Memory and forgetting processes with the firing neuron model

The aim of this paper is to present a novel algorithm for learning and forgetting within a very simplified, biologically derived model of the neuron, called firing cell (FC). FC includes the properties: (a) delay and decay of postsynaptic potentials, (b) modification of internal weights due to propagation of postsynaptic potentials through the dendrite, (c) modification of properties of the analog weight memory for each input due to a pattern of long-term synaptic potentiation. The FC model could be used in one of the three forms: excitatory, inhibitory, or receptory (gan­glion cell). The computer simulations showed that FC precisely performs the time integration and coincidence detection for incoming spike trains on all inputs. Any modification of the initial values (internal parameters) or inputs patterns caused the following changes of the interspike intervals time series on the output, even for the 10 s or 20 s real time course simulations. It is the basic evidence that the FC model has chaotic dynamical properties. The second goal is the presentation of various nonlinear methods for analysis of a biological time series. (Folia Morphol 2018; 77, 2: 221–233

A computational simulation of long-term synaptic potentiation inducing protocol processes with model of CA3 hippocampal microcircuit

An experimental study of computational model of the CA3 region presents cog­nitive and behavioural functions the hippocampus. The main property of the CA3 region is plastic recurrent connectivity, where the connections allow it to behave as an auto-associative memory. The computer simulations showed that CA3 model performs efficient long-term synaptic potentiation (LTP) induction and high rate of sub-millisecond coincidence detection. Average frequency of the CA3 pyramidal cells model was substantially higher in simulations with LTP induction protocol than without the LTP. The entropy of pyramidal cells with LTP seemed to be significantly higher than without LTP induction protocol (p = 0.0001). There was depression of entropy, which was caused by an increase of forgetting coefficient in pyramidal cells simulations without LTP (R = –0.88, p = 0.0008), whereas such correlation did not appear in LTP simulation (p = 0.4458). Our model of CA3 hippocampal formation microcircuit biologically inspired lets you understand neurophysiologic data. (Folia Morphol 2018; 77, 2: 210–220

Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound–kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome

Metabolic biomarker profiling for identification of susceptibility to severe pneumonia and COVID-19 in the general population

Biomarkers of low-grade inflammation have been associated with susceptibility to a severe infectious disease course, even when measured prior to disease onset. We investigated whether metabolic biomarkers measured by nuclear magnetic resonance (NMR) spectroscopy could be associated with susceptibility to severe pneumonia (2507 hospitalised or fatal cases) and severe COVID-19 (652 hospitalised cases) in 105,146 generally healthy individuals from UK Biobank, with blood samples collected 2007-2010. The overall signature of metabolic biomarker associations was similar for the risk of severe pneumonia and severe COVID-19. A multi-biomarker score, comprised of 25 proteins, fatty acids, amino acids, and lipids, was associated equally strongly with enhanced susceptibility to severe COVID-19 (odds ratio 2.9 [95%CI 2.1-3.8] for highest vs lowest quintile) and severe pneumonia events occurring 7-11 years after blood sampling (2.6 [1.7-3.9]). However, the risk for severe pneumonia occurring during the first 2 years after blood sampling for people with elevated levels of the multi-biomarker score was over four times higher than for long-term risk (8.0 [4.1-15.6]). If these hypothesis generating findings on increased susceptibility to severe pneumonia during the first few years after blood sampling extend to severe COVID-19, metabolic biomarker profiling could potentially complement existing tools for identifying individuals at high risk. These results provide novel molecular understanding on how metabolic biomarkers reflect the susceptibility to severe COVID-19 and other infections in the general population. National policies for mitigating the COVID-19 pandemic include stricter measures for people considered to be at high risk of severe and potentially fatal cases of the disease. Although older age and pre-existing health conditions are strong risk factors, it is poorly understood why susceptibility varies so widely in the population. People with cardiometabolic diseases, such as diabetes and liver diseases, or chronic inflammation are at higher risk of severe COVID-19 and other infections including pneumonia. These conditions alter the molecules circulating in the blood, providing potential ‘biomarkers’ to determine whether a person is more likely to develop a fatal infection. Uncovering these blood biomarkers could help to identify people who are prone to life-threatening infections despite not having ever been diagnosed with a cardiometabolic disease. To find these biomarkers, Julkunen et al. studied blood samples that had been collected from 105,000 healthy individuals in the United Kingdom over ten years ago. The data showed that individuals with biomarkers linked to low-grade inflammation and cardiometabolic disease were more likely to have died or been hospitalised with pneumonia. A score based on 25 of these biomarkers provided the best predictor of severe pneumonia. This biomarker score performed up to four times better within the first few years after blood sampling compared to predicting cases of pneumonia a decade later. The same blood biomarker changes were also linked with developing severe COVID-19 over ten years after the blood samples had been collected. The predictive value of the biomarker score was similar for both severe COVID-19 and the long-term risk of severe pneumonia. Julkunen et al. propose that the metabolic biomarkers reflect inhibited immunity that impairs response to infections. The results from over 100,000 individuals suggest that these blood biomarkers may help to identify people at high risk of severe COVID-19 or other infectious diseases. en

Atherogenic lipid profile and health behaviours in women post-menopause working in agriculture

Introduction and objective. There is a significantly higher risk of lipid disorders occurrence, including atherogenic dyslipidemia in women after menopause than it is in general population. The aim of the work was to investigate the correlation between health behaviours and the occurrence of lipid disorders in women after menopause working in agriculture. Material and methods. The study was conducted in years 2015–2016 and included 843 post-menopausal women working in agriculture. The following were used: a questionnaire including socio-demographic data, laboratory lipid tests, inventory of health behaviours. The following were estimated: logistic regression models for serum lipids concentration versus frequency of health behaviours in the examined women. Results. Adverse lipid profile was found in over a half of post-menopausal women working in agriculture, whereas the frequency of health behaviours were estimated at the average level, although the frequency of correct eating habits and health practices was significantly lower than preventive behaviours and positive psychological attitudes. A correlation was found between the frequency of health behaviours and the occurrence of lipid disorders in women after menopause working in agriculture: more frequent health practices co-existed with the lower concentration of total cholesterol and a higher concentration of HDL-cholesterol, more frequent preventive behaviours co-existed with lower concentration of LDL-cholesterol. Women with higher concentration of triglycerides undertook pro-health practices relatively more often. Conclusions. The study revealed a high prevalence of lipid disorders in postmenopausal women working in agriculture. More effective health education programmes are necessary in the area of reduction the risk factors of CVD in the population of women working in agriculture

Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial

Anna Tomusiak,1 Magdalena Strus,1 Piotr B Heczko,1 Paweł Adamski,2 Grzegorz Stefański,3 Aleksandra Mikołajczyk-Cichońska,3 Magdalena Suda-Szczurek3 1Department of Microbiology, Jagiellonian University Medical College, 2Institute of Nature Conservation, Polish Academy of Sciences, 3IBSS BIOMED SA, Kraków, Poland Objective: The main objective of this study was to evaluate whether vaginal administration of probiotic Lactobacillus results in their colonization and persistence in the vagina and whether Lactobacillus colonization promotes normalization and maintenance of pH and Nugent score. Patients and methods: The study was a multicenter, randomized, double-blind, and placebo-controlled trial. Altogether, 376 women were assessed for eligibility, and signed informed consent. One hundred and sixty eligible women with abnormal, also called intermediate, vaginal microflora, as indicated by a Nugent score of 4–6 and pH >4.5 and zero or low Lactobacillus count, were randomized. Each participant was examined four times during the study. Women were randomly allocated to receive either the probiotic preparation inVag®, or a placebo (one capsule for seven consecutive days vaginally). The product inVag includes the probiotic strains Lactobacillus fermentum 57A, Lactobacillus plantarum 57B, and Lactobacillus gasseri 57C. We took vaginal swabs during visits I, III, and IV to determine the presence and abundance of bacteria from the Lactobacillus genus, measure the pH, and estimate the Nugent score. Drug safety evaluation was based on analysis of the types and occurrence of adverse events. Results: Administration of inVag contributed to a significant decrease (between visits) in both vaginal pH (P<0.05) and Nugent score (P<0.05), and a significant increase in the abundance of Lactobacillus between visit I and visits III and IV (P<0.05). Molecular typing revealed the presence of Lactobacillus strains originating from inVag in 82% of women taking the drug at visit III, and 47.5% at visit IV. There was no serious adverse event related to inVag administration during the study. Conclusion: The probiotic inVag is safe for administration to sustainably restore the healthy vaginal microbiota, as demonstrated by predominance of the Lactobacillus bacteria in vaginal microbiota. Keywords: probiotics, Lactobacillus, bacterial vaginosis, aerobic vaginitis&nbsp

Effects of oral probiotic supplementation on gut Lactobacillus and Bifidobacterium populations and the clinical status of low-birth-weight preterm neonates: a multicenter randomized, double-blind, placebo-controlled trial

Magdalena Strus,1 Ewa Helwich,2 Ryszard Lauterbach,3 Beata Rzepecka-Węglarz,4 Katarzyna Nowicka,2 Maria Wilińska,5 Jerzy Szczapa,6 Małgorzata Rudnicka,7 Helena Sławska,8 Marek Szczepański,9 Aneta Waśko,10 Aleksandra Mikołajczyk-Cichońska,10 Anna Tomusiak-Plebanek,1 Piotr B Heczko1 1Department of Microbiology, Jagiellonian University Medical College, Kraków, Poland; 2Department of Neonatology, Institute of Mother and Child, Warszawa, Poland; 3Clinical Department of Neonatology, University Hospital, Kraków, Poland; 4Department of Neonatal Intensive Care, “UJASTEK” Medical Centre, Kraków, Poland; 5Clinical Department of Neonatology, Independent Public Clinical Hospital CMKP, Warszawa, Poland; 6Department of Neonatology, Gynecology and Obstetrics Clinical Hospital, Poznań, Poland; 7Department of Neonatology, Regional Specialist Hospital, Wrocław, Poland; 8Department of Neonatology, Specialist Hospital No. 2, Bytom, Poland; 9Clinic Department of Neonatology and Neonatal Intensive Care, University Clinical Hospital, Białystok, Poland; 10Medical Department, IBSS BIOMED S.A., Kraków, Poland Aim: Probiotic bacteria administered directly after birth to preterm neonates may improve gastrointestinal function and may reduce the incidence of late-onset sepsis, which is a frequent complication in this group. Purpose: The main objective of this study was to evaluate whether a new probiotic bacterial mixture of Lactobacillus rhamnosus KL53A and Bifidobacterium breve PB04 given to preterm, low-birth-weight neonates would influence composition of their gut microbiota and sepsis rates. Patients and methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial conducted in clinical centers of neonatal care in Poland. A probiotic or placebo preparation was given twice daily to 181 preterm low-birth-weight neonates who were eligible for enteral feeding between July 2012 and July 2013. The probiotic was given to 90 neonates, while placebo was given to 91 neonates. The gut microbiota was monitored by microbiological analysis of stool samples. Sepsis episodes were detected on the basis of clinical and laboratory findings and confirmed by blood cultures. Results: Tested probiotic administration resulted in continuous increase of the Lactobacillus and Bifidobacterium counts in the gut microbiota. The applied tested strains successfully colonized the neonates gut since they were present in over 90% of stool samples, which was confirmed by molecular analysis. Regardless of the study group (probiotic or placebo), B. breve ­colonization correlated with lower staphylococcal sepsis incidence, which was irrespective of whether ­probiotics were given. No sepsis case caused by strains included in study probiotic was recorded. Conclusion: Appropriately selected and characterized probiotic bacteria may be safely given to preterm neonates to normalize their distorted gut microbiota and may contribute to lower staphylococcal sepsis rates. Keywords: probiotics, LBW neonates, staphylococcal sepsis, gut microbiota, Lactobacillus, Bifidobacteriu