Molecular and clinical diversity in primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.

Electrophile-Promoted Nucleophilic Cyclization of 2-Alkynylindoles to Give 4-Substituted Oxazinoindolones.

A method for the synthesis of 4-organoselanyl oxazinoindolone derivatives by the cascade cyclization of N-(alkoxycarbonyl)-2-alkynylindoles using iron(III) chloride and diorganyl diselenides as promoters was developed. This protocol was applied to a series of N-(alkoxycarbonyl)-2-alkynylindoles containing different substituents. The reaction conditions also tolerated a variety of diorganyl diselenides having both electron donating and electron withdrawing groups. However, the reaction did not work for diorganyl disulfides and ditellurides. The reaction mechanism seems to proceed via an ionic pathway and the cooperative action between iron(III) chloride and diorganyl diselenides is crucial for successful cyclization. We also found that using the same starting materials, by simply changing the electrophilic source to iodine, led to the formation of 4-iodo-oxazinoindolones. The high reactivity of Csp2 -Se and Csp2 -I bonds were tested under cross-coupling conditions leading to the preparation of a new class of functionalized indole derivatives. In addition, the absorption, emission and electrochemical properties of 4-organoselanyl oxazinoindolones showed an important relationship with the substituents of the aromatic rings. The advantages of the methodology include the use of electrophilic to promote the cyclization reaction and functionalization of the indole ring, and the electronic properties presented by the prepared compounds can be exploited as probes, analyte detectors and optical materials.

Ozone use in the treatment of subclinical mastitis in dairy cows.

This research communication paper addresses the hypothesis that the use of therapeutic alternatives for mastitis, such as intramammary ozone, can cure the disease with lower costs and without harmful residues for human consumption and without formation of microbial resistance like the ones caused by indiscriminate use of antibiotics in dairy farms. The study was performed in 36 mammary quarters from 12 dairy cows with subclinical mastitis grade three. The experimental units were randomly assigned into four groups and each group received a treatment. Treatments comprised (a) 20 µg/ml ozone gas; (b) 40 µg/ml ozone gas; (c) negative control treatment of 12.5 µg/ml ozonated saline and (d) positive control treatment of 100 mg of cephalexin + 100 mg of neomycin + 10 mg of prednisolone, all by intramammary injection. In all quarters, milk was collected before and after the application of treatments for California mastitis test and evaluation of milk composition, somatic cell count, and bacterial cultures. The results indicated that the use of intramammary ozone did have a therapeutic effect, and whilst this was less than that of antibiotics, ozone does confer some advantages. Treated milk had a good composition, the treatment cost was low, milk withdrawal may not be necessary and there is no risk of antibiotic resistance.

Potassium tert-Butoxide-Promoted Tandem Cyclization of Organoselenium Alkynyl Aryl Propargyl Ethers.

Base-promoted cyclization of 3-organoselenyl-methylene-2-alkynyl aryl propargyl ethers has been developed for the synthesis of 3-butylselanyl-methylene benzofurans, 3-methyl-2-alkynyl-benzofurans, and 4-iodo-benzo[b]furan-fused selenopyrans. Under potassium tert-butoxide as the base and tetrahydrofuran as the solvent, at room temperature, 3-organoselenyl-methylene-2-alkynyl aryl propargyl ethers were converted into 3-butylselanyl-methylene benzofurans via a 5-exo-dig mode. Using the same substrate, changing the solvent to dimethylsulfoxide, 3-methyl-2-alkynyl-benzofurans were selectively obtained in good yields. From 3-butylselanyl-methylene benzofurans, 4-iodo-benzo[b]furan-fused selenopyrans were prepared through a nucleophilic cyclization promoted by molecular iodine. The optimization of the reaction conditions showed that the solvents governed the regioselectivity of this cyclization and the initial formation of the dimsyl anion by the reaction of dimethylsulfoxide with potassium tert-butoxide was crucial for the 3-methyl-2-alkynyl-benzofuran preparation. We also proposed the mechanism for the formation of the products, demonstrated that the methodology can be scaled up, and showed the application of the prepared compounds as substrate in further transformations.

Different protocols for piglet creep feeding in the farrowing stage and residual effects in the nursery phase.

This study was aimed at the effects of different Creep-feeding protocols on piglet performance and its residual effects during the nursery phase. Experimental design used was five groups: WC (without creep); DCF (dry creep feeding); WCF (wet creep feeding); LD (additional liquid creep with automatic feed dispenser plus DCF); and LLF (additional liquid creep with linear feeder plus DCF). Ten litters per treatment were selected a total 50 sows and 645 piglets. During the first two weeks of lactation, the LD treatment (2.61 and 4.20 kg) promoted greater body weight (P <0.001) than the DCF (2.55 and 3.93 kg), (WFS) (2.43 and 3.69 kg) and LLF (2.50 and 4.00 kg) treatments, but did not differ from the WC treatment (2.68 and 4.09 kg). At weaning, the WC (5.22 kg), LD (5.32 kg) and LLF (5.27 kg) treatments gave higher body weights (P <0.001) when compared to the DCF (4.97 kg) and WCF (4.69 kg) treatments. We concluded that there was no change in the behavior of the piglets, and the use of dry feed with liquid supplements did not improve weight gain. The different creep feeding systems did not influence the weight and performance of the piglets in the nursery phase.

Microencapsulated phytogenic in dog feed modulates immune responses, oxidative status and reduces bacterial (Salmonella and Escherichia coli) counts in feces.

Improving the health and immunity of pets is a concern of the guardians, while maintaining the health of the animals directly impacts the owners' health and public health. The objective of this study was to produce a dog feed containing a microencapsulated phytogenic blend, as well as determine the impact of the additive on animal health and its intestinal microbiota. The composition included microencapsulated thymol, carvacrol, and cinnamaldehyde, at 300 mg/kg of feed. Ten male beagle dogs were divided into two groups, identified as follows: the control group (C; ingested the feed without the additive) and the treated group (T; consumed feed containing the phytogenic blend). The dogs received 300 g of feed/day divided into two meals. Greater neutrophil counts in group T and lymphocyte counts were observed at the end of the experiment, as well as levels of α2-globulins and γ-globulin, while ß1 and ß2-globulins levels were lower in group T. Serum nitrogen oxide levels were higher in group T. Levels of reactive oxygen species were lower in group T at days 30 and 45, unlike activity of glutathione peroxidase that was higher. We found less bacterial contamination in the feces of dogs in group T, i.e., total bacterial count, total coliform counts, and counts of Salmonella and Escherichia coli were lower on days 30 and 45. Phytogenic blend intake reduces bacterial counts in stool and improves antioxidant/oxidative status and immune responses.

Bis-triazolylchalcogenium-Functionalized Benzothiadiazole Derivatives as Light-up Sensors for DNA and BSA.

A range of bis-triazolylchalcogenium-BTD 3 was synthesized by a copper-catalyzed azide-alkyne cycloaddition of azido arylchalcogenides 1 and 4,7-diethynylbenzo[c][1,2,5]thiadiazole 2. Eight new compounds were obtained in moderate to good yields using 1 mol % of copper(II) acetate monohydrate under mild reaction conditions. In addition, the synthesized bis-triazolylchalcogenium-BTD 3a-3h were investigated regarding their photophysical, electrochemical, and biomolecule binding properties in solution. In general, compounds presented strong absorption bands at the 250-450 nm region and cyan to green emission properties. The redox process attributed to the chalcogen atom was observed by electrochemical analysis (CV techniques). In addition, spectroscopic studies by UV-vis, steady-state emission fluorescence, and molecular docking calculations evidenced the ability of each derivative to establish interactions with calf-thymus DNA (CT-DNA) and bovine serum albumin (BSA). The behavior presented for this new class of compounds makes them a promising tool as optical sensors for biomolecules.

Efficient synthesis and antitumor evaluation of 4-aminomethyl-N-arylpyrazoles: Discovery of potent and selective agents for ovarian cancer.

A new one-pot two-step sequential methodology for synthesis of novel 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives is reported. One-pot transformation of ß-enamino diketones and arylhydrazines generated 4-iminium-N-arylpyrazole salt intermediates in situ, which were easily transformed into 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives by NaBH3CN. The products could be isolated in the free or hydrochloride salt forms. Also, it was possible to obtain the products in the zwitterionic form by ester group hydrolysis. Furthermore, all synthesised compounds were evaluated in vitro against a panel of eight human tumor cell lines. The 4-[(tert-butylamino)methyl]-N-arylpyrazole derivatives were much more powerful than the hydrochloride and zwitterionic forms. Moreover, the results suggest that the N-aryl group at the pyrazole ring is vital for modulating antiproliferative activity. The 3-carboxyethyl 4-[(tert-butylamino)methyl]-N-phenylpyrazoles 3a-g exhibited higher inhibitory activities against OVCAR-3, with GI50 values of 0.013-8.78 µM, and lower inhibitory activities against normal human cell lines. Molecular docking was performed to evaluate the probable binding mode of 3a into active site of CDK2.

Neuropathy and primary headaches affect different subgroups of inflammatory bowel disease patients.

BACKGROUND: Peripheral neuropathies (PN) and primary headaches (PH) are common comorbidities in inflammatory bowel disease (IBD) patients. We aimed to evaluate whether PN and PH affect the same subgroups of IBD patients. METHODS: Since 2004, we established a cohort study to evaluate neurological diseases in IBD patients. Over 2 years, all consecutive (N = 155) IBD patients (either Crohn's disease (CD) or ulcerative colitis (UC) were evaluated for the presence of PN and PH. PH were also evaluated in dyspeptic patients (N = 84) and IBD relatives (controls, N = 101). After neurological evaluation, symptomatic patients underwent skin wrinkling test to evaluate small fiber function and/or electromyography. RESULTS: Headaches and migraine were more prevalent in IBD than control patients: 52.3 and 34.2% vs. 40.6 and 20.8% (P < 0.05). Migraine was 2.6 times more common in CD patients than controls (CI = 1.34-5.129) and 8.6 times (13.3 times in the CD group) more common in men with IBD (P < 0.05). Headache and migraine were also more common in dyspeptic patients (P < 0.05). Chi-square, univariate, and multivariate regression analysis did not disclose any association between PN, headache, or PH (P > 0.05). Multivariate regression analysis disclosed that headaches were more prevalent in women, co-existing psychiatric disease, IBD, CD, and UC. After age, gender distribution, and prevalence of hypertension and psychiatric diseases were matched among the groups, there were still differences in the prevalence of headaches and migraine among IBD, CD, and UC versus control patients. CONCLUSION: In summary, PH and PN are common in IBD and do not affect the same subgroups of patients.

Anomalous aortic origin of the left main coronary artery associated with arterial compression-Case report.

BACKGROUND: Anomalous aortic origin of coronary artery is a rare finding, with varied presentation and symptomatology. Increasingly recognized by cardiac imaging, when found it raises questions about the appropriate approach and management. CASE PRESENTATION: We present a case of an 11-year-old female who presented with episodes of shortness of breath, angina, and syncope during exercise. Further investigation demonstrated episodes of nonsustained ventricular tachycardia on Holter and coronary angiotomography revealed that the left coronary artery had an anomalous origin from the right cusp with initial short intramural segment and significant external compression in its initial course between the aorta and the pulmonary artery. The patient was submitted to surgical correction with dissection of left coronary artery posterior to the pulmonary artery, coronary arteriotomy, roof ampliation with the autologous pericardium, and creation of neo-ostium in aorta. The patient had a satisfactory postoperative recovery, was discharged on the fifth-day post-op, and remains asymptomatic after 14 months of follow-up. Herein we present surgical video and postoperative echo and computed tomography scan.

Impacts of Escherichia coli infection in young breeder chicks on the animal behavior and cerebral activity of purinergic and cholinergic enzymes involved in the regulation of molecules with neurotransmitter and neuromodulator function.

The objective of this study was to evaluate if infection by Escherichia coli in juvenile breeder chicks alters the activity of enzymes involved in neurotransmission and cerebral immunomodulation, including acetylcholinesterase (AChE), nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (5'NT) and adenosine deaminase (ADA), as well as their effects on the pathogenesis of the disease. We divided 20 growing breeder chicks into two groups (n = 10 per group). One group was experimentally infected with 1 mL of culture medium containing 1 × 108 CFU of E. coli intraperitoneally. The other was the negative control. On the tenth day after infection, the animals were euthanized and brain samples were collected. Macroscopically, pericarditis and hepatic congestion were observed in the birds, but without histopathological lesions in the encephalon although the bacterium was present in the cerebral cortex of all animals in the infected group (i.e., they were PCR-positive). The activity of AChE, NTPDase, 5'-NT and ADA were evaluated in the cerebral homogenates of the birds after 10 days of infection. AChE activity in the cerebral cortex was lower in the infected group than in the control; there was an increase in the activity of NTPDase, 5'-nucleotidase and ADA, possibly indicating greater hydrolysis of ATP (P < 0.001), ADP (P < 0.01) and AMP (P < 0.01), followed by increased adenosine deamination (P < 0.001). Despite these changes, no apparently diseased animals were observed throughout the experimental period. Therefore, such changes in enzymatic activity may affect the functioning of the central nervous system because these enzymes are responsible for extracellular regulation of molecules that act on neurotransmission and immunomodulation such as acetylcholine, ATP and adenosine.

Fumonisin-(Fusarium verticillioides)-contaminated feed causes hepatic oxidative stress and negatively affects broiler performance in the early stage: Does supplementation with açai flour residues (Euterpe oleracea) minimize these problems?

Fusarium verticillioides is often responsible for contamination of poultry feed with the mycotoxin fumonisin. The aim of this study was to determine whether oxidative stress caused by intake of fumonisin-contaminated feed affects broiler performance at an early stage of development, as well as to test whether the addition of açai residue flour to contaminated feed would minimize these negative effects of redox metabolism. Birds were divided into four groups, with four repetitions of five animals each: control (TC) - birds that received basal feed; TCA treatment - basal feed supplemented with 2% açai flour; TF treatment - feed experimentally contaminated with fumonisin (10 ppm); TFA treatment - fumonisin-contaminated feed (10 ppm) and supplemented with açai fluor (2%). The experiment lasted 20 days, that is, the first 20 days of the chicks' lives. At the end of the experiment, the birds were weighed, and blood, intestine and liver samples were collected. The TCA and TFA had greater body weights and weight gain than did TF. Further, TCA and TFA had lower feed conversion than did TF. Açai flour intake (TCA and TFA) stimulated albumin synthesis and reduced serum AST activity. Nitrate/nitrite (NOx) levels were higher in serum of fumonisin-challenged (TF) birds than in groups; NOx levels were also higher in the livers of all test groups (TF, TCA and TFA) than in TC. Serum glutathione S-transferase (GST) activity was lower in fumonisin-consuming groups (TF and TFA); this was different from what occurred in the liver, that is, higher GST activity in TF and lower activity in TFA than in TC. Catalase activity (CAT) was also higher in the fumonisin-challenged groups (TF and TFA) and the groups supplemented with açai flour (TCA) than in TC. Serum reactive species (RS) and TBARS (lipid peroxidation) levels in the liver were lower in birds supplemented with açai flour and exposed to fumonisin. These data suggest that the addition of açai flour in the feed of early chickens improves animal performance and minimizes the effects of hepatic oxidative stress in birds fed fumonisin-contaminated feed.

Pathogenetic effects of feed intake containing of fumonisin (Fusarium verticillioides) in early broiler chicks and consequences on weight gain.

Fusarium verticillioides is often responsible for contamination of poultry feed with the mycotoxin fumonisin. The objective of the study was to determine whether fumonisin-contaminated feed in the early phase of broiler chicks causes oxidative imbalances and interferes with weight gain. One-day-old male Cobb 500 broiler chicks (n = 80) were divided into four treatments of 20 birds each, all of which were fed basal feed until the 11th day of age. From day 12, some birds were challenged with fumonisin in the feed: Control (T0) continued receiving the basal ration; treatments T1, T2, and T3 were given feed experimentally contaminated with fumonisin at concentrations of 2.5 ppm, 5 ppm and 10 ppm, respectively. After the 5th (day 17) and 10th (day 21) days, ten birds from each treatment were euthanized for blood and tissue collection to measure histopathological, biochemical and oxidative stress markers. All animals were weighed individually at the beginning of the experiment (day 12), and at 17 and 21 days of age. Birds that ingested 10 ppm of fumonisin (T3) had lower (P < 0.05) weight gain compared to those in T0. At 21 days, the body weights of the T1, T2 and T3 chicks were 1.3%, 8.97% and 18.7% lower, respectively, than those of T0. No histological lesions in the livers were observed for any treatment; however, higher levels of reactive oxygen species (ROS: day 21) and lipoperoxidation (LPO: days 17 and 21) were observed, associated with lower liver activity of the enzymes superoxide dismutase (SOD: day 21), glutathione peroxidase (GPx: day 17 and 21) and glutathione S-transferase (GST: day 21) when birds consumed 5 or 10 ppm of fumonisin. In serum, LPO levels and SOD and GPx activities were lower for groups consuming high doses of fumonisin in the diet (T2 and T3); ROS levels and GST activity were higher in these birds. Birds that consumed fumonisin-containing diets had lower levels of alanine aminotransferase, total protein and albumin (T3); as well as lower serum glucose levels (days 17 and 21), uric acid and triglycerides (day 21) in T3 than in T0. At 21 days, there were smaller crypt sizes and intestinal villi in birds that consumed high levels of fumonisin. These results suggest that fumonisin (10 ppm) in chick diet causes hepatic oxidative stress and impairs intestinal health, consequently negatively affecting weight gain.

Synthesis of Selenochromenes via Dehydration of Arylalkynols Promoted by Iron(III) Chloride and Diorganyl Diselenides.

We report here the regioselective 6-endo-dig cyclization of [2-(butylselanyl)phenyl]propynols promoted by the cooperative action between diorganyl diselenides and iron(III) chloride leading to the formation of 4-methylene-3-(organoselanyl)-selenochromenes. The results of the reaction condition optimization studies showed that the solvent, the iron source, and the amount of diorganyl diselenide had a fundamental influence on the reaction yields. In the presence of iron(III) chloride (1.5 equiv) and diorganyl diselenides (1.0 equiv), using dichloromethane as the solvent, at room temperature, 4-methylene-3-(organoselanyl)-selenochromenes were formed in moderate to good yields. The reaction conditions were found to be suitable for substrates bearing electron-donating and electron-withdrawing groups on the aromatic ring at both propargyl and alkyne positions. However, we observed a limitation in the reaction conditions when they were applied to other diorganyl dichalcogenides, such as diorganyl disulfides and diorganyl ditellurides, which did not give the corresponding products. We also elaborated on a mechanism proposal based on control experiments performed.

Selenium-promoted electrophilic cyclization of arylpropiolamides: synthesis of 3-organoselenyl spiro[4,5]trienones.

This paper describes a selenium-promoted electrophilic cyclization of arylpropiolamides allowing the synthesis of 3-organoselenyl spiro[4,5]trienones via a 5-endo-dig ipso-mode. The 3-organoselenyl-quinolinone derivative formation via 6-endo-dig was avoided using an electrophilic organoselenium species in a metal-free protocol. The use of phenylselenyl bromide (1.3 equiv.), as the electrophilic source, in nitromethane (3 mL) at 90 °C enabled the cyclization of N-(2-methoxyphenyl)-N-methyl-3-phenylpropiolamides, giving 3-organoselenyl[4,5]triene-2,6-dione derivatives. The extension of the standard conditions to the N-(4-methoxyphenyl)-phenylpropiolamides led to the corresponding 3-organoselenyl spiro[4,5]trienones having the carbonyl group at the 8-position. Besides, we demonstrated a general application of our approach by using 3-organoselenyl spiro[4,5]trienones as substrates in Suzuki cross-coupling reactions, which gave the cross-coupled products in good yields.

Synthesis of novel 3,5,6-trisubstituted 2-pyridone derivatives and evaluation for their anti-inflammatory activity.

The inflammatory response is the reaction of living tissue to an injury of a foreign nature, such as infection and irritants, and occurs as part of the body's natural defence response. Compounds capable of inhibiting cyclooxygenase (COX) enzymes, especially COX-2, have great potential as anti-inflammatory agents. Herein we present the regioselective synthesis of 49 novel compounds based on the 2-pyridone nucleus. The topical anti-inflammatory activity of seventeen compounds was evaluated in mice by croton oil (CO) induced ear edema assay. Most of the compounds exhibited a high level of in vivo anti-inflammatory activity, reducing ear edema and myeloperoxidase (MPO) activity. The most active compounds (2a and 7a) were inhibitors of COX enzymes. Compound 2a selectively inhibited the COX-2, while 7a was nonselective. Further, the compound 2a showed effective binding at the active site of COX-2 co-crystal by docking molecular study.

Evaluation of seeds ethanolic extracts of Triplaris gardneriana Wedd. using in vitro and in vivo toxicological methods.

Triplaris gardneriana Wedd. is a tree used in folk medicine to treat venereal diseases and inflammation as well as a source of biological compounds with antioxidant capacity. In order to assess the safety of these bioactive compounds, the present study aimed to determine the toxicity of an ethanolic extract of T. gardneriana, (EETg). Toxicological tests included hemolytic activity, toxicity toward the brine shrimp Artemia, cytotoxicity against breast cancer cells (MCF7) and acute oral toxicity in rodents. In addition, toxicogenomics techniques were used to determine genome expression in MCF7 cells exposed to EETg. The results showed that the extract exhibits approximately 60% of hemolytic activity at the highest tested concentration (64 µg/ml) and toxicity against nauplii of Artemia sp. (LC50 of 67.85 µg/ml). Further, EETg appears to be cytotoxic to MCF7 (cell viability reduced to 40% at 250 µg/ml after 24 hr). Genomic data demonstrated differential expression of 14 genes. Data analysis indicated possible altered pathways (e.g., xenobiotic metabolism), possible adverse health risks (e.g., hepatotoxicity), and drugs with similar gene expression profile (e.g., antimicrobials). The investigation provides important information on potentially adverse aspects of EETg, which need to be considered prior to the therapeutic utilization of this plant.Abbreviations: EETg: ethanolic extract of T. gardneriana seeds; MCF7: michigan cancer foundation-7 which refers to a human breast cell line (adenocarcinoma); NGS: next-generation sequencing; edgeR: empirical analysis of digital gene expression data in R; Consensus: consensus path database; FDR: false discovery rate; NCBI: national center for biotechnology information; KEGG: kyoto encyclopedia of genes and genomes; Ingenuity: ingenuity pathway analysis software; CMAP: connectivity map; OECD: organization for economic co-operation and development; HL-60: human promyelocytic leukemia cells; PC3: prostate cancer cells.

Prognostic value of the preoperative neutrophil-lymphocyte ratio in patients undergoing the bidirectional Glenn procedure.

INTRODUCTION: The neutrophil-lymphocyte ratio (NLR) has been associated with worse outcomes in patients undergoing coronary artery bypass graft surgery. Little is known about this association in the pediatric population who require surgery for congenital heart defects, especially in patients with a single ventricle (SV). OBJECTIVE: To analyze the association of the preoperative NLR with outcomes in patients undergoing the bidirectional Glenn procedure. METHODS: This study involved a retrospective cohort analysis of 141 consecutive patients with SV undergoing the bidirectional Glenn procedure between January 2011 and December 2017 in two centers. The preoperative NLR was included in the last hemogram test before surgery. According to the NLR level, the patients were divided into group I (NLR < 1), group II (NLR between 1 and 2), and group III (NLR > 2). The primary endpoint was total hospital length of stay (LOS), and secondary endpoints were mechanical ventilation (MV) time, intensive care unit (ICU) LOS, ventricular dysfunction, complications, and middle-term mortality. RESULTS: The average follow-up duration was 48 months. There were 61, 47, and 33 patients in groups I, II, and III, respectively. Patients in group III exhibited an increased risk of prolonged total hospital LOS (P = .00). An increase in MV time (P = .03) and ICU LOS (P = .02) was also observed in this group, and these patients experienced greater mortality in 24 months following the surgery (P = .03). There was no association between the NLR and ventricular dysfunction (P = .26) and complications (P = .46). CONCLUSION: A high preoperative NLR was associated with worse outcomes in patients with SV physiology undergoing the bidirectional Glenn procedure.

Effects of the inclusion of açai oil in diet of prepartum Holstein cows on milk production, somatic cell counts and future lactation.

We measured the effects of açai oil in the diets of prepartum cows to evaluate health, milk production and quality. Sixteen Holstein cows were divided into two groups: SOY used as control, and AÇAI, test group. Occurred inclusion of 4% soybean or açai oils was provided in the concentrate starting at 20 days prepartum [d -20 to d 0 (partum-day)]. The AÇAI diet increased (P=0.01) milk production (d 10 and 20) and reduced somatic cell count (d 20). In milk, no effects were detected (P≥0.10) for concentration of fat, lactose or protein as well as in terms of serum concentration of calcium, albumin or triglycerides. AÇAI diet tended to increase (P=0.09) serum concentrations of total protein, glutathione transferase (d 4), and total antioxidant capacity (d 4 and 10) and increased (P≤0.05) globulin, gamma-glutamyl transferase, superoxide dismutase and glutathione peroxidase (d 4). Further, AÇAI diet reduced the serum concentration of creatine kinase (P≤0.05) (d 0, 4 and 10), reactive oxygen species (d 0 and 4) and lipoperoxidation (d 0) and tended to reduce aspartate transaminase activity (P=0.07; d 0 and 4). Açai oil in the diets in prepartum cows improved their health as well as milk production and quality.

Proteomics analysis of zebrafish larvae exposed to 3,4-dichloroaniline using the fish embryo acute toxicity test.

The zebrafish (Danio rerio) is a small teleost fish that is becoming increasingly popular in laboratories worldwide and several attributes have also placed the zebrafish under the spotlight of (eco)toxicological studies. Since the 1990s, international organizations such as ISO and OECD have published guidelines for the use of zebrafish in ecotoxicological assessment of environmental toxicants such as the Fish Embryo Acute Toxicity (FET) test, OECD n° 236 guideline. This protocol uses 3,4-dichloroaniline (DCA), an aniline pesticide whose toxicity to fish species at early life stages is well known, as a positive control. Despite its use, little is known about its molecular mechanisms, especially in the context of the FET test. Therefore, this study aimed to investigate such changes in zebrafish larvae exposed to DCA (4 mg/L) for 96 hours using gel-free proteomics. Twenty-four proteins detected in both groups were identified as significantly affected by DCA exposure, and, when considering group-specific entities, 48 proteins were exclusive to DCA (group-specific proteins) while 248 were only detected in the control group. Proteins modulated by DCA treatment were found to be involved in metabolic processes, especially lipids and hormone metabolism (eg, Apoa1 and Apoa1b and vitelogenins), as well as proteins important for developmental processes and organogenesis (eg, Myhc4, Acta2, Sncb, and Marcksb). The results presented here may therefore provide a better understanding of the relationships between molecular changes and phenotype in zebrafish larvae treated with DCA, the reference compound of the FET test.