Gasserian ganglion stimulation for refractory trigeminal neuropathic pain.

BACKGROUND AND OBJECTIVE: Painful trigeminal neuropathy is a complex clinical entity due to its severity and refractoriness to pharmacological and interventional management. We describe our experience in treating refractory painful trigeminal neuropathy (RPTN) with gasserian ganglion stimulation (GGS). MATERIALS AND METHODS: Six patients with RPTN were treated with GGS in our Unit between 2019 and 2022. The following data were collected: socio-demographic characteristics, triggering event, duration of the disease and treatment received prior to surgery, pre- and post-intervention visual analogue scale (VAS) score, follow-up time, and pre- and post-intervention functionality and quality of life. RESULTS: All patients were women who had received aggressive first-, second-, and third-line pharmacological, non-pharmacological, and interventional management before being referred for GGS. Patients reported a 50%-72% decrease in pain on VAS and improved functionality during follow-up. CONCLUSIONS: GGS is a promising therapeutic alternative for patients with RPTN. Although the initial outcomes and experience are encouraging, RPTN is recommended on the basis of safety, reproducibility, and trends observed in clinical practice.

Comparison between indicine and taurine cattle DNA methylation reveals epigenetic variation associated to differences in morphological adaptive traits.

Indicine and taurine subspecies present distinct morphological traits as a consequence of environmental adaptation and artificial selection. Although the two subspecies have been characterized and compared at genome-wide level and at specific loci, their epigenetic diversity has not yet been explored. In this work, Reduced Representation Bisulphite Sequencing (RRBS) profiling of the taurine Angus (A) and indicine Nellore (N) cattle breeds was applied to identify methylation differences between the two subspecies. Genotyping by sequencing (GBS) of the same animals was performed to detect single nucleotide polymorphisms (SNPs) at cytosines in CpG dinucleotides and remove them from the differential methylation analysis. A total of 660,845 methylated cytosines were identified within the CpG context (CpGs) across the 10 animals sequenced (5 N and 5 A). A total of 25,765 of these were differentially methylated (DMCs). Most DMCs clustered in CpG stretches nearby genes involved in cellular and anatomical structure morphogenesis. Also, sequences flanking DMC were enriched in SNPs compared to all other CpGs, either methylated or unmethylated in the two subspecies. Our data suggest a contribution of epigenetics to the regulation and divergence of anatomical morphogenesis in the two subspecies relevant for cattle evolution and sub-species differentiation and adaptation.

Genomic breed composition of pure registered Brazilian Gir.

INTRODUCTION: Gir is a Bos indicus breed originally from India, first imported to Brazil in 1850. High-performance Dairy Gir has been systematically selected in Brazil from its arrival. Since the major phenotypic difference between Gir in India and Brazil is a higher milk production in the former, it is speculated that Brazilian Gir was strategically crossed with Holstein or another Bos taurus to improve milk yield. This study evaluated the purity of Brazilian Gir breed stocks from BASA Farms in Brazil, trying to identify possible admixture events with other cattle breeds based on DNA analysis. MATERIALS AND METHODS: The population included 1061 pure registered individuals genotyped using two commercial platforms with 37 k and 25 k SNPs. Admixture analysis was performed individually to estimate levels of genomic composition derived from six different reference populations, three indicine and three taurine breeds. RESULTS: A Gir ancestry of 99% or higher was found for 94.2% of the population, while the remaining showed levels of non-Gir ancestry up to 6.8%. Only five individuals were identified with possible taurine ancestry, all of them exhibiting levels lower than 2%. The remaining non-Gir ancestry identified was derived from indicine breeds. The levels of admixture observed in the population were from low to non-detectable. No consistent patterns of admixture were observed indicating sustained introgression of taurine lines as means of genetic improvement. CONCLUSION: According to these results, genetic improvement achieved by Brazilian Gir breeders is the result of within-breed selection methods applied intensively over the past five decades, rather than the result from sustained introgression.

Development of an equipment for real-time continuous monitoring of alpha and beta radioactivity in river water.

Different regulations require the monitoring of radioactivity in the environment (e.g., 2013/51/Euratom, Real Decreto 314/2016) to protect the environment and the population from abnormal radioactivity presence caused by natural reasons or discharges or accidents in nuclear installations. Nowadays, the monitoring of α- and ß-emitting radionuclides is performed discontinuously in laboratories due to the difficulties in applying classical techniques to continuous measurements. This limits the number of samples that can be measured per day, produces high costs per analysis, and introduces a significant delay between the moment of contamination and when it is detected. Plastic scintillation microspheres (PSm) represent a new possibility for continuous measurements because water samples can flow through a bed of PSm connected to a pair of photomultipliers (PMTs), allowing continuous monitoring of the activity. This idea is the basis of the Waterrad detector, which can monitor radioactivity at environmental levels in river water. This paper describes the optimization of a detection cell containing PSm, a detection chamber as well as active and passive shielding. In its final set-up, the Waterrad detector presents a background signal of 0.23 (1) cps and detection efficiencies of 1.86(7)·10-5 cps·L·Bq-1 for 3H, 7.4(8)·10-3 cps·L·Bq-1 for 90Sr/90Y and 5.5(5)·10-3 cps·L·Bq-1 for 241Am. The detection limits in the optimum window for a counting time of 5 h were 490 Bq/L for 3H, 2.3 Bq/L for 90Sr/90Y and 3.0 Bq/L for 241Am. These values indicate that Waterrad can be used as an alarm detector for monitoring radioactivity in water at activity levels similar to those of environmental samples, making it suitable for water or waste surveillance involving a high frequency of measurements.

Capability of Far-Infrared for the selective identification of red and black pigments in paint layers.

Artworks are complex objects that merit study and preservation. Far-infrared spectroscopy in ATR mode appears to be a suitable technique for this purpose because it enables information to be obtained regarding the material's composition in a non-destructive way. The use of Far-infrared is especially interesting because most organic compounds do not absorb in this energy range, suggesting the possibility of identifying inorganic pigments. Based on works performed by two research groups from the University of Bologna and the University of Tartu, this study attempts to obtain additional information regarding the capabilities and limitations of Far-infrared spectroscopy when it is applied to objects as complex as artworks. This article first studies the capability of the technique for identifying pigments by following the stability of the position of their absorption bands when mixed with linseed oil, the minimum amount of pigment necessary to be detected and how this amount changes when it is part of a paint layer. The consequences of the pigment: linseed oil interaction and the ageing process are also studied through changes in the linseed oil signal absorptions related to the acid carboxylic and carboxylate bands. The entire study leads to the conclusion that Far-Infrared in ATR mode is an interesting option for the selective identification of some inorganic pigments, but their potential application depends on each case considered.

Bos taurus haplotypes segregating in Nellore (Bos indicus) cattle.

Brazil is the largest exporter of beef in the world, and most of that beef derives from Nellore cattle. Although considered a zebu breed (Bos indicus), the history of Nellore cattle in Brazil is marked by the importation of bulls from India, the use of a Creole taurine (Bos taurus) maternal lineage to quickly expand the herds and backcrossing to Nellore bulls to recover zebu ancestry. As a consequence, the current Brazilian Nellore population carries an average taurine ancestry of approximately 1%. Although that percentage seems small, some taurine variants deviate substantially from that average, with the better-known cases being the PLAG1-Q haplotype involved with body size variation and the Guarani (PG ) polled variant producing hornless animals. Here, we report taurine haplotypes in 9074 Nellore animals genotyped for 539 657 imputed SNP markers. Apart from PLAG1-Q and PG , our analysis further revealed common taurine haplotypes (>3%) spanning genes related to immunity, growth, reproduction and hair and skin phenotypes. Using data from 22 economically important traits, we showed that many of the major QTL previously reported in the breed are at least partially driven by taurine haplotypes. As B. taurus and B. indicus haplotypes are highly divergent, presenting widely different sets of functional variants, our results provide promising targets for future scrutiny in Nellore cattle.

PSresin for the analysis of alpha-emitting radionuclides: Comparison of diphosphonic acid-based extractants.

The analysis of radionuclides is complex, with high economic and time costs. For this reason, there is a need to develop new methods and strategies to reduce these costs. One important group in the analysis of radionuclides is the actinides, which are the main constituents assessed in the total gross alpha together with radium and radon test used to measure radioactivity in drinking water. Moreover, in nuclear dismantling processes, the possible spread of the released radionuclides has to be controlled, which is measured by many techniques, depending on the radionuclides, through scintillation. This work presents a new method to analyse actinides using plastic scintillation resins (PSresins) packed in a solid-phase extraction cartridge. The proposed method combines chemical separation and sample measurement into a single step, reducing the effort, time and reagents required for analysis as well as decreasing the amount of waste generated. The PSresins compared in this study contained three selective extractants based on methylenediphosphonic acid with different radicals, which has a high affinity for tri-, tetra-, and hexavalent actinides in dilute acids. These extractants were immobilised on plastic scintillation microspheres at a ratio of 1/1:6, producing a retention and detection efficiency of 100% for 241Am, 230Th, Uranium and 238Pu. The retention and detection efficiency were 20% and 100%, respectively, for 210Po and low for 226Ra.

Epidemiologic changes in bloodstream infections in Andalucía (Spain) during the last decade.

OBJECTIVES: During the last decade, some changes in the epidemiology of invasive infections have been reported; however, specific studies with patient-level data are scarce. The aim of this study was to describe and evaluate the epidemiologic changes in bloodstream infections (BSI) during the last decade in Andalucía, Spain. METHODS: Data from two prospective cohorts of BSI in adults with the same methodology performed 10 years apart in 11 hospitals (eight tertiary and three community) in Andalucía, Spain, were compared; the 2006-7 cohort study was performed between October 2006 and March 2007, and the 2016-17 cohort study was performed between October 2016 and March 2017. Population-based incidence rates were calculated and extrapolated for 1 year. Relative risk ratios were calculated between the 2 periods. Multivariate analyses were performed by logistic regression. RESULTS: Overall, 1262 episodes of BSI were included, 563 (44.6%) in 2006-7 and 699 (55.3%) in 2016-17. Multivariate models selected the following changes in patients' features in 2016-17, after controlling for type of acquisition: higher age (odds ratio (OR) = 1.02; 95% confidence interval [CI] 1.01-1.03), lower urinary catheter (OR = 0.37; 95% CI, 0.26-0.48) and lower Pitt score (OR = 0.76; 95% CI, 0.71-0.82). Adjusted estimations considering patients' features and exposure to procedures showed a reduction in coagulase-negative staphylococci (OR = 0.47; 95% CI, 0.32-0.69), and an increase in Proteus spp. (OR = 3.12; 95% CI, 1.18-8.23) and Candida spp. (OR = 3.01; 95% CI, 1.03-8.86). CONCLUSIONS: We found relevant epidemiologic changes in BSI in our area, including rates, frequency of acquisition types, changes in patient's profiles and aetiologic agents.

Association of missense variants in GDF9 with litter size in Entlebucher Mountain dogs.

In the past two decades, average litter size (ALS) in Entlebucher Mountain dogs decreased by approximately 0.8 puppies. We conducted a GWAS for ALS using the single-step methodology to take advantage of 1632 pedigree records, 892 phenotypes and 372 genotypes (173 662 markers) for which only 12% of the dogs had both phenotypes and genotypes available. Our analysis revealed associations towards the growth differentiation factor 9 gene (GDF9), which is known to regulate oocyte maturation. The trait heritability was estimated at 43.1%, from which approximately 15% was accountable by the GDF9 locus alone. Therefore, markers flanking GDF9 explained approximately 6.5% of the variance in ALS. Analysis of WGSs revealed two missense substitutions in GDF9, one of which (g.11:21147009G>A) affected a highly conserved nucleotide in vertebrates. The derived allele A was validated in 111 dogs and shown to be associated with decreased ALS (-0.75 ± 0.22 puppies per litter). The variant was further predicted to cause a proline to serine substitution. The affected residue was immediately followed by a six-residue deletion that is fixed in the canine species but absent in non-canids. We further confirmed that the deletion is prevalent in the Canidae family by sequencing three species of wild canids. Since canids uniquely ovulate oocytes at the prophase stage of the first meiotic division, requiring maturation in the oviduct, we conjecture that the amino acid substitution and the six-residue deletion of GDF9 may serve as a model for insights into the dynamics of oocyte maturation in canids.

Genome-wide mapping of the dominance effects based on breed ancestry for semen traits in admixed Swiss Fleckvieh bulls.

Heterosis is the beneficial deviation of crossbred progeny from the average of parental lines for a particular trait. Heterosis is due to nonadditive genetic effects with dominance and epistatic components. Recent advances in genotyping technology have encouraged researchers to estimate and scan heterosis components for a range of traits in crossbred populations, applying various definitions of such components. In this study, we defined the intralocus (dominance) component of heterosis using local genetic ancestry and performed genome-wide association analysis for admixed Swiss Fleckvieh bulls and their parental populations, Red Holstein Friesian and Swiss Simmental, for semen traits. A linear mixed model for 41,824 SNP, including SNP additive genetic, breed additive, and breed dominance effects on 1,178 bulls (148 Red Holstein Friesian, 213 Swiss Simmental, and 817 Swiss Fleckvieh) with a total of 43,782 measurements was performed. In total, 19 significant regions for breed dominance were identified for volume (2 regions on Bos taurus autosome 10 and 22) and percentage of live spermatozoa (17 regions on Bos taurus autosome 3, 4, 5, 7, 13, 14, and 17), and genes associated with spermatogenesis, sperm motility, and male fertility traits were located there. No significant region for breed dominance was detected for total number of spermatozoa. The signals for breed dominance were relatively wide, most likely due to limited numbers of recombination events in a small number of generations (10-15 generations) of crossbreeding in the recent Swiss Fleckvieh composite.

Genomic clues of the evolutionary history of Bos indicus cattle.

Together with their sister subspecies Bos taurus, zebu cattle (Bos indicus) have contributed to important socioeconomic changes that have shaped modern civilizations. Zebu cattle were domesticated in the Indus Valley 8000 years before present (YBP). From the domestication site, they expanded to Africa, East Asia, southwestern Asia and Europe between 4000 and 1300 YBP, intercrossing with B. taurus to form clinal variations of zebu ancestry across the landmass of Afro-Eurasia. In the past 150 years, zebu cattle reached the Americas and Oceania, where they have contributed to the prosperity of emerging economies. The zebu genome is characterized by two mitochondrial haplogroups (I1 and I2), one Y chromosome haplogroup (Y3) and three major autosomal ancestral groups (Indian-Pakistani, African and Chinese). Phenotypically, zebu animals are recognized by their hump, large ears and excess skin. They are rustic, resilient to parasites and capable of bearing the hot and humid climates of the tropics. Many resources are available to study the zebu genome, including commercial arrays of SNP, reference assemblies and publicly available genotypes and whole-genome sequences. Nevertheless, many of these resources were initially developed to support research and subsidize industrial applications in B. taurus, and therefore they can produce bias in data analysis. The combination of genomics with precision agriculture holds great promise for the identification of genetic variants affecting economically important traits such as tick resistance and heat tolerance, which were naturally selected for millennia and played a major role in the evolution of B. indicus cattle.

Mannheimia haemolytica OmpP2-like is an amyloid-like protein, forms filaments, takes part in cell adhesion and is part of biofilms.

Mannheimia haemolytica causes respiratory disease in cattle. Amyloid proteins are a major component of biofilms; they aid in adhesion and confer resistance against several environmental insults. The amyloid protein curli is highly resistant to protease digestion and physical and chemical denaturation and binds Congo red (CR) dye. The purpose of this study was to characterize an approximately 50-kDa CR-binding amyloid-like protein (ALP) expressed by M. haemolytica. This protein resisted boiling and formic acid digestion and was recognized by a polyclonal anti-Escherichia coli curli serum, suggesting its relationship with amyloid proteins. Immunolabeling and transmission electron microscopy showed that antibodies bound long, thin fibers attached to the bacterial surface. Mass spectrometry analysis indicated that these fibers are M. haemolytica OmpP2-like proteins. The purified protein formed filaments in vitro, and antiserum against it reacted positively with biofilms. An in silico analysis of its amino acid sequence indicated it has auto-aggregation properties and eight amyloid peptides. Rabbit polyclonal antibodies generated against this ALP diminished the adhesion of ATCC 31612 and BA1 M. haemolytica strains to A549 human epithelial cells, indicating its participation in cell adhesion. ALP expressed by M. haemolytica may be important in its pathogenicity and ability to form biofilms.

Safety of percutaneous nephrolithotomy in patients on chronic anticoagulant or antiplatelet therapy.

In developed countries, the incidence of cardiovascular disease is increasing, therefore, anticoagulant and antiplatelet drugs are a widespread treatment nowadays. Percutaneous nephrolithotomy (PNL) is the first-line treatment for large or complex stones (> 2 cm) and remains an alternative for the smaller ones. The objective of this study is to analyze whether PNL surgery is a safe procedure in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. We retrospectively studied 301 patients who underwent PNL in our hospital between 2008 and 2016 and identified 46 patients on chronic antiplatelet or anticoagulation treatment. With respect to PNL outcomes, the stone-free rate was similar (78 vs 74%, p = 0.762) in both groups, without any significant differences in the overall postoperative complications (17 vs 26%, p = 0.203). The incidence of hemorrhagic complications was similar between groups (12 vs 9%, p = 0.492), as demonstrated by the mean drop in hemoglobin (Hb), which was comparable in both cohorts (2.2 ± 1.3 vs 2.0 ± 1.4 p = 0.270) and the blood transfusion rate (14% in group A and 8% in group B, p = 0.205). No thromboembolic events were found within the year after the PNL procedure. PNL is a safe and effective intervention in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. Although our study demonstrates the feasibility of this protocol, new scientific evidence aims to stratify the thromboembolic and bleeding risk of each patient to individualize the perioperative management thereafter.

The ever-evolving role of pathologists in the management of breast cancer with neoadjuvant treatment: recommendations based on the Spanish clinical experience.

PURPOSE: To compare the current international standards for neoadjuvant systemic therapy (NAST) protocols, and establish consensus recommendations by Spanish breast pathologists; and to look into the Spanish reality of defining pathological complete response in daily practice. MATERIALS AND METHODS: A modified Delphi technique was used to gain consensus among a panel of 46 experts with regard to important issues about NAST specimens, with the objective of standardize handling and analysis of these breast cancer specimens. In addition, a survey was conducted among 174 pathologists to explore the Spanish reality of post-NAST breast cancer specimens handling. RESULTS: Our survey shows that pathologists in Spain follow the same guidelines as their international colleagues and face the same problems and controversies. Among the experts, 94.1% agreed on the recommendation for a pre-treatment evaluation with a core needle biopsy, and 100% of experts agreed on the need of having properly indicated information for the post-NAST surgical specimens. However, only 82.7% of them receive properly labelled specimens and even less receive specimens where markers are identified and the degree of clinical/radiological response is mentioned. Among participants 59.9% were familiar with the residual cancer burden system for post-NAST response quantification, but only 16.1% used it regularly. CONCLUSIONS: Active participation on breast cancer multidisciplinary teams, optimal usage of core needle biopsy for timely and standardized procedures for the diagnostic analysis, and accurate diagnosis of pathological complete response and complete evaluation of the response to NAST need to become the standard practice when handling breast cancer specimens in Spain.

Effects of breed proportion and components of heterosis for semen traits in a composite cattle breed.

The aim of this study was to estimate the non-additive genetic effects of the dominance component of heterosis as well as epistatic loss on semen traits in admixed Swiss Fleckvieh, a composite of Simmental (SI) and Red Holstein Friesian (RHF) cattle. Heterosis is the additional gain in productivity or fitness of cross-bred progeny over the mid-purebred parental populations. Intralocus gene interaction usually has a positive effect, while epistatic loss generally reduces productivity or fitness due to lack of evolutionarily established interactions of genes from different breeds. Genotypic data on 38,205 SNP of 818 admixed, as well as 148 RHF and 213 SI bulls as the parental breeds were used to predict breed origin of alleles. The genomewide locus-specific breed ancestries of individuals were used to calculate effects of breed difference as well as the dominance component of heterosis, while proxies for two definitions of epistatic loss were derived from 100,000 random pairs of loci. The average Holstein Friesian ancestry in admixed bulls was estimated 0.82. Results of fitting different linear mixed models showed including the dominance component of heterosis considerably improved the model adequacy for three of the four traits. Inclusion of epistatic loss increased the accuracy of the models only for our new definition of the epistatic effect for two traits, while the other definition was so highly correlated with the dominance component that statistical separation was impossible.

Genome-wide association study and annotating candidate gene networks affecting age at first calving in Nellore cattle.

We performed a genome-wide mapping for the age at first calving (AFC) with the goal of annotating candidate genes that regulate fertility in Nellore cattle. Phenotypic data from 762 cows and 777k SNP genotypes from 2,992 bulls and cows were used. Single nucleotide polymorphism (SNP) effects based on the single-step GBLUP methodology were blocked into adjacent windows of 1 Megabase (Mb) to explain the genetic variance. SNP windows explaining more than 0.40% of the AFC genetic variance were identified on chromosomes 2, 8, 9, 14, 16 and 17. From these windows, we identified 123 coding protein genes that were used to build gene networks. From the association study and derived gene networks, putative candidate genes (e.g., PAPPA, PREP, FER1L6, TPR, NMNAT1, ACAD10, PCMTD1, CRH, OPKR1, NPBWR1 and NCOA2) and transcription factors (TF) (STAT1, STAT3, RELA, E2F1 and EGR1) were strongly associated with female fertility (e.g., negative regulation of luteinizing hormone secretion, folliculogenesis and establishment of uterine receptivity). Evidence suggests that AFC inheritance is complex and controlled by multiple loci across the genome. As several windows explaining higher proportion of the genetic variance were identified on chromosome 14, further studies investigating the interaction across haplotypes to better understand the molecular architecture behind AFC in Nellore cattle should be undertaken.