Introduction: Trauma is the most common cause of death in childhood. Tissue damage, ischemia-reperfusion injury and inflammatory response are mainly responsible for increasing serbest oxiygen radicals. In this study, we aimed to investigate the use of thiol-disulfide and ischemia-modified albumin levels as a diagnostic laboratory parameter in trauma children. Method: Of 202 children, 101 of them were hospitalized in pediatric surgical intensive care unit with trauma and 101 of others were healthy children. Levels of native thiol (-SH), total thiol (SH + SS), dynamic disulfide (SS), dynamic disulfide (SS) / total thiol (SH + SS), albumin and ischemic modified albumin (IMA) were measured from the sera of patients and healthy volunteers. For statistical analyses, SPSS 17.0 was used. Mann-Whitney U and paired correlation test were used where appropriate. p <0.05 was considered significant. Results: The mean age of the patients in the trauma group (Boys: 61 Girls: 40) was 7,88 years and the control group was 8,00 years. In trauma group, 86 of children were exposed to blunt trauma, 15 of children had penetrating trauma and 54 patients had multiple trauma. Surgical procedures were performed in 17 patients. In the trauma group, native thiol, total thiol, dynamic disulfide / total thiol, albumin and IMA levels were significantly lower than that of control (p <0.001) and their dynamic disulfide (p = 0.001) was higher compared to the control. There was no difference thiol-disulfide parametres in trauma groups sub-division as surgery(n=17) vs. follow-up(n=84) groups or multiple trauma(n=54) vs. isolated organ trauma(n=47) groups, or penetrating(n=15) or blunt trauma(n=86) groups. Conclusion: Thiol-disulfide balance and IMA levels show changes in favor of oxidative stress in children with trauma, however, it cannot be used as a laboratory marker that helps to show the system and organ affected by the trauma and to decide the surgical intervention.

Introduction Viral infections are associated with pulmonary exacerbations in children with Cystic Fibrosis (cwCF), but after 3 years of SARS-CoV-2 pandemic, whether cwCF are at higher risk of developing COVID-19 or its adverse consequences remains controversial. Methods We conducted an observational, multicenter, cross-sectional study of cwCF infected by SARS-CoV-2 between March 2020 and June 2022, (1 st to 6 th COVID-19 pandemic waves) in Spain. The study aimed to describe patients’ basal characteristics, SARS-CoV-2 clinical manifestations and outcomes, and whether there were differences across the pandemic waves. Results During study time, 351 SARS-CoV2 infections were reported among 341 cwCF. Median age was 8.5 years (range 0-17) and 51% were female. Cases were unevenly distributed across the pandemic, with most cases (82%) clustered between November 2021 and June 2022 (6 th wave, also known as Omicron Wave due to the higher prevalence of this strain in that period in Spain). Most cwCF were asymptomatic (24.8%) or presented with mild Covid-19 symptoms (72.9%). Among symptomatic, most prevalent symptoms were fever (62%) and increased cough (53%). No multisystem inflammatory syndrome (MIS-C), persisting symptoms, long-term sequelae or deaths were reported. Conclusions Spanish current data indicate that cwCF do not experience higher risks of SARS-CoV-2 infection nor worse health outcomes or sequelae. Changes in patients’ basal characteristics, clinical courses and outcomes were detected across waves. While the pandemic continues, and new SARS-CoV-2 variants are being identified, a worldwide monitoring of COVID-19 in pediatric CF patients is needed.

Many Western countries have been affected by the outbreak of COVID-19. Italy has been particularly hit at the beginning of the pandemic, immediately after China. In Italy and elsewhere women seem to be less affected then men by severe/fatal COVID-19 infection, regardless of their age. Despite the evidence that women and men are different fort this infection, very few studies consider different therapeutic approaches for the two sexes. Undoubtedly, understanding the mechanisms at the bases of these differences may help to find appropriate and sex specific therapies. Here we consider that other mechanisms but estrogen protection are involved. Several X-linked genes (such as ACE2) and Y-linked genes (SRY, SOX9) may explain sex differences. Cardiovascular comorbidities are among the major enhancers of virus lethality. In addition, the number of sex-independent non-genetic factors that can change susceptibility and mortality is enormous, and many other factors are likely to be considered, including gender and cultural habits in different countries.

Objectives The aim of this study was to assess the efficacy of a new emergency department intervention for the management of epistaxis, aiming to reduce epistaxis admissions. Design Tranexamic acid (TXA) (500mg/ml) soaked NasoPore® packing was in the pathway for epistaxis which did not terminate following 10 minutes of simple first aid. The pathway was utilised for adult patients presenting with non-traumatic, anterior epistaxis. Pre- and post-implementation admission rates and re-attendance rates were recorded by retrospective audit at a large central London hospital. Results Epistaxis admissions were reduced by 51.7% (p<0.05) following the implementation of the TXA-soaked NasoPore® pathway. Conclusions The significant reduction in epistaxis admissions demonstrates that this intervention is beneficial for patient outcomes. This has the potential to be introduced in other A&E departments and also pre-hospital settings.

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease.

This is the first study to document the genetic diversity of the white-tailed deer population on St. John, US Virgin Islands. The island population was founded by a small number of animals, has very limited hunting or predation, and recently experienced a reduction in size following an extended drought in 2015. DNA samples were collected from hair from 23 anesthetized adult deer (13 males, 10 females) ranging in age from 1-8 years (3.36+ 1.9 yr) and also from fecal DNA samples, for a total of 42 individuals analyzed for genetic diversity. The St. John deer data set averaged 4.19 alleles per marker and demonstrates the second lowest number of alleles (A) when compared to other populations of Odocoileus virginianus (4.19). Heterozygosity was similar to the other studies (0.54) with little evidence of inbreeding. To explain the level of heterogygosity and lack of inbreeding within the St. John population, three hypotheses are proposed, including the effect of intrinsic biological traits within the population, a recent infusion of highly heterogeneous loci from North American populations, and a consistent level of immigration from a nearby island. Additional work is needed to further understand the genetic history of the St. John and regional deer populations.

Introduction: In this paper we examine the relationship between vaccination against COVID-19 and both the death rate from COVID-19 and the rate of COVID-19 spread. Our goal is determine if vaccination is associated with reduced death and/or spread of disease at the local level. Methods: This analysis was conducted at the county level in the state of Pennsylvania, United States of America, with data that were collected during the first half of 2022 from the state of Pennsylvania’s Covid Dashboard ([COVID-19 Data for Pennsylvania (pa.gov)](https://www.health.pa.gov/topics/disease/coronavirus/pages/cases.aspx) . Result s: Given that, during this time period, the vaccines being used were not geared specifically toward the common variants at that time, we found no statistically significant relationship between disease spread and vaccination rate at the county level. That said, we did find a highly statistically significant relationship between death rate and vaccination rate (p-value = 0.006). Specifically, a 1% increase in vaccination rate was found to correspond to a 0.751% decrease in death rate (95% confidence interval (0.236%, 1.266%)). Conclusions: These results support previous findings from across the world that Covid vaccination is highly efficacious in preventing death from the disease. Even during a time when vaccine design was not optimally matched with the prevailing strains, vaccination was found to reduce death rate. Hence, improving global vaccine availability is vitally important, in order to achieve necessary outcomes.

Breeding drought stress tolerance is an integral part of our current and future goals of sustainable agricultural production. In the present study, we examined the natural variation of HvP5cs1 and demonstrated the utility of a wild barley allele for drought stress adaptation in cultivated barley. Sequencing the 5-end regulatory region among 49 barley accessions identified a genetically distinct allele of HvP5cs1 promoter from a wild barley ISR42-8. Allele mining of HvP5cs1 indicated quantitative variation in proline accumulation which was associated with promoter polymorphisms across the cluster of abscisic acid-responsive elements (ABRE), ABRE-related coupling elements, and MYB binding motifs. A near-isogenic line (NIL-143) harboring the HvP5cs1 allele from the highest proline accumulating wild barley ISR42-8 was developed in cultivated barley Scarlett through marker-assisted backcrossing (BC6). NIL-143 preserved the genetic competence of ISR42-8 to accumulate proline in higher concentrations under drought conditions at seedling and reproductive stages. Under drought stress, NIL-143 maintained superior membrane integrity, reduced pigment damage, and sustained photosynthetic health compared to Scarlett. NIL-143 presented a remarkable improvement in drought stress recovery than Scarlett. Further, the introgression line exhibited improved yield attributes, especially superior grain weight compared to Scarlett under field drought conditions. In conclusion, the present data uncover the genetic regulation of HvP5cs1 mediated proline accumulation and elucidate its role in drought stress adaptation and yield stability in barley.

Background: Anaphylaxis is increasing at pediatric age; however, its characterization is hampered by underdiagnosis and underreporting. The aim of this study was to identify the causes of anaphylaxis in children and adolescents in Portugal, thus contributing to a better knowledge of its etiology, clinical manifestations and management. Methods: During a 10-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 533 patients under 18 years of age with anaphylaxis were included. Results: Mean age was 8.5±4.9 years, 61% were male; 45% had asthma. Mean age at the first anaphylaxis episode was 5.3±4.7 years (ranging from 1 month to 17 years of age), 63% at preschool age. Most reactions occurred at home (57%). Food-induced anaphylaxis was the leading cause (77%). The main culprit foods were cow’s milk (32%), tree nuts (16%), shellfish (13%), egg (12%), fresh fruits (11%), fish (8%) and peanut (8%). Other causes included drugs (11%), insect-sting (5%), cold-induced anaphylaxis (4%), exercise-induced (2%), latex (1%) and idiopathic anaphylaxis (1%). Most patients (83%) were admitted to the emergency department; only 46% received adrenaline treatment. Recurrence of anaphylaxis occurred in 41% of the patients (3 or more episodes in 21%). An adrenaline autoinjector was used in 9% of the patients. Conclusions: In the Portuguese pediatric population, food is the leading cause of anaphylaxis. Undertreatment with adrenaline and high recurrence of anaphylaxis highlight the need to improve both the diagnosis and the therapeutic management of this life-threatening entity.

Spatial and temporal distribution of seabird transiting and foraging at sea is an important consideration for marine conservation planning. Using at-sea observations of seabirds (n = 317), collected during the breeding season from 2012 to 2016, we built boosted regression tree (BRT) models to identify relationships between numerically dominant seabird species (red-footed booby, brown noddy, white tern and wedge-tailed shearwater), geomorphology, oceanographic variability, and climate oscillation in the Chagos Archipelago. We documented positive relationships between red-footed booby and wedge-tailed shearwater abundance with the strength in the Indian Ocean Dipole, as represented by the Dipole Mode Index (6.7% and 23.7% contribution respectively). The abundance of red-footed boobies, brown noddies and white terns declined abruptly with greater distance to island (17.6%, 34.1% and 41.1% contribution respectively). We further quantified the effects of proximity to rat-free and rat-invaded islands on seabird distribution at sea, and identify breaking point distribution thresholds. We identified areas of increased abundance at sea and habitat use-age under a scenario where rats are eradicated from invaded nearby islands and recolonised by seabirds. Following rat eradication, abundance at sea of red-footed booby, brown noddy, and white terns increased by 14%, 17% and 3% respectively, with no important increase detected for shearwaters. Our results have implication for seabird conservation and island restoration. Climate oscillations may cause shifts in seabird distribution, possibly through changes in regional productivity and prey distribution. Invasive species eradications and subsequent island recolonization can lead to greater access for seabirds to areas at-sea, due to increased foraging or transiting through, potentially leading to distribution gains and increased competition. Our approach predicting distribution after successful eradications enables anticipatory threat-mitigation in these areas, minimising competition between colonies and thereby maximising the risk of success and the conservation impact of eradication programmes.  

Only a few studies on the nocturnal behavior of African ungulates exist so far, with mostly small sample sizes. For a comprehensive understanding of nocturnal behavior, this database needs to be expanded. Zoo animals offer a good opportunity to lay the corresponding foundations. The results can provide clues for the study of wild animals and furthermore contribute to a better understanding of animal welfare and better husbandry conditions in zoos. To tackle this open question, we developed a stand-alone open-source software based on deep learning techniques, named BOVIDS (Behavioral Observations by Videos and Images using a Deep-Learning Software). This software is used to identify ungulates in their enclosure and to determine crucial behavioral poses on video material with an accuracy of 99.4%. A case study on 25 Common Elands (Tragelaphus oryx) out of 5 EAZA zoos with a total of 11,411 hours video material out of 822 nights is conducted, yielding the first detailed description of the nightly behavior of Common Elands. Our results indicate that age and sex are influencing factors on the nocturnal activity budget, the length of behavioral phases as well as the number of phases per behavioral state during the night. Finally, the results suggest the existence of species-specific rhythms that open future research directions.

Cancer is a disease of somatic mutations. These cellular mutations compete to dominate their microenvironment and dictate the disease outcome. While a therapeutic approach to target specific driver mutations helps to manage the disease, subsequent molecular evolution of tumor cells threatens to overtake therapeutic progress. There is need for rapid, high-throughput, unbiased in-vitro discovery screening platforms that capture the native complexities of the tumor and rapidly identifiy mutations that confer chemotherapeutic drug resistance.Taking the example of CDK4/6 inhibitor (CDK4/6i) class of drugs, we show that the pooled in-vitro CRISPR screening platform enables rapid discovery of drug resistance mutations in a 3D setting. Gene edited cancer cell clones assembled into an organotypic multicellular tumor spheroid (MCTS), exposed to CDK4/6i caused selection and enrichment of the most drug resistant phenotype in a 3D setting, detectable by next gen sequencing after a span of 28 days. The platform was sufficiently sensitive to enrich for even a single drug resistant cell within a large, 2500-cell, drug-responsive complex 3D tumor spheroid. The genome-wide 3D CRISPR-mediated knockout screen (>18,000 genes) identified several genes whose disruptions conferred resistance to CDK4/6i. Further, multiple novel candidate genes were identified as top hits only in the microphysiological 3D enrichment assay platform and not the conventional 2D assays. Taken together, these findings suggest that including phenotypic 3D resistance profiling in decision trees could improve discovery and reconfirmation of drug resistance mechanisms and afford a platform for exploring non-cell autonomous interactions, selection pressures, and clonal competition.

By taking Sugeno-derivative into account, firstly, we investigate the existence of solutions to the initial value problems (IVP) of first-order differential equations with respect to non-additive measure (more precisely, distorted Lebesgue measure). It particularly occurs in the mathematical modeling of biology. We begin by expressing the differential equation in terms of ordinary derivative and the derivative with respect to the distorted Lebesgue measure. Then, by using the fixed point theorem on cones, we construct an operator and prove the existence of positive increasing solutions on cones in semi-order Banach spaces. In addition, we also use Picard’s-Lindel\”of theorem to prove the existence and uniqueness of the solution of the equation. Second, we investigate the existence of a solution to the boundary value problem (BVP) on cones with integral boundary conditions of a mix-order differential equation with respect to non-additive measures. Moreover, the Krasnoselskii fixed point theorem is also applied to both BVP and IVP and obtains at least one positive increasing solution. Examples with graphs are provided to validate the results.

Ancient DNA research has developed rapidly over the past few decades due to the improvement in PCR and next-generation sequencing (NGS) technologies, but challenges still exist. One major challenge in relation to ancient DNA research is to recover genuine endogenous ancient DNA sequences from the raw sequencing data. This is often difficult due to the degradation of ancient DNA and high levels of contamination, especially homologous contamination. In this study, we collected whole genome sequencing (WGS) data from 6 ancient samples to compare different mapping algorithms. To further explore more effective methods to separate endogenous DNA from the homologous contaminations, we attempted to recover reads based on the ancient DNA specific characteristics of deamination, depurination, and DNA fragmentation with different parameters. We propose a quick and improved pipeline for separating endogenous ancient DNA while simultaneously decreasing the homologous contaminations to a very low proportion. Overall, these recommendations for ancient DNA mapping and separation of endogenous DNA in this study could facilitate future studies of ancient DNA.

Arachnids are the most abundant land predators. Despite the importance of their functional roles as predators and the of necessity to understand their diet for conservation and nutrient fluxes, the trophic ecology of many arachnid species is not fully understood. In the case of the wandering spider, Phoneutria boliviensis F. O. Pickard-Cambridge, 1897, only selected field and laboratory observational studies about their diet exist. By using a DNA metabarcoding approach, we compared the prey found in the gut content of males and females from three distant Colombian populations of P. boliviensis. By DNA metabarcoding of the cytochrome c oxidase subunit I (COI), we detected and identified 234 prey records belonging to 96 operational taxonomic units (OTUs), as prey for this wandering predator. Our results broaden the known diet of P. boliviensis with at least 75 prey taxa not previously registered in fieldwork or laboratory experimental trials. These results suggest that P. boliviensis feeds predominantly on invertebrates (Diptera, Lepidoptera, Coleoptera and Orthoptera) and opportunistically on small squamates. Intersex and interpopulation differences are observed. Assuming that prey preference does not vary between populations, these differences are likely associated with a higher local prey availability. Finally, we suggest that DNA metabarcoding can be used for evaluating subtle differences in the diet of distinct populations of P. boliviensis, particularly when predation records in the field cannot be established or quantified using direct observation

Introduction Erectile Dysfunction (ED) is common in older age and in diabetes (DM). Phosphodiesterase type 5-inhibitors (PDE5-is) are the first-line for ED. We investigated how type of diabetes and age of males affects the PDE5-i use in the primary care setting. Methods 2018-19 general practice level quantity of all PDE5-i agents were taken from the GP Prescribing Data set in England. The variation in outcomes across practices was examined across one year, and for the same practice against the previous year. Results We included 5,761 larger practices supporting 25.8million men of whom 4.2million≥65 years old. Of these, 1.4million had T2DM, with 0.8million of these>65. 137,000 people had T1DM. 28.8million tablets of PDE5-i were prescribed within the 12 months (2018-19) period in 3.7million prescriptions (7.7 tablets/prescription), at total costs of £15.8million (£0.55/tablet). The NHS ED limit of 1 tablet/user/week suggests that 540,000 males are being prescribed a PDE5-i at a cost of £29/year each. With approximately 30,000 GPs practising, this is equivalent to one GP providing 2.5 prescriptions/week to overall 18 males. There was a 3x variation between the highest decile of practices (2.6 tablets/male/year) and lowest decile (0.96 tablets/male/year). The statistical model captured 14% of this variation and showed T1DM males were the largest users, while men age<65 with T2DM were being prescribed 4 times as much as non-DM. Those T2DM>65 were prescribed 80% of the non-DM amount. Conclusion There is wide variation in use of PDE5-is. With only 14% variance capture, other factors including wide variation in patient awareness, prescribing rules of local health providers, and recognition of the importance of male sexual health by GP prescribers might have significant impact.

Oxford Nanopore Technologies (ONT) is a third-generation sequencing technology that is gaining popularity in ecological research for its portable and low-cost sequencing possibilities. Although the technology is primarily developed for long-read sequencing, it can also be applied to sequence amplicons. The downside of ONT is the low quality of the raw reads. Hence, generating a high-quality consensus sequence is still a challenge. We present Amplicon_sorter, a tool for reference-free sorting of ONT sequenced amplicons based on their similarity in sequence and length and for building solid consensus sequences.

Aim: Pregnant women are hypothesized to have low adherence to prescribed medication, because of concerns about toxicity and harmful effects on the unborn child. However, very little is known about the actual adherence to prescribed medication during pregnancy. We determined to what extent women follow treatment recommendations regarding prescribed medication use in mid-pregnancy. Methods: Dutch women participating in the PRIDE Study completed a six-week diary on medication use. Additionally, pharmacy records were obtained. For each medication dispensed, we determined three measures of adherence: 1) whether use was reported in the diary (actual use), 2) difference between dispensing date and date of first reported use (initiation time), and 3) proportion of days with at least the correct number of doses taken (implementation adherence). Results: During the six-weeks study period, 235 of 816 women (29%) were prescribed medication. Actual use was highest for medications used for chronic conditions (88%; 95% confidence interval [95% CI] 81-93), followed by medication for pregnancy-related conditions (79%; 95% CI 71-86) and medication for occasional and short-time use (69%; 95% CI 60-77). We observed a ≥1 day delay in treatment initiation for 42% of medications dispensed for the first time in the study period. For medications that were actually used, mean implementation adherence was 74.2% (95% CI 69.3-79.2). Conclusion: Although actual use of medications dispensed was high, many pregnant women did not adhere to treatment recommendations. This non-adherence may impact maternal and child health and lead to exposure misclassification in studies in perinatal pharmacoepidemiology relying on administrative databases.