Applying a modified systematic review and integrated assessment framework (SYRINA) - a case study on triphenyl phosphate.

This work presents a case study in applying a systematic review framework (SYRINA) to the identification of chemicals as endocrine disruptors. The suitability and performance of the framework is tested with regard to the widely accepted World Health Organization definition of an endocrine disruptor (ED). The endocrine disrupting potential of triphenyl phosphate (TPP), a well-studied flame retardant reported to exhibit various endocrine related effects was assessed. We followed the 7 steps of the SYRINA framework, articulating the research objective via Populations, Exposures, Comparators, Outcomes (PECO) statements, performed literature search and screening, conducted study evaluation, performed data extraction and summarized and integrated the evidence. Overall, 66 studies, consisting of in vivo, in vitro and epidemiological data, were included. We concluded that triphenyl phosphate could be identified as an ED based on metabolic disruption and reproductive function. We found that the tools used in this case study and the optimizations performed on the framework were suitable to assess properties of EDs. A number of challenges and areas for methodological development in systematic appraisal of evidence relating to endocrine disrupting potential were identified; significant time and effort were needed for the analysis of in vitro mechanistic data in this case study, thus increasing the workload and time needed to perform the systematic review process. Further research and development of this framework with regards to grey literature (non-peer-reviewed literature) search, harmonization of study evaluation methods, more consistent evidence integration approaches and a pre-defined method to assess links between adverse effect and endocrine activity are recommended. It would also be advantageous to conduct more case studies for a chemical with less data than TPP.

Catchment area, fate, and environmental risks investigation of micropollutants in Danish wastewater.

This study aimed to investigate the spatial distribution of micropollutants in wastewater related to catchment area, and their environmental risks and fate. About 24-h flow proportional effluent (n = 26) wastewater samples were collected from eight WWTPs across Denmark. From five of these WWTPs corresponding influent samples (n = 20) were collected. Samples were enriched by multi-layer solid phase and analysed by liquid chromatography-high-resolution mass spectrometry and comprehensive two-dimensional gas chromatography with high-resolution mass spectrometry detection. We detected and quantified 79 micropollutants from a list of 291 micropollutants in at least one influent or effluent wastewater sample. From this we found that 54 micropollutants decreased in concentrations during wastewater treatment, while O-desmethylvenlafaxine, carbamazepine, amitriptyline, benzothiazole, terbutryn, and citalopram increased in concentrations through the WWTP.The toxicity of effluent wastewater samples was assessed by EC50 using Raphidocelis subcapitata (R. subcapitata) and LC50 using the crustacean Daphnia magna (D. Magna), for which six micropollutants were detected above the predicted no-effect concentration. Our study demonstrates that catchment area influences the micropollutant composition of wastewater. Out of 19 pharmaceuticals, the measured concentration in influent wastewater was predicted within a factor of 10 from sale numbers and human excretion, which demonstrates the strong influence of catchment area on micropollutant composition.

Supercritical Fluid Chromatography Coupled to High-Resolution Mass Spectrometry Reveals Persistent Mobile Organic Compounds with Unknown Toxicity in Wastewater Effluents.

Broad screening approaches for monitoring wastewater are normally based on reversed-phase liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS). This method is not sufficient for the very polar micropollutants, neglected in the past due to a lack of suitable analytical methods. In this study, we used supercritical fluid chromatography (SFC) to detect very polar and yet-undetected micropollutants in wastewater effluents. We tentatively identified 85 compounds, whereas 18 have only rarely been detected and 11 have not previously been detected in wastewater effluents such as 17α-hydroxypregnenolone, a likely transformation product (TP) of steroids, and 1H-indole-3-carboxamide, a likely TP from new synthetic cannabinoids. Suspect screening of 25 effluent wastewater samples from 8 wastewater treatment plants revealed several distinct potential pollution sources such as a pharmaceutical company and a golf court. The analysis of the same samples with LC-HRMS showed clearly how SFC increases the ionization efficiency for low-molecular-weight micropollutants (m/z < 300 Da) by a factor 2 to 87 times, which significantly improved the mass spectra for identifying very polar compounds. In order to assess which micropollutants might be of environmental concern, literature and toxicological databases were screened. There was a lack of available hazard and bio-activity data for regulatory-relevant in vitro and in vivo assays for >50% of the micropollutants. Especially, 70% of the data were lacking for the whole organism (in vivo) tests.

Occurrence and molecular characterization of human pegivirus-1 (HPgV-1) viremia in healthy volunteer blood donors from Northern Portugal.

Human pegivirus-1 (HPgV-1) is a member of the Flaviviridae family and the Pegivirus genus. Despite having been discovered 25 years ago, there is still much to know regarding HPgV-1 clinical impact, as this virus is currently not associated with any pathology. Yet, HPgV-1 prevalence and molecular characterization are still unknown in many countries, including Portugal. To fill in this knowledge gap, this study aimed to determine the occurrence and molecular characterization of HPgV-1 in a group of healthy blood donors from the north of Portugal. Blood samples from 465 Portuguese blood donors were collected from a major Hospital Center in the north of Portugal. RNA was extracted and an initial nested RT-PCR was performed targeting the conserved 5'-untranslated region  region of the HPgV-1 genome. A second nested RT-PCR targeting the E2 region was performed for genotyping. Only one sample tested positive for HPgV-1 RNA, resulting in a prevalence of approximately 0.22%. Phylogenetic analyses confirmed the characterization as genotype 2, the most prevalent in Europe.

Anaesthetic management of large meningioma excision complicated by Takotsubo and posterior reversible encephalopathy.

A 47-year-old woman with a history of a pulsatile headache, photophobia, dizziness and blurred vision was diagnosed with a massive expansive meningioma and proposed for surgical excision. During surgery, the patient began to show progressive haemodynamic instability with extreme hypotension and severe arrhythmia that only responded to epinephrine. With the continuity of haemodynamic instability, ST segment elevation and great amount of blood loss, the surgery was postponed. The follow-up brain CT scan showed evidence of posterior reversible encephalopathy syndrome and cardiac catheterisation diagnosed as Takotsubo syndrome. The patient remained sedated under aminergic support and was admitted to a cardiac intensive care unit. After clinic stabilisation, the patient underwent two more surgical procedures with special attention paid to monitoring haemodynamic stability, blood loss and cardiac output. After 70 days of admission, the patient was discharged with moderate visual impairment and follow-up consultations in neurosurgery and cardiology.

IL-31 and IL-8 in Cutaneous T-Cell Lymphoma: Looking for Their Role in Itch.

The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation.

Langerhans Cell Histiocytosis; Managing an Uncommon Condition in Pregnancy and Labor: A Case Report.

INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare heterogeneous disease that normally occurs in children under 15 years but can rarely be diagnosed in adulthood. It can affect any organ of the body, and a less favorable prognosis is expected when either liver, lung, spleen, or bone marrow are affected. Diabetes insipidus, from pituitary dysfunction, is one of the most common consequences that can develop anytime during the disease, and symptoms normally worsen during pregnancy. Pregnancy with this disease is uncommon, and when it occurs, a cesarean section is normally performed. CASE PRESENTATION: We report a 34-year-old pregnant woman (37 weeks and two days gestation) with the diagnosis of a disseminated LCH at the age of 30 who presented herself at the obstetrics emergency department due to respiratory distress. During pregnancy, her pulmonary function remained stable, and she was asymptomatic until the last two days before she was admitted. Labor was induced, with vaginal misoprostol, to achieve a vaginal birth with epidural analgesia. The child was born without complications, and the patient had an immediate clinical improvement. In the following three months, she remained asymptomatic without any worsening of her disease. CONCLUSIONS: In LCH, a cesarean section is the first choice in many cases due to pulmonary impairment. We concluded that early placement of an epidural catheter allows labor analgesia while safeguarding the possibility of an epidural anesthesia in case of urgent/emergent cesarean section. If pulmonary function remains stable, vaginal delivery is possible, thereby being less invasive and allowing for a faster recovery.

Liposome-mediated delivery of challenging chemicals to aid environmental assessment of Bioaccumulative (B) and Toxic (T) properties.

Standard aquatic toxicity tests of chemicals are often limited by the chemicals' water solubility. Liposomes have been widely used in the pharmaceutical industry to overcome poor pharmacokinetics and biodistribution. In this work, liposomes were synthesized and used in an ecotoxicological context, as a tool to assure stable dosing of technically challenging chemicals to zooplankton. Three chemicals with distinctly different characteristics were successfully incorporated into the liposomes: Tetrabromobisphenol A (TBBPA, log Kow 5.9, pKa1 7.5, pKa2 8.5), chlorinated paraffin CP-52 (log Kow 8-12) and perfluorooctanoic acid (PFOA, pKa 2.8). The size, production yield and stability over time was similar for all blank and chemical-loaded liposomes, except for when the liposomes were loaded with 10 or 100 mg g-1 PFOA. PFOA increased the size and decreased the production yield and stability of the liposomes. Daphnia magna were exposed to blank and chemical-loaded liposomes in 48 hour incubation experiments. A dose-dependent increase in body burden in D. magna and increased immobilization (LD50 = 7.6 ng CPs per individual) was observed. This confirms not only the ingestion of the liposomes but also the successful internalization of chemicals. This study shows that liposomes can be a reliable alternative to aid the study of aquatic toxicity of challenging chemicals.

Bioaccumulation Potential of CPs in Aquatic Organisms: Uptake and Depuration in Daphnia magna.

Chlorinated paraffins (CPs) are industrial chemicals, subdivided into three categories: short chain (SCCPs), medium chain (MCCPs), and long chain (LCCPs) chlorinated paraffins. SCCPs are currently restricted in Europe and North America. MC and LCCPs are being used as substitution products, but there is a knowledge gap concerning their bioaccumulation potential in aquatic organisms. In this work, we performed laboratory bioconcentration (passive uptake) and bioaccumulation (including dietary uptake) experiments with Daphnia magna using five different CP technical substances. All tested CP technical substances were bioaccumulative in D. magna, with log BCF and log BAF values ranging between 6.7-7.0 and 6.5-7.0 (L kg lipid-1), respectively. An increase in carbon chain length and an increase in chlorine content (% w/w) of the CP technical substances had significant positive effects on the log BCF and log BAF values. For the different CP technical substances, 50% depuration was achieved after 2 to 10 h when D. magna were transferred to clean media. Our results show that SC, MC, and LCCPs are (very)bioaccumulative in aquatic organisms. We believe these data can aid the ongoing policy discussion concerning the environmental risk posed by CPs.

SETAC GLB and SETAC Europe SAC: a liaison promoting the next generation of ecotoxicologists and environmental chemists.

This commentary is an introduction for students to the Society of Environmental Toxicology and Chemistry (SETAC) and its Student Advisory Council (SAC). As young academics face challenges while trying to develop their careers, SETAC and the SAC help facilitate student involvement in the various communities within the society that can help to develop the students' careers within the environmental sciences [e.g. the German Language Branch (GLB)]. This piece would also like to emphasize and pay homage to the continual cooperation between the SAC and the ESEU, which provides a scientific platform to communicate internationally and beyond the borders of SETAC, as well as offer heartfelt congratulations from the SAC to the GLB for their "20 Years SETAC GLB" and deep gratitude for their strong advocacy and support of the SAC.

Partitioning of Chlorinated Paraffins (CPs) to Daphnia magna Overlaps between Restricted and in-Use Categories.

Chlorinated paraffins (CPs) are high-production volume industrial chemicals consisting of n-alkanes (with 10 to 30 carbon atoms in the chain) with chlorine content from 30 to 70% of weight. In Europe, the use of short chain chlorinated paraffins (SCCPs) has been restricted by the Stockholm Convention on POPs due to their PBT (persistent, bioaccumulative and toxic) properties. Medium (MCCPs) and long chain (LCCPs) chlorinated paraffins are used as substitution products. In this work we studied the partitioning behavior of five different CP technical mixtures from the established categories (2 SCCPs, 1 MCCP, 1 LCCP and 1 CP technical mixture covering all categories) using passive dosing, by determining the partitioning coefficient of CP technical mixtures between silicone and water ( Ksilicone-water) as well as between organic matter and water ( Koc-water). We show that both silicone-water and organic carbon-water partition coefficients overlap between different categories of CP technical mixtures. These results indicate that in-use MCCPs and LCCPs may be equally or more bioaccumulative than restricted SCCPs. For the tested mixtures, both chlorine content and carbon chain length showed a significant correlation with both Ksilicone-water and Koc-water.

Obesity: The Metabolic Disease, Advances on Drug Discovery and Natural Product Research.

Obesity is a global health threat. OECD reported that more than half (52%) of the adult population in the European Union is overweight or obese. Obesity and obesity-related co-morbidities have deep negative effects on morbidity, mortality, professional and personal quality of life. Healthcare costs represent a negative impact of this disease, with an associated economic cost of 100 billion US$ per year in the United States. The most prescribed drugs for obesity treatment worldwide are orlistat, and phentermine/topiramate extended release, while the major prescribed drug for the same disease in the US are exenatide and dapagliflozin. The so far developed drugs, targeting weight loss, have a long history of malignant secondary effects. There is still a lack of efficient and safe drugs to treat obesity and related metabolic complications since in many cases cure cannot be reached by bariatric surgery or healthy lifestyle habits. Terrestrial and aquatic organisms are a promising source of valuable, bioactive compounds, often with interest for human health. Some of the natural compounds or organisms have been used for centuries by humans as traditional medicine foods. In this review, we give insights into the adipose tissue function and development, and the progress in traditional anti-obesity pharmacotherapy. A major focus is to highlight the state of the art of natural compounds with anti-obesity properties and their potential as candidates for drug development; an overview is given about natural compounds derived from different marine animal sources, cyanobacteria, marine phytoplankton, fungus or plants.

Evaluation of quality parameters of rectal cancer surgery at the Coloproctology Unit of Hospital de Braga

INTRODUCTION: Rectal cancer (RC) represents 1/3 of all diagnosed colorectal cancers. After the creation of specialized units to treat RC, it became fundamental to establish criteria to assess the quality of the service. Objective: To evaluate the surgical treatment provided to RC patients at the Coloproctology Unit of Hospital de Braga (BH-CU) by means of quality parameters. METHODS: We conducted an observational cross-sectional descriptive study with a convenience sample of 149 patients undergoing surgical treatment in this unit, from January 1st, 2007 to June 30, 2010. RESULTS: We observed that the postoperative mortality rate (4%) and the global dehiscence rate (14.8%) were in accordance with recommended values. Sphincter sparing surgery rate (65.8%) was higher than the recommended minimum; however, more than 12 resected ganglia (36.6%) is inferior than what is recommended. The oncological results were analyzed by the local recurrence rate (6.7%) and the two-year survival rate (91.1%); both values are in accordance with literature. CONCLUSION: We conclude that the BH-CU surgical treatment has a quality level similar to that observed in literature. (AU)

INTRODUÇÃO: O câncer do reto (CR) constitui cerca de 1/3 da totalidade dos casos de câncer colorretal diagnosticados. Após a criação de unidades especializadas no tratamento do CR, tornou-se fundamental estabelecer critérios que permitam avaliar a qualidade do tratamento prestado. Objetivo: Avaliar, segundo parâmetros de qualidade, o tratamento cirúrgico prestado aos doentes com CR, na Unidade Funcional de Coloproctologia (UFC) do Hospital de Braga (HB). MÉTODOS: Realizou-se um estudo observacional, transversal e descritivo com uma amostra de conveniência constituída por 149 doentes operados de CR entre 1º de Janeiro de 2007 e 30 de Junho de 2010. RESULTADOS: Observou-se que a taxa de mortalidade pós-operatória (4%) e a taxa global de deiscência (14,8%) se encontram dentro dos valores recomendados. A taxa de realização de cirurgia poupadora de esfíncteres (65,8%) foi superior ao limite mínimo aconselhado; no entanto, a taxa de número de gânglios ressecados superior a 12 (36,6%), encontra-se aquém do exigível. Os resultados oncológicos foram analisados através da taxa de recidiva local, 6,7%, e da taxa de sobrevida aos 2 anos, 91,1%, ambos dentro dos valores propostos na literatura. CONCLUSÃO: Concluímos que o tratamento cirúrgico prestado na UFC do HB apresenta um nível de qualidade semelhante ao globalmente recomendado. (AU)