A review of modeling pesticides in freshwaters: Current status, progress achieved and desirable improvements.

This study comprises a critical review of modeling of pesticides in surface waters. The aim was to update the status of the use of models to simulate the fate of pesticides from diffuse sources. ISI papers were selected on Scopus and the information concerning the study areas, type of pesticides (herbicides, fungicides and insecticides), the model, and the methodology adopted (i.e., calibration and/or validation, spatial and temporal scales) were analyzed. The studies were carried out in Europe (55.5%), North America (22.3%), Asia (13.9%) and South America (8.3%). The Soil and Water Assessment Tool proved to be the most used model (45.95%). Herbicides were the most modeled pesticides (71.4%), followed by insecticides (18.2%) and fungicides (10.4%). The main herbicides modeled were atrazine, metolachlor, isoproturon, glyphosate, and acetochlor. Insecticides such as chlorpyrifos and metaldehyde. Chlorothalonil, and fungicides (i.e., tebuconazole) were the most widely investigated. Based on published studies, it was found that modeling approaches for assessing the fate of pesticides are constantly evolving and the model algorithms work well with diverse watershed conditions, management strategies, and pesticide properties. Several papers reported concentrations of pesticides exceeding ecotoxicological thresholds revealing that water contamination with pesticides used in agriculture and urban areas is a priority issue of current global concern.

Role of meteorological factors in the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic in Italy.

OBJECTIVE: Understanding the evolutionary dynamics of the Coronavirus disease 2019 (COVID-19) pandemic in the coming months is a matter of great importance and urgency for governments worldwide, making fundamental decisions based on what is known about the transmission mechanisms of the virus and its survival in the environment. The present study aimed to evaluate the impact of demographic variables, solar radiation and relative humidity on the spread of the COVID-19 pandemic of the various regions in Italy. MATERIALS AND METHODS: The retrospective longitudinal study was conducted, and data used in this study was obtained from the Italian Health Ministry. Descriptive statistics included mean, frequency, and percentage, and results presented by graphs were calculated. RESULTS: The infection trend was investigated by comparing it with the demographic situation and the irradiation indices of solar ultraviolet light that are detected with the changing seasons. The present study reported that the geographic areas with higher population density and lower solar radiation during the autumn and winter months were most affected by SARS-CoV-2. CONCLUSIONS: The analysis carried out can provide a predictive model for the future phases of the COVID-19 pandemic in Italy, regardless of the adoption of lockdown measures and behavioral factors.

Zebrafish embryo extracts enhance 5-FU anti-cancer effects upon breast cancer cells.

OBJECTIVE: The inhibition of the metastatic capability of cancer cells is a pivotal aim of current anticancer strategies. We investigated herein the anti-migrating and anti-invasive properties of Zebrafish embryo extracts (SL) - an integrative formula comprising morphogenetic factors extracted from zebrafish embryos - alone or in association with 5-Fluoro-Uracil (5-FU), when added to metastatic breast cancer cells (MDA-MB-231) and in normal epithelial breast cells (MCF10A) committed toward an inflammatory phenotype upon TGF-ß1 stimulation. MATERIALS AND METHODS: Invasiveness, migrating capability, cytoskeleton architecture and related molecular factors involved in the epithelial-mesenchymal transition were studied after treatment with 5-FU, with and without SL. RESULTS: Remarkably, in both circumstances, embryo extracts amplify the migratory inhibition triggered by the anticancer drug 5-Fu. The fact that such an effect is noticed in normal as well as in cancerous cells suggests that the critical target of embryo extracts is specifically represented by the migrating/invasive phenotype. However, while 5-FU was unable in antagonizing the invasiveness of cancerous cells, the association with SL can significantly impair the invasive capability of tumor cells. These findings are noticeably associated with the reversion of the EMT phenotype in SL-treated cells, as documented by the contemporary downregulation of TCTP and some EMT-related molecular effectors, like α-SMA and Vimentin. CONCLUSIONS: Embryo fish extracts significantly counteract the migrating and invasive phenotype of cancerous and inflammatory breast cells treated with the chemotherapeutic drug 5-FU. The availability of a compound able to amplify 5-Fu activity while significantly hampering the invasive phenotype of breast cancer should provide invaluable benefits, namely if we consider that this compound is substantially deprived of side-effects.

Detection of SARS-COV-2 receptor ACE-2 mRNA in thyroid cells: a clue for COVID-19-related subacute thyroiditis.

PURPOSE: SARS-COV-2 is a pathogenic agent belonging to the coronavirus family, responsible for the current global world pandemic. Angiotensin-converting enzyme 2 (ACE-2) is the receptor for cellular entry of SARS-CoV-2. ACE-2 is a type I transmembrane metallo-carboxypeptidase involved in the Renin-Angiotensin pathway. By analyzing two independent databases, ACE-2 was identified in several human tissues including the thyroid. Although some cases of COVID-19-related subacute thyroiditis were recently described, direct proof for the expression of the ACE-2 mRNA in thyroid cells is still lacking. Aim of the present study was to investigate by RT-PCR whether the mRNA encoding for ACE-2 is present in human thyroid cells. METHODS: RT-PCR was performed on in vitro ex vivo study on thyroid tissue samples (15 patients undergoing thyroidectomy for benign thyroid nodules) and primary thyroid cell cultures. RESULTS: The ACE-2 mRNA was detected in all surgical thyroid tissue samples (n = 15). Compared with two reporter genes (GAPDH: 0.052 ± 0.0026 Cycles-1; ß-actin: 0.044 ± 0.0025 Cycles-1; ACE-2: 0.035 ± 0.0024 Cycles-1), the mean level of transcript expression for ACE-2 mRNA was abundant. The expression of ACE-2 mRNA in follicular cells was confirmed by analyzing primary cultures of thyroid cells, which expressed the ACE-2 mRNA at levels similar to tissues. CONCLUSIONS: The results of the present study demonstrate that the mRNA encoding for the ACE-2 receptor is expressed in thyroid follicular cells, making them a potential target for SARS-COV-2 entry. Future clinical studies in patients with COVID-19 will be required for increase our understanding of the thyroid repercussions of SARS-CoV-2 infection.

A polyphasic approach to characterize Weissella cibaria and Weissella confusa strains.

AIM: To study Weissella cibaria and Weissella confusa strains, lactic acid bacteria (LAB) members naturally present in food products, but not yet included in Qualified Presumption of Safety (QPS) list of European Food Safety Authority (EFSA). METHODS AND RESULTS: We carried out a comparative genome analysis of 23 sequenced W. cibaria and 7 W. confusa genomes, in parallel with a physiological and functional characterization of several strains previously isolated from sourdough-like maize bran fermentation. The genome analysis revealed the absence of dedicated pathogenicity factors. Some putative virulence genes found in Weissella genomes were also present in other LAB strains, considered safe by EFSA and commonly used as probiotics. The physiological tests carried out on our strains corroborated the genomic results. Moreover, the following functional traits of interest to application in the food sector were identified: the majority of tested strains displayed high acidification rate, high reducing ability, production of exopolysaccharides (EPS), arabinoxylan degradation ability, growth in the presence of fructo-oligosaccharides (FOS), bile and gastric juice tolerance, and antifungal activity. CONCLUSIONS: These results provide evidence for the possible use of selected strains of W. cibaria and W. confusa in the food sector. SIGNIFICANCE AND IMPACT OF THE STUDY: This polyphasic study adds to the body of knowledge on the functional and applicable characteristics of these controversial species of LAB. This knowledge contributes to design new selected cultures included in the QPS list required for food applications.

Overview of procalcitonin in pregnancy and in pre-eclampsia.

Procalcitonin (PCT), a precursor for calcitonin, is a prohormone involved in the inflammatory processes, which has been poorly studied in the context of pregnancy. During severe inflammation, PCT derives from almost all cell types, including monocytes and parenchymal tissues, making it a good predictive and diagnostic marker of an inflammatory state with rapidly increased serum levels in inflammation or sepsis. In normal pregnancy, PCT is basally expressed at very low level by decidual cells, even if decidual macrophages, which in normal pregnancy are skewed to M2 macrophages, are resistant to lipopolysaccharide (LPS)-induced production of PCT. As PCT increase is associated with an inflammatory state, several research groups investigated whether PCT can be considered a marker of pre-eclampsia, a pregnancy disease characterized by systemic inflammation. The first aim of this review is to summarize what is already known about the tissues synthesizing PCT, about the stimuli that cause the increase of circulating PCT levels and how PCT acts as a proinflammatory stimulus by itself. Secondly, we will describe the role of this prohormone in normal pregnancy and in pregnancies complicated by pre-eclampsia, highlighting the involvement of the decidual macrophages and the proinflammatory cytokine tumor necrosis factor-α in the modulation of PCT expression in the decidual microenvironment.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

This corrects the article DOI: 10.1038/onc.2017.75.

A proposal for limited criminal liability in high-accuracy endoscopic sinus surgery.

The aim of the present study is to propose legal reform limiting surgeons' criminal liability in high-accuracy and high-risk surgery such as endoscopic sinus surgery (ESS). The study includes a review of the medical literature, focusing on identifying and examining reasons why ESS carries a very high risk of serious complications related to inaccurate surgical manoeuvers and reviewing British and Italian legal theory and case-law on medical negligence, especially with regard to Italian Law 189/2012 (so called "Balduzzi" Law). It was found that serious complications due to inaccurate surgical manoeuvers may occur in ESS regardless of the skill, experience and prudence/diligence of the surgeon. Subjectivity should be essential to medical negligence, especially regarding high-accuracy surgery. Italian Law 189/2012 represents a good basis for the limitation of criminal liability resulting from inaccurate manoeuvres in high-accuracy surgery such as ESS. It is concluded that ESS surgeons should be relieved of criminal liability in cases of simple/ordinary negligence where guidelines have been observed.

Stearoyl-CoA-desaturase 1 regulates lung cancer stemness via stabilization and nuclear localization of YAP/TAZ.

Recent evidences suggest that stearoyl-CoA-desaturase 1 (SCD1), the enzyme involved in monounsaturated fatty acids synthesis, has a role in several cancers. We previously demonstrated that SCD1 is important in lung cancer stem cells survival and propagation. In this article, we first show, using primary cell cultures from human lung adenocarcinoma, that the effectors of the Hippo pathway, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are required for the generation of lung cancer three-dimensional cultures and that SCD1 knock down and pharmacological inhibition both decrease expression, nuclear localization and transcriptional activity of YAP and TAZ. Regulation of YAP/TAZ by SCD1 is at least in part dependent upon ß-catenin pathway activity, as YAP/TAZ downregulation induced by SCD1 blockade can be rescued by the addition of exogenous wnt3a ligand. In addition, SCD1 activation of nuclear YAP/TAZ requires inactivation of the ß-catenin destruction complex. In line with the in vitro findings, immunohistochemistry analysis of lung adenocarcinoma samples showed that expression levels of SCD1 co-vary with those of ß-catenin and YAP/TAZ. Mining available gene expression data sets allowed to observe that high co-expression levels of SCD1, ß-catenin, YAP/TAZ and downstream targets have a strong negative prognostic value in lung adenocarcinoma. Finally, bioinformatics analyses directed to identify which gene combinations had synergistic effects on clinical outcome in lung cancer showed that poor survival is associated with high co-expression of SCD1, ß-catenin and the YAP/TAZ downstream target birc5. In summary, our data demonstrate for the first time the involvement of SCD1 in the regulation of the Hippo pathway in lung cancer, and point to fatty acids metabolism as a key regulator of lung cancer stem cells.

How to assess appearance distress and motivation in plastic surgery candidates: Italian validation of Derriford Appearance Scale 59 (DAS 59).

OBJECTIVE: The Derriford Appearance Scale (DAS) 59 was specifically designed to measure psychosocial adjustment in patients with appearance problems. Previous studies using the DAS59 have proven it to be a reliable method of assessing the appearance-related quality of life after plastic surgery procedures. The aim of this study was to develop a valid and reliable Italian version of the DAS59. PATIENTS AND METHODS: The first Italian translation of this questionnaire was conducted according to the DAS59 protocol that was designed by the original authors of the questionnaire. Eight hundred patients participated in this study and filled out three questionnaires (DAS59, General Health Questionnaire (GHQ)12 and Beck's Depression Inventory (BDI)-II). There were 400 adult patients with a history of previous plastic surgeries and 400 adult patients without any personal history of previous plastic surgery procedures. A total of 50 patients were selected randomly for test-retest analysis. RESULTS: The overall internal consistency was excellent (α = 0.95) and equal to that of the original article that first described the scale. There was a good correlation between all the items. Domains demonstrated good internal consistency (Cronbach's alpha) and correlation within themselves. The construct validity of the Italian DAS59 was assessed under convergent validity that confirmed the correlation with scales related to other psychological conditions. GHQ12 showed relevant correlation with DAS59, while BDI-II did not. CONCLUSIONS: A valid and reliable Italian DAS59 version was developed that can be used for research and clinical assessment of patients with appearance problems and concerns, especially before and after plastic surgery procedures.

Prioritization of high-cost new drugs for HCV: making sustainability ethical.

Hepatitis C virus (HCV) infection is a major health problem worldwide. Chronic HCV infection may in the long run cause cirrhosis, hepatic decompensation and hepatocellular carcinoma, with an ultimate disease burden of at least 350,000 deaths per year worldwide. The new generation of highly effective direct acting antivirals (DAA) to treat HCV infection brings major promises to infected patients in terms of exceedingly high rates of sustained virological response (SVR) but also of tolerability, allowing even the sickest patients to be treated. Even in the face of the excellent safety and efficacy and wide theoretical applicability of these regimens, their introduction is currently facing cost and access issues denying their use to many patients in need. Health systems in all countries are facing a huge problem of distributive justice, since while they should guarantee individual rights, among which the right to health in its broader sense, therefore not limited to healing, but extended to quality of life, they must also grant equal access to the healthcare resources and keep the distribution system sustainable. In the face of a disease with a relatively unpredictable course, where many but not of all chronically infected will eventually die of liver disease, selective allocation of this costly resource is debatable. In most countries the favorite solution has been a stratification of patients for prioritization of treatment, which means allowing Interferon-free DAA treatment only in patients with advanced fibrosis or cirrhosis, while keeping on hold persons with lesser stages of liver disease. In this report, we will perform an ethical assessment addressing the issues linked to access to new therapies, prioritization and eligibility criteria, analyzing the meaning of the term "distributive justice" and the different approaches that can guide us (individualistic libertarianism, social utilitarianism and egalitarianism) on this specific matter. Even if over time the price of new DAA will be reduced through competition and eventual patent expiration, the phenomenon of high drug costs will go on in the next decades and we need adequate tools to face the problems of distributive justice that come with it.

Endoscopic dacryocystorhinostomy with and without silicone intubation: 4 years retrospective study.

The objective of this study is to assess different outcomes between endoscopic dacryocystorhinostomy (En-DCR) with and without silicone intubation. We retrospectively analyzed 84 patients (89 procedures), suffering from chronic epiphora for primary acquired nasolacrimal duct obstruction, treated with En-DCR and divided into two groups depending on silicone stent intubation. The surgical outcomes were evaluated at 7 post-operative controls using Munk's score criteria. Functional success was defined as absence of epiphora, no further episodes of dacryocystitis, and a patent ostium after fluorescein irrigation. 45 En-DCR with stent and 44 En-DCR without stent were performed. Success rate after 18 months follow-up were, respectively, 82.2 % in the stent group and 88.6 % in the non-stent group (OR 0.59) with no statistical differences. The ostial size reduction has been reported in higher percentage in the stent group, mainly due to peristomal granuloma (OR 3.64), scar tissue formation (OR 2.25), and turbinoseptal synaechia (OR 1.76). The benefits of non-intubation are less patient discomfort, reduced surgical time and costs, simpler follow-up regimen and less intubation-associated complications. En-DCR without silicone stent intubation should be the first choice of procedure, stent intubation should be reserved in selected cases with poor local conditions pre and intra-operatively assessed.

A new ethical and medico-legal issue: vascular surgery and the postoperative cognitive dysfunction.

Patients undergoing major surgery are at risk for postoperative cognitive dysfunction (POCD). The consciousness of the POCD arises new ethical and medico-legal issues that should be identified, managed and, if possible, prevented. Elderly patients still represent a real challenge for physicians and medical science. This challenge can be surmounted not only through technical progress but also by safeguarding the correct ethical behavior at the base of each relationship between a patient and his physician. Effective communication with the elderly patient is a prerequisite for clear and complete information, involving family members and caregivers when necessary. In every case, the identification of patients with pre-existing risk factors of POCD, shortening the period of time preceding the surgery and a proper technique of the procedure as well as physical and intellectual exercises, nutrition and medication play an important role in decreasing the incidence of neurocognitive deficits in the elderly.

Balance control impairment induced after OKS in patients with vestibular migraine: an intercritical marker.

The aim of the study was to assess the effects of optokinetic stimulation (OKS) on vestibular postural control in migraine patients with recurrent vertigo. 15 patients with vestibular migraine (VM) were enrolled in a posturographic study in eyes open (OE) and eyes closed (CE) condition. The tests were performed between attacks of headache and vertigo at three different time: before, during, and 60 min after OKS. Data of patients with VM were compared with those obtained from two control groups matched for sex and age (15 for each group): (a) normal subjects not suffering from migraine without history of recurrent vertigo (N group); (b) subjects suffering from migraine with no history of recurrent vertigo (M group). Mean sway path velocity and sway area were analyzed. OKS increased the instability in all groups during the stimulus, and both the velocity and area values were higher in M and VM group. However, there was not significant difference between these two groups when stability was examined in OE condition before, during and after OKS stimulation. Conversely, in CE condition a significant greater instability was induced after OKS stimulation only in VM. In particular, post-stimulus values were significantly higher than the pre-stimulus one only in this group, while no significant difference was observed in other groups. A spatial analysis of the sway area evidenced that the instability induced by the OKS in VM group occurred along the direction of OKS. We suggest that this enhanced instability observed after OKS during the intercritical period may be considered an useful marker to support the diagnostic definition of VM in the absence of other vestibular signs.

Successful rescue hysteroscopic resection of a cervical ectopic pregnancy previously treated with methotrexate with no combined safety precautions.

BACKGROUND: Cervical pregnancy (CP) is a life-threatening condition that represents less than one percent of all ectopic pregnancies. Transvaginal sonography (TVS) is the gold standard for an accurate diagnosis. For hemodinamically stable women the available treatments involve a medical therapy, alone or in combination with interventional measures (hysteroscopy, angiographic embolization or laparoscopic ligation of uterine arteries). MATERIALS AND METHODS: The authors describe a CP unsuccessfully treated with methotrexate (MTX), but resolved with hysteroscopy. CASE REPORT: A nulliparous woman arrived with low abdominal pain without vaginal bleeding at six weeks of amenorrhea. TVS revealed a gestational sac implanted in the isthmic cervical region, with a serum beta-hCG of 1,100 mUI/ml, that raised to 4,274 mUI/ml in a week, despite one intrasaccular-MTX injections and two systemic doses. The authors arranged for a hysteroscopic resection with no previous dilatation of the cervix. They did not adopt any safety precautions to their procedure. CONCLUSION: It is difficult to define the exact role of hysteroscopy regarding CP. Despite some authors dispute on its complementary function to MTX, the authors believe that it could be used as a rescue method in case of MTX failure. The final aims of a proper management are to minimize the risk of haemorrhage and preserve women's fertility.

Characteristics of spontaneous physical activity and executive functions in postmenopause.

AIM: Executive functions are susceptible to age-related changes, and menopause has also been shown to be linked with their decline. The aim of the present study was to investigate the variables related to executive functions in postmenopausal women not involved in controlled dietary and physical exercise programs and without hormone-replacement therapy. METHODS: Fifty-seven women (58.39 ±4.16 yr) were investigated for their medical history, blood lipids, insulin resistance (HOMA-IR), body composition, blood pressure, executive functions (Digit Span and Trail Making tests), maximal aerobic capacity, dietary habits, and spontaneous physical activity. RESULTS: Cluster analysis performed on the basal data of the Digit Span scores and Trail Making tests identified two subgroups: Group A (N.=24) that showed better executive functions than Group B (N.=33). Although these subgroups differed across several variables of body composition, plasma lipids, dietary habits, spontaneous physical activity, aerobic fitness, and insulin resistance, logistic regression models showed B10m/die as the only predictive variable for subgroup membership. CONCLUSION: In the absence of a physical exercise program, the knowledge of how spontaneous physical activity is organized (B10m/die) is important for executive functions of post-menopausal women. It is the specific moderate to intense physical activity characteristic of B10m/die, rather than generic physical activity, that seems to determine the maintenance or attainment of cognitive health through body movement.

Glial cell line-derived neurotrophic factor promotes invasive behaviour in testicular seminoma cells.

The glial cell line-derived neurotrophic factor (GDNF) has multiple functions that promote cell survival, proliferation and migration in different cell types. The experimental over-expression of GDNF in mouse testis leads to infertility and promotes seminomatous germ cell tumours in older animals, which suggests that deregulation of the GDNF pathway may be implicated in germ cell carcinogenesis. GDNF activates downstream pathways upon binding to its specific co-receptor GDNF family receptor-a 1 (GFRA1). This complex then interacts with Ret and other co-receptors to activate several intracellular signalling cascades. To explore the involvement of the GDNF pathway in the onset and progression of testicular germ cell tumours, we analysed GFRA1 and Ret expression patterns in seminoma samples. We demonstrated, via immunohistochemistry, that GFRA1, but not Ret, is over-expressed in in situ carcinoma (CIS) and in intratubular and invasive seminoma cells compared with normal human germ cells. Functional analysis of the GDNF biological activity was performed on TCam-2 seminoma cell line. Reverse transcription-PCR (RT-PCR) and immunohistochemical analyses demonstrate that TCam-2 cells express both GFRA1 and Ret mRNA, but only GFRA1 was detected at the protein level. In TCam-2 cells, although GDNF is not mitogenic, it is able to induce migration, as demonstrated by a Boyden chamber assay, possibly through the Src and MEK pathways. Moreover, GDNF promotes invasive behaviour, an effect dependent on pericellular protease activity, possibly through the activity of matrix metalloproteinases. GFRA1 over-expression in CIS and seminoma cells, along with the functional analyses in TCam-2 cells, suggests an involvement of the GDNF pathway in the progression of testicular germ cell cancer.

Colon cancer adrenal metastasis: case report and review of the literature.

The authors report a case of alone right adrenal metastasis from colon carcinoma discovered incidentally by CT scan imaging 4 years after colon resection in a 74-year-old man. The presence of metastasis in the adrenal glands represents the second most frequent cause of "adrenal incidentaloma", following cortical-adrenal adenomas. The most common primary tumors responsible for adrenal metastasis are carcinoma of the lung, breast and kidney. Alone adrenal metastases due to colon or rectal carcinoma is very rare. Due to their rarity, at present there are not randomised studies supporting the effectiveness of surgery. Nevertheless, on the basis of international Literature and our experience of adrenalectomy could represent the current "gold-standard" therapeutic approach.