Stan obecny w rozpoznawaniu i leczeniu złożonych przetok odbytniczych (CPF) w chorobie Leśniowskiego-Crohna (CD) w Polsce — na podstawie badania pt. „Schematy postępowania terapeutycznego u pacjentów ze złożonymi przetokami w przebiegu choroby Leśniowskie

WSTĘP: Złożona przetoka odbytu (CPF) jest chorobą stanowiącą poważne wyzwanie zarówno terapeutyczne, jak i społeczne z perspektywy pacjentów oraz ich rodzin. Głównym problemem jest konieczność zapewnienia chorym dostępu do skoordynowanej opieki, w której kluczową rolę odgrywa współpraca gastroenterologów oraz chirurgów, między innymi ze względu na wysoki odsetek niepowodzeń leczenia standardowego, prowadzącego do konieczności zastosowania rozwiązań chirurgicznych. Celem badania było uzyskanie informacji na temat obecnej praktyki postępowania z CPF w Polsce i zidentyfikowanie zwyczajów terapeutycznych lekarzy zajmujących się leczeniem chorych z CPF. MATERIAŁ I METODY: Badanie przeprowadzono od lutego do kwietnia 2018 roku i składało się z dwóch części: bezpośrednich wywiadów z lekarzami (30 gastroenterologów i 15 chirurgów) oraz analizy dokumentacji medycznej 75 pacjentów z CPF, którzy nie odpowiedzieli na standardowe leczenie, przy czym od momentu wprowadzenia kolejnego rzutu leczenia po niepowodzeniu terapii standardowej minął przynajmniej rok, ale nie więcej niż 5 lat. WYNIKI: Nie zidentyfikowano jednego, ustandaryzowanego schematu postępowania. Leczenie pacjentów z CPF, a także rola leczenia chirurgicznego różni się w zależności od wielkości i doświadczenia ośrodka medycznego. Przeprowadzona analiza dokumentacji medycznej dotyczącej 75 pacjentów pokazała, że u 41% chorych zastosowano wyłącznie leczenie farmakologiczne, natomiast u 59% leczenie farmakologiczne i chirurgiczne. Czas leczenia farmakologicznego od początku terapii do decyzji o zastosowaniu kolejnej linii leczenia w grupie łącznej wynosił średnio 12,3 miesiąca. W przypadku pacjentów leczonych chirurgicznie, średni czas od rozpoczęcia farmakologicznego leczenia CPF do decyzji o leczeniu chirurgicznym, wynosił 10–18 tygodni. WNIOSKI: Obecnie w Polsce brakuje ujednoliconego algorytmu postępowania u chorych z CPF oraz szeroko stosowanego standardu skoordynowanej opieki nad tymi chorymi. Widoczna jest pilna potrzeba wypracowania nowego paradygmatu terapeutycznego skupiającego się na zapewnieniu kompleksowej opieki chorym oraz wzmocnieniu w tym aspekcie znaczenia współpracy pomiędzy gastroenterologami oraz chirurgami

Genome Diversity and the Origin of the Arabian Horse

The Arabian horse, one of the world\u27s oldest breeds of any domesticated animal, is characterized by natural beauty, graceful movement, athletic endurance, and, as a result of its development in the arid Middle East, the ability to thrive in a hot, dry environment. Here we studied 378 Arabian horses from 12 countries using equine single nucleotide polymorphism (SNP) arrays and whole-genome re-sequencing to examine hypotheses about genomic diversity, population structure, and the relationship of the Arabian to other horse breeds. We identified a high degree of genetic variation and complex ancestry in Arabian horses from the Middle East region. Also, contrary to popular belief, we could detect no significant genomic contribution of the Arabian breed to the Thoroughbred racehorse, including Y chromosome ancestry. However, we found strong evidence for recent interbreeding of Thoroughbreds with Arabians used for flat-racing competitions. Genetic signatures suggestive of selective sweeps across the Arabian breed contain candidate genes for combating oxidative damage during exercise, and within the Straight Egyptian subgroup, for facial morphology. Overall, our data support an origin of the Arabian horse in the Middle East, no evidence for reduced global genetic diversity across the breed, and unique genetic adaptations for both physiology and conformation

Y-Chromosomal Insights into Breeding History and Sire Line Genealogies of Arabian Horses

The Y chromosome is a valuable genetic marker for studying the origin and influence of paternal lineages in populations. In this study, we conducted Y-chromosomal lineage-tracing in Arabian horses. First, we resolved a Y haplotype phylogeny based on the next generation sequencing data of 157 males from several breeds. Y-chromosomal haplotypes specific for Arabian horses were inferred by genotyping a collection of 145 males representing most Arabian sire lines that are active around the globe. These lines formed three discrete haplogroups, and the same haplogroups were detected in Arabian populations native to the Middle East. The Arabian haplotypes were clearly distinct from the ones detected in Akhal Tekes, Turkoman horses, and the progeny of two Thoroughbred foundation sires. However, a haplotype introduced into the English Thoroughbred by the stallion Byerley Turk (1680), was shared among Arabians, Turkomans, and Akhal Tekes, which opens a discussion about the historic connections between Oriental horse types. Furthermore, we genetically traced Arabian sire line breeding in the Western World over the past 200 years. This confirmed a strong selection for relatively few male lineages and uncovered incongruences to written pedigree records. Overall, we demonstrate how fine-scaled Y-analysis contributes to a better understanding of the historical development of horse breeds.Peer Reviewe

Refining the evolutionary tree of the horse Y chromosome

The Y chromosome carries information about the demography of paternal lineages, and thus, can prove invaluable for retracing both the evolutionary trajectory of wild animals and the breeding history of domesticates. In horses, the Y chromosome shows a limited, but highly informative, sequence diversity, supporting the increasing breeding influence of Oriental lineages during the last 1500 years. Here, we augment the primary horse Y-phylogeny, which is currently mainly based on modern horse breeds of economic interest, with haplotypes (HT) segregating in remote horse populations around the world. We analyze target enriched sequencing data of 5 Mb of the Y chromosome from 76 domestic males, together with 89 whole genome sequenced domestic males and five Przewalski's horses from previous studies. The resulting phylogeny comprises 153 HTs defined by 2966 variants and offers unprecedented resolution into the history of horse paternal lineages. It reveals the presence of a remarkable number of previously unknown haplogroups in Mongolian horses and insular populations. Phylogenetic placement of HTs retrieved from 163 archaeological specimens further indicates that most of the present-day Y-chromosomal variation evolved after the domestication process that started around 4200 years ago in the Western Eurasian steppes. Our comprehensive phylogeny significantly reduces ascertainment bias and constitutes a robust evolutionary framework for analyzing horse population dynamics and diversity

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Copper ecological risk assessment using DGT technique and PNEC: A case study in the Brazilian coast

Estuarine systems are vulnerable to metals stress, such as copper (Cu). Thus, the development of applicable tools to improve routine monitoring programs is increasingly necessary. In the present work a comprehensive Ecological Risk Assessment (ERA) was implemented by coupling the Measured Environmental Concentration (MEC), based on labile Cu (DGT) and the total dissolved Cu concentration. Additionally, toxicity data related to site-specific Predicted No Effect Concentration (PNEC) were used. As case study, estuarine areas were selected on Brazilian coast, previously reported as Cu release in shipyard areas. The results indicated an increase in concentrations of dissolved and labile Cu during the application of antifouling paints. In locations where more vessels in maintenance were found, the concentration of Cu-DGT exceeded the PNEC value (0.16 μg.L−1) and represented an important part of the total dissolved fraction (>93 %). The MEC/PNEC quotients, showed that shipyard areas represent a high ecological risk. Thus, it is highlighted the need for site-specific environmental assessments to manage complex ecosystems and set in environmental legislation. Consequently, the novel coupling of DGT technique and the derivation of a site-specific PNEC represent an easily applicable tool as an alternative to classical ERAs.publishedVersio

Copper ecological risk assessment using DGT technique and PNEC: A case study in the Brazilian coast

Estuarine systems are vulnerable to metals stress, such as copper (Cu). Thus, the development of applicable tools to improve routine monitoring programs is increasingly necessary. In the present work a comprehensive Ecological Risk Assessment (ERA) was implemented by coupling the Measured Environmental Concentration (MEC), based on labile Cu (DGT) and the total dissolved Cu concentration. Additionally, toxicity data related to site-specific Predicted No Effect Concentration (PNEC) were used. As case study, estuarine areas were selected on Brazilian coast, previously reported as Cu release in shipyard areas. The results indicated an increase in concentrations of dissolved and labile Cu during the application of antifouling paints. In locations where more vessels in maintenance were found, the concentration of Cu-DGT exceeded the PNEC value (0.16 μg.L−1) and represented an important part of the total dissolved fraction (>93 %). The MEC/PNEC quotients, showed that shipyard areas represent a high ecological risk. Thus, it is highlighted the need for site-specific environmental assessments to manage complex ecosystems and set in environmental legislation. Consequently, the novel coupling of DGT technique and the derivation of a site-specific PNEC represent an easily applicable tool as an alternative to classical ERAs

Assessment of minority frequency pretreatment HIV drug-resistant variants in pregnant women and associations with virologic non-suppression at term.

ObjectiveTo assess in ART-naïve pregnant women randomized to efavirenz- versus raltegravir-based ART (IMPAACT P1081) whether pretreatment drug resistance (PDR) with minority frequency variants (DesignA case-control study design compared PDR minority variants in cases with virologic non-suppression (plasma HIV RNA >200 copies/mL) at delivery to randomly selected ART-suppressed controls.MethodsHIV pol genotypes were derived from pretreatment plasma specimens by Illumina sequencing. Resistance mutations were assessed using the HIV Stanford Database, and the proportion of cases versus controls with PDR to their ART regimens was compared.ResultsPDR was observed in 7 participants (11.3%; 95% CI 4.7, 21.9) and did not differ between 21 cases and 41 controls (4.8% vs 14.6%, p = 0.4061). PDR detected only as minority variants was less common (3.2%; 95% CI 0.2, 11.7) and also did not differ between groups (0% vs. 4.9%; p = 0.5447). Cases' median plasma HIV RNA at delivery was 347c/mL, with most (n = 19/22) showing progressive diminution of viral load but not ≤200c/mL. Among cases with viral rebound (n = 3/22), none had PDR detected. Virologic non-suppression at term was associated with higher plasma HIV RNA at study entry (pConclusionsWe observed a moderate frequency of PDR that did not significantly contribute to virologic non-suppression at term. Rather, higher pretreatment plasma HIV RNA, randomization to efavirenz-based ART, and shorter duration of ART were associated with non-suppression. These findings support early prenatal care engagement of pregnant women and initiation of integrase inhibitor-based ART due to its association with more rapid suppression of plasma RNA levels. Furthermore, because minority variants appeared infrequent in ART-naïve pregnant women and inconsequential to ART-suppression, testing for minority variants may be unwarranted

Genome Diversity and the Origin of the Arabian Horse

Abstract The Arabian horse, one of the world’s oldest breeds of any domesticated animal, is characterized by natural beauty, graceful movement, athletic endurance, and, as a result of its development in the arid Middle East, the ability to thrive in a hot, dry environment. Here we studied 378 Arabian horses from 12 countries using equine single nucleotide polymorphism (SNP) arrays and whole-genome re-sequencing to examine hypotheses about genomic diversity, population structure, and the relationship of the Arabian to other horse breeds. We identified a high degree of genetic variation and complex ancestry in Arabian horses from the Middle East region. Also, contrary to popular belief, we could detect no significant genomic contribution of the Arabian breed to the Thoroughbred racehorse, including Y chromosome ancestry. However, we found strong evidence for recent interbreeding of Thoroughbreds with Arabians used for flat-racing competitions. Genetic signatures suggestive of selective sweeps across the Arabian breed contain candidate genes for combating oxidative damage during exercise, and within the “Straight Egyptian” subgroup, for facial morphology. Overall, our data support an origin of the Arabian horse in the Middle East, no evidence for reduced global genetic diversity across the breed, and unique genetic adaptations for both physiology and conformation