Sub-acute exposure of male guppies (Poecilia reticulata) to environmentally relevant concentrations of PFOA and GenX induces significant changes in the testis transcriptome and reproductive traits.

Poly- and perfluoroalkyl substances (PFAS) are frequently detected in the environment and are linked to adverse reproductive health outcomes in humans. Although legacy PFAS have been phased out due to their toxicity, alternative PFAS are increasingly used despite the fact that information on their toxic effects on reproductive traits is particularly scarce. Here, we exposed male guppies (Poecilia reticulata) for a short period (21 days) to an environmentally realistic concentration (1 ppb) of PFOA, a legacy PFAS, and its replacement compound, GenX, to assess their impact on reproductive traits and gene expression. Exposure to PFAS did not impair survival but instead caused sublethal effects. Overall, PFAS exposure caused changes in male sexual behaviour and had detrimental effects on sperm motility. Sublethal variations were also seen at the transcriptional level, with the modulation of genes involved in immune regulation, spermatogenesis, and oxidative stress. We also observed bioaccumulation of PFAS, which was higher for PFOA than for GenX. Our results offer a comprehensive comparison of these two PFAS and shed light on the toxicity of a newly emerging alternative to legacy PFAS. It is therefore evident that even at low concentrations and with short exposure, PFAS can have subtle yet significant effects on behaviour, fertility, and immunity. These findings underscore the potential ramifications of pollution under natural conditions and their impact on fish populations.

The effects of glyphosate and AMPA on the mediterranean mussel Mytilus galloprovincialis and its microbiota.

Glyphosate, the most widely used herbicide worldwide, targets the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme in the shikimate pathway found in plants and some microorganisms. While the potential for glyphosate to induce a broad range of biological effects in exposed organisms has been demonstrated, the global molecular mechanisms of toxicity and potential effects in bacterial symbionts remain unclear, in particular for ecologically important marine species such as bivalve molluscs. Here, the effects of glyphosate (GLY), its degradation product aminomethylphosphonic acid (AMPA), and a mixture of both (MIX) on the mussel M. galloprovincialis were assessed in a controlled experiment. For the first time, next generation sequencing (RNA-seq and 16S rRNA amplicon sequencing) was used to evaluate such effects at the molecular level in both the host and its respective microbiota. The results suggest that the variable capacity of bacterial species to proliferate in the presence of these compounds and the impairment of host physiological homeostasis due to AMPA and GLY toxicity may cause significant perturbations to the digestive gland microbiota, as well as elicit the spread of potential opportunistic pathogens such as Vibrio spp.. The consequent host-immune system activation identified at the molecular and cellular level could be aimed at controlling changes occurring in the composition of symbiotic microbial communities. Overall, our data raise further concerns about the potential adverse effects of glyphosate and AMPA in marine species, suggesting that both the effects of direct toxicity and the ensuing changes occurring in the host-microbial community must be taken into consideration to determine the overall ecotoxicological hazard of these compounds.

64-detector row CT cystography with virtual cystoscopy in the detection of bladder carcinoma: preliminary experience in selected patients.

PURPOSE: This study was conducted to evaluate the role of computed tomography cystography (CTC) and virtual cystoscopy (VC) with 64-slice CT in diagnosing bladder lesions using flexible cystoscopy as the reference standard. MATERIALS AND METHODS: Twenty-eight patients with suspected bladder cancer and ten patients who had undergone transurethral resection of the bladder were studied by CTC and VC in both the supine and prone positions after distending the bladder with air. The patient population was divided into three groups based on lesion size at flexible cystoscopy. Results of the CT study were compared with those of flexible cystoscopy. RESULTS: Flexible cystoscopy depicted 88 bladder lesions in the 38 patients examined. Sensitivity and specificity values of CTC and VC alone were constantly lower than those of the combined-approach (group 1: 93.10% and 92.31%; group 2: 100% and 100%; group 3: 100% and 100%, respectively). Receiver operating characteristic (ROC) curve analysis showed that the combined approach decreases the lower dimensional threshold for lesion detection (1.4 mm). CONCLUSIONS: VC and CTC with 64-slice CT are promising diagnostic techniques for bladder cancers measuring 1-5 mm. Further studies on larger patient populations are required to validate our results.

CT cystoscopy in the evaluation of bladder tumors.

The aim of the present study was to assess the role of virtual cystoscopy in the identification of bladder tumors. Fifteen patients (11 men and 4 women, median age: 61 years, range: 46-74 years) with a positive finding of bladder tumor at fiber-optic cystoscopy were studied by multislice-CT. Scans were downloaded to a workstation with the aid of a software for the processing of 3-D reconstructions, with a volume-rendering technique which allowed the "navigation" within the bladder in search of wall lesions. In this group of 15 patients, cystoscopy was able to detect 19 neoplastic lesions, 13 with a diameter >10 mm and 6 with a diameter <10 mm. Virtual cystoscopy, instead, identified 17 lesions (89%) only. In particular, all those lesions with a diameter >1 cm (13/13=100%) were correctly identified, whereas only 4 of the 6 lesions with a diameter <1 cm were depicted. The 2 false negative cases were 2 lesions with a flat morphology, measuring 5 and 6 mm. Most recent technological advances allowed the employement of virtual endoscopies, characterized by the absence of invasivity as compared with fiber-optic studies and based on data obtained by spiral- and multislice-CTs. According to our experience, virtual CT-cystoscopy revealed to be a complementary tool in the evaluation of cross-sectional images and proved to be an easy procedure without complications, well-accepted by the patients, and with a reliable detection of those bladder lesions measuring more than 5 mm in case of polypoid formations and at least 10 mm in case of flat lesions. This technique, however, does not allow the collection of a bioptic sample and--with the present resolution power of available equipments--it could be unable to correctly detect small-sized flat lesions. We, nonetheless, believe that this procedure, in the future, thanks to rapid technological improvements in virtual imaging techniques, could become a useful diagnostic tool in the management of those patients with bladder tumors. Further studies on larger study groups are therefore desirable for a more reliable validation of the technique.

[Optimization of the technique of virtual colonoscopy using a multislice spiral computerized tomography]. / Ottimizzazione della tecnica della colonscopia virtuale utilizzando un apparecchio di Tomografia Computerizzata spirale multistrato.

PURPOSE: To optimize scanning parameters for virtual colonoscopy utilizing a multislice Helical CT scanner in an in vitro study (using a homemade colonic phantom) and in a preliminary clinical study. MATERIAL AND METHODS: A colonic phantom was built using a plastic tube and 12 plastiline polyps were placed inside. The colonic phantom was studied with a multislice Helical CT scanner. Axial images were obtained with the phantom parallel to the long axis of the moving table (in order to simulate the evaluation of ascending and descending colon): oblique images were acquired with the phantom at 45 degrees relative to the long axis of the moving table (in order to simulate the evaluation of sigmoid colon and colonic flexures). Four different scanning protocols were tested: 1) slice collimation, 5 mm; slice width, 7 mm; table speed, 25 mm; reconstruction index, 5 mm; 2) slice collimation, 2.5 mm; slice width, 3 mm; table speed, 15 mm; reconstruction index, 3 mm; 3) slice collimation, 1 mm; slice width, 1.25 mm; table speed, 5 mm; reconstruction index, 1 mm; 4) slice collimation, 1 mm; slice width, 1.25 mm; table speed, 4 mm; reconstruction index, 1 mm. Quantitative analysis consisted in evaluation of the number of identified polyps and polyp size along the longitudinal axis. Qualitative analysis consisted in the evaluation of image artifacts and quality of 3D reconstructed images (step artifacts and polyp geometry distortion). This preliminary clinical study was performed in 12 patients (7 men and 5 women) who underwent multislice Helical CT colonography. We selected patients with clinical indications for conventional colonoscopy or after unsuccessful conventional colonoscopy. RESULTS: Multislice Helical CT colonography was 100% sensitive in the detection of all polyps and in all scanning protocols. With oblique scans, only a 3-mm polyp was missed during protocol 1 (sensitivity: 92%). Polyp geometry distortion was observed on longitudinal reconstructions, whereas no distortion was seen on axial images. Image quality was graded as optimal for protocols 2, 3, and 4; protocol 1 was graded as good on transverse scans and as poor on oblique scans. In our preliminary clinical study, two colonic carcinomas and three polyps were identified. CONCLUSIONS: At present, the introduction of multislice technology in virtual colonoscopy permits to improve spatial resolution and image definition. The actual clinical advantage, in terms of increased diagnostic accuracy, needs further investigation in larger clinical studies.

Effects of carvedilol on serum lipids in patients with essential hypertension.

The purpose of this study was to investigate the effect of carvedilol on serum lipids in patients with mild-to-moderate essential hypertension. Twenty-one patients with blood pressure greater than or equal to 160/95 mm Hg after a 4-week placebo run-in period were initially given 10 mg of carvedilol once daily. The dose was increased to 20 mg after 4 weeks if the target blood pressure was not achieved. The duration of treatment was 12 weeks. After 12 weeks of administration, blood pressure and the pulse rate (PR) declined significantly (blood pressure from 173/105 to 142/91 mm Hg, p less than 0.001; PR from 74 to 67 beats/min, p less than 0.001); however, serum lipids [total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein (HDL), HDL2, and HDL3], lipoprotein fraction (alpha, pre-beta, and beta), apoprotein fraction (A-I, A-II, CII, CIII, and E), and atherogenic index [(total cholesterol - HDL cholesterol) divided by HDL cholesterol] were not altered significantly. There were no side effects reported during the trial. From these results, it can be concluded that carvedilol has no adverse effect on the coronary risk profile as reflected by lipid measurements, and is an efficacious, safe, well-tolerated antihypertensive drug in patients with mild-to-moderate hypertension.