"In other wor(l)ds": la distopia in The Handmaid's Tale e Oryx and Crake di Margaret Atwood.

La seguente tesi intende porre l'attenzione sulla narrativa distopica di Margaret Atwood costituita dai romanzi The Handmaid's Tale e Oryx and Crake

Effects of photoreceptor degeneration on the architecture of retinal ganglion cells: implications for Retinitis Pigmentosa therapy

Retinitis Pigmentosa (RP), a family of inherited diseases leading to progressive photoreceptor death, is one of the major causes of blindness in the world, with no cure yet. Albeit the primary cause of the disease is, typically, a defect in a photoreceptor-specific gene, it has been shown that the degeneration of rods and cones triggers remodeling and secondary death of inner retinal neurons, and particularly of bipolar and horizontal cells. Aim of this project is to test the hypothesis that, as an effect of photoreceptor progressive loss, concomitant changes also occur in retinal ganglion cells (RGCs), the last neurons of the retinal visual pathway and the only exit of retinal information to higher brain centers. We assessed the retention of morphology, overall architecture and survival rate of RGCs in a mouse model of RP, at various stages of the disease progression. Specifically, we generated a transgenic mouse, the rd10/Thy1-GFP mutant, by crossing GFP-M mice, in which GFP is expressed in a small population of RGCs of various types, and rd10 mice, a recent model of autosomal recessive RP. Rd10 mice carry a missense mutation of the beta-subunit of the rod-specific phosphodiesterase gene, causing a typical rod-cone degeneration with a peak at postnatal day 24 (P24). The expression of GFP in a small number of RGCs in the retina of the mutant allowed the detailed study of the fine structure of these neurons at various ages. By combining immunocytochemistry, confocal microscopy and analytic morphometry, we studied RGCs in a total of 50 whole mounted retinas of 3 age groups (3, 7 and 9 months of age, thus past the complete degeneration of photoreceptors). A number of 572 RGCs were identified and grouped according to the classification of Sun et al. (2002a). In particular, 4 parameters were taken into account to identify RGCs: the diameter of the dendritic tree, the diameter of the body, the mean stratification depth within the inner plexiform layer and the typical shape of the dendritic arborization. Five RGCs of the same type, at each time point, were drawn three dimensionally with a computer assisted image analyzer. The neuronal tracings were mathematically evaluated to obtain some parameters highly indicative of dendritic tree complexity and fine architecture: the total dendritic length, the total number of nodes and the dendritic tree area. Eight different types of RGCs were analyzed and drawn (for a total of 164 cells), including type A (the largest), B (the smallest) and C (medium sized), both ON and OFF. We found a remarkable preservation of the structural complexity of all the types of RGCs studied, up to 9 months of age, even in the occurrence of major remodeling among second order neurons. In addition, at 9 months of age, the survival of cells in the GCL appeared comparable to the wt counterpart. Finally, still at 9 months, injections of cholera toxin in the eyes demonstrated the presence of anterograde axonal transport of RGCs to the lateral geniculate nucleus and to the superior colliculus. Yet, at the same age, we detected a decrease of 30% in the density of retinal blood vessels providing nourishment to ganglion cells. The remarkable, long term preservation of RGC fine structure, survival and capability of anterograde axonal transport in the retina of rd10 mutant mice, despite blood vessel impoverishment and second order neurons remodeling and degeneration, opens perspectives to therapy for RP based on ganglion cells preservation. In particular, the strategy of implanting epiretinal prostheses, directly stimulating ganglion cells, to restore vision in RP patients could be applied successfully in those cases in which ganglion cells are still viable, such in the case of the rd10 mutation

Survival analysis using the Covid-death mean-imputation (CoDMI) algorithm: a first clinical application in radiation oncology

Background/Aim: To report long-term survival results after trimodal approach for locally advanced rectal cancer (LARC) in the Covid-19 era. We herein illustrate a clinical application of Covid-death mean-imputation (CoDMI) algorithm in LARC patients with Covid-19 infection. Patients and Methods: We analyzed 94 patients treated for primary LARC. Overall survival was calculated in months from diagnosis to first event (last follow-up/death). Because Covid-19 death events potentially bias survival estimation, to eliminate skewed data due to Covid-19 death events, the observed lifetime of Covid-19 cases was replaced by its corresponding expected lifetime in absence of the Covid-19 event using the CoDMI algorithm. Patients who died of Covid-19 (DoC) are mean-imputed by the Kaplan-Meier estimator. Under this approach, the observed lifetime of each DoC patient is considered as an "incomplete data" and is extended by an additional expected lifetime computed using the classical Kaplan-Meier model. Results: Sixteen patients were dead of disease (DoD), 1 patient was DoC and 77 cases were censored (Cen). The DoC patient died of Covid-19 52 months after diagnosis. The CoDMI algorithm computed the expected future lifetime provided by the Kaplan-Meier estimator applied to the no-DoC observations as well as to the DoC data itself. Given the DoC event at 52 months, the CoDMI algorithm estimated that this patient would have died after 79.5 months of follow-up. Conclusion: The CoDMI algorithm leads to "unbiased" probability of overall survival in LARC patients with Covid-19 infection, compared to that provided by a naive application of Kaplan-Meier approach. This allows for a proper interpretation/use of Covid-19 events in survival analysis. A user-friendly version of CoDMI is freely available at https://github.com/alef-innovation/codmi

Fiber Metabolism, Procollagen and Collagen Type III Immunoreactivity in Broiler Pectoralis Major Affected by Muscle Abnormalities

The present study aimed to evaluate the muscle fiber metabolism and assess the presence and distribution of both procollagen and collagen type III in pectoralis major muscles affected by white striping (WS), wooden breast (WB), and spaghetti meat (SM), as well as in those with macroscopically normal appearance (NORM). For this purpose, 20 pectoralis major muscles (five per group) were selected from the same flock of fast-growing broilers (Ross 308, males, 45-days-old, 3.0 kg live weight) and were used for histochemical (nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) and alpha-glycerophosphate dehydrogenase (\u3b1-GPD)) and immunohistochemical (procollagen and collagen type III) analyses. When compared to NORM, we found an increased proportion (p < 0.001) of fibers positively stained to NADH-TR in myopathic muscles along with a relevant decrease (p < 0.001) in the percentage of those exhibiting a positive reaction to \u3b1-GPD. In addition, an increased proportion of fibers exhibiting a positive reaction to both stainings was observed in SM, in comparison with NORM (14.3 vs. 7.2%; p < 0.001). After reacting to NADH-TR, SM exhibited the lowest (p < 0.001) cross-sectional area (CSA) of the fibers ( 1212% with respect to NORM). On the other hand, after reacting to \u3b1-GPD, the CSA of WS was found to be significantly larger (+10%) in comparison with NORM (7480 vs. 6776 \ub5m2; p < 0.05). A profound modification of the connective tissue architecture involving a different presence and distribution of procollagen and collagen type III was observed. Intriguingly, an altered metabolism and differences in the presence and distribution of procollagen and collagen type III were even observed in pectoralis major muscle classified as NORM

Reduced representation libraries from DNA pools analysed with next generation semiconductor based-sequencing to identify SNPs in extreme and divergent pigs for back fat thickness

The aim of this study was to identify single nucleotide polymorphisms (SNPs) that could be associated with back fat thickness (BFT) in pigs. To achieve this goal, we evaluated the potential and limits of an experimental design that combined several methodologies. DNA samples from two groups of Italian Large White pigs with divergent estimating breeding value (EBV) for BFT were separately pooled and sequenced, after preparation of reduced representation libraries (RRLs), on the Ion Torrent technology. Taking advantage from SNAPE for SNPs calling in sequenced DNA pools, 39,165 SNPs were identified; 1/4 of them were novel variants not reported in dbSNP. Combining sequencing data with Illumina PorcineSNP60 BeadChip genotyping results on the same animals, 661 genomic positions overlapped with a good approximation of minor allele frequency estimation. A total of 54 SNPs showing enriched alleles in one or in the other RRLs might be potential markers associated with BFT. Some of these SNPs were close to genes involved in obesity related phenotypes

Superficial and deep changes of histology, texture and particle size distribution in broiler wooden breast muscle during refrigerated storage

Abstract Recently the poultry industry faced an emerging muscle abnormality termed wooden breast (WB), the prevalence of which has dramatically increased in the past few years. Considering the incomplete knowledge concerning this condition and the lack of information on possible variations due to the intra-fillet sampling locations (superficial vs. deep position) and aging of the samples, this study aimed at investigating the effect of 7-d storage of broiler breast muscles on histology, texture, and particle size distribution, evaluating whether the sampling position exerts a relevant role in determining the main features of WB. With regard to the histological observations, severe myodegeneration accompanied by accumulation of connective tissue was observed within the WB cases, irrespective of the intra-fillet sampling position. No changes in the histological traits took place during the aging in either the normal or the WB samples. As to textural traits, although a progressive tenderization process took place during storage (P ≤ 0.001), the differences among the groups were mainly detected when raw meat rather than cooked was analyzed, with the WB samples exhibiting the highest (P ≤ 0.001) 80% compression values. In spite of the increased amount of connective tissue components in the WB cases, their thermally labile cross-links will account for the similar compression and shear-force values as normal breast cases when measured on cooked samples. Similarly, the enlargement of extracellular matrix and fibrosis might contribute in explaining the different fragmentation patterns observed between the superficial and the deep layer in the WB samples, with the superficial part exhibiting a higher amount of larger particles and an increase in particles with larger size during storage, compared to normal breasts

The impact of morning stiffness duration on the definition of clinical inactive disease in juvenile idiopathic arthritis

Objective To investigate the impact of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinical inactive disease (CID). Methods 652 visits in which patients fulfilled 2004 or 2011 Wallace criteria for CID were examined. Parent-reported outcomes were compared among patients with no MS or with MS < or 65 15 minutes. Results Among 652 visits with CID by 2004 criteria, no MS was reported in 554 visits (85%), MS < 15 minutes in 53 (8%), and MS 65 15 minutes in 45 (7%). The frequency of altered physical function, health-related quality of life, and well-being, pain and disease activity visual analog scales was proportionally greater from patients without MS to those with longer MS. The frequency of parent subjective rating of disease state as remission was 87.7%, 58% and 27.7% among patients with no MS, MS < 15 minutes and MS 65 15 minutes, respectively. Conclusion Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered

Localization of Melatonin Receptor 1 in Mouse Retina and Its Role in the Circadian Regulation of the Electroretinogram and Dopamine Levels

Melatonin modulates many important functions within the eye by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylate cyclase. In the mouse, Melatonin Receptors type 1 (MT1) mRNAs have been localized to photoreceptors, inner retinal neurons, and ganglion cells, thus suggesting that MT1 receptors may play an important role in retinal physiology. Indeed, we have recently reported that absence of the MT1 receptors has a dramatic effect on the regulation of the daily rhythm in visual processing, and on retinal cell viability during aging. We have also shown that removal of MT1 receptors leads to a small (3–4 mmHg) increase in the level of the intraocular pressure during the night and to a significant loss (25–30%) in the number of cells within the retinal ganglion cell layer during aging. In the present study we investigated the cellular distribution in the C3H/f+/+ mouse retina of MT1 receptors using a newly developed MT1 receptor antibody, and then we determined the role that MT1 signaling plays in the circadian regulation of the mouse electroretinogram, and in the retinal dopaminergic system. Our data indicate that MT1 receptor immunoreactivity is present in many retinal cell types, and in particular, on rod and cone photoreceptors and on intrinsically photosensitive ganglion cells (ipRGCs). MT1 signaling is necessary for the circadian rhythm in the photopic ERG, but not for the circadian rhythm in the retinal dopaminergic system. Finally our data suggest that the circadian regulation of dopamine turnover does not drive the photopic ERG rhythm