Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.

Comparative Treatment of Mucocutaneous Lesions in Hereditary Haemorrhagic Telangiectasia Patients With Dual Sequential Pulsed Dye Laser and Neodymium: Yttrium-Aluminium-Garnet Versus Neodymium: Yttrium-Aluminium-Garnet Laser Alone: A Double-Blind Randomized Controlled Study With Quality-of-Life Evaluation. / [Artículo traducido] Tratamiento comparativo de lesiones mucocutáneas en pacientes con telangiectasia hemorrágica hereditaria con láser dual secuencial de colorante pulsado y neodimio: itrio-aluminio-granate versus neodimio: itrio-aluminio-granate solo: un estudio controlado aleatorizado doble ciego con evaluación de la calidad de vida.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is characterized by the presence of telangiectases and larger arteriovenous malformations in different organs. Mucocutaneous telangiectases can bleed and become an aesthetic concern, impairing quality of life (QoL). However, the best treatment approach has not been defined yet. OBJECTIVE: To evaluate the efficacy and safety of dual wavelength sequential 595/1064nm laser (DWSL) compared to 1064nm laser (Nd:YAG) alone. Secondarily, to evaluate QoL impairment in HHT patients, and its improvement with laser therapy. METHODS: A comparative randomized split-body double-blinded prospective study (DWSL vs Nd:YAG). Demographic, clinical and treatment characteristics were recorded. The severity and degree of improvement were evaluated by three blinded examiners who scored pre-treatment and post-treatment pictures on a 5-point scale. Patients fulfilled Skindex-29 and FACE-Q® tests and assessed procedure-associated pain and patient satisfaction. RESULTS: 111 treatment areas (55 treated with DWSL and 56 with Nd:YAG) from 26 patients were analyzed. The median number of laser sessions was 2 (interquartile range [IQR] 2-4; mean 2.90 vs 2.88, respectively). The median improvement score, irrespective of location, was significantly higher for Nd:YAG compared to DWSL: 3 (IQR 2-3; mean 2.61) vs 2 (IQR 2-3; mean 2.32), p=0.031. Both FACE-Q index and Skindex-29 test results improved significantly (p<0.001), and 92.4% patients reported a high degree of satisfaction (≥8). No severe adverse events were reported. CONCLUSIONS: DWSL and Nd:YAG laser are convenient, safe and effective treatment options for mucocutaneous telangiectases in HHT patients. However, Nd:YAG delivered better results with better tolerability. QoL was significantly improved by both treatments.

Accuracy of genomic within-family selection in aquaculture breeding programmes.

In aquaculture breeding programmes, selection within families cannot be applied for traits that cannot be recorded on the candidates (e.g., disease resistance or fillet quality). However, this problem can be overcome if genomic evaluation is used. Within-family genomic evaluation has been proposed for these programmes as large family sizes are available and substantial levels of linkage disequilibrium (LD) within families can be attained with a limited number of markers even in populations in global linkage equilibrium. Here, we compare by computer simulation: (i) within-family and population-wide LD; and (ii) the accuracy of within-family genomic selection when genomic evaluations are carried out either at the population level or within families. The population simulated was composed by a varying number of families of full-sibs (half for training and half for testing). The results indicate that, to practice within-family selection, performing the genomic evaluation separately for each family using only molecular information from the family could be recommended for populations either in linkage equilibrium or with a low level of disequilibrium.

The use of coancestry based on shared segments for maintaining genetic diversity.

We have evaluated the use of genomic coancestry coefficients based on shared segments for the maintenance of genetic diversity through optimal contributions methodology for populations of three different Austrian cattle breeds. This coancestry measure has been compared with the genomic coancestry coefficient calculated on a SNP-by-SNP basis and with pedigree-based coancestry. The regressions of the shared segments coancestry on the other two coefficients suggest that the former mainly reflect Identity By Descent but with the advantage over pedigree-based coancestry of providing the realized Identity By Descent rather than an expectation. The effective population size estimated from the rate of coancestry based on shared segments was very similar to those obtained with the other coefficients and of small magnitude (from 26.24 to 111.90). This result highlights the importance of implementing active management strategies to control the increase of inbreeding and the loss of genetic diversity in livestock breeds, even when the population size is reasonably large. One problem for the implementation of coancestry based on shared segments is the need of estimating the gametic phases of the SNPs which, given the techniques used to obtain the genotypes, are a priori unknown. This study shows, through computer simulations, that using estimates of gametic phases for computing coancestry based on shared segments does not lead to a significant loss in the diversity maintained. This has been shown to be true even when the size of the population is very small as it is usually the case in populations subjected to conservation programmes.

Copy number variants in a highly inbred Iberian porcine strain.

We carried out a comprehensive genomic analysis of porcine copy number variants (CNVs) based on whole-genome SNP genotyping data and provided new measures of genomic diversity (number, length and distribution of CNV events) for a highly inbred strain (the Guadyerbas strain). This strain represents one of the most ancient surviving populations of the Iberian breed, and it is currently in serious danger of extinction. CNV detection was conducted on the complete Guadyerbas population, adjusted for genomic waves, and used strict quality criteria, pedigree information and the latest porcine genome annotation. The analysis led to the detection of 65 CNV regions (CNVRs). These regions cover 0.33% of the autosomal genome of this particular strain. Twenty-nine of these CNVRs were identified here for the first time. The relatively low number of detected CNVRs is in line with the low variability and high inbreeding estimated previously for this Iberian strain using pedigree, microsatellite or SNP data. A comparison across different porcine studies has revealed that more than half of these regions overlap with previously identified CNVRs or multicopy regions. Also, a preliminary analysis of CNV detection using whole-genome sequence data for four Guadyerbas pigs showed overlapping for 16 of the CNVRs, supporting their reliability. Some of the identified CNVRs contain relevant functional genes (e.g., the SCD and USP15 genes), which are worth being further investigated because of their importance in determining the quality of Iberian pig products. The CNVR data generated could be useful for improving the porcine genome annotation.

Using engineering methods (Kaizen-PDCA and Micro-Movements Science) to improve and provide evidence regarding microsurgical hand skills.

OBJECTIVE: Microsurgical interventions involve the interaction of numerous variables, making objective analysis of skill proficiency challenging. This difficulty is even more pronounced in low-resource contexts. Continuous improvement methodologies such as Kaizen-PDCA and Micro-Movements Science can address this issue. This study aimed to demonstrate the advantages of designing and implementing microsurgical training programs using these methodologies. METHODS: Following an extensive literature review of Kaizen-PDCA and Micro-Movements Science and under the guidance of experienced neurosurgeons and engineers, a microvascular bypass training program was developed using the human placenta. Subsequently, the training program was used to analyze and describe the process of a trainee neurosurgeon in Argentina with no prior experience in microvascular anastomosis, as the operator gained proficiency. RESULTS: The trainee required 12 attempts to achieve the program goals. The longest procedural time was during the first attempt (1 h 49 min 05 s with two mistakes), while the shortest time was during the fourth attempt (53 min 29 s with three mistakes). After 12 attempts, the trainee made no mistakes, and the procedural time was reduced to 57 min 37 s. The final learning curve demonstrated a regular pattern and reached a plateau after seven attempts. CONCLUSIONS: The training program and methodology effectively assessed, facilitated, and demonstrated the acquisition of microsurgical skills. Kaizen-PDCA and Micro-Movements Science enabled the effective use of expert experience, detailed evaluation of microsurgical procedures, and integration into a continuous improvement cycle. The program structure could also be valuable for teaching, evaluating, and enhancing similar surgical procedures.

Purging deleterious mutations in conservation programmes: combining optimal contributions with inbred matings.

Conservation programmes aim at minimising the loss of genetic diversity, which allows populations to adapt to potential environmental changes. This can be achieved by calculating how many offspring every individual should contribute to the next generation to minimise global coancestry. However, an undesired consequence of this strategy is that it maintains deleterious mutations, compromising the viability of the population. In order to avoid this, optimal contributions could be combined with inbred matings, to expose and eliminate recessive deleterious mutations by natural selection in a process known as purging. Although some populations that have undergone purging experienced reduced inbreeding depression, this effect is not consistent across species. Whether purging by inbred matings is efficient in conservation programmes depends on the balance between the loss of diversity, the initial decrease in fitness and the reduction in mutational load. Here we perform computer simulations to determine whether managing a population by combining optimal contributions with inbred matings improves its long-term viability while keeping reasonable levels of diversity. We compare the management based on genealogical information with management based on molecular data to calculate coancestries. In the scenarios analysed, inbred matings never led to higher fitness and usually maintained lower diversity than random or minimum coancestry matings. Replacing genealogical with molecular coancestry can maintain a larger genetic diversity but can also lead to a lower fitness. Our results are strongly dependent on the mutational model assumed for the trait under selection, the population size during management and the reproductive rate.

Potential angiogenic biomarkers in hereditary hemorrhagic telangiectasia and other vascular diseases.

Biomarkers are new tools framed in precision and personalized medicine. Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic vascular disease with disturbances in the angiogenic pathways. Descriptive evidence supports that some angiogenesis-related molecules are differently detected in HHT patients compared to healthy subjects. These molecules are also related to diagnosis, prognosis, complications and therapy monitoring in other common vascular diseases. Despite the need for improving knowledge before applying them in daily clinical practice, there are good candidates to be considered as potential biomarkers in HHT and other vascular diseases. In the present review, the authors aim to summarize and discuss current evidence regarding the main putative angiogenic biomarkers by describing the biological role of each biomarker, the evidence related to HHT and their potential use in this and other common vascular diseases from a clinical point-of-view.

Probiotic growth-stimulating capacity and antimicrobial activities of aqueous extracts of Lentinus crinitus (L.) Fr (polyporales, basidiomycota).

Lentinus crinitus (L.) Fr is a wild macrofungus that is popular as antimicrobial and various biological activities. This study aims to determine the capacity growth stimulation of Lactobacillus paracasei and antimicrobial activity of aqueous extracts of L. crinitus obtained from wild basidiomata, mycelial biomass by liquid fermentation and spent mushroom substrate obtained by solid-state fermentation. The antimicrobial activity was investigated against bacterial and fungal pathogens and growth stimulation L. paracasei probiotic bacterium. The total carbohydrate and ß-glucan contents of the extracts were determined using colorimetric analysis. The aqueous extracts obtained showed inhibition against Fusarium oxysporum., Penicillium sp., Rhizopus oryzae, Aspergillus niger, Escherichia coli and Salmonella typhimurium. The aqueous extract obtained from wild basidiomata, and mycelial biomass showed the highest percentage of stimulation of L. paracasei growth in 48 h. The extracts obtained from L. crinitus have antimicrobial potential and stimulating capacity of the probiotic Lactobacillus paracasei. Additionally, different biotechnological techniques such as liquid and solid-state fermentation can be used to obtain aqueous extracts.

Using genome-wide information to minimize the loss of diversity in conservation programmes.

We study here the effect of using genome-wide marker data versus genealogical data in population management for the maintenance of diversity in conservation schemes using optimal contributions. We re-examine the benefits of using molecular data for different population and genome sizes and compare different management strategies according to the group of individuals where we take decisions (parents or offspring). We also study the consequences of using estimated genealogical coancestries calculated from molecular information. Using genome-wide marker data performed usually better than using genealogical data or estimated genealogical coancestry to maintain expected and observed heterozygosity. Furthermore, when we could take decisions acting on the offspring, a larger heterozygosity was maintained than when we based our decisions on the potential parents.

Scrapie-resistant sheep show certain coat colour characteristics.

Susceptibility to scrapie is known to be associated with polymorphisms at the prion protein (PrP) gene, and this association is the basis of current selective programmes implemented to control scrapie in many countries. However, these programmes might have unintended consequences for other traits that might be associated with PrP genotype. The objective of this study was to investigate the relationship between PrP genotype and coat colour characteristics in two UK native sheep breeds valued for their distinctive coat colour patterns. Coat colour pattern, darkness and spotting and PrP genotype records were available for 11 674 Badgerfaced Welsh Mountain and 2338 Shetland sheep. The data were analysed with a log-linear model using maximum likelihood. Results showed a strong significant association of PrP genotype with coat colour pattern in Badgerfaced Welsh Mountain and Shetland sheep and with the presence of white spotting in Shetland sheep. Animals with the ARR/ARR genotype (the most scrapie resistant) had higher odds of having a light dorsum and a dark abdomen than the reverse pattern. The implication of these associations is that selection to increase resistance to scrapie based only on PrP genotype could result in change in morphological diversity and affect other associated traits such as fitness.

Change climate and health. / Cambio climático y salud.

Climate change consists mainly of global warming, a result of the so-called greenhouse effect, which is caused by certain gases, including carbon dioxide (CO2), produced mainly through the combustion of fossil fuels, such as coal and oil. Global warming is a severe threat for future populations because it can cause a considerable rise in sea levels, a greater frequency and intensity of extreme meteorological phenomena and even the extinction of certain animal and plant species. In the field of health, global warming is predicted to cause a considerable increase in the incidence of diseases such as heat stroke and vector-borne infections, the start of which has already been observed. All countries of the world must therefore adopt the necessary measures to drastically reduce the emission of gases that produce a greenhouse effect. Additionally, healthcare practitioners should assume an active role in helping to raise awareness in our society about the severity of the problem and ensuring that healthcare systems are duly prepared to address the increase in disease rates predicted for global warming. The Spanish Society of Internal Medicine (SEMI) has decided to step forward, with its incorporation into the multinational project Lancet Countdown. SEMI is the first Spanish organisation to join this initiative.

Restricting coancestry and inbreeding at a specific position on the genome by using optimized selection.

Over recent years, selection methodologies have been developed to allow the maximization of genetic gain whilst constraining the rate of inbreeding. The desired rate of inbreeding is achieved by constraining the group coancestry using the numerator relationship matrix computed from pedigree. It is shown that when the method is applied to mixed inheritance models, where a QTL is segregating together with polygenes, the rate of inbreeding achieved in the region around a QTL is greater than the desired level. The constraint on group coancestry at specific positions around the QTL is achieved by using a relationship matrix computed from pedigree and genetic markers. However, the rate of inbreeding realized at the position of constraint is lower than that expected given the assumed relationship between group coancestry and the subsequent rate of inbreeding. The use of markers in the calculation of the relationship matrix allows the selection of candidates with very low or zero relationships because they are homozygous for alternative alleles, which results in a heterozygosity amongst their offspring higher than would be expected given their allele frequencies. A generation of random selection restored the expected relationship between group coancestry and inbreeding.

Kounys syndrome after rocuronium administration. / Síndrome de Kounis tras administración de rocuronio.

Kounis syndrome encompasses concepts including angina and allergic infarction described in relation to exposure to different allergens. The aim of this article is to describe a case of Kounis Syndrome type II after exposure to rocuronium as well as the patholophysiology and the treatment of this syndrome.

Highly dense linkage maps from 31 full-sibling families of turbot (Scophthalmus maximus) provide insights into recombination patterns and chromosome rearrangements throughout a newly refined genome assembly.

Highly dense linkage maps enable positioning thousands of landmarks useful for anchoring the whole genome and for analysing genome properties. Turbot is the most important cultured flatfish worldwide and breeding programs in the fifth generation of selection are targeted to improve growth rate, obtain disease resistant broodstock and understand sex determination to control sex ratio. Using a Restriction-site Associated DNA approach, we genotyped 18,214 single nucleotide polymorphism in 1,268 turbot individuals from 31 full-sibling families. Individual linkage maps were combined to obtain a male, female and species consensus maps. The turbot consensus map contained 11,845 markers distributed across 22 linkage groups representing a total normalised length of 3,753.9 cM. The turbot genome was anchored to this map, and scaffolds representing 96% of the assembly were ordered and oriented to obtain the expected 22 megascaffolds according to its karyotype. Recombination rate was lower in males, especially around centromeres, and pairwise comparison of 44 individual maps suggested chromosome polymorphism at specific genomic regions. Genome comparison across flatfish provided new evidence on karyotype reorganisations occurring across the evolution of this fish group.

Evaluation of Adherence to Nutritional Intervention Through Trajectory Analysis.

Classical pre-post intervention studies are often analyzed using traditional statistics. Nevertheless, the nutritional interventions have small effects on the metabolism and traditional statistics are not enough to detect these subtle nutrient effects. Generally, this kind of studies assumes that the participants are adhered to the assigned dietary intervention and directly analyzes its effects over the target parameters. Thus, the evaluation of adherence is generally omitted. Although, sometimes, participants do not effectively adhere to the assigned dietary guidelines. For this reason, the trajectory map is proposed as a visual tool where dietary patterns of individuals can be followed during the intervention and can also be related with nutritional prescriptions. The trajectory analysis is also proposed allowing both analysis: 1) adherence to the intervention and 2) intervention effects. The analysis is made by projecting the differences of the target parameters over the resulting trajectories between states of different time-stamps which might be considered either individually or by groups. The proposal has been applied over a real nutritional study showing that some individuals adhere better than others and some individuals of the control group modify their habits during the intervention. In addition, the intervention effects are different depending on the type of individuals, even some subgroups have opposite response to the same intervention.

Expected genetic contributions and their impact on gene flow and genetic gain.

Long-term genetic contributions (r(i)) measure lasting gene flow from an individual i. By accounting for linkage disequilibrium generated by selection both within and between breeding groups (categories), assuming the infinitesimal model, a general formula was derived for the expected contribution of ancestor i in category q (mu(i)(q)), given its selective advantages (s(i)(q)). Results were applied to overlapping generations and to a variety of modes of inheritance and selection indices. Genetic gain was related to the covariance between r(i) and the Mendelian sampling deviation (a(i)), thereby linking gain to pedigree development. When s(i)(q) includes a(i), gain was related to E[mu(i)(q))a(i)], decomposing it into components attributable to within and between families, within each category, for each element of s(i)(q). The formula for mu(i)(q) was consistent with previous index theory for predicting gain in discrete generations. For overlapping generations, accurate predictions of gene flow were obtained among and within categories in contrast to previous theory that gave qualitative errors among categories and no predictions within. The generation interval was defined as the period for which mu(i)(q), summed over all ancestors born in that period, equaled 1. Predictive accuracy was supported by simulation results for gain and contributions with sib-indices, BLUP selection, and selection with imprinted variation.

Cumulative discounted expressions of sire genotypes for the complex vertebral malformation and beta-casein loci in commercial dairy herds.

Based on discounted gene-flow principles, a set of recursive equations was developed to quantify the value of using sires with a specific genotype for an identified gene in a commercial dairy herd. Two examples were used to demonstrate the usefulness of the method. The first example deals with the implications of using sires that are known carriers of the lethal recessive genetic defect, complex vertebral malformation (CVM). The second example examines the value of using sires homozygous for the A2 allele of beta-casein. Results are presented in terms of cumulative discounted expressions. These are then multiplied by the economic values of specific genotypes to determine the cost or benefit of using these sires. In general, the degree of mortality and the required price reduction for carrier sires increased as the proportion of carrier sires used, the duration of sire use, and the initial frequency in the cow herd increased. A semen discount of 3.10 pound sterling per CVM straw used would be required to offset the expected mortality when 20% of CVM carrier sires are used for 3 yr when 5% of cows are carriers. The cumulative discounted expressions' of using sires homozygous for the A2 allele of beta-casein also increased when the proportion and duration of carrier sire use and the initial frequency of the A2 allele increased. Assuming an A2A2 cow is worth 160 pound sterling more than a non-A2A2 cow, the expected benefit of using A2A2 sires in a 100-cow herd for 5 yr would be 57 pound sterling,120 for a 20-yr planning horizon. The results of this study demonstrate how the starting gene frequency in the herd, and the proportion and duration of use of sires of particular genotypes are critical to the economic implications of using single genes in commercial dairy farms.