pochi anni fa, quando un crescente interesse verso queste sostanze ha sollevato serie preoccupazioni circa la loro attività cancerogena, gli effetti sulla riproduzione e la tossicità epatica e renale. L'esposizione umana ai PFC avviene principalmente attraverso la dieta, per questo motivo la Commissione Europea ha pubblicato la raccomandazione 161/2010 sul controllo di tali contaminanti nei prodotti alimentari da parte degli Stati Membri. Il perfluorottano sulfonato (PFOS) e l’acido perfluorottanoico (PFOA) sono i composti più importanti e studiati, anche per il fatto che il primo è stato classificato come POP (inquinante organico persistente) durante la Convenzione di Stoccolma del 2009. Lo scopo del presente lavoro è stato quello di effettuare un monitoraggio preliminare sulla presenza di queste due molecole in latte bovino disponibile commercialmente in Italia. Per la loro determinazione è stato usato un metodo sensibile ed efficiente, basato su un’estrazione liquido-liquido, seguita da due passaggi di purificazione su cartucce SPE ed analisi in un sistema UPLC-MS/MS. I dati, ottenuti dall’analisi di 22 campioni di latte bovino, mostrano la frequente presenza di tali sostanze anche se a concentrazioni relativamente basse (concentrazioni di PFOS e PFOA da 15 ng/L a 67 ng/L e da 24 a 32 ng/L rispettivamente). Questi risultati, in linea con i pochi dati disponibili in letteratura, evidenziano una contaminazione abbastanza ridotta del latte vaccino, sottolineando però la necessità di approfondire diversi aspetti per effettuare una corretta valutazione del rischio legato ai PFC, sia nel latte che nei prodotti lattiero caseari.

La presenza di micotossine nelle materie prime desta grande preoccupazione a causa delle importanti implicazioni nella sicurezza di alimenti e mangimi. Lo scopo di questo lavoro è stato quello di mettere a punto e validare una metodica analitica rapida e semplice, in cromatografia liquida ad ultra prestazione accoppiata a spettrometria di massa-tandem (UPLC-MS/MS), per la determinazione simultanea di differenti micotossine: aflatossine (B1, B2, G1, G2), ocratossina A, fumonisine (B1, B2), deossinivalenolo e zearalenone in matrici biologiche. Il metodo sviluppato per l’analisi di campioni di mangime secco per cani ha mostrato prestazioni adeguate ed è stato applicato a 49 campioni reperibili in commercio, al fine di valutare la sua efficacia e di ottenere alcuni dati preliminari sulla contaminazione da micotossine in alimenti per cani disponibili sul mercato italiano. Lo studio ha evidenziato una percentuale alta di campioni positivi, contenenti principalmente fumonisine, deossinivalenolo e ocratossina A; tutti i tenori si sono dimostrati inferiori al limite di legge previsto (Racc. CE 576/2006). Una seconda metodica è stata messa a punto e validata per l’identificazione e la quantificazione micotossine in campioni di formaggio; per questa matrice è stata inserita anche l’aflatossina M1, specifica dei prodotti lattiero - caseari. Le differenti proprietà chimico-fisiche degli analiti e la complessità della matrice hanno implicato alcune difficoltà nello sviluppo della metodica. Tuttavia, il metodo validato si è mostrato rapido, semplice ed affidabile ed è stato applicato a diversi tipi di formaggi per verificarne la versatilità. I risultati preliminari hanno mostrato l’assenza di contaminazione da parte delle micotossine in oggetto. Entrambi i metodi si sono dimostrati utili per il monitoraggio di contaminanti in matrici complesse ad oggi ancora poco studiate., The occurrence of mycotoxins contamination in various crops is of major concern as it has major implications for food and feed safety. The aim of the study was the set up and the validation of fast and simple methods by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) for the simultaneous determination of different mycotoxins: aflatoxins (B1, B2, G1, G2), ochratoxin A, fumonisins (FB1, FB2), deoxynivalenol and zearalenone in biological matrices. A method was developed for the analysis of samples of dried pet-food; the method showed appropriate performances and was applied to 49 commercial samples in order to test its efficacy and gain some preliminary data about mycotoxins contamination in dog food available in the Italian market. The results have shown a quite high percentage of positive samples, mainly contaminated by fumonisin, deoxynivalenol and ochratoxin A. All the observed values were below the limits specified by regulations (Rec. CE 2006/576). A second method was set up and validated for the identification and quantification of mycotoxins in cheese samples; for this matrix it was included also the aflatoxin M1, which is specific of dairy products. Different chemical-physical properties of the analytes and the complex composition of the matrix led to some difficulties to the development of the method. Finally, the method validated has proved to be rapid, simple and reliable and was applied to different types of cheeses to prove its versatility. Preliminary results have shown the absence of all mycotoxins detected. Both methods are useful tools for the monitoring of mycotoxins contamination in unconventional matrices, not subjected to wide studies until now.

La presenza di micotossine nelle materie prime desta grande preoccupazione a causa delle importanti implicazioni nella sicurezza di alimenti e mangimi. Lo scopo di questo lavoro è stato quello di mettere a punto e validare una metodica analitica rapida e semplice, in cromatografia liquida ad ultra prestazione accoppiata a spettrometria di massa-tandem (UPLC-MS/MS), per la determinazione simultanea di differenti micotossine: aflatossine (B1, B2, G1, G2), ocratossina A, fumonisine (B1, B2), deossinivalenolo e zearalenone in matrici biologiche. Il metodo sviluppato per l’analisi di campioni di mangime secco per cani ha mostrato prestazioni adeguate ed è stato applicato a 49 campioni reperibili in commercio, al fine di valutare la sua efficacia e di ottenere alcuni dati preliminari sulla contaminazione da micotossine in alimenti per cani disponibili sul mercato italiano. Lo studio ha evidenziato una percentuale alta di campioni positivi, contenenti principalmente fumonisine, deossinivalenolo e ocratossina A; tutti i tenori si sono dimostrati inferiori al limite di legge previsto (Racc. CE 576/2006). Una seconda metodica è stata messa a punto e validata per l’identificazione e la quantificazione micotossine in campioni di formaggio; per questa matrice è stata inserita anche l’aflatossina M1, specifica dei prodotti lattiero - caseari. Le differenti proprietà chimico-fisiche degli analiti e la complessità della matrice hanno implicato alcune difficoltà nello sviluppo della metodica. Tuttavia, il metodo validato si è mostrato rapido, semplice ed affidabile ed è stato applicato a diversi tipi di formaggi per verificarne la versatilità. I risultati preliminari hanno mostrato l’assenza di contaminazione da parte delle micotossine in oggetto. Entrambi i metodi si sono dimostrati utili per il monitoraggio di contaminanti in matrici complesse ad oggi ancora poco studiate., The occurrence of mycotoxins contamination in various crops is of major concern as it has major implications for food and feed safety. The aim of the study was the set up and the validation of fast and simple methods by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) for the simultaneous determination of different mycotoxins: aflatoxins (B1, B2, G1, G2), ochratoxin A, fumonisins (FB1, FB2), deoxynivalenol and zearalenone in biological matrices. A method was developed for the analysis of samples of dried pet-food; the method showed appropriate performances and was applied to 49 commercial samples in order to test its efficacy and gain some preliminary data about mycotoxins contamination in dog food available in the Italian market. The results have shown a quite high percentage of positive samples, mainly contaminated by fumonisin, deoxynivalenol and ochratoxin A. All the observed values were below the limits specified by regulations (Rec. CE 2006/576). A second method was set up and validated for the identification and quantification of mycotoxins in cheese samples; for this matrix it was included also the aflatoxin M1, which is specific of dairy products. Different chemical-physical properties of the analytes and the complex composition of the matrix led to some difficulties to the development of the method. Finally, the method validated has proved to be rapid, simple and reliable and was applied to different types of cheeses to prove its versatility. Preliminary results have shown the absence of all mycotoxins detected. Both methods are useful tools for the monitoring of mycotoxins contamination in unconventional matrices, not subjected to wide studies until now.

We describe a patient with double trisomy 9q34.1-->qter and 21pter-->q22.1 resulting from 3:1 segregation of a maternal balanced translocation. The patient shows a clinical syndrome similar to that observed in patients with duplication of the chromosome 9q distal region, while no signs of trisomy 21 were observed. The use of high resolution banding and FISH were of fundamental importance for the cytogenetic diagnosis and for definition of the breakpoints on both chromosomes 9 and 21.

This project explores children's television programming in Philadelphia from the 1940s through the 1960s. Though Philadelphia was the third-largest television market during this period, very little scholarship on its shows exists. The city's broadcasting infrastructure allowed stations to provide programming to air nationally, and many children's shows that began as local Philadelphia fare became national hits. Personalities such as Dick Clark and Ed McMahon went on to national fame after appearing on Philadelphia television. Philadelphia stations created television series for children that were both entertaining and educational. The city was important to the history of the medium, and it was also at the forefront of the attempts to teach through television. The first efforts at in-school television were pioneered in Philadelphia, but the commercial stations had a commitment to education as well. Many shows had explicit educational goals, while others taught by example and encouraged social education. Though critics lamented the state of children's shows as frivolous entertainment as early as the 1950s, Philadelphia stations rose above the criticism and met the criteria that child experts put forth for programming. By examining in detail the children's shows that Philadelphia produced during this time period, it becomes evident that Philadelphia programming elevated what local television was expected to achieve. Shows were just as wholesome and enlightening, if not more so, than their nationally-known counterparts. Philadelphia programming deserves to be recognized as important in the history of children's television and should be remembered as imaginative, creative, and full of passionate people willing to try new approaches to children's entertainment.

The present study was undertaken to analyze the effects on unitary activity of inferior olive (10) neurons elicited by activation of cerebellar lateral nucleus (LN), in rats submitted to the chronic destruction of MDJ structures, i.e. in animals in which the LN-evoked effects in 10 should be depended only on activation of GABAergic cells of LN. It has been observed that about two-thirds of the olivocerebellar neurons are significantly affected by LN stimulation, and > 68% of those cells were inhibited. Two-thirds of the inhibitory responses were compatible with a monosynaptic linkage, whereas the remaining inhibitions were probably due to polisynaptic linkages. The majority of LN-induced inhibitions was abolished or greatly reduced following application of GABA antagonists.

Laparoscopic robot-assisted surgery has been created to reduce the patient risk of inappropriate scope movements by an assistant and to perform operations quicker and with greater ease. The Authors report their experience in laparoscopic robot-assisted right adrenalectomy for Conn's syndrome and right ovariectomy for benign ovarian mass.Case 1. CT scan: solid right adrenal mass (diam. 2 cm). An anterior transperitoneal approach was used to perform the right adrenalectomy. The surgeon was placed at the ventral side of the patient and robotic-device was placed at the backside.adrenocortical adenoma (diam. 3 x 2.5 x 1.5 cm). Case 2. CT scan: left iliac mass (diam. 3.5 cm) with origin in the left ovary. The patient was positioned in the gynecological position. The surgeon was positioned on right side of the patient and robot-device on left side. Left ovariectomy was performed.ovarian serous cyst.Operating time was 180 min. for the adrenalectomy and 25 min. for the ovariectomy. No blood loss or complications for both operations were encountered. Image was steady and lens cleaning was unnecessary.The robot device (AESOP 2000) facilitated the procedures by enhancing stability of the image and reducing the need for lens cleaning. We believe that this method is feasible and could be advantageous especially for cholecystectomy, Nissen funduplication or ovariectomy but at the moment there are no comparative studies to establish the real value of this device.

The term perfluorinated compounds (PFCs) defines synthetic fully-fluorinated compounds; since the 50s they have been largely employed in a wide range of industrial and consumer applications, due to their chemical and physical properties. Only recently, research on their potential adverse effects on both the environment and human health has been conducted, highlighting carcinogenic activity, toxic effects on reproduction, liver and kidney. Human exposure to PFCs is mainly through diet, and in particular fishery products are one of the most contaminated food. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the two most important and investigated compounds of this group. The aim of this work was to carry out a preliminary monitoring on the presence of these two molecules in 50 bass muscle samples, of which 30 reared and 20 fished, collected from different Italian areas of the Mediterranean Sea. The method used was based on extraction with organic solvent followed by two purification steps: one with salts and one with dispersive solid phase. The extract was finally analysed by means of an ultra performance liquid chromatographytandem mass spectrometric system. Data showed a relevant contamination of this species and evidenced a significant difference of concentrations between fished (PFOS 112.4- >2000 ng/L and PFOA 3.3-487.0 ng/L) and reared basses (PFOS 11.1-104.5 ng/L and PFOA