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Abstract 1. Seasonal variations in rodent infestations were studied at poultry farms in central Argentina as well as the environmental factors associated with rodent infestations at poultry farms. 2. During the summer and winter of 1998 rodent infestation was monitored at 10 poultry farms by means of tracking stations, and 21 environmental variables were selected that a priori could be related with the extent of rodent infestation. 3. There was a higher rodent infestation in winter than in summer. 4. Species detected by rodent sightings at the poultry farms included Akodon azarae , Calomys spp. (C. laucha and possibly C. musculinus) and Mus musculus. 5. In summer, rodent infestation was positively associated with the perimeter of the farm, whereas there was an inverse relationship with the maintenance conditions of the sheds. In winter, rodent infestation was positively associated with the percentage of the borders of the farm covered with vegetation, and with the amount of plant cover, especially the amount of plant cover which was above 20 cm in height. 6. There was no significant relationship between rodent infestation and the time lag since the last application of rodenticide (first-generation anticoagulant) at the farms. 7. These results suggest that strategies for controlling rodents based solely on chemical methods may not be good enough for efficient rodent control. Farms which are properly managed, with a better control of vegetation growth at both the perimeter and within the internal area, in addition to a higher maintenance of sheds have appreciably lower rodent infestations. [ABSTRACT FROM AUTHOR]

Stoma surgery is frequently used to treat conditions such as colorectal cancer and inflammatory diseases. While it can extend patients' lives, it often introduces challenges that negatively affect quality of life. Convex skin barriers are commonly recommended for managing flat or retracted stomas and addressing irregular peristomal surfaces, such as creases or folds. Despite the variety of convex products available, there is limited evidence guiding their proper selection and use. This study explores the application of Esteem Body ™ with Leak Defence ™ Soft Convexity by Convatec, focusing on achieving stoma protrusion and peristomal skin flattening to protect against leakage in patients with an ostomy. Eighteen Italian stomacare nurses participated in three expert panel meetings. These sessions reviewed the latest literature on the five main characteristics of convexity, assessed abdominal planes and stoma profiles, and discussed the device's safety, efficacy, usability, and potential impact on patient outcomes. The expert panel developed an algorithm to guide the selection of appropriate convexity based on stoma and abdominal profiles. The proper use of Esteem Body ™ with Leak Defence ™ Soft Convexity can significantly improve clinical outcomes by optimizing leakage prevention, enhancing stomacare nurses' decision-making, and improving patients' quality of life.

Corneal transplantation is the most frequent transplant worldwide. Tissue characteristics allow storage and transport, even between continents, increasing its accessibility around the world. Donor infection with Trypanosoma cruzi is not defined as a corneal discarding factor, although the transplant is not recommended preventively, as in any infectious diseases. Herein, by means of polymerase chain reaction (PCR) strategies, we analyzed parasite presence in ocular tissue from 10 deceased donors with Chagas diseases. Among them, positive findings were obtained in corneas, scleras, and eye muscle samples of three, two, and one donor, respectively. Moreover, among the six T. cruzi defined populations, TcV and TcVI parasites were found in some samples based on group-specific amplification strategies. Our findings point out the actual possibility of T. cruzi transmission due to corneal transplantation and makes donor's serological status knowledge mandatory regardless of graft provenance. Failing that, we suggest a posttransplant follow-up of recipients from seropositive donors.

The magnetic resonance imaging (MRI) performance of two liposome formulations incorporating amphiphilic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-like Gd III complexes has been investigated both in vitro and in vivo. The complexes differ in one donor group of the coordination cage (carboxylate versus carboxoamide), and in the length (C 12 versus C 18 ) and the point of attachment of the aliphatic chains to the chelators. The in vitro 1 H relaxometric characterisation of the systems, performed with a newly developed relaxation model that takes into account the contributions of the Gd III chelates pointing in- and outwards of the liposome, indicates that their efficacy is optimal in the range 0.5-1.5 T. The tetracarboxylic C 12 -containing liposomes (LIPO-GdDOTA(GAC 12 ) 2 ; GA=glutaric acid) are four-fold more efficient than the monoamide C 18 -based analogue (LIPO-GdDOTAMA(C 18 ) 2 ). Such a difference is also found in vivo at 1 T in a melanoma tumour model on mice. A few hours after intravenous injection, the T 1 contrast enhancement in the organs where the nanovesicles typically distribute (liver, spleen, kidneys and tumour) is much higher for LIPO-GdDOTA(GAC 12 ) 2 . Interestingly, after about 7 h post-injection the contrast enhancement observed for the more efficient liposomes decreases rapidly and becomes lower than for LIPO-GdDOTAMA(C 18 ) 2 . The relaxometric data and the quantification of the Gd III complexes in the organs, determined ex vivo by inductively coupled plasma mass spectrometry, indicate that: 1) the differences in the contrast enhancement can be attributed to the different rate of water exchange and rotational dynamics of the Gd complexes, and 2) the rapid contrast decrease is caused by a faster clearance of GdDOTA(GAC 12 ) 2 from the organs. This is also confirmed by using a newly synthesised amphiphilic cyanine-based fluorescent probe (Cy5-(C 16 ) 2 ). As one of the main limitations for the clinical translation of liposomes incorporating amphiphilic imaging agents is related to their very long persistence in the body, the results reported herein suggest that the clearance of the probes can be accelerated, without compromising their role, by a proper selection of the lipophilic portion of the incorporated compound as well as of the ligand site at which the aliphatic tails are linked. Then, GdDOTA(GAC 12 ) 2 complex may represent a good candidate for the development of improved MRI protocols based on paramagnetically labelled lipidic nanoparticles., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The design of long circulating liposomes co-loaded with the glucocorticoid prednisolone phosphate (PLP) and the amphiphilic paramagnetic contrast agent Gd-DOTAMA(C(18))(2) allowed the MRI-guided in vivo visualization of the delivery and biodistribution of PLP, as well as the monitoring of drug efficacy. The performance of this theranostic probe was investigated in a mouse model bearing a melanoma B16 syngeneic tumor. The release kinetics of the drug were evaluated in vitro where it displayed a peculiar behavior characterized by a fast process (completed in few hours) involving only a small portion (<5%) of the drug. Interestingly, the incorporation of the amphiphilic imaging reporter in the liposomal bilayer slightly increased the amount of the fast-release portion (<10%), thus suggesting that it could be attributed to a drug fraction embedded in the liposomal bilayer. In fact, the release of a hydrophilic imaging probe encapsulated in the inner core of the same long circulating liposomes formulated for carrying the drug, displayed different, single-step, kinetics. The in vivo monitoring of the antitumor activity of the nanomedicine revealed that the incorporation of the MRI probe into the liposome bilayer did not significantly affect the drug efficacy. The in vivo experiments also indicated a relevant and fast liposome uptake from macrophage-rich organs like spleen and liver, which reduced the tumor accumulation of the liposomes. The accumulation of the amphipatic MRI label caused the occurrence of a long-term residual T(1) contrast still detectable 1week after injection., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Two novel Gd-based contrast agents (CAs) for the molecular imaging of matrix metalloproteinases (MMPs) were synthetized and characterized in vitro and in vivo. These probes were based on the PLG*LWAR peptide sequence, known to be hydrolyzed between Gly and Leu by a broad panel of MMPs. A Gd-DOTA chelate was conjugated to the N-terminal position through an amide bond, either directly to proline (compd Gd-K11) or through a hydrophilic spacer (compd Gd-K11N). Both CA were made strongly amphiphilic by conjugating an alkyl chain at the C-terminus of the peptide sequence. Gd-K11 and Gd-K11N have a good affinity for β-cyclodextrins (K(D) 310 and 670 µ m respectively) and for serum albumin (K(D) 350 and 90 µ m respectively), and can be efficiently cleaved in vitro at the expected site by MMP-2 and MMP-12. Upon MMP-dependent cleavage, the CAs lose the C-terminal tetrapeptide and the alkyl chain, thus undergoing to an amphiphilic-to-hydrophilic transformation that is expected to alter tissue pharmacokinetics. To prove this, Gd-K11 was systemically administered to mice bearing a subcutaneous B16.F10 melanoma, either pre-treated or not with the broad spectrum MMP inhibitor GM6001 (Ilomastat). The washout of the Gd-contrast enhancement in MR images was significantly faster for untreated subjects (displaying MMP activity) with respect to treated ones (MMP activity inhibited). The washout kinetics of Gd-contrast enhancement from the tumor microenvironment could be then interpreted in terms of the local activity of MMPs., (Copyright © 2012 John Wiley & Sons, Ltd.)

Murine melanoma B16 cells display on the extracellular side of the plasma membrane a large number of reactive protein thiols (exofacial protein thiols, EPTs). These EPTs can be chemically labeled with Gd-DO3A-PDP, a Gd(III)-based MRI contrast agent bearing a 2-pyridinedithio chemical function for the recognition of EPTs. Uptake of gadolinium up to 10(9) Gd atoms per cell can be achieved. The treatment of B16 cells ex vivo with a reducing agent such as tris(2-carboxyethyl)phosphine (TCEP) results in an increase by 850% of available EPTs and an increase by 45% of Gd uptake. Blocking EPTs with N-ethylmaleimide (NEM) caused a decrease by 84% of available EPTs and a decrease by 55% of Gd uptake. The amount of Gd taken up by B16 cells is therefore dependent upon the availability of EPTs, whose actual level in turn changes according to the extracellular redox microenvironment. Then Gd-DO3A-PDP has been assessed for the labeling of tumor cells in vivo on B16.F10 melanoma tumor-bearing mice. Gd-DO3A-PDP (or Gd-DO3A as the control) has been injected directly into the tumor region at a dose level of 0.1 μmol and the signal enhancement in MR images followed over time. The washout kinetics of Gd-DO3A-PDP from tumor is very slow if compared to that of control Gd-DO3A, and 48 h post injection, the gadolinium-enhancement is still clearly visible. Therefore, B16 cells can be labeled ex vivo as well as in vivo according to a common EPTs-dependent route, provided that high levels of the thiol reactive probe can be delivered to the tumor.

This work aims at developing a MRI method that allows to get more insight into the understanding of the in vivo fate of liposomes and their payload. The method relies on the temporal assessment of the contrast changes induced by the presence of a classical relaxation agent versus the effect induced by a CEST (chemical exchange saturation transfer) agent. Liposomes were loaded with the paramagnetic complexes, Gd-HPDO3A and [Tm-DOTMA](-) [Na](+), in order to endow the nanovesicles with the characteristic properties of T(1)/T(2) and CEST/T(2) MRI agents, respectively. The paramagnetically loaded liposomes were injected directly into the tumor (B16 melanoma xenograft in mice) where they generate T(1), T(2), and CEST MR contrasts that were quantitatively monitored over time (0-48h). The kinetic of each contrast enhancement reports about peculiar properties relative to the fate of the liposomes in the tumor environment. A kinetic model has been set-up to fit the experimental multicontrast data in order to extract the relevant information about the cellular uptake of the liposomes and the release of their payload. Upon comparing conventional stealth liposomes with pH-sensitive ones, it has been shown that the latter ones differ essentially in the step associated with the release of the drug that is likely occurring in the endosomal acidic vesicles., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

The 1918 discovery of oil in the bed of the Red River, which forms the border between Texas and Oklahoma, led to a U.S. Supreme Court case that involved the extensive use of expert witnesses in fields such as geology, geography, and ecology. What began as a dispute between the two states soon became a multisided controversy involving those states, the federal government, Native Americans, and individual placer-mining claimants. After the federal attorneys introduced scientific experts into the dispute, including the plant ecologist Henry Chandler Cowles and the geographer Isaiah Bowman, fresh from negotiations at the Paris Peace Conference, Texas attorneys fielded their own team of opposing experts. Charged with the task of determining the location of the border, defined as the south bank of the river at the time of the 1819 treaty with Spain, the scientific experts presented the court with volumes of evidence and elaborate arguments, much of it contradictory and involving creative interpretations of existing theories. The case exhibited all the now-familiar features of a trial using expert witnesses, for which it represents an early, overlooked, and particularly complex example.