Of Potions, Poisons, Polygonum and Pre‐emptive Polymorphism

There are scores of references to plants and herbs in William Shakespeare's plays; he was obviously very knowledgeable about their perceived effects. The secret to the highly potent love potion Oberon asks Puck to find, lies in the purple, yellow and white flower, ‘love‐in‐idleness’, a folk name for the wild pansy (Viola tricolour). When scientists from Royal Society of Chemistry and Quest International put this to the test 400 years later, they concluded that ‘Wild pansies were noted in herbal folklore medicine

Intensive care unit course of infants and children after cranial vault reconstruction for craniosynostosis

<p>Abstract</p> <p>Background</p> <p>Craniosynostosis (CSS) results from the premature closure of one or more cranial sutures, leading to deformed calvaria at birth. It is a common finding in children with an incidence of one in 2000 births. Surgery is required in order to release the synostotic constraint and promote normal calvaria growth. Cranial vault remodeling is the surgical approach to CSS repair at our institution and it involves excision of the frontal, parietal, and occipital bones. The purpose of this article is to describe the post-operative course of infants and children admitted to our PICU after undergoing cranial vault remodeling for primary CSS.</p> <p>Findings</p> <p>Complete data was available for analyses in only 82 patients, 44 males (M) and 38 females (F); M: F ratio was 1:1.2. Patients (pts) age in months (mo) ranged from 2 mo to 132 mo, mean 18.2 ±-24.9 mo and weights (wt) ranged from 4.7 kg to 31.4 kg, mean 10.24 ± 5.5 Kg.. Duration of surgery (DOS) ranged from 70 minutes to 573 minutes mean 331.6 ± 89.0 minutes. No significant correlation exist between duration of surgery, suture category, patient's age or use of blood products (P > 0.05). IOP blood loss was higher in older pts (P < 0.05) and it correlates with body temperature in the PICU (P < .0001). Post-op use of FFP correlated with intra-operative PRBC transfusion (P < 0.0001). More PRBC was transfused within 12 hrs-24 hrs in PICU compared to other time periods (P < 0.05). LOS in PICU was < 3 days in 68% and > 3 days in 32%. Pts with fever had prolonged LOS (P < 0. 05); re-intubation rate was 2.4% and MVD were 1.83 days. Repeat operation for poor cosmetic results occurred in 9.7% of pts.</p> <p>Conclusions</p> <p>Post-op morbidities from increased use of blood products can be minimized if cranial vault remodeling is done at a younger age in patients with primary CSS. PICU length of stay is determined in part by post-op pyrexia and it can be reduced if extensive evaluations of post-op fever are avoided.</p

Consequences of chronic diseases and other limitations associated with old age - A scoping review

Funding Information: This work supported in part by the LTC INTER COST, Evaluation of the Potential for Reducing Health and Social Expenses for Elderly People Using the Smart Environment, through the Ministry of Education, Youth and Sports, Czech Republic, under Project LTC18035; and in part by the project of Excellence, University of Hradec Kralove, FIM, Czech Republic (ID: 2205–2019). First author – Petra Maresova is principle investigator of LTC18035 INTER COST project, from which Petra Maresova, Ondrej Krejcar and Kamil Kuca are funded for all expenses including personal costs. Ehsan Javanmardi is funded from project of Excellence ID: 2205–2019 for personal costs. Sabina Barakovic, Jasmina Barakovic Husic and Signe Tomsone are members of COST ACTION 16226 of which also Petra Maresova and Ondrej Krejcar are paticipants, while this article also ACKnowledge this project CA16226. Funding Information: The authors would like to hereby acknowledge COST Action CA16226 for their networking support. The Indoor Living Space Improvement: Smart Habitat for the Elderly played a role of networking platform for knowledge sharing and interchanging ideas for joint research and publication, what was the base for creating this study. Based on CA16226 project LTC18035 INTER COST was proposed for national funding support of COST ACTION Framework. COST is a funding agency that helps innovation and research networks. Our Action was instrumental in connecting research programmes throughout the EU region. Their contribution has made it possible for scientists to connect with each other and share their ideas and findings. This allows for more research and better innovation. More information can be found at www.cost.eu. The authors would also like to acknowledge the Excellence 2019 internal research project, Faculty of Informatics and Management, University of Hradec Kralove, Czech Republic. Publisher Copyright: © 2019 The Author(s).Background: The phenomenon of the increasing number of ageing people in the world is arguably the most significant economic, health and social challenge that we face today. Additionally, one of the major epidemiologic trends of current times is the increase in chronic and degenerative diseases. This paper tries to deliver a more up to date overview of chronic diseases and other limitations associated with old age and provide a more detailed outlook on the research that has gone into this field. Methods: First, challenges for seniors, including chronic diseases and other limitations associated with old age, are specified. Second, a review of seniors' needs and concerns is performed. Finally, solutions that can improve seniors' quality of life are discussed. Publications obtained from the following databases are used in this scoping review: Web of Science, PubMed, and Science Direct. Four independent reviewers screened the identified records and selected relevant publications published from 2010 to 2017. A total of 1916 publications were selected. In all, 52 papers were selected based on abstract content. For further processing, 21 full papers were screened." Results: The results indicate disabilities as a major problem associated with seniors' activities of daily living dependence. We founded seven categories of different conditions - psychological problems, difficulties in mobility, poor cognitive function, falls and incidents, wounds and injuries, undernutrition, and communication problems. In order to minimize ageing consequences, some areas require more attention, such as education and training; technological tools; government support and welfare systems; early diagnosis of undernutrition, cognitive impairment, and other diseases; communication solutions; mobility solutions; and social contributions. Conclusions: This scoping review supports the view on chronic diseases in old age as a complex issue. To prevent the consequences of chronic diseases and other limitations associated with old age related problems demands multicomponent interventions. Early recognition of problems leading to disability and activities of daily living (ADL) dependence should be one of essential components of such interventions.publishersversionPeer reviewe

Decreased Toll-like receptor 8 expression and lower TNF-alpha synthesis in infants with acute RSV infection

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (TLRs) are part of the innate immune system, able to recognize pathogen-associated molecular patterns and activate immune system upon pathogen challenge. Respiratory syncytial virus (RSV) is a RNA virus particularly detrimental in infancy. It could cause severe lower respiratory tract disease and recurrent infections related to inadequate development of anti-viral immunity. The reason could be inadequate multiple TLRs engagement, including TLR8 in recognition of single-stranded viral RNA and diminished synthesis of inflammatory mediators due to a lower expression.</p> <p>Methods</p> <p>Intracellular TLR8 expression in peripheral blood monocytes from RSV-infected infants was profiled and compared to healthy adults and age matched controls. Whether the observed difference in TLR8 expression is a transitory effect, infants in convalescent phase (4-6 weeks later) were retested. Specific TLR8-mediated TNF-α production in monocytes during an acute and convalescent phase was analyzed.</p> <p>Results</p> <p>RSV-infected and healthy infants had lower percentage of TLR8-expressing monocytes than healthy adults whereas decreased of TLR8 protein levels were detected only for RSV-infected infant group. Lower protein levels of TLR8 in monocytes from RSV-infected infants, compared to healthy infants, negatively correlated with respiratory frequency and resulted in lower TNF-α synthesis upon a specific TLR8 stimulation. In the convalescent phase, levels of TLR8 increased, accompanied by increased TNF-α synthesis compared to acute infection.</p> <p>Conclusions</p> <p>Lower TLR8 expression observed in monocytes, during an acute RSV infection, might have a dampening impact on early anti-viral cytokine production necessary to control RSV replication, and subsequently initiate an adaptive Th1 type immune response leading to severe disease in infected infants.</p

Curcumin Promotes A-beta Fibrillation and Reduces Neurotoxicity in Transgenic Drosophila

The pathology of Alzheimer's disease (AD) is characterized by the presence of extracellular deposits of misfolded and aggregated amyloid-β (Aβ) peptide and intraneuronal accumulation of tangles comprised of hyperphosphorylated Tau protein. For several years, the natural compound curcumin has been proposed to be a candidate for enhanced clearance of toxic Aβ amyloid. In this study we have studied the potency of feeding curcumin as a drug candidate to alleviate Aβ toxicity in transgenic Drosophila. The longevity as well as the locomotor activity of five different AD model genotypes, measured relative to a control line, showed up to 75% improved lifespan and activity for curcumin fed flies. In contrast to the majority of studies of curcumin effects on amyloid we did not observe any decrease in the amount of Aβ deposition following curcumin treatment. Conformation-dependent spectra from p-FTAA, a luminescent conjugated oligothiophene bound to Aβ deposits in different Drosophila genotypes over time, indicated accelerated pre-fibrillar to fibril conversion of Aβ1–42 in curcumin treated flies. This finding was supported by in vitro fibrillation assays of recombinant Aβ1–42. Our study shows that curcumin promotes amyloid fibril conversion by reducing the pre-fibrillar/oligomeric species of Aβ, resulting in a reduced neurotoxicity in Drosophila

Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population

Age-related macular degeneration (AMD) is a common cause of blindness in the elderly. Caucasian patients are predominantly affected by the dry form of AMD, whereas Japanese patients have predominantly the wet form of AMD and/or polypoidal choroidal vasculopathy (PCV). Although genetic association in the 10q26 (ARMS2/HTRA1) region has been established in many ethnic groups for dry-type AMD, typical wet-type AMD, and PCV, the contribution of the 1q32 (CFH) region seem to differ among these groups. Here we show a single nucleotide polymorphism (SNP) in the ARMS2/HTRA1 locus is associated in the whole genome for Japanese typical wet-type AMD (rs10490924: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 4.1 \times 10 ^{ - 4}$$\end{document}, OR = 4.16) and PCV (rs10490924: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 3.7 \times 10 ^{ -8}$$\end{document}, OR = 2.72) followed by CFH (rs800292: \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 7.4 \times 10 ^{ -5}$$\end{document}, OR = 2.08; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 2.6 \times {10^{ - 4}}$$\end{document}, OR = 2.00), which differs from previous studies in Caucasian populations. Moreover, a SNP (rs2241394) in complement component C3 gene showed significant association with PCV (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p = 2.5 \times {10^{ - 3}}$$\end{document}, OR = 3.47). We conclude that dry-type AMD, typical wet-type AMD, and PCV have both common and distinct genetic risks that become apparent when comparing Japanese versus Caucasian populations

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.