Pooled analysis of cardiac safety in patients with cancer treated with pertuzumab

Background: Pertuzumab, a human epidermal growth factor receptor (HER) 2 dimerization inhibitor, has demonstrated promising efficacy in combination with trastuzumab in patients with metastatic breast cancer. As HER signaling pathways are not only involved in oncogenesis, but also in myocardial homeostasis, an analysis of cardiac safety data was undertaken in a large group of patients treated with pertuzumab. Patients and methods: A complete database of patients treated with full-dose pertuzumab was used to describe the incidence of asymptomatic left ventricular systolic dysfunction (LVSD) and symptomatic heart failure (HF). Results: Information for 598 unique patients was available for the current analysis. Of the patients treated with pertuzumab alone (n = 331) or pertuzumab in combination with a non-anthracycline-containing cytotoxic (n = 175) or trastuzumab (n = 93), 23 (6.9%), 6 (3.4%), and 6 (6.5%), respectively, developed asymptomatic LVSD and 1 (0.3%), 2 (1.1%), and 1 (1.1%), respectively, displayed symptomatic HF. None of the 15 patients receiving both pertuzumab and erlotinib demonstrated LVSD. Conclusions: Patients treated with pertuzumab experienced relatively low levels of asymptomatic LVSD or symptomatic HF. There was no notable increase in cardiac side-effects when pertuzumab was given in combination with other anticancer agent

Submicronic Filtering Media Based on Electrospun Recycled PET Nanofibers: Development, Characterization, and Method to Manufacture Surgical Masks

The disposal of single-use personal protective equipment has brought a notable environmental impact in the context of the COVID-19 pandemic. During these last two years, part of the global research efforts has been focused on preventing contagion using nanotechnology. This work explores the production of filter materials with electrohydrodynamic techniques using recycled polyethylene terephthalate (PET). PET was chosen because it is one of the materials most commonly present in everyday waste (such as in food packaging, bags, or bottles), being the most frequently used thermoplastic polymer in the world. The influence of the electrospinning parameters on the filtering capacity of the resulting fabric was analyzed against both aerosolized submicron particles and microparticulated matter. Finally, we present a new scalable and straightforward method for manufacturing surgical masks by electrospinning and we validate their performance by simulating the standard conditions to which they are subjected to during use. The masks were successfully reprocessed to ensure that the proposed method is able to reduce the environmental impact of disposable face masks. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Genetic variability of functional longevity in five rabbit lines

The objectives of this study were to analyse the differences in the genetic determination of functional longevity in five Spanish lines of rabbits and to check how different systematic factors might affect this genetic determination. Four of the lines were maternal (lines A, V, H and LP), these lines were established selecting base generation animals according to different criteria, but in the subsequent generations all of them were selected for litter size at weaning. The other is the paternal line R, this line was constituted by selecting animals with an outstanding daily growth rate. The trait analysed, length of productive life, was the time in days between the date of the first positive pregnancy test and the date of culling or death of a doe. Four models extended from the Cox proportional hazard model were used to analyse data of each line separately and jointly. The complete model (Model 1) included the fixed effect of year-season (YS) combination, positive palpation order (OPP), that is, reproductive cycle, physiological status of the doe (PS) at service and number of kits born alive (NBA) in each kindling as time-dependent factors. The inbreeding coefficient was fitted as a continuous covariate and the animal’s additive genetic effect was also fitted to the model (Model 1). The other models were identical to Model 1 but excluding OPP (Model 2) or PS (Model 3) or NBA (Model 4), which were explored to assess the consequence on additive variance estimates of not correcting for these animal-dependent factors. Estimated effective heritabilities of longevity were 0.07 ± 0.03, 0.03 ± 0.02, 0.14 ± 0.09, 0.05 ± 0.04, 0.02 ± 0.01 and 0.04 ± 0.01 for lines A, V, H, LP, R and for the merged data set, respectively. Removing the PS from the model led to an increase in the estimated additive genetic variance in all lines (0.17 ± 0.05, 0.05 ± 0.03, 0.29 ± 0.19, 0.29 ± 0.20, 0.07 ± 0.04 and 0.05 ± 0.02 for lines A, V, H, LP, R and the merged data set, respectively). The highest hazard of death and/or culling was observed during the first two parities and decreased as the order of parity progressed. Does non-pregnant-non-lactating had the highest risk of death or culling. The does that had zero kits born alive incurred the highest risk, and this risk decreased as the NBA increased. In conclusion, the consideration of longevity as selection criterion for the studied rabbit lines is not recommended.info:eu-repo/semantics/acceptedVersio

Genetic selection of maternal lines and digestive efficiency in rabbits: long term selection for litter size at weaning versus hyper selection for reproductive longevity

The objective of the present paper is to evaluate how long-term selection for litter size at weaning or short-term hyper selection for reproductive longevity, affect the digestive utilisation of growing and lactating rabbits. A digestibility trial was carried out during the 3rd week of lactation with a total of 27 multiparous does: 14 females came from a line selected for litter size at weaning over 32 generations (V), and 13 from a recently constituted, long lived-productive line (LP). Another digestibility trial was performed during the growing period with a total of 48 growing rabbits (24 from each line). After a 7 d adaptation period, faeces were collected individually for 4 d (from 13 to 16 d of lactation or from 49 to 53 d of age, respectively). Daily feed intake and weight gain recorded during the experimental growing period were similar for both lines (137 g of dry matter (DM)/d and 48 g/d, respectively). Growing rabbits from the V-line showed greater values for the digestibility of the DM and OM (+1 percentage point; P<0.10) and signifi cantly higher values for the acid detergent fi bre (+3 percentage points; P=0.03) than animals from the LP line. No signifi cant differences for the apparent digestibility coeffi cients of crude protein, neutral detergent fi bre, crude fi bre and gross energy were observed between lines, these being on average 65.7, 23.0, 10.7 and 52.6%, respectively. Females from the LP line were initially heavier (+258 g of live weight; P=0.06), and presented a signifi cantly greater daily feed intake (+22 g DM/d; P=0.04) and milk yield (+37 g/d; P=0.01) during the pre-experimental and faeces collection phases (from 6 to 16 d of lactation). V-line lactating does displayed greater values for digestibility for all those nutrients evaluated (from +0.9 and +3.7 percentage points for the crude protein and acid detergent fi bre) compared to the LP line females, although these were only signifi cant for the DM, organic matter and gross energy (+2.3, +2.5, +2.1 percentage points; P<0.05). In conclusion, rabbits selected for litter size at weaning seem to have greater effi ciency for digestive utilisation than those hyper selected for reproductive longevity.This study has been supported by the Spanish CICYT project AGL 2004-02710/GAN.Pascual Amorós, JJ.; Ródenas, L.; Martínez, E.; Cervera, C.; Blas, E.; Baselga, M. (2008). Genetic selection of maternal lines and digestive efficiency in rabbits: long term selection for litter size at weaning versus hyper selection for reproductive longevity. World Rabbit Science. 16(3). doi:10.4995/wrs.2008.62516

Late reproductive senescence in a rabbit line hyper selected for reproductive longevity, and its association with body reserves

The aim of the present study was to investigate differences in reproductive and body traits during successive parities between two genetic lines. The LP line was constituted by means of selection of animals having an extremely high number of parities (at least 25) and an average reproductive performance compared to the V line selected for litter size at weaning during 31 generations. The two lines were found to have an equal reproductive performance in the first three parities, but the LP line had higher reproductive performance from the fourth parturition onwards. The low reproductive performance after the third parity in the V line was suggested to be caused by constrained environmental conditions in the test station. A line by parity interaction was also observed for body weight, since body weight declined going from the third to the fourth parity in the LP line but not the V line. Thus, it was concluded that hyper selection for reproductive longevity and average prolificacy successfully delayed reproductive senescence, and that this newly founded line showed less environmental sensitivity, which might have been mediated by a higher body reserve

Recent Technological Developments on LGAD and iLGAD Detectors for Tracking and Timing Applications

This paper reports the last technological development on the Low Gain Avalanche Detector (LGAD) and introduces a new architecture of these detectors called inverse-LGAD (iLGAD). Both approaches are based on the standard Avalanche Photo Diodes (APD) concept, commonly used in optical and X-ray detection applications, including an internal multiplication of the charge generated by radiation. The multiplication is inherent to the basic n++-p+-p structure, where the doping profile of the p+ layer is optimized to achieve high field and high impact ionization at the junction. The LGAD structures are optimized for applications such as tracking or timing detectors for high energy physics experiments or medical applications where time resolution lower than 30 ps is required. Detailed TCAD device simulations together with the electrical and charge collection measurements are presented through this work.Comment: Keywords: silicon detectors, avalanche multiplication, timing detectors, tracking detectors. 8 pages. 8 Figure

The relevance of caseous lymphadenitis as a cause of culling in adult sheep

Four hundred and ninety-eight culled sheep received at the Ruminant Clinical Service of the Veterinary Faculty of Zaragoza, Spain, were examined in life and after humanitarian sacrifice in order to reach the final diagnosis of the cause of culling and to evaluate the presence of caseous lymphadenitis (CLA) lesions. One hundred and forty-seven of the 498 studied animals (29.52%) showed CLA compatible lesions that were subsequently confirmed by Corynebacterium pseudotuberculosis isolation. One hundred and seven of the 147 CLA affected animals presenting the visceral clinical form of the disease (72.79%), while only 32 animals were affected by the superficial form (21.77%). In addition, eight animals were found to be affected in both the visceral and the superficial presentations (5.44%). Eighty-four of the 147 CLA-affected animals (57.14%) did not show any concurrent disease, considering, in this case, CLA the main cause of culling (84/498: 16.87%). In the superficial presentation, the retropharyngeal lymph node, as a sole lesion, was the most frequently affected (13/32: 40.63%). Further, in the visceral form of the disease, 85.06% of the affected animals had the lesions located in the respiratory system (91/107: 85.06%). CLA was revealed as an important cause of culling in sheep production

Genomic characterization of a novel group A lamb rotavirus isolated in Zaragoza, Spain

An ovine rotavirus (OVR) strain, 762, was isolated from a 30-day-old lamb affected with severe gastroenteritis, in Zaragoza, Spain, and the VP4, VP7, VP6, NSP4, and NSP5/NSP6 genes were subsequently characterized molecularly. Strain OVR762 was classified as a P[14] rotavirus, as the VP4 and VP8* trypsin-cleavage product of the VP4 protein revealed the highest amino acid (aa) identity (94% and 97%, respectively) with that of the P11[14] human rotavirus (HRV) strain PA169, isolated in Italy. Analysis of the VP7 gene product revealed that OVR762 possessed G8 serotype specificity, a type common in ruminants, with the highest degree of aa identity(95–98%) shared with serotype G8 HRV, bovine rotavirus, and guanaco (Lama guanicoe) rotavirus strains. Moreover, strain OVR762 displayed a bovine-like NSP4 (genotype E2) and NSP5/NSP6 (genotype H3), and a VP6 genotype I2, as well as a long electropherotype pattern. This is the first report of a lamb rotavirus with P[14] and G8 specificities, providing additional evidence for the wide genetic and antigenic diversity of group A rotaviruses

Combinatorial experimental protocols for Erbicin-derived immunoagents and Herceptin

Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erbicin is linked to a human RNase and in Erb-hcAb it is linked to the key structural and functional regions of a human IgG. Herceptin is an anti-ErbB2 humanised antibody successfully used in the immunotherapy of breast cancer. We report here that the Erbicin-derived immunoagents target on breast cancer cells an ErbB2 epitope different than that of Herceptin. This finding led us to verify the effects of Herceptin on breast cancer cells when it was used in combination with the Erbicin-derived immunoagents. The results indicated that in combination experiments the antitumour action of Herceptin and that of the novel agents were significantly increased in an additive fashion. An inspection of the mechanism of action of Erb-hRNase or Erb-hcAb combined with Herceptin provided evidence that the antibody combinations engendered an increased downregulation of the ErbB2 receptor, and led to an enhanced apoptotic cell death