We present a rare case of an elderly man with degenerated bioprosthetic aortic valve complicated by infectious endocarditis 6 months after Covid-19 infection, who was treated successfully with valve-in valve after antibiotic therapy for the acute phase of infection, with excellent result and no complication early after the procedure and in follow-up visits.

Monomeric-to-Pentameric Aggregation of Molecular Cs4PbBr6 Halide Perovskite: a First-Principles Investigation

1,1-diamino-2,2-dinitroethene (FOX-7) is a novel energetic material with high performance and low sensitivity. In order to deeply understand the reaction mechanism in the initiation “hot spots” of FOX-7 and reveal the growth mechanism of these initiation “hot spots” in the explosion process, the detailed mechanisms of bimolecular reaction of NO2 and FOX-7, as well as the subsequent reactions have been investigated by the quantum chemical calculations. The mechanism of NO2 and FOX-7 bimolecular reaction and the catalytic effect of NO2 were revealed by three key dissociation paths. It is demonstrated that the NO2 molecule plays an important role in promoting the decomposition of the FOX-7 molecule, and the main exothermic pathways were the reactions between oxidizing intermediates (NO, NO2), and reducing intermediates (CO, NH3).

A series of 8-hydroxyquinoline derivatives were characterized and tested as potential antennas in a set of designed lanthanide complexes. The molecular structure and ligand localized nature of the excited states were studied in the framework of the multiconfigurational methods CASSCF/NEVPT2 combined with TDDFT- based approaches, which allows applying a fragmentation scheme in the analysis of the most probable sensitization pathway via antenna effect. The photophysical properties of all the complexes and antennas were carefully analyzed, and the most probable energy transfer pathways were elucidated. Rate constants for photophysical processes involved in the mechanism were calculated, showing a significant contribution of the vibronic coupling in all cases and the predominant intersystem-crossing between S1 and T1 states was demonstrated from the analysis of the nature of the wave function of those states. The energy transfer process described herein demonstrates the possibility of Eu(III) and Nd(III) sensitization by the studied ligands. The proposed methodology gives a complete picture of the antenna excited state dynamics.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare disease characterized by recurrent severe itching and jaundice. Coronavirus disease 2019 (COVID-19) is a multisystemic acute viral disease and the liver is frequently affected. Here, we wanted to present a BRIC case triggered by COVID-19 infection, discussing it together with current information.

Biofilms are typically heterogeneous in morphology, structure, and composition, resulting in non-uniform mechanical properties. The distribution of mechanical properties, in turn, determines the biofilm mechanical behavior, such as deformation and detachment. Most past studies neglected heterogeneity of biofilms. In this study, an image-based modeling approach was developed to transform two-dimensional optical coherence tomography biofilm images to a pixel-scale non-Newtonian viscosity map of the biofilm. The spatial distribution of non-Newtonian viscosity was applied in an established Oldroyd-B constitutive model and implemented using the phase-field continuum approach for the deformation and stress analysis. The heterogeneous model was able to predict deformations and stresses more accurately than a homogenous one. This is the first time, to the best of our knowledge, that an image-based approach is used to map the mechanical heterogeneity of biofilms for computational studies. It provides an efficient method to characterize biofilm mechanical behavior.

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

Background: Maintaining dose-dense, interval-compressed chemotherapy improves survival in Ewing sarcoma patients but is limited by myelosuppression. Romiplostim is a thrombopoietin receptor agonist that may be useful in the treatment of chemotherapy-induced thrombocytopenia (CIT). Methods: Patients aged between 3 and 33 years with Ewing sarcoma from 2010-2020 were reviewed. CIT was defined as a failure to achieve 75,000 platelets per microliter by day 21 after the start of any chemotherapy cycle. Fisher exact test was used for univariate analysis and Pearson’s correlation coefficient was used for the association between continuous variables. Results: 27 out of 42 patients (64%) developed isolated CIT, delaying one to four chemotherapy cycles per patient. CIT occurred during consolidation therapy in 24/27(88.9%) and with ifosfamide/etoposide cycles in 24/27 (88.9%). Univariate analysis failed to identify risk factors for CIT. The use of radiation approached significant (p value=0.056). Ten patients received romiplostim. The median starting dose was 3 (range 1-5) mcg/kg. Doses were escalated weekly by 1-2 mcg/kg to 4-10 mcg/kg and continued throughout chemotherapy. A higher romiplostim dose was associated with a higher change in average platelet counts from baseline r= 0.73 (p=0.04). No romiplostim-related adverse events were identified aside from mild headache. Conclusions: CIT is the primary reason for the inability to maintain treatment intensity in Ewing sarcoma. The concurrent use of romiplostim with chemotherapy is safe and feasible, and efficacy was associated with higher romiplostim doses.

In recent decades, warming temperatures and changes in land use are supposed to have enabled several tick species to expand their distribution limit northwards. The progression of ticks to new areas may introduce new and emerging tick-borne pathogens as well as increase existing diseases. Aside from climatic conditions, ticks are dependent on hosts for survival, and rodents often act as important hosts for ticks and as pathogen reservoirs. At northern latitudes, rodents often undergo multi-annual population cycles, and the periodic absence of hosts may inhibit the further progression of ticks. We investigated the potential role of common shrews (Sorex araneus) to serve as a stable host source to immature life stages of a generalist tick Ixodes ricinus and a specialist tick I. trianguliceps, during decreasing abundances of bank voles (Myodes glareolus). We tested whether ticks would have a propensity to parasitize a certain host type dependent on host population size and composition in two high latitude locations in southern Norway, by comparing tick burdens on trapped animals. We found that I. ricinus larvae showed an equal propensity to parasitize both host types as the host population composition changed, but voles had a higher level of parasitism by nymphs (p< 0.004). An overall larger host population size favored the parasitism of voles by larvae (p= 0.027), but not by nymphs (p= 0.074). I. trianguliceps larvae showed a higher propensity to parasitize shrews, regardless of host population size or composition (p= 0.004), while nymphs parasitized shrews more as vole abundance increased (p= 0.002). The results indicate that common shrews may have the potential to act as a replacement host during periods of low rodent availability, but long-term observations encompassing complete rodent cycles may determine whether shrews are able to maintain tick range expansion despite low rodent availability.

Drug-related adverse reactions are among the main reasons for harm to patients under care worldwide and even their deaths. The pharmacovigilance system has been proven to be an effective method of avoiding or alleviating such adverse events. In 2019, after two decades of implementation of the drug-related adverse reaction reporting system, China formally implemented a pharmacovigilance system with the Pharmacovigilance Quality Management Standards and a series of supporting technical documents created to improve the safety of medication given to patients. China’s pharmacovigilance system has faced many problems and challenges during its implementation. This spontaneous reporting system is the main source of data for China’s medication vigilance activities, but it has not provided sufficiently powerful evidence for regulatory decision-making. In conformity to the health-centered drug regulatory concept, the Chinese government has accelerated the speed of examination and approval of urgently needed clinical drugs and orphan drugs along with the requirement to improve the safety supervision of these drugs after their listing. China’s marketing authorization holders（MAHs）must strengthen its pharmacovigilance capabilities as the primary responsible department for drug safety. Chinese medical schools generally lack professional courses on pharmacovigilance. The regulatory authorities have recognized such problems and have made efforts to improve the professional capacity of pharmacovigilance personnel and to strengthen cooperation with stakeholders through the implementation of an action plan of medication surveillance and the establishment of patient-based adverse events reporting system and active surveillance systems, which will help China bridge the gap to bring its pharmacovigilance practice up to standards.

Objective:Compare the efficacy of intravenous ferric derisomaltose (FDI) with oral iron in pregnant women with persistent iron deficiency. Design:Single-centre, open-labelled, randomised controlled trial. Setting:Danish university hospital. Population:Women 14–21 weeks pregnant with persistent iron deficiency (ferritin <30 µg/L). Methods:Allocation to 1,000 mg intravenous FDI (single-dose) or 100 mg elemental oral iron daily (FA). Assessment of blood tests, patient reported outcomes (fatigue and quality of life) and adverse events throughout eighteen weeks’ follow-up. Main_outcome_measures:Proportion of non-anaemic (haemoglobin ≥11 g/dL) women throughout follow-up (primary endpoint), assessed by Kaplan-Meier estimates compared between groups by risk difference analysis. Change in haematological markers and patient reported outcomes, assessed by restricted maximum likelihood estimates compared between groups by a repeated measures mixed model. Results:From July 2017 through February 2020, 100 women were randomised to FDI and 101 to FA. In the FDI vs. FA group 89% vs. 88% were non-anaemic prior to inclusion. Throughout follow-up, 91% vs. 73% were non-anaemic in favor of FDI (18% difference, 95% CI 0.10–0.25, p<0.001). The haemoglobin least-squares mean increase was significantly greater in the FDI vs. FA group at week six (0.4 vs. -0.2 g/dL, p<0.001), twelve (0.5 vs. 0.1 g/dL, p<0.001) and eighteen (0.8 vs. 0.5 g/dL, p=0.01). Improvements in patient reported fatigue and psychological well-being were greater in the FDI group at weeks three and six. The incidence of treatment related adverse events was comparable across treatments. Conclusions:FDI was superior for avoiding anaemia compared to oral treatment, and biochemical superiority was accompanied by improved fatigue and psychological well-being.

Background: As pediatric implantable cardioverter defibrillator (ICD) utilization increases, hospital admission rates will increase. Data regarding hospitalizations among pediatric patients with ICDs is lacking. In addition, hospital mortality rates are unknown. This study aimed to evaluate 1) trends in hospitalization rates of admissions over 20 years, 2) hospital mortality, and 3) factors associated with hospital mortality among pediatric admissions with ICDs. Methods: The Kids’ Inpatient Database (2000-2016) was used to identify all hospitalizations with an existing ICD 20 years of age. ICD9/10 codes were used to stratify admissions by underlying diagnostic category as: 1) congenital heart disease (CHD), 2) primary arrhythmia, 3) primary cardiomyopathy, or 4) other. Trends were analyzed using linear regression. Hospital and patient characteristics among hospital deaths were compared to those surviving to discharge using mixed multivariable logistic regression, accounting for hospital clustering. Results: Of 42,570,716 hospitalizations, 4165 were admitted <21 years with an ICD. ICD admissions increased four-fold (p = 0.002) between 2000-2016. Hospital death occurred in 54 (1.3%). In multivariable analysis, cardiomyopathy (OR 3.5, 95%CI 1.1–11.2, p=0.04) and CHD (OR 4.8, 95%CI 1.5–15.6, p=0.01) were significantly associated with mortality. In further exploratory multivariable analysis incorporating a coexisting diagnosis of heart failure, only the presence of heart failure remained associated with mortality (OR 8.6, 95%CI 3.7-20.0, p<0.0001). Conclusions: Pediatric ICD hospitalization are increasing over time and hospital mortality is low (1.3%). Hospital mortality is associated with cardiomyopathy or CHD; however, the underlying driver for in-hospital death may be heart failure.

Introduction: A subset of patients who develop post-surgical heart block have recovery of atrioventricular-node function. Factors predicting recovery are not understood. We sought to investigate our center’s incidence of post-surgical heart block and examine factors associated with recovery of atrioventricular-node function. Methods: Patients 0 – 21 years who underwent cardiac surgery between January 2010 – December 2019 at a free-standing children’s hospital and experienced postoperative heart block were included. Demographics, clinical and operative variables were analyzed. Results: Of 6333 surgical hospitalizations, 128 (2%) patients were included. Of the 128 patients included, 90 (70%) had return of atrioventricular-node function, and 38 (30%) had permanent pacemaker placement. Of the 38 patients who underwent pacemaker placement, 6 (15.8%) had recovery of atrioventricular-node function noted on long-term follow-up. Median time to from onset of heart block to late atrioventricular-node recovery was 13 days (IQR 5 – 117). Patients with single-ventricle physiology ( p = 0.04), greater weight ( p = 0.03) and shorter cardiopulmonary bypass time ( p =0.015) were more likely to have recovery. The use of postoperative steroids was similar between all groups ( p = 0.445). Infectious or wound complications were similar between pacemaker groups ( p = 1). Conclusions: Two percent of patients who underwent cardiac surgery developed postoperative heart block, and 0.6% underwent pacemaker placement. Early recovery of atrioventricular-node was associated with greater weight at time of surgery, single-ventricle physiology and shorter cardiopulmonary bypass time. Late recovery of atrioventricular-node conduction following pacemaker placement occurred in 15.8% of patients.

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.

Engineering microscopic collectives of cells or microrobots is challenging due to the often-limited capabilities of the individual agents, our inability to reliably program their motion and local interactions, and difficulties visualising their behaviours. Here, we present a low-cost, modular and open-source Dynamic Optical MicroEnvironment (DOME) and demonstrate its ability to augment microagent capabilities and control collective behaviours using light. The DOME offers an accessible means to study complex multicellular phenomena and implement de-novo microswarms with desired functionalities. Corresponding author(s) Email:    thomas.gorochowski@bristol.ac.uk sabine.hauert@bristol.ac.uk

Creatine Kinase (CK/CK-MB) testing is an essential lab test approaching patients with chest or epigastric pain. we report a 38-year-old man with acute pancreatitis and elevated CK/CK-MB level without myocardial involvement. Acute pancreatitis may be considered as a false positive cause of CK/CK-MB test in patients presenting with chest pain.

Herein, we report the mechanism of Ir(III)-catalyzed intermolecular branch-selective allylic C−H amidation, including the influence of substituent effect on yield and regioselectivity. The sequence of amidation reaction is alkene coordination, allylic C−H activation, oxidative addition of methyl dioxazolone, reductive elimination of allyl-Ir-nitrenoid complex, amine protonation and proto-demetallation. The apparent activation energy of amidation between hexene and methyl dioxazolone is 17.8 kcal/mol, and the energy difference between two transition state for formation amide is only 2.8 kcal/mol. The introduction of more electron-deficient groups at the allyl terminal increases the apparent activation energy, conversely, the introduction of electron-donating groups significantly reduces the apparent activation energy. Among them, the apparent activation energy of the reaction between aniline group substituted allyl and methyl dioxazolone is only 13.8 kcal/mol, which further improves the reaction yield. In addition, the introduction of more electron-withdrawing groups on dioxazolone can significantly improve the regioselectivity. When 3,4,5,-trifluorophenyl substituted dioxazolone and hexene occur C−N bond coupling reaction, the energy difference of the two transition states is as high as 9.0 kcal/mol, indicating that the regioselectivity is greatly improved. The mechanism explanation of allylic C−H amidation will provide strong theoretical support for streamlined synthesis of allyl branched amides.

The study of plant community dynamics has a long tradition. However, this field has barely incorporated the tools developed in the modern study of ecological networks. Key for this incorporation is the availability of a theoretical model able to incorporate field data about plant-plant interactions. In this study I introduce the Recruitment and Replacement (R&R) model that explicitly incorporates empirical networks of plant-plant interactions that occur during recruitment. The R&R model is built on fundamental demographic rates and incorporates competition for space between adults, intra- and inter-specific effects of established plants on recruitment and the colonization of vacant space. The basic analysis of the model provides predictions regarding different aspects of plant community dynamics, like the environmental conditions and species properties under which facilitation of recruitment is more likely to occur, the effect of recruitment facilitation on invasion, the effects of plant-plant interactions on equilibrium abundances and community stability, and the network properties that should relate to species equilibrium abundances. Many of these predictions agree with findings from published meta-analyses, supporting the general validity of the recruitment networks framework as a general approach to integrate the study of plant community dynamics into the study of ecological networks.

Patients and their families are discouraged from the restrictions on hospital visits for coronavirus Infection control. This separation might further deteriorate the mental health of both vulnerable patients and their family members. Home care could be a preferable solution to this problem.

Survival of patients with recurrent and metastatic Ewing sarcoma (ES) has not markedly improved in the last 40 years; the main reason for the poor prognosis of these patients is drug resistance. However, intrinsic and acquired resistance may occur in response to both traditional chemotherapy and targeted drugs. These complex mechanisms plausibly include instability of the genetic material, enhanced drug efflux and metabolism, positive DNA repair, inhibition of tumor cell apoptosis, miRNAs, the tumor microenvironment, cancer stem cells, autophagy, and the activation of cell proliferation pathways. The development and application of nanoparticles bring new hope for reversing drug resistance in ES, accompanied with encouraging results from preclinical trials. In this review, we elucidate the molecular mechanisms underlying drug resistance in ES and propose putative strategies to overcome this resistance to improve prognosis of patients with ES.

Background: Arterial Stiffness (AS) is a novel marker shown to be an independent predictor of coronary artery disease (CAD). However, AS has been minimally studied for its predictive value in CAD outcomes post-management. This review summarizes the current knowledge of AS and its potential role as a risk stratifying marker in coronary bypass graft (CABG) patients. Methods: A scoping review was performed to discover the existing primary research on AS and its role as a predictive marker of outcomes in CAD. MeSH terms were formulated for the database search. A pre-set inclusion and exclusion criteria were created for appropriate article retrieval. A qualitative analysis and syntheses of these articles was conducted. Results: The search returned a total of 11 articles from 2005 to 2020 discussing the prognostic implications of AS in CAD management. A majority of the articles found prognostic value of AS in medically-managed and percutaneous-revascularized patients. Only 3 studies examined outcomes of CABG in-relation to pre-operative AS, which were extremely limited in scope, though did show prognostic correlation of post-op acute kidney injury. Conclusions: Despite the strong relationship of AS and CAD, few studies have looked at its prognostic value in patients undergoing surgical revascularization. Given the expanding evidence for AS as a marker of CAD and the progression of point-of-care technology to assess AS, this state-of-the-art measure could be a valuable risk stratifying tool for surgeons considering CABG for their patients, though further original research is needed.

Payments for ecosystem services (PES) provide innovative solutions for global environmental governance. China, the largest developing country, always faces serious ecological and environmental problems. China created an Ecological compensation mechanism which combines the PES mechanism with the government’s standardized management, which has achieved remarkable results. Government-led, social participation, and market-oriented operation are its main characteristics. More importantly, the mechanism helps China achieve its anti-poverty goals. Part of its experiences have been transformed into formal institutions, i.e., Grain-for-Green plan. However, some problems have also plagued further development of it, such as the lack of environmental property rights, the single source of funds and the shortage of standardized ecological value assessment technology. We suggest that it is necessary to further improve the stability of China’s Eco-compensation mechanism. The achievement of China’s Eco-compensation mechanism provides useful guidance for other developing countries. For example, improving the role of government administrative power, and the flexibility of the system through the policy “sandbox” i.e., the policy pilot, encouraging the participation of multi-stakeholder groups, and so on. Last but most important, the policy and institutions must be closely integrated with the state of the nation for it to be sustainable.

Rates of obstetric anal sphincter injuries among immigrant womenMarie-Louise MarschalekKlinik Floridsdorf, Vienna, AustriaLinked article: This is a mini commentary on Sorbye et al.The Norwegian-wide cohort study by Sorbye et al addresses the question of whether the maternal region of origin and birthplace have an influence on the risk of obstetric anal sphincter injury (BJOG 2021).Obstetric anal sphincter injuries (OASI), as a complication of vaginal delivery, are associated with potential long-term complications such as anal and fecal incontinence, perineal pain, sexual dysfunction and increased rates of caesarean section in subsequent deliveries. Established risk factors for OASI are high birthweight, operative vaginal delivery and prolonged second stage of labor.When it comes to ethnicity as a risk factor, retrospective studies suggest Asian women are at increased risk for OASI (Brown J et al. Aust N Z J Obstet Gynaecol. 2018;58(1):79-85.). However, it has remained unclear whether the biological or the migration factor is the cause.Maternal origin, immigrant status and duration of residence have been the subject of many studies, in order to identify risks of various adverse obstetric outcomes, with known increased risk of both giving birth to small for gestational age fetuses, and preterm delivery (Urquia et al. BJOG 2010 Apr;117(5):591-601.)The present study analyzed a 9-year comprehensive data set from birth registries, and concluded that, compared to Norwegian women, women from South Asia were most likely to experience OASI, with an aOR of 2.24, followed by women from Southeast/East Asian/Pacific and Sub-Saharan Africa. Furthermore, the authors found newly arrived migrant women to be at highest risk for OASI.Migrant women are exposed to a new physical and social environment, with limited language competence a significant factor in preventing social integration, resulting in limited health literacy and sub-optimal care after migration.Language skills are particularly significant in OASI cases, being important for collaboration between the woman and birth attendant during delivery. Interestingly, a difference was found regarding whether the partner was Norwegian-born or foreign-born, indicating that good communication at giving birth was important. The inference is that an understanding of the birth process and an explanation of the difficulties that might arise is an advantage. Undoubtedly educating women during pregnancy itself about OASI risks is of value.Sorbye et al do not address the topic of perineal laceration protection techniques, experience of birth attendants or birth position. As studies have identified certain positions, such as the lithotomy position, to be a risk factor for OASI, whilst others, such as the lateral position, are considered to be protective, this information would have been interesting.In other nationwide studies the incidence of OASI is shown to have increased, explained by improved awareness, diagnostic recognition and documentation (Andrews V et al. BJOG. 2006;113:195‐200.). However, in this and another recent study, the incidence has decreased in Norway and Sweden, possibly due to implemented perineal protection programs for midwives/physicians (Gyhagen et al. Acta Obstet Gynecol Scand. 2021 Aug 25).Sorbye and colleagues highlight the influence of environmental factors on OASI, which in theory could be preventable, and confirm that there are migration specific factors. Hence, the vulnerable group of migrant women need special attention and care in order to reduce morbidity.

Introduction: Cystic Fibrosis is a disease that causes inflammation, oxidative stress and metabolic changes that lead to nutrient deficiency, such as vitamin D. On the other hand, it is suggested that vitamin D has anti-inflammatory and antioxidant action. Objective: To evaluate the prevalence of hypovitaminosis D and the association between serum 25 hydroxyvitamin D levels with markers of oxidative stress and inflammation in patients with cystic fibrosis. Method: Cross-sectional study carried out with 48 patients with Cystic Fibrosis in children, adolescents and adults in the Northeast region/Brazil. Blood collection was performed for analysis of 25-hydroxyvitamin D, calcium, parathyroid hormone, inflammatory process (C-reactive protein -PCR and alpha-1-acid glycoprotein-A1-A1GPA) and oxidative stress (malondialdehyde-MDA and total antioxidant capacity-CAOT. Statistical analysis was performed using the “Statistical Pacage for the Social Sciences”, adopting a significance level of p<0.05. Results: Insufficiency/deficiency of D was found in 64.6% of patients. After multiple linear regression analysis, MDA showed an inverse association with blood values of 25-Hydroxyvitamin D (p < 0.05) Results: Insufficiency/deficiency of D was found in 64.6% of patients. After multiple linear regression analysis, MDA showed an inverse association with blood values of 25-Hydroxyvitamin D (p < 0.05) conditioned on the presence of inflammatory process markers. When only oxidative stress is evaluated, this association disappears. Conclusion: In conclusion, there was a high prevalence of hypovitaminosis D, with 25 (OHD) levels associated with greater oxidative stress when combined with inflammatory markers. Improved vitamin D levels may be an alternative to reduce the damage caused by excess oxidative stress and inflammation in CF patients.