The occurrence of Bisphenol A and Phthalates in Portuguese wines and the migration of selected substances from coatings in contact with a wine simulant

O Bisfenol A (BPA) e ésteres do ácido ftálico (ftalatos) são substâncias que podem ocorrer em diversos alimentos por contaminação proveniente de várias fontes, nomeadamente através da migração a partir de materiais e embalagens. Estas substâncias podem ser prejudiciais à saúde dado apresentarem propriedades de disrupção endócrina, por isso o seu controlo é muito importante. No presente trabalho foi realizado um estudo para a determinação da ocorrência de BPA e ftalatos em vinhos disponíveis no mercado e foi feita uma estimativa da exposição do consumidor a estes contaminantes a partir da ingestão de vinho. Dada a inter-relação entre estas substâncias e os materiais em contato com alimentos, incluindo vinhos, foi feito também um estudo de migração de dois revestimentos (epóxi-fenólico e poliéster-fenólico) usados em embalagens metálicas. O BPA foi monitorizado em 16 amostras de vinho por cromatografia HPLC/FD. Este composto foi detetado em 13 amostras em níveis acima do limite de deteção (0,57 μg/l), sendo a concentração mais elevada de 3,52 μg/l, encontrada num vinho tinto. A exposição do consumidor ao BPA foi estimada usando valores médios de limite inferior e limite superior de BPA calculados a partir dos dados experimentais (LI e LS) para um consumo de vinho médio (0,116 l) e elevado (0,75 l). Os resultados para o consumo médio foram de 4,8% (LI) e 7,2% (LS) relativamente ao t-TDI atual (0,04 μg / kg de peso corporal dia) enquanto que para o consumo elevado foram de 31% (LI) e 46,5% (LS). Foram determinados 11 ftalatos em 19 amostras de vinho, das quais 3 eram vinhos do Porto, por GC/MS. Pelo menos um ftalato foi detetado em todas as amostras analisadas. Os dois ftalatos mais comuns foram o dietil hexil ftalato (DEHP) e o dibutil ftalato (DBP) com concentrações médias variando nos intervalos 30,33 μg/l - 39,59 μg/l e 21,91 μg/l - 22,59 μg/l, respetivamente. A exposição do consumidor foi também estimada, obtendo-se resultados inferiores a 1% do TDI em vigor, para o consumo médio e elevado. Os três vinhos do Porto apresentaram valores significativamente elevados de DBP, a amostra mais contaminada atingiu 825 μg/l. Além disso, o di-isobutil ftlalato (DiBP), um composto não permitido em materiais destinados ao contato com alimentos, foi encontrado em níveis de 106 μg/l numa das amostras. A migração a partir de revestimentos de resina epóxi e poliéster foi analisada segundo diferentes técnicas analíticas. Em primeiro lugar foram realizados ensaios para identificar as substâncias potencialmente migrantes. As amostras foram analisadas por GC/MS, acoplada a injeção após dessorção térmica direta com e sem extração prévia. Foram testados diversos solventes de extração (acetonitrilo, diclorometano e iso-octano). Os resultados permitiram selecionar três migrantes de cada revestimento para monitorização em condições de migração: BPA, ε-Caprolactona e óxido de fosfina-butil(difenil) do revestimento de epóxi, e, butil(difenil)-neopentilglicol, um oligómero cíclico e 1,3 dioxano-5-metanal-5-etil do revestimento de poliéster. Foi feito um estudo de migração destes compostos usando uma solução etanólica a 20%, a 60 ° C durante 3, 5 e 10 dias. O BPA, o óxido de fosfina-butil(difenil), o oligómero cíclico e o dioxano apresentaram um libertação mais rápida do que o ε-Caprolactona e o butil(difenil)-neopentilglicol.This work studied the occurrence of bisphenol A (BPA) and phthalates in commercially available wines along with the migration of compounds from coatings commonly used in food applications. BPA was monitored in 16 wine samples using a HPLC/FD chromatographic methodology. Thirteen samples contained the contaminant at levels above the Limit of Detection (0.57 μg/l); the most contaminated sample was a red wine with 3.52 μg/l. An exposure assessment was performed using lower bound (LB) and higher bound (HB) averages calculated from the data, for an average wine consumer (0.116 l) and a high wine consumer (0.75 l). The results for an average consumer were 4.8% (LB) and 7.2% (HB) of the current t-TDI (0.04 μg/ kg bw day), while for high consumers the results were 31% (LB) and 46.5% (HB). Eleven phthalate compounds were monitored in 19 wine samples, 3 of which were fortified wines, by means of a GC/MS detection method. At least one phthalate was detected in all the samples analyzed; the two most common contaminants were Diethyl Hexyl Phthalate (DEHP) and Dibutyl Phthalate (DBP) with averages ranging 30.33 μg/l -39.59 μg/l and 21.91 μg/l – 22.59 μg/l respectively. An exposure assessment was made; the estimated daily intakes from wine consumption were below 1% of the TDIs in vigor for both average and high consumers. The three Port wines were significantly contaminated by DBP, with the most contaminated sample reaching 825 μg/l. Additionally, Di-isobutyl phthalate (DiBP), which is non-permitted food contact material, was found at levels of 106 μg/l in one sample. A migration study was made using epoxy and polyester coatings used in food contact materials. The samples were first screened using GC/MS, by means of a direct thermal desorption method and a liquid extraction using aggressive solvents (acetonitrile, dichloromethane and iso-octane). The results allowed selecting three migrants from each coating: BPA, ε-Caprolactone and butyldiphenyl phosphine oxide from the epoxy coating and neopentyl glycol, a cyclic oligomer and 1,3 Dioxane-5-methanal-5 ethyl from the polyester coating. While BPA, butyldiphenyl phosphine oxide, the cyclic oligomer and the dioxane were rapidly released in the simulant; a slower migration rate was observerd for ε-Caprolactone and neopentyl glycol

Deciduoid mesothelioma of the thorax: A comprehensive review of the scientific literature.

AbstractObjectiveDeciduoid mesothelioma is a rare variant of malignant epithelioid mesothelioma. It often involves the peritoneum, but also thoracic cases have been reported. The aim of the present review is to describe the demographic, clinical, radiological, and pathological features of such a rare variant of thoracic mesothelioma, and the state of the art regarding the therapeutic approaches currently available.Data sourceEnglish‐language articles published from 1985 to June 2016, and related to thoracic deciduoid mesothelioma cases were retrieved using the Pubmed database.Study selectionThe search terms were "mesothelioma," "thoracic mesothelioma," "epithelial mesothelioma," "pleural mesothelioma," and "deciduoid mesothelioma."ResultsForty‐four cases included in 16 articles, published in the period under investigation, were analyzed in detail.ConclusionsThe mean age of the patients was 63 years, and the male to female ratio 1.7:1. Approximately 58% had exposure to asbestos, and 73% had a smoking history; familiarity was rarely reported. The most common anatomical site of origin was the right pleura, and the most frequent clinical manifestations were chest pain, dyspnea, cough, and weight loss. Thoracic X‐ray and computed tomography were the imaging techniques most employed for diagnosis and surgical planning. The pathological diagnosis was obtained by examination of surgical or biopsy specimens in most cases. The best treatment strategy of deciduoid mesothelioma is a matter of debate; nevertheless a multidisciplinary approach is currently the best option for the choice of the adequate therapeutic scheme

New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents

In the search for a more effective chemotherapy for the treatment of Chagas´ disease and human African trypanosomiasis, caused by Trypanosoma cruzi and Trypanosoma brucei parasites, respectively, the use of organometallic compounds may be a promising strategy. In this work, eight new heterobimetallic compounds are described including four 5-nitrofuryl containing thiosemicarbazones as bioactive ligands (HL1-HL4) and dppf = 1,1′-bis(diphenylphosphino) ferrocene as an organometallic co-ligand. Complexes of the formula [MII(L)(dppf)](PF6) with M = Pd or Pt were synthesized and fully characterized in the solid state and in solution, including the determination of the molecular structure of four of them by single crystal X-ray diffraction methods. Most compounds showed activity in the low micromolar or submicromolar range against both parasites, with the platinum compounds being more active than the palladium analogues. Activity was significantly increased by generation of the M-dppf compounds (3-24 fold increase with respect to free ligands HL for T. cruzi and up to 99 fold increase with respect to HL for T. brucei). The inclusion of the organometallic co-ligand also led to lower toxicity in mammalian cells and higher selectivity towards both parasites when compared to the free HL compounds. The complexes interact with DNA and affect the redox metabolism of the parasites. Furthermore, the most active and selective compound of the new series showed no in vivo toxicity in zebrafish embryos.Fil: Rodríguez Arce, Esteban. Universidad de la República; UruguayFil: Putzu, Eugenia. Universidad de la República; UruguayFil: Lapier, Michel. Universidad de Chile; ChileFil: Maya, Juan Diego. Universidad de Chile; ChileFil: Olea Azar, Claudio. Universidad de Chile; ChileFil: Echeverría, Gustavo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Medeiros, Andrea. Instituto Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Sardi, Florencia. Instituto Pasteur de Montevideo; UruguayFil: Comini, Marcelo. Instituto Pasteur de Montevideo; UruguayFil: Risi, Gastón. Instituto Pasteur de Montevideo; UruguayFil: Salinas, Gustavo. Instituto Pasteur de Montevideo; UruguayFil: Abad Villamor, Ana Isabel. Instituto Superior Técnico; PortugalFil: Pessoa, João Costa. Instituto Superior Técnico; PortugalFil: Otero, Lucía. Universidad de la República; UruguayFil: Gambino, Dinorah. Universidad de la República; Urugua

New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents

In the search for a more effective chemotherapy for the treatment of Chagas’ disease and human African trypanosomiasis, caused by Trypanosoma cruzi and Trypanosoma brucei parasites, respectively, the use of organometallic compounds may be a promising strategy. In this work, eight new heterobimetallic compounds are described including four 5-nitrofuryl containing thiosemicarbazones as bioactive ligands (HL1–HL4) and dppf = 1,1′-bis(diphenylphosphino) ferrocene as an organometallic co-ligand. Complexes of the formula [MII(L)(dppf)](PF6) with M = Pd or Pt were synthesized and fully characterized in the solid state and in solution, including the determination of the molecular structure of four of them by single crystal X-ray diffraction methods. Most compounds showed activity in the low micromolar or submicromolar range against both parasites, with the platinum compounds being more active than the palladium analogues. Activity was significantly increased by generation of the M-dppf compounds (3–24 fold increase with respect to free ligands HL for T. cruzi and up to 99 fold increase with respect to HL for T. brucei). The inclusion of the organometallic co-ligand also led to lower toxicity in mammalian cells and higher selectivity towards both parasites when compared to the free HL compounds. The complexes interact with DNA and affect the redox metabolism of the parasites. Furthermore, the most active and selective compound of the new series showed no in vivo toxicity in zebrafish embryos.Instituto de Física La Plat

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

HIV Infection Indicator Disease-Based Active Case Finding in a University Hospital: Results from the SHOT Project

In 2014, UNAIDS launched renewed global targets for HIV control to achieve by 2025, known as “the three 95”: 95% of people living with HIV (PWH) diagnosed, of which 95% are receiving treatment, of which 95% are on sustained virological suppression. In Italy, new HIV diagnoses have been steadily decreasing since 2012. However, in 2020, 41% of new diagnoses presented with less than 200 CD4+ cells/µL and 60% with less than 350 CD4+ cells/µL. Implementing testing and early treatment is a key strategy to prevent AIDS, late presentation, and HIV transmission. We selected non-Infectious Diseases Units based on the European project HIDES and engaged colleagues in a condition-guided HIV screening strategy. We enrolled 300 patients, of which 202 were males (67.3%) and 98 were females (32.7%). Most of the screening was performed in Infectious Diseases (ID) and Hematologic wards. In total, we diagnosed eleven new HIV infections with a hospital prevalence in the study population of 3.7%. Five (45.4%) had a CD4 count <100/mm3, one (9.1%) <200/mm3, and one (9.1%) <300/mm3. Regarding risk factors, 81.8% declared having had unprotected sexual intercourse and 54.5% were heterosexual. All patients promptly started a combination antiretroviral regimen and 10 (90.9%) obtained an undetectable HIV-RNA status. Eight of the eleven (72.7%) patients are currently on follow-up in our outpatient clinic. A proactive indicator disease-guided screening can help avoid missed opportunities to diagnose HIV infection in a hospital setting. Implementing this kind of intervention could favor early diagnosis and access to treatment

HIV Infection Indicator Disease-Based Active Case Finding in a University Hospital: Results from the SHOT Project

In 2014, UNAIDS launched renewed global targets for HIV control to achieve by 2025, known as “the three 95”: 95% of people living with HIV (PWH) diagnosed, of which 95% are receiving treatment, of which 95% are on sustained virological suppression. In Italy, new HIV diagnoses have been steadily decreasing since 2012. However, in 2020, 41% of new diagnoses presented with less than 200 CD4+ cells/µL and 60% with less than 350 CD4+ cells/µL. Implementing testing and early treatment is a key strategy to prevent AIDS, late presentation, and HIV transmission. We selected non-Infectious Diseases Units based on the European project HIDES and engaged colleagues in a condition-guided HIV screening strategy. We enrolled 300 patients, of which 202 were males (67.3%) and 98 were females (32.7%). Most of the screening was performed in Infectious Diseases (ID) and Hematologic wards. In total, we diagnosed eleven new HIV infections with a hospital prevalence in the study population of 3.7%. Five (45.4%) had a CD4 count 3, one (9.1%) 3, and one (9.1%) 3. Regarding risk factors, 81.8% declared having had unprotected sexual intercourse and 54.5% were heterosexual. All patients promptly started a combination antiretroviral regimen and 10 (90.9%) obtained an undetectable HIV-RNA status. Eight of the eleven (72.7%) patients are currently on follow-up in our outpatient clinic. A proactive indicator disease-guided screening can help avoid missed opportunities to diagnose HIV infection in a hospital setting. Implementing this kind of intervention could favor early diagnosis and access to treatment

Effect of the metal ion on the anti T. cruzi activity and mechanism of action of 5-nitrofuryl-containing thiosemicarbazone metal complexes

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major health problem worldwide. In this work, we report the development of palladium and platinum metal complexes with 5-nitrofuryl-containing thiosemicarbazones (L) as bioactive ligands against T. cruzi and PTA (1,3,5-triaza-7-phosphaadamantane) as co-ligand. Eight new complexes of the formula [MCl(L)(PTA)] with M = Pd or Pt were synthesized and fully characterized. Most complexes showed similar activities against T. cruzi to those of the corresponding free thiosemicarbazone ligands. No significant differences between palladium and platinum complexes were observed. Metal compounds with the phenylthiosemicarbazone derivative were the most active ones (IC50 = 9.84 +/- 0.32 and 4.94 +/- 0.24 mu M for Pd2+ and Pt2+, respectively). The prepared complexes were not toxic on mammalian cells, showing selective indexes of more than 10-20. The ability of the complexes to be reduced in the parasite, which leads to toxic free radical species, was confirmed by the detection of OH center dot and nitroanion free radical species by ESR spectroscopy experiments. Gel electrophoresis and fluorescence experiments were consistent with an intercalating-like mode of DNA interaction for the complexes, but DNA interaction does not seem to be the main mechanism of anti T. cruzi action for these compounds. The results obtained show that complexation of the bioactive ligands with the selected metals is a valid strategy to obtain improved metal-based antiparasitic compounds

Activity of EGFR TKIs in Caucasian Patients With NSCLC Harboring Potentially Sensitive Uncommon EGFR Mutations

reserved21noUncommon epidermal growth factor receptor (EGFR) mutations reported in non–small-cell lung cancer, accounting approximately 10%-15% of all EGFR mutations, are a heterogeneous group characterized by different clusters: exon 20 insertion and mutations, exon 18 mutations, and complex mutations. Although available data confirming the intrinsic resistance of exon 20 insertions to EGFR tyrosine kinase inhibitors (TKIs) of first- and second-line generation, data about exon 18 and complex mutations are suggesting the activity of EGFR TKIs. In this clinical study, we showed exon 18 and EGFR complex mutations might be considered sensitive uncommon mutations, showing interesting survival results.mixedPassaro A.; Prelaj A.; Bonanno L.; Tiseo M.; Tuzi A.; Proto C.; Chiari R.; Rocco D.; Genova C.; Sini C.; Cortinovis D.; Pilotto S.; Landi L.; Bennati C.; Camerini A.; Toschi L.; Putzu C.; Cerea G.; Spitaleri G.; Cappuzzo F.; de Marinis F.Passaro, A.; Prelaj, A.; Bonanno, L.; Tiseo, M.; Tuzi, A.; Proto, C.; Chiari, R.; Rocco, D.; Genova, C.; Sini, C.; Cortinovis, D.; Pilotto, S.; Landi, L.; Bennati, C.; Camerini, A.; Toschi, L.; Putzu, C.; Cerea, G.; Spitaleri, G.; Cappuzzo, F.; de Marinis, F