Background: The planning and management of health policy is directly linked to evidence-based research. To obtain the most rigorous results in research it is important to have a representative sample. However, ethnic minorities are often not accounted for in research. Migration, equality, and diversity issues are important priorities which need to be considered by researchers. The aim of this systematic review (SR) is to explore the literature examining the experiences of minority language users in Health and Social Care Research (HSCR). Method: A SR of the literature was conducted. SPIDER framework and Cochrane principles were utilized to conduct the review. Five databases were searched, yielding 5311 papers initially. A SR protocol was developed and published in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020225114analysis. Results: Following the title and abstract review by two reviewers, 74 papers were included, and a narrative account was provided. Six themes were identified: 1. Disparities in healthcare; 2. Maternal health; 3. Mental health; 4. Methodology in health research; 5. Migrant and minority healthcare; 6. Racial and ethnic gaps in healthcare. Results showed that language barriers (including language proficiency) and cultural barriers still exist in terms of recruitment, possibly effecting the validity of the results. Several papers acknowledged language barriers but did not act to reduce them. Conclusion: Despite research highlighting cultures over the past 40 years, there is a need for this to be acknowledged and embedded in the research process. We propose that future research should include details of languages spoken so readers can understand the sample composition to be able to interpret the results in the best way, recognising the significance of culture and language. If language is not considered as a significant aspect of research, the findings of the research cannot be rigorous and therefore the validity is compromised.

Blood flow disturbance of veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be risk factor of weaning failure. We report an alternative position of cannulae of VV-ECMO which can maintain blood flow. The recirculation rate could be controlled by adjusting a position of return cannula using dilutional ultrasound monitoring.

The genus Apocynum contains perennial bast fiber plants that are spread worldwide. Apocynum species have great application prospect in salt-alkali regions, are rich in flavonoids, and possess medicinal significance. Here, we report the draft genomes of two species, Apocynum venetum and Apocynum hendersonii, and elucidate their evolutionary relationship. The high synteny and collinearity between A. venetum and A. hendersonii suggested that the two species experienced the same WDG event, indicating that divergence might be more recent. Comparative analysis revealed that ApF3H and differentially evolved ApUFGT genes are critical for determining natural variation in flavonoid biosynthesis between relatives. ApF3H-1 enhanced the total flavonoid content and promoted the antioxidant capacity of transformed plants compared to the wild-type plant. ApUFGT5 and 6 explained the diversification of flavonoids or their derivatives. These data provide biochemical insight and knowledge on the genetic regulation of flavonoid biosynthesis, supporting the adoption of these genes in breeding programs aimed at the multipurpose use of plants.

A document by Raymond De Vries. Click on the document to view its contents.

Actinopterygian fishes (subclass Actinopterygii) display considerable diversity regarding forms of parental behaviors and types of carer sex. Contrary to caregiver sex, parental behaviors were not traced at the subclass level. In order to understand the evolutionary history of parental care in the ray-finned fishes, parental care states were mapped upon an existing supertree using parsimony ancestral state reconstruction. We investigated the evolution of substrate guarding, mouthbrooding, external egg carrying and internal gestation. We aimed to test the general hypothesis, according to which, more advanced forms of care were always preceded by simpler ones. We show that, in this subclass, parental care traits evolved from ancestors devoid of parental care. The transition from the ancestral state of no care to substrate guarding was the most frequent, whereas the other transitions recorded low scores. The data supported the evolution of mouthbrooding from substrate guarding, whilst external egg carrying arose from both substrate guarding and the ancestral state, which might suggest independent evolutionary routes of external egg carrying. Consequently, our results did not fully corroborate the general hypothesis mentioned above. Internal gestation evolved both in clades devoid of parental care and in clades descendant from substrate guarders ancestors.

This paper investigates the decay rates of continuous-time singular systems with unbounded delays. By introducing an auxiliary system for the original system, the positivity and asymptotic stability conditions of the system are investigated first. Then, µ-stability criteria, which are applied to characterize the decay rates of the systems, are proposed, and the relation between the system matrices and µ-stability is studied. Those results include the stability of positive singular systems with bounded time-varying delays and time-varying delays with linear growth rate as special cases. Finally, a numerical example is given to illustrate the obtained theoretical results.

A document by Emma Magavern. Click on the document to view its contents.

The emerging issue of rising gabapentinoid misuse is being recognised alongside the lack of current evidence supporting the safe and effective deprescribing of gabapentinoids. This scoping review aimed to assess the extent and nature of gabapentinoid deprescribing interventions in adults, either in reducing dosages, or prescribing of, gabapentinoids. Electronic databases were searched on 23rd February 2022 without restrictions. Eligible studies included randomised, non-randomised and observational studies that assessed an intervention aimed at reducing/ceasing the prescription/use of a gabapentinoid in adults for any indication in a clinical setting. The research outcomes investigated type of intervention, prescribing rates, cessations, patient outcomes, and adverse events. Extracted outcome data was categorised as either short (≤ 3 months), intermediate (>3 but <12 months) or long (≥ 12 months) term. A narrative synthesis was conducted. The four included studies were conducted in primary and acute care settings. Intervention were of dose reducing protocols, education and/or pharmacological-based approaches. In the randomised trials, gabapentinoid use could be ceased in at least one-third of participants. In the two observational trials, gabapentinoid prescribing rates decreased by 9%. Serious adverse events and adverse events specifically related to gabapentinoids were reported in one trial. No study included patient-focussed psychological interventions in the deprescribing process, nor provided any long-term follow-up. This review highlights the lack of existing evidence in this area. Due to limited available data, our review was unable to make any firm judgements on the most effective gabapentinoid deprescribing interventions in adults, highlighting the need for more research in this area.

Aim: Develop PBPK models of semaglutide to estimate the pharmacokinetic profile for subcutaneous (SC) injections in children and adolescents with healthy and obese body weights. Methods: Pharmacokinetic modeling and simulations of semaglutide SC injections were performed using the Transdermal Compartmental Absorption & Transit (TCAT™) model implemented in GastroPlus™ v.9.5 modules. A PBPK model of semaglutide was developed and verified in the adult population, by comparing the simulated plasma exposure with the observed data, and further scaled to the pediatric populations with normal and obese body weight. Results: The Semaglutide PBPK model was successfully developed in adults and scaled to the pediatric population. Our P-PBPK simulations indicated a significant increase in Cmax values for the 10-14 years pediatric population with healthy body weights, which was higher than the observed values in adults at the reference dose. Since gastrointestinal adverse events are related to increased semaglutide exposure, peak concentrations outside the target range may represent a safety risk for this pediatric age group. Besides, PBPK models indicated that body weight was inversely related to semaglutide exposure in children and adolescents, which is in line with the results observed in population pharmacokinetic studies in adults. Conclusion: Due to the absence of semaglutide pharmacokinetic data for the pediatric population, these PBPK models will aid in the development of dosing regimens and sampling times. Thus, increasing the efficiency of future pediatric clinical trial studies which can be replaced or improved by PBPK models.

Objectives: This study aims to explore the clinical value of prenatal ultrasonography in the diagnosis of the common arterial trunk (CAT) classification and associated deformities. Materials and methods: The two-dimensional ultrasound images spatiotemporal image correlations (STICs) and clinical data of 108 foetuses diagnosed with CAT malformations were retrospectively analysed, their CAT types were classified, and the correlations between these different types and foetal malformations and pregnancy outcomes were analysed. Results: Among the 108 foetuses, there were 47 cases (43.5%) of type A1, 51 cases (47.3%) of type A2, 9 cases (8.3%) of type A3 and 1 case of type A4 (0.9%), of which 22 cases (20.4%) were isolated CAT, 56 cases (51.8%) had complex intra-cardiac structural abnormalities, 30 cases (27.8%) had intra-cardiac or extra-cardiac structural abnormalities, 17 cases had 1 other system abnormality, and 5 cases had 2 other system abnormalities. Four cases were combined with 3 other system abnormalities, while 4 cases were combined with 4 other system abnormalities, among which the facial and physical abnormalities had the highest incidence (40.0%). The STIC images were completely displayed in 88 cases (81.5%). Isolated CAT and CAT combined with other malformations were significantly correlated with foetal pregnancy outcomes ( P < 0.05). Conclusions: Prenatal ultrasonography had a high clinical application value for classifying CAT. Pregnancy outcomes were highly correlated with the classification and combined intra-cardiac and extra-cardiac structural malformations. The early assessment of foetal prognosis before birth has great value for clinical intervention.

Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play essential roles in purinergic signaling in the nervous system. Several studies suggest a link between Panx1-based channels activity and neurodegenerative disorders including Parkinson’s disease (PD), but experimental evidence is limited. Here, we applied behavioral and molecular screening of zebrafish larvae to examine the role of Panx1 in both pathological and normal conditions, using electrical stimulation in a microfluidic chip and RT-qPCR. A zebrafish model of PD was produced by exposing wildtype (panx1a+/+) and Panx1a knock-out (panx1a-/-) zebrafish larvae to 250µM 6-hydroxydopamine (6-OHDA). After 72hrs treatment with 6-OHDA a reduced electric-induced locomotor activity was observed in 5 days post fertilization (dpf) panx1a+/+ larvae. The 5dpf panx1a-/- larvae were not different from affected. The RT-qPCR data showed a reduction in tyrosine hydroxylase (TH) expression level in both panx1a+/+ and panx1a-/- groups. However, TH expression of 6-OHDA exposed panx1a-/- larvae was not decreased when compared to untreated mutants. Extending 6-OHDA treatment duration to 120hrs caused a significant reduction in the locomotor response of 7dpf panx1a-/- larvae when compared to the untreated panx1a-/- group. The RT-qPCR data also confirmed a significant decrease in TH expression levels after 120hrs treatments with 6-OHDA for both genotypes. Our results suggest that the absence of Panx1a channels compromised dopaminergic signaling in 6-OHDA-treated zebrafish larvae. We here propose that zebrafish Panx1a models offer great opportunities to shed light on the physiological and molecular basis of PD. Panx1a might play a preventive role on PD progression, and therefore deserves further investigation

The occurrence of hematuria during a right heart catheterization can be a sign of renal perforation, a rare but life-threatening complication that could be developed due to the misdirection of wire into the abdominopelvic venous plexus. We showed this complication could be managed with venoplasty of the common iliac vein.

Mycophenolate mofetil has an important role as immunosuppressive agent in solid organ transplant recipients. Exposure to the active mycophenolic acid (MPA) can be monitored using therapeutic drug monitoring. We present three cases in which MPA exposure severely decreased after oral antibiotic co-administration. By diminishing gut bacteria β-glucuronidase activity, oral antibiotics seem to prevent deglucuronidation of the inactive MPA-7-O-glucuronide metabolite to MPA and thereby prevent its enterohepatic recirculation. This pharmacokinetic interaction could result in rejection, which makes it clinically relevant in solid organ transplant recipients, especially when therapeutic drug monitoring frequency is low. Routine screening for this interaction, preferably supported by clinical decision support systems, is advised.

A 53-year-old woman with a history of acute myeloid leukemia received a second allogenic hematopoietic stem cell transplant (HSCT) and was prescribed, among other medications, acyclovir and letermovir (480 mg daily oral dose) for prophylaxis of respectively herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit (ICU) for dyspnea and oliguria. Laboratory investigations revealed acute kidney injury, but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma suspected a mitochondrial toxicity. Letermovir therapy was interrupted and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (40.7 h) that was not significantly influenced by continuous venovenous hemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B1*5/*15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted non-functional OATP1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.

Introduction Very preterm birth is associated with lung function impairment later in life, but several aspects have not been studied. We aimed to comprehensively assess lung function at school age in very preterm infants and term controls, with special emphasis on bronchopulmonary dysplasia (BPD), sex and bronchodilator response. Methods At 12 years of age, 136 children born very preterm (85 with and 51 without BPD), and 56 children born at term performed spirometry, body plethysmography, impulse oscillometry, measurement of diffusion capacity and multiple breath washout, before and after bronchodilator inhalation. Results Airway symptoms and a diagnosis of asthma were more common in children born very preterm. These children had more airflow limitation, seen as lower FEV 1 (p<0.001), FEV 1/FVC (p=0.011) and FEF 25-75 (p<0.001), and a higher total and peripheral airway resistance compared to term born controls. There was no difference in total lung capacity, but air trapping and lung clearance index were higher in children born very preterm. Diffusion capacity was lower in children born very preterm, especially in those with a diagnosis of BPD. In most other tests, the differences between preterm-born children with or without BPD were smaller than between children born preterm versus at term. Boys born preterm had more lung function deficits than preterm born girls. In children born very preterm, airway obstruction was to a large extent reversible. Conclusion At 12 years of age, children born very preterm had lower lung function than children born at term in most aspects. Airway obstruction improved markedly after bronchodilator inhalation, and there was only little difference between children with or without BPD.

Title: Symptomatic Hyperammonemia Secondary to Recombinant Erwinia AsparaginaseCatherine E. Martin, Pharm.D., Department of Pharmacy – Ambulatory Service, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAMira A. Kohorst, M.D., Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAAsmaa Ferdjallah, M.D., M.P.H, Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAJessica L. Kalmes, APRN, C.N.P., M.S.N, Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAHeather M. Johnson, APRN, C.N.P., M.S.N, Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAPaul J. Galardy, M.D., Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAShakila P. Khan, M.D., Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology/Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USAAlexis K. Kuhn, Pharm.D., Department of Pharmacy – Ambulatory Service, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USACorresponding author: Catherine E. Martin; address: 200 First Street SW, Rochester, MN 55905; phone: 507-284-2695; fax: 507-266-4912; email: martin.catherine3@mayo.eduMain text word count: 967Number of tables, figures, and supporting information: NoneShort running title: Hyperammonemia after recombinant Erwinia asparaginaseKeywords: Asparaginase, hyperammonemia, pediatrics, Erwinia, leukemiaAbbreviations

Probing the structures of amyloid-beta (Aβ) peptides in the early steps of aggregation is extremely difficult experimentally and computationally. Yet, this knowledge is extremely important as small oligomers are the most toxic species. Experiments and simulations on Aβ42 monomer point to random coil conformations with either transient helical or β-strand content. Our current conformational description of small Aβ42 oligomers is funneled toward amorphous aggregates with some β-sheet content and rare excited states with well-ordered assemblies of β-sheets. In this study, we emphasize another view based on metastable α-helix bundle oligomers spanning the C-terminus residues which are predicted by the machine-learning AlphaFold2 method and supported indirectly by low-resolution experimental data on many amyloid polypeptides. This finding has consequences in designing drugs to reduce aggregation and toxicity.

An 80-year-old woman with paroxysmal atrial fibrillation (AF) and typical atrial flutter (AFL) presented for a combined AF and AFL radiofrequency ablation.

A document by Yijie Zhu . Click on the document to view its contents.

Classical molecular dynamics simulations were used to study the separation of carbon dioxide from methane by three formulations of the deep eutectic solvent (DES) ethaline (choline chloride: ethylene glycol at 1:2, 1:4 and 1:8 molar ratios), in the bulk and confined inside carbon and titania slit pores of two different pore widths, 2 nm and 5 nm. The highest permselectivities (~20) are observed for 1:2 ethaline in a 5 nm carbon pore, followed by the 1:4 DES in a 5 nm graphite pore, 1:2 ethaline in a 2 nm carbon pore and the 1:8 bulk DES. Our results indicate that variations in the ratio of ethylene glycol, which in turn affect the interactions of all DES species with the gas molecules and the different pore walls, plus confinement effects resulting from varying the pore sizes, can affect the gas separation performance of these systems in complex ways.

Sex-biased mortality can occur in birds during development, for example due to sexual differences in energy requirement and/or environmental sensitivity, or the effects of sex hormones or sex differences in expression of mutations linked to sex chromosomes. Urban habitats often provide poorer conditions for nestling development resulting in higher offspring mortality compared to natural habitats, which may accelerate sex differences in offspring mortality in cities. To test this hypothesis, we examined sex-specific offspring mortality in great tits (Parus major), using 660 samples of dead offspring collected in two urban and two forest sites between 2013-2019. Overall, the sex ratio of dead offspring was significantly male-biased (56.80%). When habitats and age groups were analysed separately, the sex ratio of dead offspring was significantly male-biased in urban habitat (57.60%) and in young nestlings (58.62%), and non-significantly in the forest habitat (56.58%) and in unhatched embryos (54.11%) or in old nestlings (54.55%). However, these estimates were associated with wide confidence intervals, thus sex ratios of dead offspring did not differ significantly among study sites and between age groups when these were analysed together. 70.30% of unhatched eggs was not fertilized, and their proportion did not differ between urban and forest habitats. These results suggest male-biased offspring mortality in great tits, and highlight the need of large datasets to detect subtle differences between habitats and developmental stages.

Bird song is crucial for attracting mates and defending territories, but different types of song or different singing behaviours may be involved in acquiring or maintaining each resource. Furthermore, male songbirds may adjust when and where they sing throughout the breeding season, depending on their breeding stage. However, such relationships remain untested in several avian taxa. Here, we studied male Bermuda White-eyed Vireos (Vireo griseus bermudianus), a passerine with two distinct song types (discrete and rambling), to test the mate attraction, territory defence, and nesting stage hypotheses. We compare song rate and song perch height among different stages of the breeding season and during the non-breeding season. We show that male vireos produce both song types during the breeding and non-breeding seasons, suggesting dual roles in mate choice and territorial defence. Singing rate did not differ between the two seasons, but, within the breeding season, males without nesting duties had significantly higher song rates than males with nesting duties. Song rate was lowest during the nestling stage, which coincided with the highest rate of nest predation. Song perch height was higher during the breeding season versus non-breeding season, among males without nesting duties compared to males with nesting duties, and when males produced discrete versus rambling songs. Our findings suggest that male vireos increase their conspicuousness to prospecting females by increasing singing rate and song perch height, and that they sing during the breeding and non-breeding seasons to defend year-round territories. Collectively, our study supports the mate attraction and territory defence hypotheses of bird song and suggests that Bermuda White-eyed Vireos adjust their singing rate in response to nest predation risk.

A dual-polarized symmetrically cross-slotted square patch (SCSSP) antenna with multimode resonance is proposed for 5G millimeter-wave broadband applications. A symmetrical cross-slot is etched on the square patch surface to change the original E-field distribution where a whole square patch is cut into four disconnected equal parts. For both polarizations, this etching also tunes the resonance frequencies of the two modes to be sufficiently close to each other. Therefore, the antenna can realize good impedance performance within the wide designated bandwidth. Dual-polarized radiation of the SCSSP is vertically excited by three bow-tie-shaped slots and fed by two orthogonal substrate integrated coaxial lines. Simulated and measured results show that the fabricated prototype achieves a broad overlapped impedance bandwidth of 50.0% (24-40 GHz), isolation higher than 30 dB between the two input ports, stable radiation pattern, and low cross-polarization over the operating band. Moreover, the proposed SCSSP antenna with compact size, planar shape, and simple vertical feeding is very well-suited for two-dimensional array design.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the globe. Both established cardiovascular disease (eCVD) and future CVD (fCVD) need to further explore the mechanisms. This article briefly introduces current major studies on axis and CVD, which were published in cardiovascular journals and non-cardiovascular journals (Table 1 & Table 2), and brings up and discusses the new origins of fCVD linking to major risk factors in early life due to unhealthy “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] lifestyle referred as to a “Golden Hoop Curse”, and the “brain-heart-gut” axis—a fresh theory on novel mechanisms of fCVD (Figure 1 & Figure 2), which are mediated by E(e)SEEDi lifestyle and microbiome. As a new theory, the “brain-heart-gut” axis will help us to earlier and better prevent and control both eCVD and fCVD with healthy E(e)SEEDi lifestyle.