Successful Control of Ebola Virus Disease: Analysis of Service Based Data from Rural Sierra Leone

IntroductionThe scale and geographical distribution of the current outbreak in West Africa raised doubts as to the effectiveness of established methods of control. Ebola Virus Disease (EVD) was first detected in Sierra Leone in May 2014 in Kailahun district. Despite high case numbers elsewhere in the country, transmission was eliminated in the district by December 2014. We describe interventions underpinning successful EVD control in Kailahun and implications for EVD control in other areas.MethodsInternal service data and published reports from response agencies were analysed to describe the structure and type of response activities, EVD case numbers and epidemic characteristics. This included daily national situation reports and District-level data and reports of the Sierra Leone Ministry of Health and Sanitation, and Médecins Sans Frontières (MSF) patient data and internal epidemiological reports. We used EVD case definitions provided by the World Health Organisation over the course of the outbreak. Characteristics assessed included level of response activities and epidemiological features such as reported exposure (funeral-related or not), time interval between onset of illness and admission to the EVD Management Centre (EMC), work-related exposures (health worker or not) and mortality. We compared these characteristics between two time periods—June to July (the early period of response), and August to December (when coverage and quality of response had improved). A stochastic model was used to predict case numbers per generation with different numbers of beds and a varying percentage of community cases detected.ResultsThere were 652 probable/confirmed EVD cases from June-December 2014 in Kailahun. An EMC providing patient care opened in June. By August 2014 an integrated detection, treatment, and prevention strategy was in place across the district catchment zone. From June-July to August-December 2014 surveillance and contact tracing staff increased from 1.0 to 8.8 per confirmed EVD case, EMC capacity increased from 32 to 100 beds, the number of burial teams doubled, and health promotion activities increased in coverage. These improvements in response were associated with the following changes between the same periods: the proportion of confirmed/probable cases admitted to the EMC increased from 35% to 83% (χ² p-value<0·001), the proportion of confirmed patients admitted to the EMC <3 days of symptom onset increased from 19% to 37% (χ² p-value <0·001), and reported funeral contact in those admitted decreased from 33% to 16% (χ² p-value <0·001). Mathematical modelling confirmed the importance of both patient management capacity and surveillance and contact tracing for EVD control.DiscussionOur findings demonstrate that control of EVD can be achieved using established interventions based on identification and appropriate management of those who are at risk of and develop EVD, including in the context of ongoing transmission in surrounding regions. Key attributes in achieving control were sufficient patient care capacity (including admission to specialist facilities of suspect and probable cases for assessment), integrated with adequate staffing and resourcing of community-based case detection and prevention activities. The response structure and coverage targets we present are of value in informing effective control in current and future EVD outbreaks.     

Genomic chronicle of SARS-CoV-2: a mutational analysis with over 1 million genome sequences

Use of information technologies to analyse big data on SARS-CoV-2 genome provides an insight for tracking variations and examining the evolution of the virus. Nevertheless, storing, processing, alignment and analyses of these numerous genomes are still a challenge. In this study, over 1 million SARS-CoV-2 genomes have been analysed to show distribution and relationship of variations that could enlighten development and evolution of the virus. In all genomes analysed in this study, a total of over 215M SNVs have been detected and average number of SNV per isolate was found to be 21.83. Single nucleotide variant (SNV) average is observed to reach 31.25 just in March 2021. The average variation number of isolates is increasing and compromising with total case numbers around the world. Remarkably, cytosine deamination, which is one of the most important biochemical processes in the evolutionary development of coronaviruses, accounts for 46% of all SNVs seen in SARS-CoV-2 genomes within 16 months. This study is one of the most comprehensive SARS-CoV-2 genomic analysis study in terms of number of genomes analysed in an academic publication so far, and reported results could be useful in monitoring the development of SARS-CoV-2.     

Theoretical calculations of the catalytic triad in short-chain alcohol dehydrogenases/reductases

Three highly conserved active site residues (Ser, Tyr, and Lys) of the family of short-chain alcohol dehydrogenases/reductases (SDRs) were demonstrated to be essential for catalytic activity and have been denoted the catalytic triad of SDRs. In this study computational methods were adopted to study the ionization properties of these amino acids in SDRs from Drosophila melanogaster and Drosophila lebanonensis. Three enzyme models, with different ionization scenarios of the catalytic triad that might be possible when inhibitors bind to the enzyme cofactor complex, were constructed. The binding of the two alcohol competitive inhibitors were studied using automatic docking by the Internal Coordinate Mechanics program, molecular dynamic (MD) simulations with the AMBER program package, calculation of the free energy of ligand binding by the linear interaction energy method, and the hydropathic interactions force field. The calculations indicated that deprotonated Tyr acts as a strong base in the binary enzyme-NAD⁺ complex. Molecular dynamic simulations for 5 ns confirmed that deprotonated Tyr is essential for anchoring and orientating the inhibitors at the active site, which might be a general trend for the family of SDRs. The findings here have implications for the development of therapeutically important SDR inhibitors.     

Plastic surgeon's life: marvelous for mind, exhausting for body

Surgery is accepted as one of the most demanding professions that create both physical and mental strain on the performers. Therefore, the authors aimed to elucidate the mental burden of surgeons, which is dedicated to operative stress. They also tested the hypotheses that participating in surgery creates mental stress on surgeons that leads to cardiovascular changes, and that this stress is more pronounced for actual operators than for first assistants. The method chosen for this purpose was an analysis of heart rate variability. Twelve surgeons (five plastic surgery staff and seven plastic surgery residents) were monitored by a digital ambulatory Holter recorder on at least two occasions. Half of the recordings were carried out on operating days and the other half on office days. Heart rate variability indices (low frequency, high frequency, high frequency/low frequency ratio, and heart rate) were analyzed from those recordings using computerized research tool software. The heart rate variability indices of the operators showed statistically significant differences between operating days and office hours in favor of an increased sympathetic and decreased parasympathetic activity for the former. For first assistants, three of the parameters, with the exception of heart rate, changed in favor of a sympathetic predominance over parasympathetic activity; these changes were also statistically significant. These results showed a sympathetic hyperactivity for both operators and first assistants during the operations. When the sympathovagal balance of the actual operators was compared with that of assistants, the former group showed a more pronounced sympathetic arousal. This difference is accepted as a proof for the mental stress of the surgery being the main factor responsible for the sympathetic hyperactivity that we detected during the operations. Surgeons continuously face a unique mental strain that other professions rarely bring forth, and these psychological stressors are associated with alterations in cardiac autonomic control that may contribute to the development of cardiac disease. Prolonged sympathetic hyperactivity could anticipate cardiac discomfort in more experienced surgeons with marginal cardiac reserve. Such cardiac diseases would be reconsidered as occupation-related illnesses, which might be reimbursed to the physician. In addition, the legal responsibility of surgeons concerning their unfavorable results might be assessed with more understanding with a realization of their undue working conditions.     

Cloning, expression, purification and characterization of fructose-1,6-bisphosphate aldolase from Anoxybacillus gonensis G2

The fructose-1,6-bisphosphate aldolase gene from the thermophilic bacterium, Anoxybacillus gonensis G2, was cloned and sequenced. Nucleotide sequence analysis revealed an open reading frame coding for a 30.9 kDa protein of 286 amino acids. The amino acid sequence shared approximately 80-90% similarity to the Bacillus sp. class II aldolases. The motifs that are responsible for the binding of a divalent metal ion and catalytic activity completely conserved. The gene encoding aldolase was overexpressed under T7 promoter control in Escherichia coli and the recombinant protein purified by nickel affinity chromatography. Kinetic characterization of the enzyme was performed at 60 degrees C, and K(m) and V(max) were found to be 576 microM and 2.4 microM min(-1) mg protein(-1), respectively. Enzyme exhibits maximal activity at pH 8.5. The activity of enzyme was completely inhibited by EDTA.     

Neuroprotective Effects of β-Myrcene Following Global Cerebral Ischemia/Reperfusion-Mediated Oxidative and Neuronal Damage in a C57BL/J6 Mouse

The aim of this study was to investigate the effects of β-myrcene (MYR) on oxidative and histological damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. Mice (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) global cerebral I/R, (3) MYR, and (4) MYR + I/R. The SH group was used as a control and received 0.1 % carboxymethyl cellulose (CMC) as a vehicle following a medial incision without carotid occlusion. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and treated with the vehicle intraperitoneally (i.p.) for 10 days. In the MYR group, mice were given 200 mg/kg MYR dissolved in 0.1 % CMC for 10 days following a medial incision without carotid occlusion. In the MYR + I/R group, the I/R procedure was performed exactly as in the I/R group, and they were then treated with the same dose of MYR for 10 days. Cerebral I/R induced oxidative stress via an increase in thiobarbituric acid reactive substances (TBARS) formation and a decrease in the antioxidant defense systems, including glutathione (GSH), catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MYR treatment protected against the oxidative effects of I/R by inducing significant increases in GSH, GPx, and SOD and a significant decrease in the formation of TBARS. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by MYR treatment. This study has demonstrated that MYR effectively attenuates oxidative and histological damage in the brain caused by global I/R. The beneficial effects of MYR probably contribute to its strong antioxidant and radical scavenging properties. In conclusion, MYR may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, may be a viable and safe alternative treatment for ischemic stroke in humans.     

A model for evaluating the effect of son or daughter preference on population size

This paper develops a micro probabilistic model to describe the family extension process. The parameters are: the probability that a newborn is a boy (P), the number of desired boys (B), the number of desired girls (G), and the maximum possible number of children (N). This maximum is a stopping rule rather than a biological maximum. The variables are the ultimate number of boys and girls. According to this model, each couple determines B, G, and N, at the beginning of the reproductive period and continues to reproduce until at least B and at least G are achieved, or until the total number of children reaches N. The probability distribution of the ultimate number of boys and girls in the population is derived for this model. Simulation techniques are used to generate offspring. The results showed that the population size increases with the absolute differences, [B-G] for fixed N. They also suggested that son or daughter preference may be an important factor in fertility determinants, which may have important implications in population policies.     

Reproduction efficiency of the Horse Leech,Haemopis sanguisuga (Linnaeus, 1758)

The aquaculture sector has recently focused on alternative food sources due to increased costs and limited resources. Live food sources, such as invertebrates, have important roles in digestion processes of fish. It was aimed to determine the reproduction efficiency of the horse leech, Haemopis sanguisuga, which is expected to be used as an alternative live nutritional source in aquaculture in this study. The study was conducted at ambient temperature in the laboratory conditions for three months. A total of 25 gravid leeches with an average body mass of 6.91 ± 2.20 g were used. The leeches lost up to 75% of their body mass and laid 4.30 ± 1.49 cocoons at 12.0 ± 8.2 days interval during cocoon laying period. Leeches stopped laying cocoon when the temperature fell to 16 °C. The average of offspring hatched from the cocoons was 6.45 ± 2.86. The length–body mass relationship of the offspring was exponential (W = 0.012L^2.809, R² = 0.898). The results from the current study indicate that the basic biological parameter affecting the reproduction efficiency of H. sanguisuga is the size of the broodstock leeches, and reproduction activity weakens the broodstocks.     

Epibrassinolide prevents tau hyperphosphorylation via GSK3β inhibition in vitro and improves Caenorhabditis elegans lifespan and motor deficits in combination with roscovitine

Glycogen synthase kinase 3β (GSK3β) is considered an important element of glycogen metabolism; however, it has many other regulatory roles. Changes in the GSK3β signaling mechanism have been associated with various disorders, such as Alzheimer’s disease (AD), type II diabetes, and cancer. Although the effects of GSK3β inhibitors on reducing the pathological effects of AD have been described, an effective inhibitor has not yet been developed. Epibrassinolide (EBR), a brassinosteroid (BR), is structurally similar to mammalian steroid hormones. Our studies have shown that EBR has an inhibitory effect on GSK3β in different cell lines. Roscovitine (ROSC), a cyclin-dependent kinase (CDK) inhibitor, has also been identified as a potential GSK3 inhibitor. Within the scope of this study, we propose that EBR and/or ROSC might have mechanistic action in AD models. To test this hypothesis, we used in vitro models and Caenorhabditis elegans (C. elegans) AD strains. Finally, EBR treatment successfully protected cells from apoptosis and increased the inhibitory phosphorylation of GSK3β. In addition, EBR and/or ROSC treatment had a positive effect on the survival rates of C. elegans strains. More interestingly, the paralysis phenotype of the C. elegans AD model due to Aβ42 toxicity was prevented by EBR and/or ROSC. Our findings suggest that EBR and ROSC administration have neuroprotective effects on both in vitro and C. elegans models via inhibitory GSK3β phosphorylation at Ser9.