Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.

Primary ovarian ependymoma is a rare neuroectodermal neoplasm that can arise from immature ovarian teratoma. Due to the paucity of this entity, a complete molecular analysis of these tumors has not been done, thus creating a challenge for finding an effective and safe therapeutic treatment. In limited literature, patient with primary ovarian ependymoma showed various responses to an array of individualized therapies ranging from surgeries and chemotherapies. Here, we present a 38-year-old female with persistent ovarian ependymoma with molecular profile similar to traditional central nervous system ependymoma that is irresponsive to multiple cytoreduction and clinical experimental therapies. Therefore, a prompt recognition and reporting of this entity can greatly aid in expanding the understanding and standardization of therapies for this neoplasm.

Background: Detection of small proportion of serious bacterial infections (SBI) with potentially life threating course in a large group of children with fever admitted to emergency department (ED) is still complicated. Measurement of immature granulocytes (IG) percentage may be used as a marker of bacterial infections. The aim of the study was to evaluate whether the IG percentage is a useful additional predictive marker of SBI. Methods: This study included 258 children with febrile infections admitted to the ED. Clinical follow-up, microbiological and radiological tests were used as reference standards for the definition of SBI. Study population was categorized into two groups: (i) infected patients with no suspicion of SBI (n = 75); (ii) patients with suspicion of SBI (n = 183). IG percentage, white blood cell count (WBC) and C-reactive protein (CRP) levels were analyzed from the first routine blood samples at hospital admission. Results: A statistically significant difference in IG percentage levels was observed in children with SBI and those without - the mean IG percentage was 1.2% for the SBI group, 0.3% for those without SBI. The cutoff level of IG percentage to predict SBI was 0.45 (84% specificity, 66% sensitivity, 90% positive predictive value). We combine variables and evaluate their additive values. The sensitivity of WBC to detected SBI improved from 74% to 85% when IG percentage was added to the prediction models. When CRP, WBC and IG percentage were combined, the sensitivity to predict SBI increased to 93%, the specificity to 86%. (95% CI 77–93%). Receiver operator characteristic analysis to predict SBI showed an area under the curve (AUC) of 0.80 for IG percentage. Conclusion: Addition of IG percentage to traditionally used markers of SBI as WBC and CRP may help to identify children with serious bacterial infections. Furthermore IG percentage can be rapidly obtained from the traditional full blood count without any extra sampling and costs.

Treating clubfoot in walking age children is debated, despite studies showing that using Ponseti casting principles can correct the mid-foot effectively. We aimed to explore techniques and approaches for management of older children with clubfoot and identify areas of management consensus. A mixed-methods cross-sectional electronic survey on delayed presenting clubfoot (DPC) was sent to 88 clubfoot practitioners (response rate 56.8%). We collected data on decision-making, casting, imaging, orthotics, surgery, re-currence, rehabilitation, multidisciplinary care and contextual factors. The quantitative data were analysed using descriptive statistics and the qualitative data were analysed using conventional content analysis. Many respondents used the Pirani score and some used the PAVER score to aid deformity severity assessment and correctability [1,2]. Ponseti casting principles were consistently applied with a stepwise approach. Con-textual factors influenced the timing of the treatment, the decision to treat a bilateral deformity simultaneously, and casting intervals. Differences were seen around orthotic usage and use of tibialis anterior tendon transfer following full correction. The survey identified consensus areas in overall principles of management for delayed presenting clubfoot and implementation of Ponseti principles, indicating these principles are well recognized as a multidisciplinary approach for older children with clubfoot. Some dif-ferences in approach may reflect different economic or social contexts. The principles can be adapted well for different geographical and healthcare contexts.

The rearing temperature of the immature stages can have a significant impact on the life-history traits and the ability of adult mosquitoes to transmit diseases. This review assessed published evidence of the effects of temperature on the immature stages, life-history traits, insecticide susceptibility, and expression of enzymes in the adult Anopheles mosquito. Original articles published through 31 March 2021 were systematically retrieved from Scopus, Google Scholar, Science Direct, PubMed, ProQuest and Web of Science databases. After applying eligibility criteria, 29 studies were included. The review revealed that immature stages of Anopheles arabiensis were more tolerant (in terms of survival) to a higher temperature than An. funestus and An. quadriannulatus. Higher temperatures resulted in smaller larval size and decreased hatching and pupation time. The development rate and survival of Anopheles stephensi were significantly reduced at a higher temperature than a lower temperature. Increasing temperatures decreased the longevity, body size, length of the gonotrophic cycle and fecundity of Anopheles mosquitoes. Anopheles mosquitoes exposed at 18° or 30 °C had a higher risk of dying compared to those exposed at 25 °C. Increasing temperature also significantly increased NOS expression and decreased insecticide toxicity. Both extreme low and high temperatures affect Anopheles mosquito development and survival. Climate change could have diverse effects on Anopheles mosquitoes. There seems to be inconclusive evidence of the effects of temperature on the development and survival of Anopheles species, and more studies are needed to clarify this relationship.

Aedes aegypti is the main vector of various arboviruses including dengue, yellow fever, Zika and chikungunya virus. This mosquito species originated in Africa but has a wide range of distribution, colonising various ecological zones. The transmission dynamics of arboviruses depends on environmental factors, but also on mosquito life history traits including development time, fecundity, and longevity. The objective of the current study was to assess the Aedes aegypti immature development time, adult longevity, fecundity and body variation from different sampling localities. Aedes aegypti mosquitoes were collected as eggs from different geographical zones and cohorts of mosquitoes were reared in standardized laboratory conditions to assess the life history traits parameters. Emerged adults were discriminated into morphotypes according to the density of white scales on the first abdominal tergite. The means of fecundity, longevity, development time and body size were assessed, and linear models were fitted to the traits parameters to assess the effects of other covariables. Average Aedes aegypti development time was estimated to 7.35 days; 7.40 days; 6.98 days and 7.40 days respectively for Dori, 1200 logements, Bobo-Dioulasso and Toudweogo. The fecundity did not vary across study sites and was not associated with the body size. The longevity varied according to the study sites with the mosquitoes from Bobo-Dioulasso having the longest longevity while the shortest longevity was found at Dori. Fed mosquitoes had longer longevity compared to unfed ones. Morphological identification showed that Aedes aegypti aegypti-like mosquitoes were more predominant than Aedes aegypti formosus-like mosquitoes in all the study sites, suggesting the predominance of Aedes aegypti in the urban environment. Our data suggest that the geographical origin of Aedes aegypti mosquitoes in Burkina Faso has a little effect on its life history traits.

As a matter of course, the first gene must be formed in the absence of gene. On the other hand, many biopolymers including gene are produced under the genetic system in extant organisms. Thus far, no idea explaining how the first gene was formed in the absence of gene, has been proposed except the idea based on the GADV hypothesis. GADV means four amino acids; Gly [G], Ala [A], Asp [D] and Val [V]. In this article, a reliable answer to the question, how the first gene was generated, is provided. The idea is as follows. The first gene (genetic information) was formed by random joining of anticodons, GNCs, which were carried by primeval anticodon stem-loop (AntiC-SL) tRNAs produced during repeated cycles of random joining of nucleotides and degradation of oligonucleotides. However, it might be difficult for many persons to accept the idea, because tRNAs and metabolic pathways using various proteins, which are produced under genetic functions, must be used to form the first gene. Then, it is reconsidered based on definition of genetic information and minimum necessary things to generate the first gene in this article, how the first gene was generated. Consequently, it could be reconfirmed that five prototypes of members (genetic code, tRNA, metabolism, cell structure and protein) composing the fundamental life system, except gene, are certainly necessary to generate the first gene. Namely, it can be concluded that the first gene was formed through nucleotide metabolism with immature [GADV]-proteins, primeval AntiC-SL tRNA formation with immature [GADV]-proteins, formations of single-stranded (GNC)n codon sequence by random joining of anticodons, GNCs, carried by AntiC-SL tRNAs, double-stranded (ds)-(GNC)n RNA and maturation of an immature [GADV]-protein, which was produced from one strand of the ds-RNA. Thus, the first gene was formed using the five primitive or prototypes of members, which were produced in the absence of gene. There would be no other way for generating the first gene.

Proteins having a variety of functions play many essential roles in maintaining various life activities in organisms. Various methods, by which new protein functions can be artificially produced, have progressed rapidly upon development in recombinant DNA technology and effective screening techniques. However, the obtainable scope of the new functions has been restricted in a narrow range, because only functions of presently existing proteins can be used. On the other hand, it has been considered that it would be impossible to create an entirely new protein, which does not show any meaningful homology with any other amino acid sequences of previously existing proteins. The reason is because one amino acid sequence for a protein cannot be selected out from an extraordinary large amino acid sequence diversity as ~10130. As a matter of course, it is impossible to design an amino acid sequence of a protein in advance and a gene encoding the protein cannot be also formed through random process. Nevertheless, extant organisms have generated a variety of entirely new proteins in some way to make full use of them. This means that extant organisms have equipped a mechanism with which entirely new proteins can be produced under the present core life system composed of protein, tRNA (genetic code) and gene. In this article, first I introduce the mechanism, with which entirely new proteins are created in extant organisms, and further propose a novel strategy for application of the mechanism to protein engineering through creation of entirely new proteins, which could contribute to development of various industries.