Background Uterine artery embolization (UAE) and myomectomy are uterus-sparing treatments for uterine fibroids. Each carries a different risk and efficacy profile. Despite this there is a lack of direct comparison between the two techniques making treatment choice decisions difficult. Objectives To compare the therapeutic efficacy and complications of UAE versus myomectomy. Search strategy A systematic search of The Cochrane Library, Medline, and EMBASE databases was conducted using a pre-defined search strategy. The review was prospectively registered on PROSPERO (CRD42021259347). Selection Criteria All randomised controlled trials and cohort studies published between January 1995 and August 2021 directly comparing UAE and myomectomy were included. Data Collection and Analysis Meta-synthesis of raw data was performed using Review Manager 5.4.1 from the Cochrane Collaboration. A pooled estimate of efficacy was established using a fixed-effect model. Main results 8 studies were identified. UAE was associated with lower complication rates (OR 0.56; 95% CI 0.40-0.79), increased improvement in bleeding (OR 1.61 95% CI 1.07-2.43) and a shorter total recovery time (7.72 days versus 36.63 days). Whilst myomectomy was associated with a higher post-procedure quality of life (mean difference -10.56; 95% CI -15.34 - -5.79) and lower re-intervention rate (OR 5.16; 95% CI 2.41-11.04). No significant difference in procedural failure rate was seen (OR 0.67; 95% CI 0.30-1.50). Given concerns with UAE and future fertility limited post-procedure fertility outcomes were identified. Conclusions: Given differences in efficacy profiles a personalised approach to treatment discussions should be maintained. Funding: None Keywords: Uterine artery embolization, myomectomy, uterine fibroid
Selection on quantitative traits by divergent climatic conditions can lead to substantial trait variation across a species range. In the context of rapidly changing environments, however, it is equally important to understand selection on trait plasticity. To evaluate the role of selection in driving divergences in traits and their associated plasticity within a widespread species, we compared molecular and quantitative trait variation in Populus fremontii (Fremont cottonwood) populations throughout Arizona. Using SNP data and genotypes from 16 populations reciprocally planted in three common gardens, we first performed QST-FST analyses to detect selection on traits and trait plasticity. We then explored the mechanistic basis of selection using trait-climate and plasticity-climate regressions. Three major findings emerged: 1) There was significant genetic variation in traits expressed in each of the common gardens and in the phenotypic plasticity of traits across gardens. 2) Based on QST-FST comparisons, there was evidence of selection in all traits measured; however, this result varied from no effect in one garden to highly significant in another, indicating that detection of past selection is environmentally dependent. We also found strong evidence of divergent selection on plasticity across environments for two traits. 3) Traits and/or their plasticity were often correlated with population source climate (R2 up to 0.77 and 0.66, respectively). This suggests that steep climate gradients across the Southwest have played a major role in shaping the evolution of divergent phenotypic responses in populations and genotypes now experiencing climate change.
Adolescence is a critical stage of rapid biological, emotional and social change and development. Adolescents and young adults (AYA) with asthma and allergies need to develop the knowledge and skills to self-manage their health independently. Healthcare professionals (HCP), parents and their wider network play an essential role in supporting AYA in this process. Previous work showed significant limitations in transition care across Europe. In 2020, the first evidence-based guideline on effective transition for AYA with asthma and allergies was published by EAACI. We herein summarize practical resources to support this guideline’s implementation in clinical practice. For this purpose, multi-stakeholder Task Force members searched for resources in peer review journals and grey literature. These resources were included if relevant and of good quality, and were pragmatically rated for their evidence-basis and user friendliness. Resources identified covered a range of topics and targeted healthcare professionals, AYA, parents/carers, schools, workplace, and wider community. Most resources were in English, web-based and had limited evidence-basis. This position paper provides a valuable selection of practical resources for all stakeholders to support effective transitional care for AYA with asthma and allergies. Future research should focus on developing validated, patient-centred tools to further assist evidence-based transition care.
A fracture of the mastoid bone should be considered in the work-up of a head and neck traumatic injury. A well-pneumatized mastoid can absorb forceful impacts, protecting middle and inner ear structures. Fractures of the mastoid, followed by Valsalva maneuver can lead to subcutaneous cervical emphysema.
Objective To test equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy. Design Parallel, two-arm equivalence randomised controlled trial with an equivalence margin of 5%. Setting Single centre in Australia. Population 278 pregnant women with iron deficiency. Methods Participants received either 500 mg (n=152) or 1000mg (n=126) of intravenous ferric carboxymaltose in the second or third trimester. Main outcome measures The proportion of participants requiring additional intravenous iron (500mg) to achieve and maintain ferritin >30ug/L (diagnostic threshold for iron deficiency) at 4 weeks post-infusion, and at 6 weeks, and 3-, 6- and 12-months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth, and safety outcomes. Results The two doses were not equivalent within a 5% margin at any timepoint. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500 mg group compared with 5/67 (8%) in the 1000 mg group (difference in proportions, 0.283 95% confidence interval (0.177, 0.389)). Overall, participants in the 500 mg arm received twice the repeat infusion rate (0.81 (SD= 0.824 vs 0.40 (SD= 0.69), rate ratio 2.05, 95% CI (1.45, 2.91)). Conclusions Administration of 1000mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500 mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained.
The coastline of Sub-Saharan Africa hosts highly diverse fish communities of high conservation value, which are also key resources for local livelihoods. However, many costal ecosystems are threatened by overexploitation and their conservation state is frequently unknown due to limited monitoring budgets and challenges associated with their vast spatial extents. Here, we evaluated the potential of citizen science-based eDNA surveys to alleviate such chronic data deficiencies and assessed fish communities in Mozambique using two 12S metabarcoding primer sets. Samples were either collected by scientific personnel or trained local community members and results from the two metabarcoding primer sets were combined using a newly created data merging approach. Irrespective of the background of sampling personnel, a high average fish species richness was recorded (38±20 OTUs sample-1). Individual sections of the coastline largely differed in the occurrence of threatened and commercially important species, highlighting the need for regionally differentiated management strategies. A detailed comparison of the two applied primer sets revealed an important trade-off in primer choice with MiFish primers amplifying a higher number of species but Riaz primers performing better in the detection of threatened fish species. This trade-off could be partly resolved by applying our data-merging approach, which has the potential to provide a more robust baseline-data for decision-making processes. Overall, our study provides encouraging results but also highlights that eDNA-based monitoring will require further improvements of e.g., reference databases and local analytical infrastructure to facilitate routine applications in Sub-Saharan Africa.
Whole-genome sequencing for generating SNP data is increasingly used in population genetic studies. However, obtaining genomes for massive numbers of samples is still not within the budgets of many researchers. It is thus imperative to select an appropriate reference genome and sequencing coverage to ensure the accuracy of the results for a specific research question, while balancing cost and feasibility. To evaluate the effect of the choice of the reference genome and sequencing coverage on downstream analyses, we used five confamilial reference genomes of variable relatedness and three levels of sequencing coverage (3.5x, 7.5x and 12x) in a population genomic study on two caddisfly species: Himalopsyche digitata and H. tibetana. Using these 30 datasets (five reference genomes × three coverages × two target species), we estimated population genetic indices (inbreeding coefficient, nucleotide diversity, pairwise and genome-wide FST) based on variants and population structure (PCA and admixture) based on genotype likelihood estimates. The results showed that both distantly related reference genomes and lower sequencing coverage lead to degradation of resolution. In addition, choosing a more closely related reference genome may significantly remedy the defects caused by low coverage. Therefore, we conclude that population genetic studies would benefit from closely related reference genomes, especially as the costs of obtaining a high-quality reference genome continue to decrease. However, to determine a cost-efficient strategy for a specific population genomic study, a trade-off between reference genome relatedness and sequencing depth can be considered.
Sickle Cell Disease (SCD) has a complex array of symptoms and is associated with high healthcare expenditures. A comprehensive care program may help to reduce expenditures of children with SCD. This research describes SCD comprehensive care program enrollees’ expenditure patterns by level of hospitalization risk over a three-year period and estimates whether coordination of care services reduced costs for those with different risk levels. Medicaid claims data were collected for program patients with SCD. Data from the one year prior to program enrollment categorized patients as High, Medium, or Low risk for incurring inpatient expenditures. We compared utilization risk groups on inpatient expenditures by year after program enrollment. The trends in expenditures are shown in the subgroup analyses (descriptively). 361 program enrollees ages 1 to 27y had SCD; 8.9% were categorized as High risk of utilizing hospitalization services, 47.9% were at Medium risk, and 43.2% were at Low risk. The High Utilization and Medium Utilization Risk groups showed trends of expenditure reduction, but the trends may be due to regression of extreme group costs toward the mean. The lack of a statistically significant cost benefit might be due to small sample size, low engagement in the program services, short duration of intervention, and inability to distinguish the appropriateness of healthcare utilization for SCD.
Background: Heart transplant from controlled donation after circulatory death (cDCD) is an emerging strategy that is rapidly expanding and may help increase the heart donor pool. Materials and Methods: The use of thoracoabdominal normothermic regional perfusion (TANRP) with extracorporeal membrane oxygenation device has allowed to perform cardiac transplantation after cDCD. Several experiences have been carried out in recent years, however the maximum cold ischemia time is still unknown. We present a successful case of heart transplantation using a graft from cDCD from another hospital with 201 minutes of cold ischemia time, the longest published in Europe. Discussion and conclusion: Heart transplant from cDCD could be a good alternative to brain dead donation. This experience suggests than nonlocal cardiac donation in controlled asystole could tolerate long periods of cold ischemia time and break the main barriers in cardiac donation after circulatory death.
Viral infection in cell culture and tissue is modeled with delay reaction-diffusion equations. It is shown that progression of viral infection can be characterized by the viral replication number, time-dependent viral load and the speed of infection spreading. These three characteristics are determined through the original model parameters including the rates of cell infection and of virus production in the infected cells. The clinical manifestations of viral infection, depending on tissue damage, correlate with the speed of infection spreading, while the infectivity of a respiratory infection depends on the viral load in the upper respiratory tract. Parameter determination from the experiments on Delta and Omicron variants allows the estimation of the infection spreading speed and viral load. Different variants of the SARS-CoV-2 infection are compared confirming that Omicron is more infectious and has less severe symptoms than Delta variant. Within the same variant, spreading speed (symptoms) correlates with viral load allowing prognosis of disease progression.
Background. Children with a brain tumor are at risk of developing sleep problems. It remains unclear whether these problems arise at an early or later stage, and insights can facilitate timely interventions. The aim of this study is to examine sleep problems and contributing factors shortly after diagnosis. Methods. Children 6-16 years with a newly diagnosed (≤3 months) primary brain tumor were recruited for a prospective study. Sleep was measured using actigraphy and questionnaires (PROMIS Sleep Disturbance and Sleep Related Impairment, self- and parent-reports). Prevalence of clinical sleep problems were established using PROMIS cut-off scores. Mean PROMIS scores, prevalence of sleep problems and actigraphic outcomes were compared to norms (t-test, chi-square, linear regression). Demographic and medical risk factors were explored with multivariable linear regression models. Results. Sixty-nine children (68% male, mean age 11.6±2.8 years, 53±28 days after diagnosis) participated. Parents reported more sleep disturbances (mean T=53.7, P<.01) compared to norms. Rates of self- and parent-reported severe sleep disturbances were elevated (11% versus 5% in norms, P<.04). Parents also reported higher rates of moderate sleep disturbance (31%) and sleep related impairment (42%) than norms (25%, P<.03). Actigraphic outcomes did not differ from norms. Only shorter time since diagnosis was identified as independent risk factor (self-reported sleep disturbances, B=-.11, 95%CI -0.19;-0.03). Conclusions. Sleep problems are more frequently reported by children and parents shortly after pediatric brain tumor diagnosis, compared to healthy controls. Attention for sleep around brain tumor diagnosis is important, as sleep is vital for recovery and health-related quality of life.
The dominant method for generating Chinese hamster ovary (CHO) cell lines that produce high titers of biotherapeutic proteins utilizes selectable markers such as dihydrofolate reductase (Dhfr) or glutamine synthetase (Gs), alongside inhibitory compounds like methotrexate (MTX) or methionine sulfoximine (MSX), respectively. Recent work has shown the importance of asparaginase (Aspg) for growth in media lacking glutamine–the selection medium for Gs-based selection systems. We generated a Gs/Aspg double knockout CHO cell line and evaluated its utility as a novel dual selectable system via co-transfection of Gs-Enbrel and Aspg-Enbrel plasmids. Using the same selection conditions as the standard Gs system, the resulting cells from the Gs/Aspg dual selection showed substantially improved specific productivity and titer compared to the standard Gs selection method, however, with reduced growth rate and viability. Following adaptation in selection medium, the cells improved viability and growth while still achieving ~5-fold higher specific productivity and ~3-fold higher titer than Gs selection alone. We anticipate that with further optimization of culture medium and selection conditions this approach would serve as an effective addition to workflows for the industrial production of recombinant biotherapeutics.
Objective: To evaluate the functional capacity, pulmonary function and quality of life of children and adolescents with sickle cell anemia (SCA) and to test the reproducibility of functional capacity tests in this population. Method: Cross-sectional study with volunteers with SCA genotype Hb-SS (SCAG), aged 6 to 18 years matched in age and gender to the control group (CG). Spirometry, 5-repetition sit-to-stand test (5STS-test), modified shuttle walk test (MSWT), and Pediatric Quality of Life Questionnaire (PedsQL) were performed. The reproducibility of 5STS-test and MSWT was evaluated: Results: 48 volunteers of SCAG and 48 of CG were evaluated. Pulmonary function of SCAG (FVC: 92 ± 15% pred.; FEV 1 /FVC: 84 ± 8% pred.) was worse than the CG (104 ± 15% pred.; FEV 1 /FVC: 90 ± 6% pred.) p < 0.05. SCAG had worse functional capacity registered by distance walked: 576m (515-672m) and 5STS-test: 8 seconds (7.4-8.9seconds) compared to the CG who showed distance walked: 1010m (887- 1219m) and 5STS-test: 7 seconds (7.0-8.1seconds), p < 0.001. SCAG had worse quality compared to CG, p < 0.05. The reproducibility was good of MSWT (ICC 0.99 (0.98-0.99 IC-95%)) and 5STS-test (ICC 0.80 (0.69 – 0.88), p < 0.001 . Conclusion: Children and adolescents with sickle cell anemia showed worse capacity to walk or run, and to perform sit-to-stand test. Additionally, they have poor quality of life when compared with their control peers. The MSWT and 5STS-test showed reproducible to be applied in pediatric individual with SCA.
Genetic variation is described from the perspective of an individual. All the different levels of genetic information and variation are covered, ranging from whether an organism is unmixed or hybrid, has variations in genome, chromosomes and more locally in DNA regions, epigenetic variants or alterations in selfish genetic elements. Genetic constitution and heterogeneity of microbiota are highly relevant for health and wellbeing of an individual. Mutation rates vary widely for variation types e.g. due to sequence context. Genetic information guides numerous aspects in organisms. Types of inheritance, whether Mendelian or non-Mendelian, zygosity, sexual reproduction and sex determination are covered. Functions of DNA and functional effects of variations are introduced, along with mechanism that reduce and modulate functional effects, including TARAR countermeasures and intraindividual genetic conflict. TARAR countermeasures for tolerance, avoidance, repair, attenuation and resistance are essential for life, integrity of genetic information and gene expression. The genetic composition, effects of variations and their expression are considered also in diseases and personalized medicine. The text synthesizes knowledge and insight on individual genetic heterogeneity and organizes and systematizes the central concepts.
Previous studies showed a sequence encoding an auxiliary protein (PlaS) downstream of the phospholipase A1 (PlaA1) gene of Serratia marcescens. There is an interaction between PlaA1 and PlaS, which may be closely related to the high enzymatic activity property of phospholipase A1. In order to further investigate the interaction mechanism, it is necessary to explore binding sites of the interaction between PlaA1 and PlaS and the regulatory mechanism for enzymatic properties by molecular docking and site-directed mutagenesis. The results showed that the active center site of PlaA1 was encapsulated internally, and a “catalytic pocket” was formed externally by Leu197-Ser249. The docking process of PlaA1 and PlaS involved 29 and 30 amino acids, respectively, of which Phe186 and Lys238 of PlaA1 are involved in forming π-bonds and multiple hydrogen bonds. Therefore, Phe186 and Lys238 were site-directed mutated to Ala to obtain the mutant enzymes PlaA1 F186A and PlaA1 K238A, respectively. The results showed that the mutant enzymes showed no significant changes in optimum temperature and pH but poor stability. The kinetic parameters indicated that the affinity between PlaA1 and substrates was weakened, and the catalytic efficiency was reduced after mutation. Therefore, it demonstrated that Phe186 and Lys238 of PlaA1 provided non-covalent bonds conducive to the enzymatic activity and stability in the interaction between PlaA1 and PlaS, which would provide some theoretical basis for further rational design and modification of phospholipase A1 subsequently.
The ithomiine butterflies (Nymphalidae: Danainae) represent the largest known radiation of Mullerian mimetic butterflies. They dominate by number the mimetic butterfly communities, which include species such as the iconic neotropical Heliconius genus. Despite recent studies carried out on ithomiine ecology and genetic structure, no reference genome was available for the tribe. Here, we generated high-quality, chromosome-scale genome assemblies of two Melinaea species, Melinaea marsaeus and Melinaea menophilus, and a draft genome of Ithomia salapia. We obtained genomes with a size ranging from 396 Mb to 503 Mb across the three species and scaffold N50 of 40.5 Mb and 23.2 Mb for the two chromosome-scale assemblies. Using collinearity analyses we identified massive rearrangements between the two closely related Melinaea species. A detailed annotation of transposable elements and genes was performed, resulting in the identification of 24,341, 31,081 and 31,976 genes in I. salapia, M. marsaeus and M. menophilus, respectively. We used a specialist annotation to target chemosensory genes, which is crucial for host plant detection and mate recognition in mimetic species. A comparative genomic approach revealed independent gene expansions in ithomiines and particularly in gustatory receptor genes. These first three genomes of ithomiine mimetic butterflies constitute a valuable addition and a welcome comparison to existing biological models of mimicry, such as Heliconius, and will enable further understanding of the mechanisms of adaptation and the genetic bases underpinning mimicry.
Background: Dexmedetomidine could be an ideal adjuvant to propofol during gastrointestinal endoscopy because it provides both analgesia and sedation without respiratory depression. This study investigates the effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy. Methods: 90 adult patients were randomly assigned to Group Control , Group DEX0.5 (0.5 μg/kg dexmedetomidine), or Group DEX1.0 (1.0 μg/kg dexmedetomidine) . Anaesthesia during endoscopy was implemented by plasma target-controlled infusion (TCI) of propofol with different doses of dexmedetomidine. TCI concentration of the first patient for each group was 2.5 μg/ml and the consecutive adjacent concentration gradient was 0.5 μg/mL. EC50 of TCI propofol for gastrointestinal endoscopy was determined by using the modified Dixon’s up-and-down method. Cardiovascular variables were also measured. Results: EC50 of TCI propofol and 95% confidence interval (CI) for gastrointestinal endoscopy were, 3.77 (3.48-4.09), 2.51 (2.27-2.78) and 2.10 (1.90-2.33) μg/mL in Group Control, Group DEX0.5 and Group DEX1.0. The average percent change from baseline in HR was 2.8 (8.9), -7.4 (7.7) and -10.5 (8.8) (P＜0.001), and the average percent change from baseline in MAP was -10.6 [-24.7; 3.5], -9.5 [-29.2; 11.4] and -4.0 [-27.3; 15.5] (P = 0.034) in Group Control, Group DEX0.5 and Group DEX1.0, respectively. Conclusions: Dexmedetomidine reduced the EC50 of TCI propofol. A 0.5-1 μg/kg dexmedetomidine caused a decrease in HR without bradycardia. The decrease in dosage of propofol with increasing doses of dexmedetomidine caused more stable MAP. Dexmedetomidine is an ideal adjuvant drug to propofol during gastrointestinal endoscopy.
It is comprehended that the systems without any limitation on their Zeno action are enthralled in a vast class of hybrid systems. This article is influenced by a new category of non-autonomous second order measure differential problems with state-dependent delay (SDD) and non-instantaneous impulse (NII). Some new sufficient postulates are created that guarantee solvability and approximate controllability. We employ the fixed point strategy and theory of Lebesgue–Stieltjes integral in the space of piecewise regulated functions. The measure of non-compactness is applied to establish the existence of a solution. Moreover, the measured differential equations generalize the ordinary impulsive differential equations. Thus, our findings are more prevalent than that encountered in the literature. At last, an example is comprised that exhibits the significance of the developed theory.