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Hypospadias is the most common congenital malformation, affecting 1 in 200–300 newborn males. No single procedure is standard for all types of hypospadias. Our objective is to assess our skill and report our experience in terms of feasibility and result of Snodgrass repair for various types of hypospadias. We analyzed 97 cases of hypospadias with or without chordee with adequate urethral plate who underwent Snodgrass repair from 2009 to 2014 by single surgeon. Age ranges at the time of surgery from 18 months to 28 years. Common site was distal penile in 42 cases (40.74%) followed by mid-penile in 32 cases (31.04%). Twenty-five patients had clinically notable chordee. Technique involved incision of urethral plate up to mid-glans and continuous uninterrupted subcuticular suture technique with PDS for urethroplasty with use of various second layers as per need and availability. Overall complication rate was 7.76%. Overall success rate was 92.24%. Complications include meatal stenosis, superficial skin blackening, complete dehiscence, and hematoma one each, and four cases had urethrocutaneous fistula. Patients were cosmetically and functionally normal with maximum follow-up of 5 years. TIP is a novel and an attractive single-stage technique due to its adaptability, relative ease, and low complication rate for anterior hypospadias. Its use can be extended in mid- and proximal hypospadias where degloving only is sufficient for orthoplasty.

Adaptive behavior requires integrating prior with current information to anticipate upcoming events. Brain structures related to this computation should bring relevant signals from the recent past into the present. Here we report that rats can integrate the most recent prior information with sensory information, thereby improving behavior on a perceptual decision-making task with outcome-dependent past trial history. We find that anticipatory signals in the orbitofrontal cortex about upcoming choice increase over time and are even present before stimulus onset. These neuronal signals also represent the stimulus and relevant second-order combinations of past state variables. The encoding of choice, stimulus and second-order past state variables resides, up to movement onset, in overlapping populations. The neuronal representation of choice before stimulus onset and its build-up once the stimulus is presented suggest that orbitofrontal cortex plays a role in transforming immediate prior and stimulus information into choices using a compact state-space representation. The orbitofrontal cortex encodes outcomes, expected rewards and values, but it is unclear how this region uses this information to inform action selection. Here, the authors show that lateral orbitofrontal cortex anticipates upcoming choices and combines recent prior information with current sensory information.

Iberian pigs and its crosses are produced to obtain high-quality meat products. The objective of this work was to evaluate a wide panel of DNA markers, selected by biological and functional criteria, for association with traits related to muscle growth, fatness, meat quality and metabolism. We used 18 crossbred Iberian pigs with divergent postnatal growth patterns for whole genome sequencing and SNP discovery, with over 13 million variants being detected. We selected 1023 missense SNPs located on annotated genes and showing different allele frequencies between pigs with makerdly different growth patterns. We complemented this panel with 192 candidate SNPs obtained from literature mining and from muscle RNAseq data. The selected markers were genotyped in 480 Iberian × Duroc pigs from a commercial population, in which phenotypes were obtained, and an association study was performed for the 1005 successfully genotyped SNPs showing segregation. The results confirmed the effects of several known SNPs in candidate genes (such as LEPR , ACACA, FTO, LIPE or SCD on fatness, growth and fatty acid composition) and also disclosed interesting effects of new SNPs in less known genes such as LRIG3 , DENND1B , SOWAHB, EPHX1 or NFE2L2 affecting body weight, average daily gain and adiposity at different ages, or KRT10 , NLE1 , KCNH2 or AHNAK affecting fatness and FA composition. The results provide a valuable basis for future implementation of marker-assisted selection strategies in swine and contribute to a better understanding of the genetic architecture of relevant traits.

Antioxidant supplementation in critical periods may be useful for improvement of piglet early viability and development. We have evaluated the effects of maternal perinatal diet inclusion of a high vitamin E level (VE, 100 mg all-rac-α-tocopheryl acetate /kg), hydroxytyrosol (HT, 1.5 mg/kg), or their combination (VEHT), in comparison to a control diet (C, 30 mg all-rac-α-tocopheryl acetate /kg), on the offspring homeostasis and metabolism, analysing the weaned piglets’ adipose tissue transcriptome and adipocyte morphology. Diets were provided to pregnant Iberian sows (n = 48, 12 per treatment) from gestation day 85 to weaning (28 days postpartum) and 48 piglets (n = 12 per treatment) were sampled 5 days postweaning for dorsal subcutaneous adipose tissue analyses. RNA obtained from 6 animals for each diet was used for paired-end RNA sequencing. Results show that supplementation of sows’ diet with either vitamin E or hydroxytyrosol had substantial effects on weaned piglet adipose transcriptome, with 664 and 587 genes being differentially expressed, in comparison to C, respectively (q-value<0.10, Fold Change>1.5). Genes upregulated in C were mainly involved in inflammatory and immune response, as well as oxidative stress, and relevant canonical pathways and upstream regulators involved in these processes were predicted as activated, such as TNF, IFNB or NFKB. Vitamin E, when supplemented alone at high dose, activated lipid biosynthesis functions, pathways and regulators, this finding being accompanied by increased adipocyte size. Results suggest an improved metabolic and antioxidant status of adipose tissue in animals born from sows supplemented with individual antioxidants, while the combined supplementation barely affected gene expression, with VEHT showing a prooxidant/proinflamatory functional profile similar to C animals. Different hypothesis are proposed to explain this unexpected result. Findings allow a deeper understanding of the processes taking place in adipose tissue of genetically fat animals and the role of antioxidants in the regulation of fat cells function.

As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from ‘transplantable’ DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.

Zimislecel is an allogeneic stem cell–derived islet-cell therapy. This phase 1–2 study supports the hypothesis that zimislecel can restore physiologic islet function and thus treat persons with type 1 diabetes.

The design and synthesis of a small library of 2-styrylquinoline derivatives containing a push-pull system, aimed at displacing their fluorescence emission towards the NIR region, is described. We describe here their synthesis, fluorescent characterization and pharmacological evaluation against different amyloid proteins. Their study showed that these compounds are capable to change their spectroscopic properties upon protein interaction, resulting in changes in the absorption and emission wavelengths, together with increased fluorescence intensity. They also showed sensitivity to pH and environment polarity, exhibiting red shifts in lower polarity environments with regard to aqueous media. Inner charge transfer is observed and employed for detecting the interaction of these compounds with protein aggregates. The study of the alterations in the fluorescence intensity allows to calculate the dissociation constant values for the protein-sensor interaction. These spectroscopic results were the basis for the use of these compounds to visualize β-amyloid plates with selectivity over phosphorylated tau in samples of cerebral tissue from deceased Alzheimer patients under fluorescence microscopy, using immunofluorescence techniques. Pharmacological assays showed that the compounds inhibit the aggregation of the Aβ1–42 and AcPHF6 peptides, representing tau protein. They also showed neuroprotective activity following okadaic acid insult.

IntroductionThe ASD Therapeutic Day Unit is a tertiary care unit that consists of 20 beds, designed to facilitate the evaluation and treatment of children and adolescents with ASD who present high psychiatric comorbidity with behavioral problems, communication/language problems, sensory, and/or in the management of their repetitive and restricted interests. In addition to diagnosis and genetic counseling and clinical care, we offer the possibility of performing an individualized pharmacogenetic study in order to offer appropriate pharmacological treatment to patients with ASD and comorbidities.ObjectivesThe objective is to promote pharmacological tolerability, avoid unwanted side effects, as well as avoid the use of polypharmacy, in children with a tendency to poor drug metabolism.MethodsA review of the medical history of the patients included in the Blood Extraction Program of the ASD Day Therapeutic Unit is carried out during the year 2022. The existing medications at admission, the results of the pharmacogenetic analyzes carried out, and the pertinent changes in the pharmacological treatment of these children.Results37 children were included in the program during 2022. The genes CYP1A2, CYP2C19, CYP2D6, CYP3A4 and 5-HTT were analyzed. The variant studied is described, as well as the observed genotype and the expected phenotype.Of the 37 patients, 11 maintained the same pharmacological treatment as at the beginning of admission, 5 were not taking pharmacological treatment and 25 underwent a treatment modification.The most frequently modified treatment was risperidone with aripiprazole (n=10), secondly risperidone with guanfacine (n=5), and thirdly fluoxetine with aripiprazole (n=2).Furthermore, the degree of pharmacological polytreatment was reduced. 18 patients switched to a single drug, instead of 14. 11 patients 2 drugs (instead of 14), 3 patients 3 drugs instead of 4 and 5 patients remained without drug treatment.ConclusionsPatients with ASD have worse tolerability to pharmacological treatments than other patients with severe mental disorders.The use of pharmacogenetics allows improving the cost/effectiveness of medical prescription, avoiding undesirable side effects or lack of effectiveness in the treatment of patients with ASD.Promoting the implementation of pharmacogenetics in patients with ASD (among others) would improve the clinical situation of these patients more effectively and would improve the economic expenditure derived from erroneous prescription and/or excessive polypharmacy.Disclosure of InterestNone Declared

This paper presents and evaluates a set of methods to classify individual Scopus publications using their references back to the second generation, where each publication can be assigned fractionally into up to five ASJC (All Science Journal Classifications) categories, excluding the Multidisciplinary area and the miscellaneous categories. Based on proposals by Glänzel et al. (Glänzel et al., Scientometrics 44:427–439, 1999a, Glänzel et al., Scientometrics 46:431–441, 1999b, Glänzel, W., Thijs, B., & Huang, Y. (2021). Improving the precision of subject assignment for disparity measurement in studies of interdisciplinary research. In: W. Glänzel, S. Heeffer, PS. Chi, R. Rousseau (eds), Proceedings of the 18th International Conference of the International Society of Scientometrics and Informetrics (ISSI 2021), Leuven University Press, pp. 453–464. https://kuleuven.limo.libis.be/discovery/fulldisplay?docid=lirias3394551&context=SearchWebhook&vid=32KUL_KUL:Lirias&search_scope=lirias_profile&tab=LIRIAS&adaptor=SearchWebhook&lang=en ), some additional parameters are established that allow different results to be obtained depending on how category membership is weighted or how the acceptance thresholds for multiple assignments are established. Various classifications are obtained, and then compared with each other, with the original ASJC Scopus journal classification, and with the AAC (Author’s Assignation Collection) classification of a previous study (Álvarez-Llorente et al., Álvarez-Llorente et al., Profesional de la Información, 2023) in which the papers’ corresponding authors assign them the most appropriate categories. Classifications in which a high threshold is set for allowing assignments to multiple categories, combined with the use of first- and second-generation references and averaging over the number of references, provide the most promising results, improving over other reference-based reclassification proposals in terms of granularity, and over the Scopus classification itself in such aspects as the homogeneity of the publications assigned to a category. They also show greater coincidence with the AAC classification.

The objective of this experiment was to test the effect of total or partial substitution of dietary fish oil (FO) by linseed oil (LO) in Atlantic salmon feeding on performance, liver and muscle fatty acid composition, selected lipogenic and lipolytic enzyme activities, and flesh oxidative stability. For 12 wk, fish (220 ± 12 g of initial BW) were fed five experimental diets in which the FO was serially replaced by 25, 50, 75, and 100% LO. Total FO replacement by LO did not (P = 0.20) affect fish final weight, biometric indices, or i.m. fat contents. Liver and muscle neutral lipid (NL) composition responded to dietary treatments in different ways. Whereas the sum of n-3 PUFA in muscle followed a linear and quadratic pattern with increasing levels of LO, a linear (P = 0.005) effect was observed in the liver NL fraction. Total n-3 and n-6 PUFA contents in the polar lipid fraction (PL) were unaffected (P = 0.356) by dietary input of LO in muscle. Activity of liver glucose-6-P-dehydrogenase (G6PD) was greater with increasing levels of LO (P = 0.004). A time effect (P < 0.001) was observed in the concentration of lipid peroxidation products, expressed as thiobarbituric acid reactive substances, in fish flesh stored under refrigeration for 9 d; however, the progressive inclusion of LO in the feed did not affect (P = 0.125) flesh oxidation stability. In summary, LO can totally replace FO in Atlantic salmon feed without affecting growth performance and muscle susceptibility to lipid oxidation. Fatty acid metabolism in the liver was affected by LO, promoting G6PD activity and eicosatetraenoic acid accumulation; however, a 100% LO replacement decreased (P < 0.001) concentrations of eicosapentaenoic and docosahexaenoic acids in salmon muscle.