Filter life span in postoperative cardiovascular surgery patients requiring continuous renal replacement therapy, using a post dilution regional citrate anticoagulation continuous hemofiltration circuit

Background: Regional citrate anticoagulation (RCA) is the recommended standard for continuous renal replacement therapy (CRRT). This study assesses its efficacy in patients admitted to critical care following cardiovascular surgery and the influence of standard antithrombotic agents routinely used in this specific group. Methods: Consecutive cardiovascular surgery patients treated with post-dilution hemofiltration with RCA were included in this prospective observational study. The primary outcome of the study was CRRT circuit life-span adjusted for reasons other than clotting. The secondary outcome evaluated the influence of standard antithrombotic agents (acetylsalicylic acid [ASA], low molecular weight heparin [LMWH] or fondaparinux as thromboprophylaxis or treatment dose with or without ASA) on filter life. Results: Fifty-two patients underwent 193 sessions of CVVH, after exclusion of 15 sessions where unfractionated heparin was administered. The median filter life span was 58 hours. Filter life span was significantly longer in patients receiving therapeutic dose of LMWH or fondaparinux (79 h [2–110]), in comparison to patients treated with prophylactic dose of LMWH or fondaparinux (51 h [7–117], p < 0.001), and patients without antithrombotic prophylaxis (42 h [2–91], p < 0.0001). 12 bleeding episodes were observed; 8 occurred in patients receiving treatment dose anticoagulation, 3 in patients receiving prophylactic dose anticoagulation and 1 in a patient with no antithrombotic prophylaxis. Conclusions: A post dilution hemofiltration with RCA provides prolonged filter life span when adjusted for reasons other than clotting. Patients receiving treatment dose anticoagulation had a significantly longer filter life span than those who were on prophylactic doses or ASA alone

Patient with chronic kidney disease after heart transplantation due to severe chronic heart failure

W pracy przedstawiono przypadek 55-letniego mężczyzny zakwalifikowanego do przeszczepienia serca w trybie elektywnym z powodu ciężkiej niewydolności serca na podłożu kardiomiopatii niedokrwiennej i z przewlekłą chorobą nerek, którego hospitalizowano z powodu zaostrzenia niewydolności serca. Po początkowym ustabilizowaniu stanu hemodynamicznego u chorego doszło do nagłego zatrzymania krążenia. Po skutecznej resuscytacji pacjenta przekazano do Kliniki Kardiochirurgii GUMed w celu leczenia urządzeniem wspomagającym pracę komór i po 70 dniach wykonano u niego przeszczepienie serca. Po przeszczepieniu nastąpiło pogorszenie funkcji nerek. W pracy omówiono możliwe przyczyny pogorszenia funkcji nerek u pacjentów poddawanych przeszczepieniu serca.A 55-year-old male qualified for heart transplantationdue to severe ischaemic heart failure and withchronic kidney disease was admitted to hospitalbecause of heart failure decompensation. Afterinitial stabilization of hemodynamic state a suddencardiac arrest occurred. The patient was transferredto Cardiac Surgery Clinic and was treated with leftventricular assist device. After 70 days of mechanicalsupport a heart transplantation was performed.Shortly after transplantation worsening of chronickidney disease was observed. The possible causesof chronic kidney disease in patients undergoingheart transplantation are discussed in the article

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Detection and characterization of male sex chromosome abnormalities in the UK Biobank study

Purpose: The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes. Methods: We analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to extensive routine health record data. Results: Only 49 of 213 (23%) of men whom we identified with KS and only 1 of 143 (0.7%) with 47,XYY had a diagnosis of abnormal karyotype on their medical records or self-report. We observed expected associations for KS with reproductive dysfunction (late puberty: risk ratio [RR] = 2.7; childlessness: RR = 4.2; testosterone concentration: RR = -3.8 nmol/L, all P < 2 x 10(-8)), whereas XYY men appeared to have normal reproductive function. Despite this difference, we identified several higher disease risks shared across both KS and 47,XYY, including type 2 diabetes (RR = 3.0 and 2.6, respectively), venous thrombosis (RR = 6.4 and 7.4, respectively), pulmonary embolism (RR = 3.3 and 3.7, respectively), and chronic obstructive pulmonary disease (RR = 4.4 and 4.6, respectively) (all P Conclusion: KS and 47,XYY were mostly unrecognized but conferred substantially higher risks for metabolic, vascular, and respiratory diseases, which were only partially explained by higher levels of body mass index, deprivation, and smoking. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.Peer reviewe

Differentiable Functions on Normed Linear Spaces

In this article, we formalize differentiability of functions on normed linear spaces. Partial derivative, mean value theorem for vector-valued functions, continuous differentiability, etc. are formalized. As it is well known, there is no exact analog of the mean value theorem for vector-valued functions. However a certain type of generalization of the mean value theorem for vector-valued functions is obtained as follows: If ||ƒ'(x + t · h)|| is bounded for t between 0 and 1 by some constant M, then ||ƒ(x + t · h) - ƒ(x)|| ≤ M · ||h||. This theorem is called the mean value theorem for vector-valued functions. By this theorem, the relation between the (total) derivative and the partial derivatives of a function is derived [23].Shinshu University, Nagano, JapanGrzegorz Bancerek. Cardinal numbers. Formalized Mathematics, 1(2):377-382, 1990.Grzegorz Bancerek. The fundamental properties of natural numbers. Formalized Mathematics, 1(1):41-46, 1990.Grzegorz Bancerek. König's theorem. Formalized Mathematics, 1(3):589-593, 1990.Grzegorz Bancerek. The ordinal numbers. Formalized Mathematics, 1(1):91-96, 1990.Grzegorz Bancerek and Krzysztof Hryniewiecki. Segments of natural numbers and finite sequences. Formalized Mathematics, 1(1):107-114, 1990.Grzegorz Bancerek and Andrzej Trybulec. Miscellaneous facts about functions. Formalized Mathematics, 5(4):485-492, 1996.Czesław Byliński. The complex numbers. Formalized Mathematics, 1(3):507-513, 1990.Czesław Byliński. Finite sequences and tuples of elements of a non-empty sets. Formalized Mathematics, 1(3):529-536, 1990.Czesław Byliński. Functions and their basic properties. Formalized Mathematics, 1(1):55-65, 1990.Czesław Byliński. Functions from a set to a set. Formalized Mathematics, 1(1):153-164, 1990.Czesław Byliński. The modification of a function by a function and the iteration of the composition of a function. Formalized Mathematics, 1(3):521-527, 1990.Czesław Byliński. Partial functions. Formalized Mathematics, 1(2):357-367, 1990.Czesław Byliński. Introduction to real linear topological spaces. Formalized Mathematics, 13(1):99-107, 2005.Agata Darmochwał. The Euclidean space. Formalized Mathematics, 2(4):599-603, 1991.Noboru Endou, Yasunari Shidama, and Keiichi Miyajima. The product space of real normed spaces and its properties. Formalized Mathematics, 15(3):81-85, 2007, doi:10.2478/v10037-007-0010-y.Hiroshi Imura, Morishige Kimura, and Yasunari Shidama. The differentiable functions on normed linear spaces. Formalized Mathematics, 12(3):321-327, 2004.Jarosław Kotowicz. Real sequences and basic operations on them. Formalized Mathematics, 1(2):269-272, 1990.Anna Lango and Grzegorz Bancerek. Product of families of groups and vector spaces. Formalized Mathematics, 3(2):235-240, 1992.Hiroyuki Okazaki, Noboru Endou, Keiko Narita, and Yasunari Shidama. Differentiable functions into real normed spaces. Formalized Mathematics, 19(2):69-72, 2011, doi: 10.2478/v10037-011-0012-7.Beata Padlewska and Agata Darmochwał. Topological spaces and continuous functions. Formalized Mathematics, 1(1):223-230, 1990.Jan Popiołek. Real normed space. Formalized Mathematics, 2(1):111-115, 1991.Konrad Raczkowski and Paweł Sadowski. Real function differentiability. Formalized Mathematics, 1(4):797-801, 1990.Laurent Schwartz. Cours d'analyse, vol. 1. Hermann Paris, 1967.Yasunari Shidama. Banach space of bounded linear operators. Formalized Mathematics, 12(1):39-48, 2004.Andrzej Trybulec. Binary operations applied to functions. Formalized Mathematics, 1(2):329-334, 1990.Andrzej Trybulec. On the sets inhabited by numbers. Formalized Mathematics, 11(4):341-347, 2003.Wojciech A. Trybulec. Vectors in real linear space. Formalized Mathematics, 1(2):291-296, 1990.Zinaida Trybulec. Properties of subsets. Formalized Mathematics, 1(1):67-71, 1990.Edmund Woronowicz. Relations and their basic properties. Formalized Mathematics, 1(1):73-83, 1990.Edmund Woronowicz. Relations defined on sets. Formalized Mathematics, 1(1):181-186, 1990.Hiroshi Yamazaki and Yasunari Shidama. Algebra of vector functions. Formalized Mathematics, 3(2):171-175, 1992

Linear Transformations of Euclidean Topological Spaces

We introduce linear transformations of Euclidean topological spaces given by a transformation matrix. Next, we prove selected properties and basic arithmetic operations on these linear transformations. Finally, we show that a linear transformation given by an invertible matrix is a homeomorphism.Institute of Informatics, University of Białystok, PolandJesse Alama. The rank+nullity theorem. Formalized Mathematics, 15(3):137-142, 2007, doi:10.2478/v10037-007-0015-6.Grzegorz Bancerek. Cardinal numbers. Formalized Mathematics, 1(2):377-382, 1990.Grzegorz Bancerek. The fundamental properties of natural numbers. Formalized Mathematics, 1(1):41-46, 1990.Grzegorz Bancerek. The ordinal numbers. Formalized Mathematics, 1(1):91-96, 1990.Grzegorz Bancerek, Mitsuru Aoki, Akio Matsumoto, and Yasunari Shidama. Processes in Petri nets. Formalized Mathematics, 11(1):125-132, 2003.Grzegorz Bancerek and Krzysztof Hryniewiecki. Segments of natural numbers and finite sequences. Formalized Mathematics, 1(1):107-114, 1990.Czesław Byliński. Functions and their basic properties. Formalized Mathematics, 1(1):55-65, 1990.Czesław Byliński. Functions from a set to a set. Formalized Mathematics, 1(1):153-164, 1990.Czesław Byliński. Partial functions. Formalized Mathematics, 1(2):357-367, 1990.Czesław Byliński. The sum and product of finite sequences of real numbers. Formalized Mathematics, 1(4):661-668, 1990.Agata Darmochwał. Families of subsets, subspaces and mappings in topological spaces. Formalized Mathematics, 1(2):257-261, 1990.Agata Darmochwał. The Euclidean space. Formalized Mathematics, 2(4):599-603, 1991.Noboru Endou, Takashi Mitsuishi, and Yasunari Shidama. Dimension of real unitary space. Formalized Mathematics, 11(1):23-28, 2003.Krzysztof Hryniewiecki. Basic properties of real numbers. Formalized Mathematics, 1(1):35-40, 1990.Katarzyna Jankowska. Matrices. Abelian group of matrices. Formalized Mathematics, 2(4):475-480, 1991.Artur Korniłowicz. On the real valued functions. Formalized Mathematics, 13(1):181-187, 2005.Eugeniusz Kusak, Wojciech Leończuk, and Michał Muzalewski. Abelian groups, fields and vector spaces. Formalized Mathematics, 1(2):335-342, 1990.Anna Lango and Grzegorz Bancerek. Product of families of groups and vector spaces. Formalized Mathematics, 3(2):235-240, 1992.Robert Milewski. Associated matrix of linear map. Formalized Mathematics, 5(3):339-345, 1996.Beata Padlewska and Agata Darmochwał. Topological spaces and continuous functions. Formalized Mathematics, 1(1):223-230, 1990.Karol Pąk. Basic properties of determinants of square matrices over a field. Formalized Mathematics, 15(1):17-25, 2007, doi:10.2478/v10037-007-0003-x.Karol Pąk. Basic properties of the rank of matrices over a field. Formalized Mathematics, 15(4):199-211, 2007, doi:10.2478/v10037-007-0024-5.Karol Pąk. Solutions of linear equations. Formalized Mathematics, 16(1):81-90, 2008, doi:10.2478/v10037-008-0012-4.Karol Pąk. Linear map of matrices. Formalized Mathematics, 16(3):269-275, 2008, doi:10.2478/v10037-008-0032-0.Andrzej Trybulec and Czesław Byliński. Some properties of real numbers. Formalized Mathematics, 1(3):445-449, 1990.Wojciech A. Trybulec. Non-contiguous substrings and one-to-one finite sequences. Formalized Mathematics, 1(3):569-573, 1990.Zinaida Trybulec. Properties of subsets. Formalized Mathematics, 1(1):67-71, 1990.Edmund Woronowicz. Relations and their basic properties. Formalized Mathematics, 1(1):73-83, 1990.Xiaopeng Yue, Xiquan Liang, and Zhongpin Sun. Some properties of some special matrices. Formalized Mathematics, 13(4):541-547, 2005.Katarzyna Zawadzka. The sum and product of finite sequences of elements of a field. Formalized Mathematics, 3(2):205-211, 1992.Katarzyna Zawadzka. The product and the determinant of matrices with entries in a field. Formalized Mathematics, 4(1):1-8, 1993

Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association

The identification of multiple signals at individual loci could explain additional phenotypic variance (‘missing heritability’) of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Tridimensional model structure and patterns of molecular evolution of Pepino mosaic virus TGBp3 protein

<p>Abstract</p> <p>Background</p> <p><it>Pepino mosaic virus </it>(PepMV) is considered one of the most dangerous pathogens infecting tomatoes worldwide. The virus is highly diverse and four distinct genotypes, as well as inter-strain recombinants, have already been described. The isolates display a wide range on symptoms on infected plant species, ranging from mild mosaic to severe necrosis. However, little is known about the mechanisms and pattern of PepMV molecular evolution and about the role of individual proteins in host-pathogen interactions.</p> <p>Methods</p> <p>The nucleotide sequences of the triple gene block 3 (TGB3) from PepMV isolates varying in symptomatology and geographic origin have been analyzed. The modes and patterns of molecular evolution of the TGBp3 protein were investigated by evaluating the selective constraints to which particular amino acid residues have been subjected during the course of diversification. The tridimensional structure of TGBp3 protein has been modeled <it>de novo </it>using the Rosetta algorithm. The correlation between symptoms development and location of specific amino acids residues was analyzed.</p> <p>Results</p> <p>The results have shown that TGBp3 has been evolving mainly under the action of purifying selection operating on several amino acid sites, thus highlighting its functional role during PepMV infection. Interestingly, amino acid 67, which has been previously shown to be a necrosis determinant, was found to be under positive selection.</p> <p>Conclusions</p> <p>Identification of diverse selection events in TGB3p3 will help unraveling its biological functions and is essential to an understanding of the evolutionary constraints exerted on the <it>Potexvirus </it>genome. The estimated tridimensional structure of TGBp3 will serve as a platform for further sequence, structural and function analysis and will stimulate new experimental advances.</p