ACVIM consensus statement on the treatment of immune-mediated hemolytic anemia in dogs

Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases

The Interaction of Hypotaurine and Other Sulfinates with Reactive Oxygen and Nitrogen Species:A Survey of Reaction Mechanisms

Considerable strides have been made in understanding the oxidative mechanisms involved in the final steps of the cysteine pathway leading to taurine. The oxidation of sulfinates, hypotaurine and cysteine sulfinic acid, to the respective sulfonates, taurine and cysteic acid, has never been associated with any specific enzyme. Conversely, there is strong evidence that in vivo formation of taurine and cysteic acid is the result of sulfinate interaction with a variety of biologically relevant oxidants. In the last decade, many experiments have been performed to understand whether peroxynitrite, nitrogen dioxide and carbonate radical anion could be included in the biologically relevant reactive species capable of oxidizing sulfinates. Thanks to this work, it has been possible to highlight two possible reaction mechanisms (direct and indirect reaction) of sulfinates with reactive oxygen and nitrogen species.The sulfinates oxidation, mediated by peroxynitrite, is an example of both reaction mechanisms: through a two-electron-direct-reaction with peroxynitrite or through a one-electron-indirect-transfer reaction. In the indirect mechanism, the peroxynitrite homolysis releases hydroxyl and nitrogen dioxide radical and in addition the degradation of short-lived adduct formed by peroxynitrite and CO2 can generate carbonate radical anion. The reaction of hypotaurine and cysteine sulfinic acid with peroxynitrite-derived radicals is accompanied by extensive oxygen uptake with the generation of transient intermediates, which can begin a reaction by an oxygen-dependent mechanism with the sulfonates, taurine, and cysteic acid as final products. Due to pulse radiolysis studies, it has been shown that transient sulfonyl radicals (RSO2(•)) have been produced during the oxidation of both sulfinates by one-electron transfer reaction.The purpose is to analyze all the aspects of the reactive mechanism in the sulfinic group oxidation of hypotaurine and cysteine sulfinic acid through the results obtained from our laboratory in recent years

Classification of High-Grade Serous Ovarian Cancer Using Tumor Morphologic Characteristics

IMPORTANCE: Despite similar histologic appearance among high-grade serous ovarian cancers (HGSOCs), clinical observations suggest vast differences in gross appearance. There is currently no systematic framework by which to classify HGSOCs according to their gross morphologic characteristics. OBJECTIVE: To develop and characterize a gross morphologic classification system for HGSOC. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included patients with suspected advanced-stage ovarian cancer who presented between April 1, 2013, and August 5, 2016, to the University of Texas MD Anderson Cancer Center, a large referral center. Patients underwent laparoscopic assessment of disease burden before treatment and received a histopathologic diagnosis of HGSOC. Researchers assigning morphologic subtype and performing molecular analyses were blinded to clinical outcomes. Data analysis was performed between April 2020 and November 2021. EXPOSURES: Gross tumor morphologic characteristics. MAIN OUTCOMES AND MEASURES: Clinical outcomes and multiomic profiles of representative tumor samples of type I or type II morphologic subtypes were compared. RESULTS: Of 112 women (mean [SD] age 62.7 [9.7] years) included in the study, most patients (84% [94]) exhibited a predominant morphologic subtype and many (63% [71]) had a uniform morphologic subtype at all involved sites. Compared with those with uniform type I morphologic subtype, patients with uniform type II morphologic subtype were more likely to have a favorable Fagotti score (83% [19 of 23] vs 46% [22 of 48]; P = .004) and thus to be triaged to primary tumor reductive surgery. Similarly, patients with uniform type II morphologic subtype also had significantly higher mean (SD) estimated blood loss (639 [559; 95% CI, 391-887] mL vs 415 [527; 95% CI, 253-577] mL; P = .006) and longer mean (SD) operative time (408 [130; 95% CI, 350-466] minutes vs 333 [113; 95% CI, 298-367] minutes; P = .03) during tumor reductive surgery. Type I tumors had enrichment of epithelial-mesenchymal transition (false discovery rate [FDR] q-value, 3.10 × 10-24), hypoxia (FDR q-value, 1.52 × 10-5), and angiogenesis pathways (FDR q-value, 2.11 × 10-2), whereas type II tumors had enrichment of pathways related to MYC signaling (FDR q-value, 2.04 × 10-9) and cell cycle progression (FDR q-value, 1.10 × 10-5) by integrated proteomic and transcriptomic analysis. Abundances of metabolites and lipids also differed between the 2 morphologic subtypes. CONCLUSIONS AND RELEVANCE: This study identified 2 novel, gross morphologic subtypes of HGSOC, each with unique clinical features and molecular signatures. The findings may have implications for triaging patients to surgery or chemotherapy, identifying outcomes, and developing tailored therapeutic strategies

Precipitation control over inorganic nitrogen import-export budgets across watersheds: a synthesis of long-term ecological research

ABSTRACT We investigated long-term and seasonal patterns of N imports and exports, as well as patterns following climate perturbations, across biomes using data from 15 watersheds from nine Long-Term Ecological Research (LTER) sites in North America. Mean dissolved inorganic nitrogen (DIN) import-export budgets (N import via precipitation-N export via stream flow) for common years across all watersheds was highly variable, ranging from a net loss of 0Ð17 š 0Ð09 kg N ha 1 mo 1 to net retention of 0Ð68 š 0Ð08 kg N ha 1 mo 1 . The net retention of DIN decreased (smaller import-export budget) with increasing precipitation, as well as with increasing variation in precipitation during the winter, spring, and fall. Averaged across all seasons, net DIN retention decreased as the coefficient of variation (CV) in precipitation increased across all sites (r 2 D 0Ð48, p D 0Ð005). This trend was made stronger when the disturbed watersheds were withheld from the analysis (r 2 D 0Ð80, p < 0Ð001, n D 11). Thus, DIN exports were either similar to or exceeded imports in the tropical, boreal, and wet coniferous watersheds, whereas imports exceeded exports in temperate deciduous watersheds. In general, forest harvesting, hurricanes, or floods corresponded with periods of increased DIN exports relative to imports. Periods when water throughput within a watershed was likely to be lower (i.e. low snow pack or El Niño years) corresponded with decreased DIN exports relative to imports. These data provide a basis for ranking diverse sites in terms of their ability to retain DIN in the context of changing precipitation regimes likely to occur in the future

Postoperative Complications in the Ahmed Baerveldt Comparison Study During Five Years of Follow-up

To compare the late complications in the Ahmed Baerveldt Comparison Study during 5 years of follow-up

Persistence of dissolved organic matter explained by molecular changes during its passage through soil

Dissolved organic matter affects fundamental biogeochemical processes in the soil such as nutrient cycling and organic matter storage. The current paradigm is that processing of dissolved organic matter converges to recalcitrant molecules (those that resist degradation) of low molecular mass and high molecular diversity through biotic and abiotic processes. Here we demonstrate that the molecular composition and properties of dissolved organic matter continuously change during soil passage and propose that this reflects a continual shifting of its sources. Using ultrahigh-resolution mass spectrometry and nuclear magnetic resonance spectroscopy, we studied the molecular changes of dissolved organic matter from the soil surface to 60 cm depth in 20 temperate grassland communities in soil type Eutric Fluvisol. Applying a semi-quantitative approach, we observed that plant-derived molecules were first broken down into molecules containing a large proportion of low-molecular-mass compounds. These low-molecular-mass compounds became less abundant during soil passage, whereas larger molecules, depleted in plant-related ligno-cellulosic structures, became more abundant. These findings indicate that the small plant-derived molecules were preferentially consumed by microorganisms and transformed into larger microbial-derived molecules. This suggests that dissolved organic matter is not intrinsically recalcitrant but instead persists in soil as a result of simultaneous consumption, transformation and formation

Antenatal allopurinol for reduction of birth asphyxia induced brain damage (ALLO-Trial); a randomized double blind placebo controlled multicenter study

<p>Abstract</p> <p>Background</p> <p>Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy.</p> <p>Methods/Design</p> <p>The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia.</p> <p>Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20).</p> <p>Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated.</p> <p>We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test_2-sided). Analysis will be by intention to treat and it allows for one interim analysis.</p> <p>Discussion</p> <p>In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia.</p> <p>Trial registration number</p> <p>Clinical Trials, protocol registration system: NCT00189007</p

Primate-specific evolution of noncoding element insertion into PLA2G4C and human preterm birth

Background The onset of birth in humans, like other apes, differs from non-primate mammals in its endocrine physiology. We hypothesize that higher primate-specific gene evolution may lead to these differences and target genes involved in human preterm birth, an area of global health significance. Methods We performed a comparative genomics screen of highly conserved noncoding elements and identified PLA2G4C, a phospholipase A isoform involved in prostaglandin biosynthesis as human accelerated. To examine whether this gene demonstrating primate-specific evolution was associated with birth timing, we genotyped and analyzed 8 common single nucleotide polymorphisms (SNPs) in PLA2G4C in US Hispanic (n = 73 preterm, 292 control), US White (n = 147 preterm, 157 control) and US Black (n = 79 preterm, 166 control) mothers. Results Detailed structural and phylogenic analysis of PLA2G4C suggested a short genomic element within the gene duplicated from a paralogous highly conserved element on chromosome 1 specifically in primates. SNPs rs8110925 and rs2307276 in US Hispanics and rs11564620 in US Whites were significant after correcting for multiple tests (p < 0.006). Additionally, rs11564620 (Thr360Pro) was associated with increased metabolite levels of the prostaglandin thromboxane in healthy individuals (p = 0.02), suggesting this variant may affect PLA2G4C activity. Conclusions Our findings suggest that variation in PLA2G4C may influence preterm birth risk by increasing levels of prostaglandins, which are known to regulate labor.Children’s Discovery InstituteMarch of Dimes Birth Defects FoundationNational Institute of General Medical Sciences (U.S.) (grant T32 GM081739)Washington University (Saint Louis, Mo.) (Mr. and Mrs. Spencer T. Olin Fellowship for Women in Graduate Study)Sigrid Jusélius FoundationSigne and Anne Gyllenberg FoundationAcademy of FinlandVanderbilt University (Turner-Hazinski grant award

Monitoring biological wastewater treatment processes: Recent advances in spectroscopy applications

Biological processes based on aerobic and anaerobic technologies have been continuously developed to wastewater treatment and are currently routinely employed to reduce the contaminants discharge levels in the environment. However, most methodologies commonly applied for monitoring key parameters are labor intensive, time-consuming and just provide a snapshot of the process. Thus, spectroscopy applications in biological processes are, nowadays, considered a rapid and effective alternative technology for real-time monitoring though still lacking implementation in full-scale plants. In this review, the application of spectroscopic techniques to aerobic and anaerobic systems is addressed focusing on UV--Vis, infrared, and fluorescence spectroscopy. Furthermore, chemometric techniques, valuable tools to extract the relevant data, are also referred. To that effect, a detailed analysis is performed for aerobic and anaerobic systems to summarize the findings that have been obtained since 2000. Future prospects for the application of spectroscopic techniques in biological wastewater treatment processes are further discussed.The authors thank the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, COMPETE 2020 (POCI-01-0145-FEDER-006684) and the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge the financial support to Daniela P. Mesquita and Cristina Quintelas through the postdoctoral Grants (SFRH/BPD/82558/2011 and SFRH/BPD/101338/2014) provided by FCT - Portugal.info:eu-repo/semantics/publishedVersio

Two Types of Planning in Neighborhoods

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68338/2/10.1177_0739456X8400300209.pd