Prevalence of PICC-related thrombosis in patients with hematological malignancies: a systematic review.

PURPOSE: To estimate the prevalence of peripherally inserted central catheter (PICC)-related venous thrombosis in patients with hematological malignancies. METHODS: A systematic review of observational studies that evaluated the occurrence of PICC-related venous thrombosis in children, adults, and older people with hematological malignancies was conducted. Searches were carried out on June 12th, 2023 on PubMed, CINAHL, Embase, Web of Science Core Collection, Scopus, and LILACS, and to gray literature on Google Scholar, and ProQuest Dissertations and Theses Global. Eligibility criteria were applied independently by two reviewers, first on the titles and abstracts on the Rayyan platform and then on the full text of eligible studies. Risk of bias was assessed by the JBI checklist. Data were summarized descriptively, and the meta-analysis was carried out using the MetaXL 5.3 software. The review followed JBI guidelines and PRISMA for reporting. RESULTS: In the 40 studies included, prevalence of PICC-related venous thrombosis was 9% in general, 9% in adults, and 6% in children with hematological malignancies. Most studies only evaluated cases of symptomatic thrombosis (n = 25; 64%). CONCLUSION: Patients with hematological malignancies using PICC have an estimated prevalence of PICC-related venous thrombosis of 9%, and this rate may be underestimated due to the consideration of mostly symptomatic cases.

Virtual opioid poisoning education and naloxone distribution programs: A scoping review.

The global opioid poisoning crisis is a complex issue with far-reaching public health implications. Opioid Poisoning Education and Naloxone Distribution (OPEND) programs aim to reduce stigma and promote harm reduction strategies, enhancing participants' ability to apply life-saving interventions, including naloxone administration and cardiopulmonary resuscitation (CPR) to opioid poisoning. While virtual OPEND programs have shown promise in improving knowledge about opioid poisoning response, their implementation and evaluation have been limited. The COVID-19 pandemic has sparked renewed interest in virtual health services, including OPEND programs. Our study reviews the literature on fully virtual OPEND programs worldwide. We analyzed 7,722 articles, 30 of which met our inclusion criteria. We extracted and synthesized information about the interventions' type, content, duration, the scales used, and key findings. Our search shows a diversity of interventions being implemented, with different study designs, duration, outcomes, scales, and different time points for measurement, all of which hinder a meaningful analysis of interventions' effectiveness. Despite this, virtual OPEND programs appear effective in increasing knowledge, confidence, and preparedness to respond to opioid poisoning while improving stigma regarding people who use opioids. This effect appears to be true in a wide variety of populations but is significantly relevant when focused on laypersons. Despite increasing efforts, access remains an issue, with most interventions addressing White people in urban areas. Our findings offer valuable insights for the design, implementation, and evaluation of future virtual OPEND programs.

Intensive versus less intensive blood pressure targets after mechanical thrombectomy in acute ischemic stroke: a systematic review and network meta-analysis.

Hemodynamic management, specifically blood pressure, is essential to reduce mortality and preserve functional capacity. However, the literature is uncertain about the best blood pressure target to be adopted after performing mechanical thrombectomy in patients with acute ischemic stroke. Randomized clinical trials that compared blood pressure goals after mechanical thrombectomy were searched in the following databases: MEDLINE/PubMed, Embase, Scopus, Biomedcentral, and Cochrane Library. The last search was on September 19, 2023. The results obtained were used to construct network meta-analyses. A total of 1556 participants were enrolled from 4 randomized controlled trials (OPTIMAL-BP, ENCHANTED2/MT, BP-TARGET, BEST-II). The last article was not included in the network meta-analysis because it did not have common blood pressure targets. The outcomes compared were: mRS (modified Rankin scale), eTICI/mTICI scale scores, symptomatic and any intracerebral hemorrhage, post-intervention NIHSS, and post-intervention infarct volume. The outcomes using the mRS scale showed that better outcomes were reached with less intensive blood pressure targets when comparing < 120 mmHg vs. ≤ 180 mmHg, OR: 0.71 (95% CI 0.54 - 0.94), in the outcome of mRS 0-1. And for the mRS 0-2 outcome with comparisons < 120 mmHg vs. ≤ 180 mmHg, with OR: 0.59 (95% CI 0.44 - 0.77) and < 140 mmHg vs. ≤ 180 mmHg, with OR: 0.61 (95% CI 0.41 - 0.89). In patients with large vessel occlusion treated with mechanical thrombectomy and who achieved good reperfusion, intensive blood pressure lowering is not effective and might be harmful respect to non intensive blood pressure control in recanalized patients.

Donation barriers, enablers, patterns and predictors of milk bank donors in the United States and United Kingdom.

Pasteurised donor human milk is recommended for very low birthweight infants who do not have access to their mother's milk. Although the use of donor milk continues to increase, little is known about the donation experiences of milk bank donors. We aimed to describe and compare enablers, barriers and patterns of human milk donation and identify factors predicting donation volume in a convenience sample of approved milk bank donors in the United Kingdom and the United States. A cross-sectional online survey was conducted from August 2022 to December 2022. Approved milk bank donors (n = 556) from three milk banks in the United States (n = 369, Mothers' Milk Bank of Florida, Mother's Milk Bank of North Texas and Northwest Mothers Milk Bank) and one milk bank in the United Kingdom (n = 187, Hearts Milk Bank) completed the survey. A substantial portion of donors in both settings reported participating in other forms of milk exchange (51% of U.S. donors vs. 39% of UK donors, p = 0.009). Top donation barriers reported in both settings were completing the serological screening and having enough space to store collected milk. Most donors started donating when their infant was 3 months old or older and reported donating mature milk. The most common source of information related to milk banking in each setting was the internet (United Kingdom-70% vs. United States - 63%, p = 0.112). Variables that predicted lifetime donation volume differed between the United States and the United Kingdom, highlighting the importance of setting-specific milk banking research.

Layered double hydroxides (LDHs) as efficient and safe carriers for miRNA inhibitors: In vitro and in vivo assessment of biocompatibility.

Layered double hydroxides (LDHs) have been employed as nano-sized carriers for therapeutic/bio-active molecules, including small interfering RNAs (siRNAs). However, the potential of LDHs nanoparticles for an efficient and safe antisense oligonucleotide (AMO) delivery still requires studies. In this research, we have tested the suitability of a Mg-Al-LDH-based nanocarrier loaded with a miRNA-196b-5p inhibitor. LDHs (and LDH-Oligo complex) were synthesized by the coprecipitation method followed by physicochemical characterization as hydrodynamic size, surface charge, crystallinity, and chemical groups. Thymic endothelial cell line (tEnd.1) were transfected with LDH-Oligo and were evaluated for i. cell viability by MTT, trypan blue, and propidium iodide assays; ii. transfection efficiency by flow cytometry, and iii. depletion of miRNA-196b-5p by RT-qPCR. In addition, Drosophila melanogaster larvae were fed LDHs and evaluated for: i. larval motility; ii. pupation rate; iii. larval-pupal transition; iv. lethality, and v. emergence rate. We demonstrated that LDHs nanoparticles are stable in aqueous solutions and exhibit a regular hexagonal shape. The LDH-AMO complex showed a transfection efficiency of 93.95 ± 2.15 % and induced a significant depletion of miRNA-196b-5p 48h after transfection. No cytotoxic effects were detected in tEnd.1 cells at concentrations up to 50 µg/ml, as well as in Drosophila exposed up to 500 µg of LDH. In conclusion, our data suggest that LDHs are biocompatible and efficient carriers for miRNA inhibitors and can be used as a viable and effective tool in functional miRNA inhibition assays.

Adsorption of contaminants by nanomaterials synthesized by green and conventional routes: a critical review.

Nanomaterials, due to their large surface area and selectivity, have stood out as an alternative for the adsorption of contaminants from water and effluents. Synthesized from green or traditional protocols, the main advantages and disadvantages of green nanomaterials are the elimination of the use of toxic chemicals and difficulty of reproducing the preparation of nanomaterials, respectively, while traditional nanomaterials have the main advantage of being able to prepare nanomaterials with well-defined morphological properties and the disadvantage of using potentially toxic chemicals. Thus, based on the particularities of green and conventional nanomaterials, this review aims to fill a gap in the literature on the comparison of the synthesis, morphology, and application of these nanomaterials in the adsorption of contaminants in water. Focusing on the adsorption of heavy metals, pesticides, pharmaceuticals, dyes, polyaromatic hydrocarbons, and phenol derivatives in water, for the first time, a review article explored and compared how chemical and morphological changes in nanoadsorbents synthesized by green and conventional protocols affect performance in the adsorption of contaminants in water. Despite advances in the area, there is still a lack of review articles on the topic.

Prevalence of adverse events in pronated intubated adult COVID-19 patients: A systematic review with meta-analysis.

AIM: To present the pooled estimated prevalence of adverse events in pronated intubated adult COVID-19 patients. DESIGN: A systematic review and meta-analysis. DATA SOURCES: This study used the Cochrane Library, CINAHL, Embase, LILACS, Livivo, PubMed, Scopus, and Web of Science databases as data sources. METHODS: The studies were meta-analysed using JAMOVI 1.6.15 software. A random-effects model was used to identify the global prevalence of adverse events, confidence intervals and the heterogeneity data. Risk of bias was assessed using the Joanna Briggs Institute tool, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of the 7904 studies identified, 169 were included for full reading, and 10 were included in the review. The most prevalent adverse events were pressure injuries (59%), haemodynamic instability (23%), death (17%) and device loss or traction (9%). CONCLUSION: The most prevalent adverse events in mechanically ventilated pronated patients with COVID-19 are pressure injuries, presence of haemodynamic instability, death and device loss or traction. IMPLICATIONS FOR THE PATIENT CARE: The evidence identified in this review can help improve the quality and safety of patient care by helping to design care protocols to avoid the development of adverse events that can cause permanent sequelae in these patients. IMPACT: This systematic review addressed the adverse events related to prone position in intubated adult COVID-19 patients. We identified that the most prevalent adverse events in these patients were pressure injuries, haemodynamic instability, device loss or traction and death. The results of this review may influence the clinical practice of nurses who work in intensive care units and, consequently, the nursing care provided not only to COVID-19 patients but for all intubated patients due to other reasons in intensive care units. REPORTING METHOD: This systematic review adhered to the PRISMA reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: As this is a systematic review, we analysed data from primary studies conducted by many researchers. Thus, there was no patient or public contribution in this review.

Anti-Toxoplasma gondii screening of MMV pandemic response box and evaluation of RWJ-67657 efficacy in chronically infected mice.

Toxoplasmosis is a significant public health concern with limited therapeutic options. The medicines for malaria venture (MMV) developed the pandemic response box (PRB) containing 400 drug-like molecules with broad pathogen activity. The aim of this work is to evaluate PRB compounds for their anti-Toxoplasma gondii activity and identify promising candidates for further evaluation. Screening identified 42 selective compounds with half effective concentration (EC50) ranging from 2.4 to 913.1 nm and half cytotoxic concentration (CC50) ranging from 6 µm to >50 µm. Selectivity index (SI) values (CC50/EC50) ranged from 11 to 17 708. Based on its in silico and in vitro profile and its commercial availability, RWJ-67657 was selected for further studies. Molecular docking analysis showed RWJ-67657 is predicted to bind to T. gondii p38 mitogen-activated protein kinase (TgMAPK). Oral administration of RWJ-67657 (20 mg kg day−1/10 days) significantly reduced parasite burden in chronically infected mice compared to mock-treated group (P < 0.01). These findings highlight the PRB as a promising source for anti-T. gondii compounds, with several showing favourable drug properties, including MMV1634492, MMV002731, MMV1634491, MMV1581551, MMV011565, MMV1581558, MMV1578577, MMV233495 and MMV1580482, firstly described here as anti-T. gondii agents. RWJ-67657 emerges as a valuable drug candidate for experimental chronic cerebral toxoplasmosis therapy.

Comparison of Breastfeeding and Pumping Experiences of Milk Bank Donors in the United States and United Kingdom.

Background/Objective: As human milk banking services expand, information about lifestyle characteristics and infant feeding experiences of milk bank donors is relatively limited. Our goal was to describe and compare milk bank donors' demographic, clinical, and lifestyle characteristics, and breastfeeding experiences in a variety of geographic settings. Methods: A cross-sectional online survey was conducted from August 2022 to December 2022 with approved donors from three milk banks in the United States (n = 369), and one milk bank in United Kingdom (n = 187). Results: Donors in all settings were predominantly in their early 30s, White, married, educated, and identified as female. U.K. donors reported more frequently being on maternity leave (33% versus 5%, p < 0.001), predominantly feeding directly at the breast in the first 3 months postpartum (51% versus 28%, p < 0.001), and breastfeeding a single child longer (21.2 versus 13.3 months, p < 0.001) than U.S. donors. Significantly more U.S. donors reported pumping due to work (34% versus 11%, p < 0.001) and pumping multiple times per day (57% versus 36%, p < 0.001). Most donors reported receiving information about breastfeeding from a health care provider (94% United States and 88% United Kingdom, p = 0.022), while the internet was the most popular source of information about pumping (65% United States and 64% United Kingdom, p = 0.751). Conclusion: Factors not directly related to milk banking (e.g., maternity leave, sources of breastfeeding/pumping assistance) may have an impact on how donors feed their children and ultimately on their milk donation pattern. The impact of donor characteristics and feeding practices on donation patterns warrants further investigation.

Drug-excipient compatibility studies in formulation development: A case study with benznidazole and monoglycerides.

Monoglycerides (MGs) such as glycerol monolaurate (GML) and glycerol monostearate (GMS) have been used as excipients in oral formulations because of their emulsifying effect as well as their ability to inhibit the precipitation and intestinal efflux of drugs. Excipient-drug compatibility studies, however, have been underexplored. In this study, benznidazole (BNZ) was selected as a drug model due to the difficulty in improving its solubility and because of the potential impact on public health (it is the only drug currently used to treat Chagas disease). The effect of different processing conditions (maceration, ball milling, and melting) on the physical-chemistry properties of BNZ/MGs mixtures was investigated to guide the rational development of new solid formulations. GML was more effective in improving the solubility of BNZ, which could be due to its more malleable structure, less hydrophobic nature, and greater interaction with BNZ. The formation of hydrogen bonds between the imidazole group of BNZ and the polar region of GML was confirmed by spectroscopy analyses (IR, 1H NMR). The higher the monoglyceride content in the mixture, the higher the BNZ solubility. Regardless of the method of processing the mixture, the drug was found to be crystalline. Polarized light microscopy analysis showed the presence of spherulites. Overall, these findings suggest that preparation methods of BNZ:MGs formulations that involve thermal or/and mechanical treatment have a low impact on the solid properties of the material, and this allows for the production of formulations with reproducible performance.

Repurposing the Medicines for Malaria Venture's COVID Box to discover potent inhibitors of Toxoplasma gondii, and in vivo efficacy evaluation of almitrine bismesylate (MMV1804175) in chronically infected mice.

Toxoplasmosis, caused by the obligate intracellular parasite Toxoplasma gondii, affects about one-third of the world's population and can cause severe congenital, neurological and ocular issues. Current treatment options are limited, and there are no human vaccines available to prevent transmission. Drug repurposing has been effective in identifying anti-T. gondii drugs. In this study, the screening of the COVID Box, a compilation of 160 compounds provided by the "Medicines for Malaria Venture" organization, was conducted to explore its potential for repurposing drugs to combat toxoplasmosis. The objective of the present work was to evaluate the compounds' ability to inhibit T. gondii tachyzoite growth, assess their cytotoxicity against human cells, examine their absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, and investigate the potential of one candidate drug through an experimental chronic model of toxoplasmosis. Early screening identified 29 compounds that could inhibit T. gondii survival by over 80% while keeping human cell survival up to 50% at a concentration of 1 µM. The Half Effective Concentrations (EC50) of these compounds ranged from 0.04 to 0.92 µM, while the Half Cytotoxic Concentrations (CC50) ranged from 2.48 to over 50 µM. Almitrine was chosen for further evaluation due to its favorable characteristics, including anti-T. gondii activity at nanomolar concentrations, low cytotoxicity, and ADMET properties. Administering almitrine bismesylate (Vectarion®) orally at dose of 25 mg/kg/day for ten consecutive days resulted in a statistically significant (p < 0.001) reduction in parasite burden in the brains of mice chronically infected with T. gondii (ME49 strain). This was determined by quantifying the RNA of living parasites using real-time PCR. The presented results suggest that almitrine may be a promising drug candidate for additional experimental studies on toxoplasmosis and provide further evidence of the potential of the MMV collections as a valuable source of drugs to be repositioned for infectious diseases.

The effect of caffeine on exercise performance is not influenced by ADORA2A genotypes, alone or pooled with CYP1A2 genotypes, in adolescent athletes.

PURPOSE: This study investigated the influence of the different genotypes of ADORA2A (1976 C > T, rs 5751876), alone or pooled with CYP1A2 (163 C > A rs 762551) genotypes, on the ergogenic effects of caffeine (CAF) on various aspects of physical performance in male adolescent athletes. METHODS: Ninety male adolescent athletes (age = 15.5 ± 2 years) were classified according to their genotypes for 1976 C > T ADORA2A (TT homozygous or CADORA2A allele carriers) and 163 C > A CYP1A2 (AA homozygous or CCYP1A2 allele carriers). Participants were further divided in four groups (1-TTADORA2A + AACYP1A2; 2-TTADORA2A + AC/CCCYP1A2; 3-AACYP1A2 + CT/CCADORA2A;4-AC/CCCYP1A2 + CT/CCADORA2A). Using a randomized, crossover, counterbalanced, and double-blind design, participants ingested CAF (6 mg kg-1) or a placebo (PLA, 300 mg of cellulose) one hour before performing a sequence of physical tests: handgrip strength, agility test, countermovement jump (CMJ), Spike Jump (SJ), sit-ups, push-ups, and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). RESULTS: CAF enhanced handgrip strength (CAF: 35.0 ± 9.2 kg force; PLA: 33.5 ± 8.9 kg force; p = 0.050), CMJ height (CAF: 49.6 ± 12.3 cm; PLA: 48.3 ± 13.6 cm; p = 0.013), SJ height (CAF: 54.7 ± 13.3 cm; PLA: 53.1 ± 14.8 cm; p = 0.013), number of sit-ups (CAF: 37 ± 8; PLA: 35 ± 8; p = 0.001), and distance covered on the Yoyo IR1 test (CAF: 991.6 ± 371.0 m; PLA: 896.0 ± 311.0 m; p = 0.001), This CAF-induced improvement on exercise performance was, however, independent of genotypes groups (all p > 0.05). CAF had no effect on agility (CAF: 15.8 ± 1.2 s; PLA: 15.9 ± 1.3 s; p = 0.070) and push-up (CAF: 26.6 ± 12.0; PLA: 25.0 ± 11.0; p = 0.280) tests. CONCLUSION: The acute caffeine intake of 6.0 mg.kg-1 improves several aspects of physical performance, which seems to be independent of ADORA2A genotypes, alone or in combination with CYP1A2 genotypes.

Prevalence of cholelithiasis in lion tamarins (Leontopithecus spp.) kept under human care by using abdominal ultrasound.

BACKGROUND: Cholelithiasis is a digestive system disorder of multifactorial origin that occurs due to stones formed in the gallbladder. This study aimed at investigating by abdominal ultrasound examination the prevalence of cholelithiasis in lion tamarins kept under human care. METHODS: Thirty lion tamarins from five Brazilian zoos, including 17 golden lion tamarins and 13 golden-headed lion tamarins, were evaluated. RESULTS: Considering all lion tamarins, the overall frequency of cholelithiasis was 53.3% (16/30). There were no significant differences between species and sex. Cholelithiasis was predominant (75.0%) in lion tamarins older than 5 years. Septate gallbladder was observed in 86.6% (26/30) of the lion tamarins. Of these, 53.8% (14/26) had gallstones. Biochemical analysis revealed a moderate positive correlation between gamma-glutamyl transferase and the number of gallstones. CONCLUSIONS: Asymptomatic cholelithiasis is frequent in lion tamarins kept under human care. Therefore, systematic monitoring through ultrasound should be part of the preventive care of these animals.

Dressing to prevent surgical site infection in adult patients with cancer: a systematic review with meta-analysis.

PURPOSE: To identify the most effective dressing for application to surgical wounds with primary closure to prevent surgical site infection (SSI) in adult patients with cancer undergoing elective surgeries. METHODS: This systematic review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, with online searches conducted in the CINHAL, Cochrane Central, LILACS, PubMed, Scopus, Embase, Livivo, and Web of Science databases. An additional search was conducted in gray literature using Google Scholar. The risk of bias was assessed using RoB 2.0. The certainty of evidence was evaluated using the Grading of Recommendations Assessment and Development and Evaluation, and the results were synthesized in a descriptive manner and using meta-analysis. RESULTS: Eleven randomized clinical trials were conducted to compare different types of dressing-silver dressing with absorbent dressing (n = 3), mupirocin dressing with paraffin/no dressing (n = 1), honey-based dressing with absorbent dressing (n = 1), vitamin E and silicone-containing dressing with absorbent dressing (n = 1), and negative pressure wound therapy with absorbent dressing (n = 4)-and compare the usage duration of absorbent dressing (n = 1). Nine trials presented a low risk of bias, and two were classified as having uncertain bias. Compared with absorbent dressing, silver dressing did not reduce the risk of developing any type of SSI in 894 clinical trial participants (risk relative RR: 0.72; 95% confidence interval [CI] [0.44, 1.17] p = 0.18). Compared with absorbent dressing, negative pressure wound therapy did not reduce the risk of developing any type of SSI in the 1041 participants of two clinical trials (RR 0.68; 95% CI [0.31, 1.26] p = 0.22). The certainty of evidence of the three meta-analyses was considered low or very low for the prevention of SSI. We believe that this low certainty of evidence can be improved by conducting new studies in the future. CONCLUSION: There is no evidence regarding which dressing is the most effective in preventing SSI in adult patients with cancer.

Body composition in patients with hepatic glycogen storage diseases.

OBJECTIVES: The present study aimed to evaluate the body composition of hepatic glycogen storage disorders (GSDs) through dual energy x-ray absorptiometry. METHODS: This was an exploratory, observational, cross-sectional study. Twenty-four patients with GSD (type Ia: n = 13, Ib: n = 5, III: n = 2, and IX-α/ß/γ: n = 4; female sex: n = 13; age <8 y: n = 3, 8-19 y: n = 14, and >19 y: n = 7) were included. Three-day dietary records were collected in the week preceding dual energy x-ray absorptiometry. Body composition findings were correlated with clinical parameters, uncooked cornstarch (UCCS) regimen, dietary intake, and markers of treatment adherence. RESULTS: An elevated fat mass (FM) index was found in 16 of 21 patients (age 8-19 y: n = 10 and >19 y: n = 6; GSD type Ia: n = 12, Ib: n = 2, III: n = 1, and IX-γ: n = 1). A lean mass (LM) index evaluation showed no LM deficits in relation to corresponding reference populations. Relative skeletal muscle index values were decreased in 2 of 7 adult patients (type Ib: n = 1 and IX-α: n = 1). UCCS (g/d) correlated positively with the FM index (rs = 0.7; P ≤ 0.01). In contrast, relative UCCS intake (g/kg body weight) was negatively associated with LM/kg (rs = -0.8; P ≤ 0.01). CONCLUSIONS: These findings suggest a high frequency of elevated FM in patients with hepatic GSDs. We also suggest that treatment with UCCS is associated with excess weight in these patients. Additionally, the treatment strategy can impair protein intake, and lead to a decrease in LM.

Structure-guided engineering of key amino acids in UGT85B1 controlling substrate and stereo-specificity in aromatic cyanogenic glucoside biosynthesis.

Cyanogenic glucosides are important defense molecules in plants with useful biological activities in animals. Their last biosynthetic step consists of a glycosylation reaction that confers stability and increases structural diversity and is catalyzed by the UDP-dependent glycosyltransferases (UGTs) of glycosyltransferase family 1. These versatile enzymes have large and varied substrate scopes, and the structure-function relationships controlling scope and specificity remain poorly understood. Here, we report substrate-bound crystal structures and rational engineering of substrate and stereo-specificities of UGT85B1 from Sorghum bicolor involved in biosynthesis of the cyanogenic glucoside dhurrin. Substrate specificity was shifted from the natural substrate (S)-p-hydroxymandelonitrile to (S)-mandelonitrile by combining a mutation to abolish hydrogen bonding to the p-hydroxyl group with a mutation to provide steric hindrance at the p-hydroxyl group binding site (V132A/Q225W). Further, stereo-specificity was shifted from (S) to (R) by substituting four rationally chosen residues within 6 Å of the nitrile group (M312T/A313T/H408F/G409A). These activities were compared to two other UGTs involved in the biosynthesis of aromatic cyanogenic glucosides in Prunus dulcis (almond) and Eucalyptus cladocalyx. Together, these studies enabled us to pinpoint factors that drive substrate and stereo-specificities in the cyanogenic glucoside biosynthetic UGTs. The structure-guided engineering of the functional properties of UGT85B1 enhances our understanding of the evolution of UGTs involved in the biosynthesis of cyanogenic glucosides and will enable future engineering efforts towards new biotechnological applications.

The Role of the IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) Polymorphisms of Impulsive and Aggressive Personality Traits in Cocaine/Crack Users.

Cytokines and nitric oxide have been associated with impulsive and aggressive personality traits. We conducted the first study that investigated the role of SNPs in cytokines and nitric oxide genes and the influence in the progression of aggressive and impulsive behavior in 107 of cocaine and crack users. In this case-control, IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms were determined by Real-Time PCR. In addition, the relationship between these polymorphisms and Impulsivity and Aggression was determined. We found that the physical aggressiveness sub score was negatively correlated with the C allele of -819C/T polymorphism of the IL-10 (b = -0.14; p = 0.04). The T allele of the SNP -786T/C of the ENOS gene positively predicts traits of physical aggressiveness (b = 0.14; p = 0.04). The GA genotype (b = 0.22; p = 0.01) and the A allele (b = 0.15; p = 0.02) of -308 G/A polymorphism of the TNFA were positively correlated with aggressiveness physical. The GA genotype (b = 0.20; p = 0.03) was positively correlated with aggressiveness verbal. IL-10 (-819C/T), TNFA (-308G/A) and ENOS (-786T/C) polymorphisms might be associated with high risk of aggressive and impulsive behavior.

Critical review of the toxicity mechanisms of bisphenol F in zebrafish (Danio rerio): Knowledge gaps and future directions.

Replacement chemicals for bisphenol A, such as bisphenol F (BPF), are detected in aquatic environments worldwide and can potentially exert negative effects on aquatic organisms. We synthesized peer-reviewed literature reporting molecular and physiological responses in zebrafish following exposure to BPF, as BPF is closely related to BPA structure and is a dominant replacement chemical in the marketplace. Global concentrations of BPF in aquatic environments were compiled and compared to physiological and behavioral impacts reported in zebrafish (e.g., developmental abnormalities, oxidative stress, immunotoxicity, endocrine disruption, and neurotoxicity). Using computational approaches, we elucidate BPF-mediated molecular networks and reveal novel biomarkers associated with BPF exposure. Functional classes of proteins including inflammatory cytokines, ATPases, peroxidases, and aromatic l-amino decarboxylases represent novel, underexplored targets of toxicity. Most revealing of this critical review is that few studies report biological responses to BPF at levels present in aquatic environments. Recommendations for future investigations based on knowledge gaps include: (1) Mechanistic studies in the central nervous system of zebrafish to address neurotoxicity; (2) Behavioral assays in zebrafish that assess the effects of BPF on anxiolytic, social, and fear-related behaviors; (3) Studies that broaden understanding of potential endocrine disrupting effects of BPF, for example insulin signaling is predicted to be sensitive to BPF exposure; (4) Studies into metabolic disruption with a focus on glutathione and aromatic amino acids, based upon pathway analysis data; (5) Studies utilizing mixture exposures with other BPA analogs to reflect environmental conditions more accurately.

Laryngeal Paralysis Following Endotracheal Intubation in a Dog: A Case Report.

The occurrence of laryngeal paralysis following endotracheal intubation in dogs is rare. A one-year-old canine was presented with aspiration pneumonia in the postoperative period following general anesthesia for acetabular denervation surgery. After a month of treatment for aspiration pneumonia, the patient had inspiratory stridor and dyspnea, and the diagnosis of unilateral laryngeal paralysis was made through laryngoscopy. Along with the benefits of endotracheal intubation come many risks. Laryngeal paralysis can be a serious complication, predisposing the patient to aspiration. This report is the second in veterinary medicine to describe laryngeal paralysis as a possible complication after endotracheal intubation in a dog.