A comparison of surgical techniques for perineal wound closure following perineal excision: a systematic review and network meta-analysis.

BACKGROUND: To mitigate pelvic wound issues following perineal excision of rectal or anal cancer, a number of techniques have been suggested as an alternative to primary closure. These methods include the use of a biological/dual mesh, omentoplasty, muscle flap, and/or pelvic peritoneum closure. The aim of this network analysis was to compare all the available surgical techniques used in the attempt to mitigate issues associated with an empty pelvis. METHODS: An electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science was performed (Last date of research was March 15th, 2023). Studies comparing at least two of the aforementioned surgical techniques for perineal wound reconstruction during abdominoperineal resection, pelvic exenteration, or extra levator abdominoperineal excision were included. The incidence of primary healing, complication, and/or reintervention for perineal wound were evaluated. In addition, the overall incidence of perineal hernia was assessed. RESULTS: Forty-five observational studies and five randomized controlled trials were eligible for inclusion reporting on 146,398 patients. All the surgical techniques had a comparable risk ratio (RR) in terms of primary outcomes. The pooled network analysis showed a lower RR for perineal wound infection when comparing primary closure (RR 0.53; Crl 0.33, 0.89) to muscle flap. The perineal wound dehiscence RR was lower when comparing both omentoplasty (RR 0.59; Crl 0.38, 0.95) and primary closure (RR 0.58; Crl 0.46, 0.77) to muscle flap. CONCLUSIONS: Surgical options for perineal wound closure have evolved significantly over the last few decades. There remains no clear consensus on the "best" option, and tailoring to the individual remains a critical factor.

The role of policy in social-ecological interactions of nitrogen management in the Mississippi River basin.

Excess nitrogen (N) loading in the Mississippi River basin is a major water quality issue, encompassing large spatial scales and feedbacks between social and biophysical entities. Effective management depends on reductions in agricultural N loading, mainly from the Corn Belt region in the upper reaches of the basin. In this study, we evaluated the role of federal Nutrient Task Force policy on N management from 2000 to 2015. We analyzed trends in nitrate (NO3 - ) concentrations from monitoring data in 148 priority watersheds. We compared water quality trends with state nutrient reduction strategies, monitoring efforts, and land use. Of the 148 watersheds, 13 displayed a significant decrease in NO3 - concentrations, 24 displayed a significant increase, 51 displayed a nonsignificant trend, and 60 had insufficient data to analyze. We demonstrate that policy efforts on a large scale are slow to establish, but states and watersheds that showed signs of policy acting successfully could serve as examples for improved N management moving forward. Despite considerable variability, states with the most comprehensive strategies, evidenced by word count and presence of recommended elements, were almost exclusively located in the Corn Belt region. States with more thorough nutrient reduction strategies also tended to have a larger number of monitoring sites in priority watersheds (R = .42), demonstrating the potential for adaptive management. States with the most consistent improvements in NO3 - concentrations tended to have the most comprehensive policies, whereas variation in water quality trends was partly attributed to land use factors including slope and dominance of corn (Zea mays L.) and soy [Glycine max (L.) Merr.].

Evaluation of ammonia and odour emissions from animal slurry and digestate storage in the Po Valley (Italy).

Ammonia and odour emissions from one lagoon (Lagoon 1: pig slurry) and three tanks (Tank 2: cow slurry; Tank 3: digestate from pig slurry and energy crops; Tank 4: digestate from pig and cow slurries plus energy crop) used for slurry storage were sampled for two years (2015-2017) in livestock farms that differed for animal breeding and manure management (anaerobic digestion). On average, the ammonia emission rate (AER) was higher for Tank 3 (AER of 30.68 ± 28.1 g N-NH3 m-2 d-1) than for Lagoon 1 and Tank 2 and 4, i.e. 9.29 ± 14.89 gN-NH3 m-2 d-1, 9.38 ± 13.75 g N-NH3 m-2 d-1, 15.74 ± 21.91 g N-NH3 m-2 d-1, respectively. PLS regression analysis (R2 = 0.544; R2Adj. = 0.484) indicated that temperature was the main predictor of ammonia emitted, followed by concentration in the slurry of total ammonia and the relative percentage of volatile solids (VS). On the other hand, PLS analysis (R2 = 0.529, R2adj. = 0.417) indicated that odour emissions from animal slurry storages depended similarly upon total solids and VS (both referred to fresh weight) slurry contents, TAN/TKN ratio and degrees of biological stability (measured by anaerobic biogas potential - ABP), resulting in the Specific Odours Emission Rates (SOER) of 12,124 ± 7,914 and 35,207 ± 41,706 OUE m-2 h-1, 65,430 ± 45,360 and 43,971 ± 53,350 OUE m-2 h-1, for Lagoon 1 and Tanks 2, 3 and 4. These results suggest covering the tanks to limit both ammonia and odour emissions.

Inherited cancer syndromes in 220 Italian ovarian cancer patients.

BACKGROUND: A subsets of ovarian carcinomas (OCs) are related to inherited conditions including Hereditary Breast and Ovarian Cancers (HBOC) and Lynch Syndrome (LS). The identification of inherited conditions using genetic testing might be a strategic model for cancer prevention that include benefits for the ovarian cancer patients and for their family members. METHODS: We describe a retrospective Italian experience for the identification of inherited conditions in 232 patients affected by OCs using both somatic and germline analyses. RESULTS: Immunohistochemical and microsatellite analyses performed on OCs identified 20 out of 101 MMR defective cancers and 15 of these were from patients carriers of the MMR germline pathogenetic variants. BRCA1 and BRCA2 testing offered to 198 OC patients revealed 67 (34%) pathogenetic variant carriers of BRCA1/2 genes. Interestingly LS patients revealed a mean age of OC onset of 45.4 years, which was significantly lower than the mean age of OCs onset of HBOC patients. CONCLUSIONS: Somatic and germline analyses offered to OC patients has proved to be an efficient strategy for the identification of inherited conditions involving OC also in absence of suggestive family histories. The identification of LS and HBOC syndromes through OC patients is an effective tool for OC prevention.

The Impact of Federal and State Conservation Programs on Farmer Nitrogen Management.

The U.S. federal government, as well as many state and local governments, operate a number of conservation programs aimed at ameliorating the environmental problems associated with agriculture. While motives and barriers to conservation program participation and adoption of conservation practices have been extensively studied, the direct impacts of programs on ongoing farm operations remains underexplored. To examine the effects of conservation programs on nitrogen management, an aspect of crop production with significant environmental impacts we conducted interviews with 154 corn producers in three Midwestern U.S. states with a range of program experiences. We found that programs shifted farmer N management behavior through three social processes: (1) engaging farmers in the conservation system by introducing them to the state and federal conservation agencies, (2) incentivizing trialing of specific N management practices, and (3) increasing practice adoption through continued program engagement. Working-lands programs were far more effective at shifting on-farm nutrient management practices than land retirement, certification, or outreach-based programs, though all programs had the indirect benefit of increasing farmer familiarity with conservation agencies and programs. Working-lands programs directly motivated practice adoption; including soil testing regimes, implementing nutrient management plans, and splitting nitrogen applications to improving availability; by reducing producer risk and providing technical assistance, especially whole-farm planning. The additional benefits of all programs were moderated by participant selection bias, in particular that program participants were more predisposed to conservation efforts by existing stewardship and innovation attitudes.

Anaerobic digestion coupled with digestate injection reduced odour emissions from soil during manure distribution.

This work aimed to measure the odour impact of untreated cow and pig slurries and treated (digestate and liquid fraction of digestate) manures when they were used on soil at a field scale, while also testing different spreading methods, i.e. surface vs. injection. Five experiments were performed in 2012-2016 on different farms. Odours were quantitatively (specific odour emission rate - SOER) (OUEm-2h-1) measured by using dynamic olfactometry and qualitatively, i.e. to obtain an "odour fingerprint", by using an electronic nose (EN). Anaerobic digestion was effective in allowing the reduction of potential odour emission from digestates, so that when they were dosed on soil, odours emitted were much lower than those from soils on which untreated slurries were used. Slurries/digestate injection reduced much more odour emitted by soils so that SOER tended to become more similar to that of the control (untreated soil) although the odours were slightly greater. Odour fingerprint data indicated that there was a direct correlation between SOER and odour fingerprints. This was due to the ability of EN to detect ammonia, S-compounds and methane that were (the first two mainly), also, responsible for odours. Very good regression was found for Log SOER and EN by using a Partial Least Square (PLS) approach (R2=0.73; R2cv=0.66; P<0.01) for matrices used to fertilize soils in lab tests. Unfortunately, regression was not so good when odour data from field experiments on soil were used, so that EN cannot be proposed to replace olfactometry. EN fingerprints for control (Blank) and injected organic matrices were virtually identical, due to the creation of cavities in the soil during the injection that decreased the treated surface. Anaerobic digestion and subsequent digestate injection allowed us to reduce odour impact, avoiding annoyance to local inhabitants.

Effects of dietary polyphenols on metabolic syndrome features in humans: a systematic review.

Dietary polyphenols constitute a large family of bioactive substances potential beneficial effect on metabolic syndrome (MetS). This review summarizes the results of clinical studies on patients with MetS involving the chronic supplementation of a polyphenol-rich diet, foods, extracts or with single phenolics on the features of MetS (obesity, dyslipidemia, blood pressure and glycaemia) and associated complications (oxidative stress and inflammation). Polyphenols were shown to be efficient, especially at higher doses, and there were no specific foods or extracts able to alleviate all the features of MetS. Green tea, however, significantly reduced body mass index and waist circumference and improved lipid metabolism. Cocoa supplementation reduced blood pressure and blood glucose. Soy isoflavones, citrus products, hesperidin and quercetin improved lipid metabolism, whereas cinnamon reduced blood glucose. In numerous clinical studies, antioxidative and anti-inflammatory effects were not significant after polyphenol supplementation in patients with MetS. However, some trials pointed towards an improvement of endothelial function in patients supplemented with cocoa, anthocyanin-rich berries, hesperidin or resveratrol. Therefore, diets rich in polyphenols, such as the Mediterranean diet, which promote the consumption of diverse polyphenol-rich products could be an effective nutritional strategy to improve the health of patients with MetS. © 2016 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

Short-term experiments in using digestate products as substitutes for mineral (N) fertilizer: Agronomic performance, odours, and ammonia emission impacts.

Anaerobic digestion produces a biologically stable and high-value fertilizer product, the digestate, which can be used as an alternative to mineral fertilizers on crops. However, misuse of digestate can lead to annoyance for the public (odours) and to environmental problems such as nitrate leaching and ammonia emissions into the air. Full field experimental data are needed to support the use of digestate in agriculture, promoting its correct management. In this work, short-term experiments were performed to substitute mineral N fertilizers (urea) with digestate and products derived from it to the crop silage maize. Digestate and the liquid fraction of digestate were applied to soil at pre-sowing and as topdressing fertilizers in comparison with urea, both by surface application and subsurface injection during the cropping seasons 2012 and 2013. After each fertilizer application, both odours and ammonia emissions were measured, giving data about digestate and derived products' impacts. The AD products could substitute for urea without reducing crop yields, apart from the surface application of AD-derived fertilizers. Digestate and derived products, because of high biological stability acquired during the AD, had greatly reduced olfactometry impact, above all when they were injected into soils (82-88% less odours than the untreated biomass, i.e. cattle slurry). Ammonia emission data indicated, as expected, that the correct use of digestate and derived products required their injection into the soil avoiding, ammonia volatilization into the air and preserving fertilizer value. Sub-surface injection allowed ammonia emissions to be reduced by 69% and 77% compared with surface application during the 2012 and 2013 campaigns.

Endometrial cancer cells can express fibrinogen: Immunohistochemistry and RT-PCR analysis.

We investigated whether endometrial cancer (EC) cells can express fibrinogen. Consecutive patients treated for EC were enrolled (cases). A control group of women who had hysterectomy for benign conditions was identified in a case:control ratio of 4:1. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were performed to identify the presence of fibrinogen and the mRNA of its three chains (α, ß, γ) in the tissue specimens from both cases and controls. Sixteen EC cases and 4 benign controls were included. Immunohistochemistry failed in one case of EC. In 12/15 (80%) cases versus 0 controls, a moderate-to-intense positivity for fibrinogen was observed (p = 0.09; OR: 32.1; 95%CI: 1.4-752.9). Six (37.5%) women among the cases versus 0 controls expressed RNA for at least one chain of fibrinogen (p = 0.25). All the cases (6/6, 100%) with positive RT-PCR had moderate-to-intense positive immunohistochemistry. Molecular and immunohistochemistry show that some cases of EC have the capability to express fibrinogen and the mRNA of at least one of its chains.

Production costs and operative margins in electric energy generation from biogas. Full-scale case studies in Italy.

The purpose of this study was to observe the economic sustainability of three different biogas full scale plants, fed with different organic matrices: energy crops (EC), manure, agro-industrial (Plants B and C) and organic fraction of municipal solid waste (OFMSW) (Plant A). The plants were observed for one year and total annual biomass feeding, biomass composition and biomass cost (€ Mg(-1)), initial investment cost and plant electric power production were registered. The unit costs of biogas and electric energy (€ Sm(-3)biogas, € kWh(-1)EE) were differently distributed, depending on the type of feed and plant. Plant A showed high management/maintenance cost for OFMSW treatment (0.155 € Sm(-3)biogas, 45% of total cost), Plant B suffered high cost for EC supply (0.130 € Sm(-3)biogas, 49% of total cost) and Plant C showed higher impact on the total costs because of the depreciation charge (0.146 € Sm(-3)biogas, 41% of total costs). The breakeven point for the tariff of electric energy, calculated for the different cases, resulted in the range 120-170 € MWh(-1)EE, depending on fed materials and plant scale. EC had great impact on biomass supply costs and should be reduced, in favor of organic waste and residues; plant scale still heavily influences the production costs. The EU States should drive incentives in dependence of these factors, to further develop this still promising sector.

Analysis of the Dreissena polymorpha gill proteome following exposure to dioxin-like PCBs: mechanism of action and the role of gender.

PCBs are a persistent environmental problem due to their high stability and lipophilicity. The non-ortho- and the mono-ortho-substituted PCBs (dioxin-like-PCBs) share a common and well-described toxicity mechanism in vertebrates, initially involving binding to cytosolic AhRs. Invertebrate AhRs, however, show a lack of dioxin binding, and little information is available regarding the mechanism of toxicity of dl-PCBs in invertebrates. In this study, a proteomic approach was applied to analyse the variations in the pattern of the gill proteome of the freshwater mussel Dreissena polymorpha. Mussels were exposed to a mixture of dl-PCBs, and to perform a more in-depth evaluation, we chose to investigate the role of gender in the proteome response by analysing male and female mussels separately. The results revealed significant modulation of the gill tissue proteome: glycolysis and Ca(2+) homeostasis appear to be the main pathways targeted by dl-PCBs. In light of the differences between the male and female gill proteome profiles following exposure to dl-PCBs, further in-depth investigations of the role of gender in the protein expression profiles of a selected biological model are required.

First evidence of protein profile alteration due to the main cocaine metabolite (benzoylecgonine) in a freshwater biological model.

Illicit drugs represent not only a great social problem but are also considered an environmental problem because their use and, often, abuse release large amounts of parent compounds, and especially their metabolites, into freshwaters. One of the most commonly used drugs is cocaine, which is the second most prevalent drug in Europe (accounting for almost 30% of all cocaine users worldwide). Cocaine is rapidly metabolised in humans to benzoylecgonine (35-54%), ecgonine methyl ester (32-49%) and norcocaine (5%), which are eliminated in the urine and are only partially removed by wastewater treatment plants (WWTPs). Because no studies have previously been carried out to evaluate the possible risks due to cocaine and its metabolites in non-target organisms, we applied a multi-disciplinary approach to investigate the possible environmental risk related to benzoylecgonine (BE), the main metabolite of cocaine. Previous studies carried out by means of a biomarker suite and the redox-proteomic approach showed an imbalance of anti-oxidant enzyme activities and several genotoxic effects to be caused by environmental BE concentrations in the freshwater bivalve Zebra mussel (Dreissena polymorpha). This report presents the results obtained in the last step of this study, based on a proteomics analysis. We analysed the protein expression profile in the gills of Zebra mussels exposed to two different concentrations (0.5 and 1 µg/L) of BE for 14 days through 2-DE and mass spectrometry analysis (RP-UPLC ESI-LTQ-Orbitrap). Our results highlight significant changes in some proteins in gill cells whose functions are crucial for overall metabolism. In particular, we detected a probable effect of BE on calcium homeostasis and a consequent imbalance of oxidative stress, as verified for vertebrates.

Illicit drugs as new environmental pollutants: cyto-genotoxic effects of cocaine on the biological model Dreissena polymorpha.

The increase in global consumption of illicit drugs has produced not only social and medical problems but also a potential new environmental danger. Indeed, it has been established that drugs consumed by humans end up in surface waters, after being carried through the sewage system. Although many studies to measure concentrations of several drugs of abuse in freshwater worldwide have been conducted, no data have been available to evaluate their potentially harmful effects on non-target organisms until now. The present study represents the first attempt to investigate the cyto-genotoxic effects of cocaine, one of the primary drugs consumed in Western Countries, in the biological model Dreissena polymorpha by the use of a biomarker battery. We performed the following tests on Zebra mussel hemocytes: the single cell gel electrophoresis (SCGE) assay, the apoptosis frequency evaluation and the micronucleus assay (MN test) for the evaluation of genotoxicity and the lysosomal membranes stability test (neutral red retention assay; NRRA) to identify the cocaine cytotoxicity. We exposed the molluscs for 96 h to three different nominal concentrations in water (40 ng L(-1); 220 ng L(-1); and 10 µg L(-1)). Cocaine caused significant (p<0.05) primary DNA damage in this short-term experiment, but it also caused a clear increase in micronucleated cells and a marked rise in apoptosis, which was evident in samples from even the lowest environmental cocaine concentration. Because cocaine decreased the stability of lysosomal membranes, we also highlighted its cytotoxicity and the possible implications of oxidative stress for the observed genotoxic effects.

[Clinic use of Laser Doppler Flowmetry (LDF) in the study of subfoveal choroidal circulation]. / Impiego clinico del Laser Doppler Flussometria (LDF) nello studio della circolazione coroideale sottofoveale.

Today our knowledge of the choroidal circulation is limited: we know its anatomy, but, on the other hand, its physiopathology remains to be fully. The choroid is involved in a number of important ocular diseases. The Laser Doppler Flowmetry (LDF) is a technique that allows non-invasive measurement of haemodynamic parameters of the subfoveal choroidal circulation. It is easy to use in daily clinic activity. The aim of this mini-review is to describe LDF studies of the choroidal circulation performed in healthy subjects under different environmental conditions, in subjects with ocular diseases, as well as studies of the effects of various drugs can induce on this circulation.

Changing patterns in HIV-1 non-B clade prevalence and diversity in Italy over three decades.

BACKGROUND: HIV-1 non-B subtypes have recently entered Western Europe following immigration from other regions. The distribution of non-B clades and their association with demographic factors, over the entire course of the HIV-1 epidemic, have not been fully investigated in Italy. METHODS: We carried out a phylogenetic analysis of HIV-1 pol sequences derived from 3670 patients followed at 50 Italian clinical centres over nearly three decades. RESULTS: Overall, 417 patients (11.4%) carried non-B subtypes. The prevalence of non-B strains increased from 2.6% in 1980-1992 to 18.9% in 1993-2008 (P<0.0001) in a subset of 2479 subjects with a known year of diagnosis. A multivariate analysis on a subset of 1364 patients for whom relevant demographic data were available indicated that African ethnicity, heterosexual route of infection and year of diagnosis were independently associated with non-B HIV-1 infection (P ≤ 0.0001). All pure subtypes, except for clade K, and seven circulating recombinant forms were detected, accounting for 56.6 and 34.1% of the non-B infections, respectively. The F1 subtype was the most prevalent non-B clade among Europeans and was acquired heterosexually in half of this patient population. Unique recombinant forms accounted for 9.4% of the non-B sequences and showed a B/F1 recombination pattern in one-third of cases. CONCLUSIONS: The circulation of non-B clades has significantly increased in Italy in association with demographic changes. Spread of the F1 subtype and B/F recombinants appears to predominate, which may result in a redistribution of the relative proportions of the different strains, and this could lead to overlapping epidemics. Thus, the HIV-1 landscape in Italy may in future be distinct from that of the rest of Europe.

The effects of hypoxia on the ERG in paediatric cerebral malaria.

BACKGROUND/AIMS: Cerebral malaria (CM) is a disease of high mortality worldwide. It can be associated with malarial retinopathy (MR) resulting from impaired perfusion within the retinal microvasculature. Areas of capillary non-perfusion (CNP) appear white (retinal whitening) on ophthalmoloscopy. In this study, electrophysiological investigations were performed to investigate the physiological consequences of these hypoxic and ischaemic changes. METHODS: Children admitted with CM were assessed for inclusion in the study. Those with MR underwent further detailed fundus assessment to quantify retinal whitening and were then designated a severity score. Electrophysiological recordings were performed using a miniganzfeldt stimulator with calibration to the International Society for Clinical Electrophysiology of Visual (ISCEV) standards. ERG data were then analysed with respect to presence of MR and also graded disease severity. RESULTS: Thirty-one children were recruited with a diagnosis of CM, 20 had MR (group 1), and 11 had absent MR (group 2). Statistical analyses of these two groups showed a significant relationship between reduced single flash cone b wave amplitude (CBWA) and increased severity of retinal whitening/CNP (P<0.05). Cone and maximal response b : a wave ratios remained >1 in all subjects. CONCLUSION: Retinal whitening/CNP in MR is associated with significant changes in ERG cone b wave function. The relatively high b : a ratio is compatible with the high frequency of MR resolution without sequelae.

Cytotoxic and genotoxic effects of in vitro exposure to triclosan and trimethoprim on zebra mussel (Dreissena polymorpha) hemocytes.

Pharmaceuticals and personal care products (PPCPs) have been detected in several aquatic ecosystems for a number of years, but the potential for biological effects in exposed non-target organisms is only now being reported. In this study the potential cellular damage due to two of the main PPCPs found in aquatic environments was investigated by in vitro exposures. Hemolymph samples of the freshwater bivalve Dreissena polymorpha were collected and treated with increasing concentrations of the antibacterial agent Triclosan (TCS) and the antibiotic Trimethoprim (TMP). Doses selected for TCS were 0.1, 0.15, 0.2, and 0.3 microM, while 0.2, 1, and 5 microM for TMP exposures, respectively. We evaluated the potential genotoxicity on hemocytes by the SCGE (single cell gel electrophoresis) assay and apoptosis frequency evaluation, while the cytotoxicity was measured by the lysosomal membranes stability test (NRRA, neutral red retention assay). TCS genotoxicity increased in a dose-dependent manner and this pharmaceutical significantly affects hemocyte functionality due to severe DNA injuries at very low doses. In contrast, TMP seems to be less dangerous than TCS for D. polymorpha because the cytotoxic and the moderate genotoxic effects noticed were obtained only at very high concentration levels.

In vivo experiments for the evaluation of genotoxic and cytotoxic effects of Triclosan in Zebra mussel hemocytes.

In this work, we investigated the possible genotoxic and cytotoxic effects of the antibacterial agent Triclosan in hemocytes of the freshwater bivalve Zebra mussel (Dreissena polymorpha). For this study, we used several biomarkers for in vivo experiments (96h of exposure) carried out at three possible environmental Triclosan concentrations (1, 2, 3nM). We used the single cell gel electrophoresis (SCGE) assay, the micronucleus test (MN test) and the measure of the apoptotic frequency (Halo assay) to measure the genotoxic potential of Triclosan, and the neutral red retention assay (NRRA) as a measure of lysosomal membrane stability to identify general cellular stress. We observed significant increases in all of the genotoxic biomarkers examined as early as 24h after initial exposure, as well as a clear destabilization of lysosomal membranes (after 48h), indicating that this chemical is potentially dangerous for the entire aquatic biocoenosis. A comparison of these in vivo data with existing data from in vitro experiments allowed us to suggest possible mechanisms of action for Triclosan in this bivalve. Although further studies are needed to confirm the possible modes of action, our study is the first to report on the effects of this widespread antibiotic on freshwater invertebrates.

PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients.

BACKGROUND: It has been reported that KRAS mutations (and to a lesser extent KRAS mutations with the BRAF V600E mutation) negatively affect response to anti-epidermal growth factor receptor (EGFR) mAbs in metastatic colorectal cancer (mCRC) patients, while the biological impact of the EGFR pathway represented by PI3K/PTEN/AKT on anti-EGFR treatment is still not clear. PATIENTS AND METHODS: We analysed formalin-fixed samples from a cohort of 32 mCRC patients treated with cetuximab by means of EGFR immunohistochemistry, EGFR and PTEN FISH analysis, and KRAS, BRAF, PI3KCA, and PTEN genomic sequencing. RESULTS: Ten (31%) of 32 patients showed a partial response to cetuximab and 22 (69%) did not [nonresponder (NR)]. EGFR immunophenotype and FISH-based gene status did not predict an anti-EGFR mAb response, whereas KRAS mutations (24%) and PI3K pathway activation, by means of PI3KCA mutations (13%) or PTEN mutation (10%)/loss (13%), were significantly restricted to, respectively, 41% and 37% of NRs. CONCLUSION: These findings suggested that KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab. In line with this, patients carrying KRAS mutations or with activated PI3K profiles can benefit from targeted treatments only by switching off molecules belonging to the downstream signalling of activated EGFR, such as mammalian target of rapamycin.

Organochlorine pesticide residues in sediment cores of sunderban wetland, northeastern part of Bay of Bengal, India, and their ecotoxicological significance.

This paper presents the first comprehensive report of the organochlorine pesticide residues (OCs) such as hexachlorocyclohexane isomers (HCHs), dichlorodiphenyltrichloroethane and its six metabolites (DDTs), and hexachlorobenzene (HCB) in core sediments (<63-microm particle size) from the Indian Sunderban wetland. The pooled mean values of the mass fraction of SigmaHCHs, HCB, and SigmaDDTs in the sediments were 0.05-12, 0.05-1.4, and 0.05-11.5 ng g(-1) dry weight, respectively. The vertical distribution of pesticides reveals an erratic pattern. The concentration of four isomers of HCHs reveals a heterogenic distribution where gamma-HCH (lindane) and beta-HCH shared the dominant part. The mass fraction of HCB did not show any sharp spatial variation. The prevailing sequence of DDT metabolites indicates an active degradation of the parent compound in the sediments and/or inputs of already degraded pp'DDT to the region. Peak concentrations of HCH isomers and DDT metabolites have the potential to induce ecotoxicological impact as per the sediment quality guidelines.