Light-induced charge generation in polymeric nanoparticles restores vision in advanced-stage retinitis pigmentosa rats.

Retinal dystrophies such as Retinitis pigmentosa are among the most prevalent causes of inherited legal blindness, for which treatments are in demand. Retinal prostheses have been developed to stimulate the inner retinal network that, initially spared by degeneration, deteriorates in the late stages of the disease. We recently reported that conjugated polymer nanoparticles persistently rescue visual activities after a single subretinal injection in the Royal College of Surgeons rat model of Retinitis pigmentosa. Here we demonstrate that conjugated polymer nanoparticles can reinstate physiological signals at the cortical level and visually driven activities when microinjected in 10-months-old Royal College of Surgeons rats bearing fully light-insensitive retinas. The extent of visual restoration positively correlates with the nanoparticle density and hybrid contacts with second-order retinal neurons. The results establish the functional role of organic photovoltaic nanoparticles in restoring visual activities in fully degenerate retinas with intense inner retina rewiring, a stage of the disease in which patients are subjected to prosthetic interventions.

Blame It on the Metabolite: 3,5-Dichloroaniline Rather than the Parent Compound Is Responsible for the Decreasing Diversity and Function of Soil Microorganisms.

Pesticides are key stressors of soil microorganisms with reciprocal effects on ecosystem functioning. These effects have been mainly attributed to the parent compounds, while the impact of their transformation products (TPs) has been largely overlooked. We assessed in a meadow soil (soil A) the transformation of iprodione and its toxicity in relation to (i) the abundance of functional microbial groups, (ii) the activity of key microbial enzymes, and (iii) the diversity of bacteria, fungi, and ammonia-oxidizing microorganisms (AOM) using amplicon sequencing. 3,5-Dichloroaniline (3,5-DCA), the main iprodione TP, was identified as a key explanatory factor for the persistent reduction in enzymatic activities and potential nitrification (PN) and for the observed structural changes in the bacterial and fungal communities. The abundances of certain bacterial (Actinobacteria, Hyphomicrobiaceae, Ilumatobacter, and Solirubrobacter) and fungal (Pichiaceae) groups were negatively correlated with 3,5-DCA. A subsequent study in a fallow agricultural soil (soil B) showed limited formation of 3,5-DCA, which concurred with the lack of effects on nitrification. Direct 3,5-DCA application in soil B induced a dose-dependent reduction of PN and NO3--N, which recovered with time. In vitro assays with terrestrial AOM verified the greater toxicity of 3,5-DCA over iprodione. "Candidatus Nitrosotalea sinensis" Nd2 was the most sensitive AOM to both compounds. Our findings build on previous evidence on the sensitivity of AOM to pesticides, reinforcing their potential utilization as indicators of the soil microbial toxicity of pesticides in pesticide environmental risk analysis and stressing the need to consider the contribution of TPs in the toxicity of pesticides on the soil microbial community.IMPORTANCE Pesticide toxicity on soil microorganisms is an emerging issue in pesticide risk assessment, dictated by the pivotal role of soil microorganisms in ecosystem services. However, the focus has traditionally been on parent compounds, while transformation products (TPs) are largely overlooked. We tested the hypothesis that TPs can be major contributors to the soil microbial toxicity of pesticides using iprodione and its main TP, 3,5-dichloroaniline, as model compounds. We demonstrated, by measuring functional and structural endpoints, that 3,5-dichloroaniline and not iprodione was associated with adverse effects on soil microorganisms, with nitrification being mostly affected. Pioneering in vitro assays with relevant ammonia-oxidizing bacteria and archaea verified the greater toxicity of 3,5-dichloroaniline. Our findings are expected to advance environmental risk assessment, highlighting the potential of ammonia-oxidizing microorganisms as indicators of the soil microbial toxicity of pesticides and stressing the need to consider the contribution of TPs to pesticide soil microbial toxicity.

Assessment of the impact of three pesticides on microbial dynamics and functions in a lab-to-field experimental approach.

The toxicity of pesticides on soil microorganisms is as an emerging area of concern. Novel and well-standardized tools could be now used to provide a robust assessment of the ecotoxicity of pesticides on soil microorganisms. We followed a tiered lab-to-field approach to assess the toxicity of three pesticides, widely used at EU level, (chlorpyrifos (CHL), isoproturon (IPU) and tebuconazole (TBZ)) on (i) the abundance of 11 microbial taxa and 8 functional microbial groups via q-PCR and (ii) the activity of enzymes involved in biogeochemical cycles via fluorometric analysis. Correlation of microbial measurements with the concentration of pesticides, and their transformation products (TPs) in soil enabled the identification of the compounds driving the effects observed. At lab tests (×1, ×2 and ×10 the recommended dose), CHL and TBZ significantly reduced the relative abundance of ammonia-oxidizing bacteria (AOB) and archaea (AOA) which recovered by the end of the study, while all pesticides induced a persistent reduction in the relative abundance of sulfur-oxidizing bacteria (SOB). The two demethylated metabolites of IPU (MD-IPU and DD-IPU) adversely affected P-cycling enzymes and leucine aminopeptidase (Leu). At field tests (×1, ×2 and ×5 the recommended dose), a persistent reduction on the relative abundance of AOA was induced by all pesticides, but only CHL and its hydrolysis product 3,5,6 trichloro-2-pyridynol (TCP) soil levels were negatively correlated with AOA relative abundance. Our findings suggest that ammonia-oxidizing microorganisms constitute the most responsive microbial group to pesticides and could be potential candidates for inclusion in pesticide risk assessment.

Macular translocation with 360 degrees retinotomy for management of retinal pigment epithelial tear: long-term results.

BACKGROUND: To determine long-term functional and morphological changes after full macular translocation (FMT) with 360° retinotomy in patients with retinal pigment epithelium (RPE) tears, in light of the increasing number of reports of this complication following vascular endothelial growth factor (VEGF)-modulating therapy. METHODS: We retrospectively reviewed a consecutive series of six patients with RPE tears secondary to neovascular age-related macular degeneration who underwent FMT with 360° retinotomy between March 2005 and June 2006. Preoperative and postoperative visual acuity, fundus fluorescein angiography (FA) and optical coherence tomography (OCT) were reviewed. RPE tears occurred spontaneously in three cases and after intravitreal triamcinolone in three cases. Preoperative and postoperative best-corrected visual acuity was converted to logarithm of the minimal angle of resolution visual acuity for analysis. RESULTS: Mean postoperative follow-up was 39 months (range 36-50 months). At 12, 24 and 36 months mean visual acuity increased by 6.00 (5.3), 5.57 (5.54) and 6.67 (4.76) lines, respectively. This improvement was maintained at final examination. FA and OCT revealed pigment epithelium atrophy extending to the new fovea in one case only, which also had longer symptom duration. CONCLUSIONS: Long-term follow-up of FMT showed significant improvement in the majority of patients. FMT may be an option for cases of RPE tears of recent onset. Further investigations are necessary to determine FMT's role in tears developing during the course of anti-VEGF therapy.

Implications of bevacizumab on vascular endothelial growth factor and endostatin in human choroidal neovascularisation.

AIM: To evaluate the implications of intravitreal bevacizumab on proangiogenic vascular endothelial growth factor (VEGF) with regard to the endogenous angiogenesis inhibitor endostatin in human choroidal neovascularisation (CNV) secondary to age-related macular degeneration. METHODS: Retrospective review of an interventional case series of 48 patients who underwent full macular translocation surgery with removal of CNV. Twenty-five patients were treated with intravitreal bevacizumab injection 1 to 154 days prior to surgery (bevacizumab CNV). Twenty-three CNV without any kind of previous treatment were used as controls (control CNV). CNV were stained for CD34, cytokeratin18, VEGF, endostatin and E-selectin. A "predominance score of VEGF over endostatin" (PS) was defined by the difference between VEGF and endostatin staining scores. RESULTS: Bevacizumab CNV revealed a weaker VEGF expression in endothelial cells (p = 0.0245) but significantly more intense endostatin in retina pigment epithelium (RPE) (p = 0.0001) and stroma (p<0.0001). Consequently, PS was significantly lower in RPE (p = 0.02), vessels (p = 0.03) and stroma (p = 0.0004) in bevacizumab CNV. The intensity of E-selectin expression in bevacizumab CNV was comparable with that in control CNV. CONCLUSIONS: A shift within the angiogenic balance in terms of decreased VEGF predominance over endostatin is detected in human CNV treated with bevacizumab.

Vitrectomy for epiretinal membranes: visual outcome and prognostic criteria.

The treatment of choice for epiretinal membranes (ERM) causing marked retinal distortion and substantial visual impairment remains vitreoretinal surgery. The purpose of this study was to evaluate the results of surgery performed in our department and to investigate the prognostic value of different factors such as preoperative best-corrected visual acuity (BCVA), pre-existing cystoid macular edema (CME), intra-operative peeling of the internal limiting membrane (ILM), age and duration of symptoms. Eighty-eight consecutive eyes of 88 patients were operated on for ERM from July 1998 to June 2000. Both idiopathic and secondary cases were included. In all cases the ERM was successfully removed from the fovea. Mean BCVA after surgery increased from Snellen 0.2 (hand motion (HM) - 0.6) to Snellen 0.5 (HM - 1.0) (p<0.0001). Our results confirm the efficacy of surgical removal of the ERM in improving the visual acuity. Although not statistically significant, mean postoperative BCVA was slightly better in the group without pre-existing CME (p>0.05) and in the group where peeling of the ILM was performed (p>0.05). The data suggest that early surgery is likely to decrease the risk of developing irreversible macular damage (p<0.05). Because accelerated nuclear sclerosis with visual impairment is a common phenomenon after vitrectomy, one might consider performing a phaco-emulsification at the same time, especially in the elderly.

Posterior uveitis: an under-recognized adverse effect of pamidronate: 2 case reports.

Ocular adverse effects of pamidronic acid are rare but well documented. Pamidronate, an inhibitor of bone resorption used primarily in the management of tumor-induced hypercalcemia and Paget's disease, is reported to cause conjunctivitis, anterior uveitis, and infrequently episcleritis and scleritis. It is hypothesized that an allergic or immunologic phenomenon caused by drug-indued immune complex formation is at fault. The reason why the uvea is a target organ is unclear. The acute inflammatory response seems unrelated to the dose of the drug, the way of administration, or the activity of Paget's disease or malignancy. We report two cases of pamidronate-induced posterior uveitis, following the WHO Causality Assessment Guide of Suspected Adverse Reactions. Uveitis and scleritis have been reported in association with a variety of topical, intraocular, periocular, and systemic medications. Seven criteria were proposed to establish causality of adverse events by drugs. Only systemically administered biphosphonates meet all seven criteria. Where pamidronate is currently considered as the drug of choice in diverse strategies, the adverse ocular effects should be well known to physicians in order to make rapid diagnosis and stop the drug causing adverse reaction.

Silicone oil tamponade in the vitreoretinal surgery.

This retrospective study aimed to evaluate the influence of a temporary silicone oil (SiO) tamponade on intraocular pressure (IOP). We reviewed 131 procedures with a temporary SiO tamponade for different indications. Visual outcome and anatomic results after the SiO removal were also analyzed. Relatively good visual and anatomic results can be achieved by a temporary SiO tamponade with an acceptable complication rate.

Silicone oil vs. gas for the treatment of full-thickness macular hole.

The purpose of this study is to evaluate the anatomic and visual outcomes, as well as the complications, of macular hole surgery with SF6-gas tamponade versus silicone-oil tamponade. Fifty-four (54) eyes with idiopathic macular hole underwent vitrectomy and peeling of the internal limiting membrane (ILM) around the hole. Nineteen (19) eyes were treated with SF6-gas tamponade (group 1) and the other thirty-five (35) eyes with silicone-oil tamponade (group 2). An excellent anatomic success rate was obtained in both groups (94.7% in group 1 and 97.1% in group 2). Nevertheless, the postoperative visual acuity (VA) in the group treated with silicone-oil tamponade was significantly better than in the group treated with gas tamponade (P = 0.0217). Forty-seven (47) of the eyes in group 1 and 74% in group 2 achieved a VA = 0.4 or better. The most frequent potentially vision threatening complication we observed was RPE alterations in 35% of the eyes in group 1 and in only one eye in group 2. None of the eyes developed a retinal detachment during the follow-up period. In conclusion, the treatment of idiopathic macular holes by vitrectomy and ILM peeling provides a very good anatomic success rate. An excellent recovery of visual acuity, up to 1.0, was more frequently observed in the group treated with silicone oil tamponade.

Adult respiratory distress syndrome. A histopathologic study.

The results of an anatomohistopathologic study carried out on subjects who died from various causes in resuscitation centers are reported with specific reference to the evolutive phases of the adult respiratory distress syncrome (ARDS). While a precise anatomohistopathologic diagnosis of non-clinically diagnosed ARDS in its initial phase is considered possible, the importance of recognizing this pathology in cadavers and living patients is emphasized because of the medico-legal implications involved.

[The pneumothorax as complication of continuous artificial ventilation (author's transl)]. / Der Pneumothorax als Komplikation langanhaltender Atmungs-Reanimation

The authors discuss briefly the main lesions produced during intensive therapy in 500 patients who died under treatment in the Intensive Care Unit of Padova during the period Dec. 13, 1971--Sept. 9, 1974. Specifically 36 cases of pneumothorax induced by automatic respiration are analyzed from a clinical and pathological viewpoint.