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This review highlights the rheological and phase proportions variation induced by cooling events from superliquidus temperature (melt) to subliquidus temperatures. It provides a comprehensive view of the rheological response of magmatic systems undergoing dynamic cooling and shear deformation. The two main parameters which are of importance to model the rheological properties of such crystallizing systems and which are simultaneously poorly investigated so far are crystallization and strain rates. The response to relatively high deformation rates results in shear thinning behavior in partly crystallized systems under variable shear rate and it should be considered in magmatic processes. Due to the sluggish crystallization of SiO$_{2}$-rich melts, data are mainly available for mafic systems, which does not allow a general reappraisal. An attempt to model available literature data for less evolved systems in dynamic scenarios and a comparison with MELTS algorithm approach (thermodynamic equilibrium conditions) is provided. Since there are difficulties in comparing experimental data gained using different methodologies, we focus mainly on data obtained with the concentric cylinder technique. This highlights the fact that a general experimental protocol is needed in order to compare and model viscosity data to predict the dynamic rheological evolution for volcanic rocks.

Hundreds of thousands of people die each year as a result of sudden cardiac death, and many are due to heart rhythm disorders. One of the major causes of these arrhythmic events is Brugada syndrome, a cardiac channelopathy that results in abnormal cardiac conduction, severe life-threatening arrhythmias, and, on many occasions, death. This disorder has been associated with mutations and dysfunction of about two dozen genes; however, the majority of the patients do not have a definite cause for the diagnosis of Brugada Syndrome. The protein-coding genes represent only a very small fraction of the mammalian genome, and the majority of the noncoding regions of the genome are actively transcribed. Studies have shown that most of the loci associated with electrophysiological traits are located in noncoding regulatory regions and are expected to affect gene expression dosage and cardiac ion channel function. Noncoding RNAs serve an expanding number of regulatory and other functional roles within the cells, including but not limited to transcriptional, post-transcriptional, and epigenetic regulation. The major noncoding RNAs found in Brugada Syndrome include microRNAs; however, others such as long noncoding RNAs are also identified. They contribute to pathogenesis by interacting with ion channels and/or are detectable as clinical biomarkers. Stem cells have received significant attention in the recent past, and can be differentiated into many different cell types including those in the heart. In addition to contractile and relaxational properties, BrS-relevant electrophysiological phenotypes are also demonstrated in cardiomyocytes differentiated from stem cells induced from adult human cells. In this review, we discuss the current understanding of noncoding regions of the genome and their RNA biology in Brugada Syndrome. We also delve into the role of stem cells, especially human induced pluripotent stem cell-derived cardiac differentiated cells, in the investigation of Brugada syndrome in preclinical and clinical studies.

James V Gruber,1 Robert Holtz2 1JVG Innovative Consulting, Washington, NJ, USA; 2BioInnovation Laboratories, Inc., Denver, CO, USACorrespondence: James V Gruber, Email Gruberjv@embarqmail.comIntroduction: Pyrroloquinoline quinone is a bacterial-derived redox factor that has been shown to have numerous benefits in humans. Recently, a model for examining the ability of normal human epidermal keratinocytes (NHEKs) to demonstrate anti-inflammatory benefits via nod-like receptor protein (NLRP)-activated caspase-1 release was reported. The question of whether PQQ2Na might have anti-inflammatory benefits that function through NLRP-activated release of active caspase-1 has not been explored. In addition, it has been reported that PQQ2Na will induce mitochondrial biogenesis in humans when taken orally. Whether or not this effect occurs in skin cells is presently unknown.Methods: The inflammation studies followed previously published methods that demonstrated both UVB and ATP were able to upregulate the NLRP-activated release of caspase-1 in NHEKs. In addition, NHEK and normal dermal human fibroblasts (NHDF) were treated with PQQ2Na to see if the molecule might stimulate mitochondrial biogenesis measured by increased expression of cyclooxygenase-1 (COX-1) and succinate dehydrogenase complex, subunit A (SDHA).Results: At non-cytotoxic concentrations between 5 μg/mL and 100 μg/mL in NHEKs and between 0.1 μg/mL and 5 μg/mL in fibroblasts, the PQQ2Na had no influence on cellular mitochondrial biogenesis. In ATP-activated NHEKs at concentrations of PQQ2Na between 0.05 μg/mL and 50 μg/mL, there was no influence of PQQ2Na on release of active caspase-1. In NHEKs irradiated with 60mJ/cm2 of UVB radiation as previously described and treated with 0.05 μg/mL to 50 μg/mL of PQQ2Na, the molecule showed a dose-dependent benefit at reducing the expression of active caspase-1 in the irradiated cells.Discussion: Benefits of PQQ2Na on various skin cell types which had not been investigated previously were addressed. Surprisingly, the PPQ2Na had no apparent influence on skin cell mitochondrial biogenesis. However, the molecule has a strong suppressing influence on UVB-induced active caspase-1 release in UVB-irradiated NHEKs.Keywords: pyrroloquinoline quinone disodium, inflammasomes, mitochondrial biogenesis, caspase-1, inflammation

BackgroundType 1 diabetes (T1D) is a chronic condition that typically affects young age group people and is estimated to afflict approximately 154,000 people younger than 20 years in the United States. Since T1D typically impacts children, parents must play an active role in helping their child manage the condition. This creates a substantial burden and responsibility for the parents. ObjectiveThis pilot study sought to find ways to help parents with children with T1D in coping with stresses related to managing and monitoring their child’s disease by providing informational support, either about parenting a child with T1D or general parenting messages through different channels. MethodsParents (N=120) of children with T1D were recruited through an email listserv through local T1D Facebook groups. A total of 102 participants were included in the analysis. We conducted a 2×2 experimental study over an 8-week period to test 2 types of messages (diabetes specific vs general parenting) and the medium in which the messages were delivered (Facebook vs SMS text message). Diabetes behavior, informational support, emotional support, and quality of life were the main outcomes of interest. ResultsThe results suggested that the participants in the diabetes message groups showed improvement in diabetes behaviors (F1,99=3.69; P=.05) and were more satisfied with the intervention (F3,98=4.59; P=.005). There were no differences between message and medium groups on informational support, emotional support, or quality of life. ConclusionsThe results of this study demonstrate that the medium—Facebook or SMS text messaging—does not matter for parents’ perceptions of social support or quality of life. The diabetes message group reported higher levels of disease management. Finally, the groups with the diabetes support messages were more satisfied than those who received general parenting messages. The findings provide starting guidance for the development of social support interventions for this population.

Endometriosis is characterized by the presence of endometrial tissues outside the uterine lining, typically on the external surface of the uterus, the ovaries, fallopian tubes, abdominal wall, or intestines. The prevalence of endometriosis in North America, Australia, and Europe is ~1–5% in women of reproductive age. Treatment options for endometriosis are limited. While over-the-counter medications may be used to reduce acute pain, hormonal treatments are common and may interfere with fertility. In more severe cases, laparoscopic excision procedures and even hysterectomies are used to treat the pain associated with endometriosis. Nutritional interventions may be helpful in the prevention and treatment of endometriosis and associated pain. Reducing dietary fat and increasing dietary fiber have been shown to reduce circulating estrogen concentrations, suggesting a potential benefit for individuals with endometriosis, as it is an estrogen-dependent disease. Meat consumption is associated with greater risk of developing endometriosis. Anti-inflammatory properties of plant-based diets may benefit women with endometriosis. Additionally, seaweed holds estrogen-modulating properties that have benefitted postmenopausal women and offers potential to reduce estradiol concentrations in pre-menopausal women. Furthermore, consumption of vitamin D has been shown to reduce endometrial pain via increased antioxidant capacity and supplementation with vitamins C and E significantly reduced endometriosis symptoms, compared with placebo. More randomized clinical trials are needed to elucidate the role of diet in endometriosis.

The methionine addiction of cancer cells is known as the Hoffman effect. While non-cancer cells in culture can utilize homocysteine in place of methionine for cellular growth, most cancer cells require exogenous methionine for proliferation. It has been suggested that a biochemical basis of this effect is the increased utilization of methionine for S-adenosylmethionine, the major methyl donor for a variety of cellular methyltransferases. Recent studies have pointed to the role of S-adenosylmethionine-dependent protein arginine methyltransferases (PRMTs) in cell proliferation and cancer. To further understand the biochemical basis of the methionine addiction of cancer cells, we compared protein arginine methylation in two previously described isogenic cell lines, a methionine-addicted 143B human osteosarcoma cell line and its less methionine-dependent revertant. Previous work showed that the revertant cells were significantly less malignant than the parental cells. In the present study, we utilized antibodies to detect the asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) products of PRMTs in polypeptides from cellular extracts and purified histone preparations of these cell lines fractionated by SDS-PAGE. Importantly, we observed little to no differences in the banding patterns of ADMA- and SDMA-containing species between the osteosarcoma parental and revertant cell lines. Furthermore, enzymatic activity assays using S-adenosyl-ʟ-[methyl-3H] methionine, recombinantly purified PRMT enzymes, cell lysates, and specific PRMT inhibitors revealed no major differences in radiolabeled polypeptides on SDS-PAGE gels. Taken together, these results suggest that changes in protein arginine methylation may not be major contributors to the Hoffman effect and that other consequences of methionine addiction may be more important in the metastasis and malignancy of osteosarcoma and potentially other cancers.

Background and objectiveThe body posture can influence gas exchange, respiratory mechanics, and mucociliary clearance and different positions can be used as a therapeutic strategy to improve in gas exchange and can also help physiotherapists to assist patients who have difficult or restrictions to stay seated or the ones who stay in the same position for a long period. The objective of this study was to evaluate the effect of different positions on respiratory system impedance in obese and eutrophic subjects, using Impulse Oscillometry System (IOS).MethodsThe IOS parameters were evaluated in seated (Se), right lateral decubitus (RL), left lateral decubitus (LL), and supine (Su).ResultsSixty two volunteers were allocated in obese group (OG) or eutrophic group (EG) according to BMI. In seated position, OG showed higher impedance than EG for R5: 0.55 (0.31; 0.93) and 0.33 (0.24; 0.52); R20: 0.39 (0.23; 0.54) and 0.32 (0.03; 0.41); R5-R20: 0.13 (0.02; 0.47) and 0.01 (-0.08; 0.27); X5: -0.20 (-0.51; 0.16) and -0,10 (-0.016; -0.04); Fres: 20.59 (11.54; 36.45 and 10.69 (7.56; 24.7) (pConclusionThe respiratory system impedance is increased in OG, with greater contribution of peripheral resistance. The higher values of resistance and reactance were obtained in the supine position, in both groups, with lower differences obtained in the right and left lateral decubitus.

BackgroundTreatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis.MethodsIn this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration.FindingsOf 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses.InterpretationAlthough inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition.FundingAmerican Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

The chrysanthemum is one of the main ornamental species in the world. It has great relevance in the market. Aphids are the main pests that affect the chrysanthemum crop and cause various types of damage to this plant. The objective of this study was to evaluate the influence of different cropping systems using photoselective screens on the population density of aphids in cut chrysanthemum. The study was carried out in an experimental area of the Federal Institute of Espírito Santo – Campus Itapina (Brazil) in a randomized complete block design, according to the split-plot scheme over time. The experiment was established in 3 blocks of 12 m in length with plots of 3 m containing different photoselective screens (red, silver, and black) and the control treatment (open field). Repeated evaluations at different times were done at 0, 15, 30, 45, and 60 d. Data were checked for normality and homoscedasticity and submitted to the Tukey’s test (P

IntroductionIn spite of promising medical, sociological, and engineering strategies and interventions to reduce the burden of disease, malaria remains a source of significant morbidity and mortality, especially among children in sub-Saharan Africa. In particular, progress in the development and administration of chemotherapeutic agents is threatened by evolved resistance to most of the antimalarials currently in use, including artemisinins.MethodsThis study analyzed the prevalence of mutations associated with antimalarial resistance in Plasmodium falciparum from 95 clinical samples collected from individuals with clinically confirmed malaria at a hospital in Bo, Sierra Leone between May 2017 and December 2018. The combination of polymerase chain reaction amplification and subsequent high throughput DNA sequencing was used to determine the presence of resistance-associated mutations in five P. falciparum genes – pfcrt, pfmdr1, pfdhfr, pfdhps and pfkelch13. The geographic origin of parasites was assigned using mitochondrial sequences.ResultsRelevant mutations were detected in the pfcrt (22%), pfmdr1 (>58%), pfdhfr (100%) and pfdhps (>80%) genes while no resistance-associated mutations were found in the pfkelch13 gene. The mitochondrial barcodes were consistent with a West African parasite origin with one exception indicating an isolate imported from East Africa.DiscussionDetection of the pfmdr1 NFSND haplotype in 50% of the samples indicated the increasing prevalence of strains with elevated tolerance to artemeter + lumefantrine (AL) threatening the combination currently used to treat uncomplicated malaria in Sierra Leone. The frequency of mutations linked to resistance to antifolates suggests widespread resistance to the drug combination used for intermittent preventive treatment during pregnancy.

In a recent study, we demonstrated a relationship between self-reported sleep deprivation and youth susceptibility to initiate electronic nicotine delivery systems (ENDS) use; however, we were hampered by cross-sectional data. This study builds on our previous work by performing secondary analysis using the nationally representative Population Assessment of Tobacco and Health study datasets from wave 4.5 (2017–2018) and wave 5 (2018–2019) among respondents aged 12–17. Using a longitudinal cohort design, we assessed the extent self-reported sleep troubles at wave 4.5 related to transition from never-to-ever ENDS use by wave 5. We assessed youth who reported never having used any type of tobacco previously and who reported not using alcohol or other illicit substances the previous year. We ran four Poisson regression models on the dependent variable never-to-ever ENDS users at wave 5 and self-reported sleep troubles in the past year at wave 4.5. We controlled for demographic and sociographic factors and, in our final model, tobacco availability in home, exposure to ENDS advertising on social media, past year anxiety, depression, body mass index, physical activity, close friends that use ENDS, perceived harm of ENDS, school performance, sensation seeking, and the susceptibility of youth to initiate ENDS. Even when controlling for these factors, sleep troubles at wave 4.5 significantly and positively related to ENDS initiation by wave 5 (Past year sleep trouble: RR = 1.48 95 % CI = [1.14–1.93]). This key and novel finding has important implications for preventing youth ENDS use via protective self-care and social-environmental approaches.

Telemedicine has garnered considerably more attention during the COVID-19 pandemic than in any time previously. However, before the beginning of the pandemic, many individuals had not accessed care in this manner. The purpose of this study was to understand the central reasons that individuals had not used telemedicine before the pandemic. Therefore, we conducted a convenience sample survey in March?April 2020, and 539 participants living in the United States answered questions about exploring their reasons for not having used telemedicine. Descriptive statistics and correlations were conducted to analyze the data. Two themes emerged from these data, including the importance of the patient?provider relationship and that access to technology was not the issue for this particular population. Although technology was not a barrier, many, specifically older participants, had concerns over privacy and security. As the world gains some control over the COVID-19 pandemic and medical appointments begin to return to a new normal, the implication for the continued use of telemedicine is still important to address as this will become a standard of care.

Chemically variable primitive basalts undergo mixing during ascent from the mantle. Here the authors show observations from magma–magma reaction experiments which demonstrate how isothermal mixing between chemically variable basalts creates and modifies crystal cargoes erupted in oceanic settings.

Tyrannosaurid dinosaurs were ecologically unique vertebrates as the sole clade of large terrestrial carnivores (adults >400 kg) in their continent-spanning habitats. Expanded ligaments between metatarsals, inferred by gross morphology of attachment correlates, have been hypothesized to have strengthened their specialized arctometatarsus. We tested the hypothesis of ligament presence with scanning electron microscopy and histological thin sections of putative attachment sites in a third metatarsal of the tyrannosaurid Gorgosaurus libratus, compared with a thin section from the unspecialized metatarsals of the early theropod Coelophysis bauri. In the Gorgosaurus metatarsal, Sharpey´s fibers and rough, pitted surface textures consistent with ligament coalescence occur at expansive distal regions and localized rugosities are ideally located for resisting torsional loading on the foot. Sparser Sharpey’s fibers occur at expected locations in other arctometatarsus-bearing coelurosaurs. In contrast, the Coelophysis metatarsal lacked Sharpey’s fibers or rugosity at the sectioned location, acting as a definitive negative control for identifying these features in tyrannosaurids. With soft-tissue correlates confirmed as ligament entheses, we conclude that tyrannosaurids possessed distinctive and specific ligament attachments to the third metatarsal lacking in other large carnivorous dinosaurs. Histological evidence for extensive distal intermetatarsal ligaments is consistent with greater inferred agility in derived tyrannosaurid dinosaurs than in earlier lineages of large theropods.

Although chemical insecticides are successfully used in agriculture, several problems may be related to their indiscriminate use. This has encouraged the development of alternative methods for pest insect control and societal pressure for pesticide-free products. The jatropha (J. curcas) and castor bean (Ricinus communis) are plants that have shown insecticidal potential. Thus, the objective of this work was to study the effects of leaves of R. communis and J. curcas of different ages on the cabbage aphid (Myzus persicae). Five solution concentrations and five leaf types were used. Each treatment consisted of ten individuals M. persicae, kept in Petri dishes (10.0 x 1.2 cm), about kale leaf discs. Each Petri dish was considered a repeat, totaling ten. An airbrush connected to a compressor calibrated at constant pressure and 5 mL of solution per repetition was used for direct application. The cabbage discs were immersed in the different treatments for five seconds and offered to aphids in the indirect application. For both tests, evaluations were performed 72 hours after application. Data were submitted to linear regression analysis and means test. There was an interaction between the application type, leaf type, and concentrations for both plants. We argue that at their different ages, jatropha and castor bean leaves have insecticidal potential in the management of M. persicae.

**Background:** Epidural analgesia can be associated with high costs and postsurgical risks such as hypotension, despite its widespread use and value in providing opioid-sparing pain management. We tested the hypothesis that liposomal bupivacaine (LB) might be a reliable alternative to epidural analgesia in this real-world study. **Objectives:** To compare economic outcomes and hypotension incidence associated with use of LB and epidural analgesia for abdominal surgery. **Methods:** This retrospective analysis identified records of adults who underwent abdominal surgeries between January 2016 and September 2019 with either LB administration or traditional epidural analgesia using the Premier Healthcare Database. Economic outcomes included length of stay, hospital costs, rates of discharge to home, and 30-day hospital readmissions. Secondary outcomes included incidence of postsurgical hypotension and vasopressor use. Subgroup analyses were stratified by surgical procedure (colorectal, abdominal) and approach (endoscopic, open). A generalized linear model adjusted for patient and hospital characteristics was used for all comparisons. **Results:** A total of 5799 surgical records (LB, n=4820; epidural analgesia, n=979) were included. Compared with cases where LB was administered, cases of epidural analgesia use were associated with a 1.6-day increase in length of stay (adjusted rate ratio [95% confidence interval (CI), 1.2 [1.2-1.3]]; _P_

Abstract The load‐shedding scenario describes an unscheduled load reduction in a power plant so that it produces only the electricity that is needed by the plant itself. The reason for such a scenario is a collapse of power supply in the transmission network. In the subsequent restoration of the electrical supply, different options are distinguished. An essential part of each option is island operating or black start capable thermal power plants. The load‐shedding scenario is complex and multilayered. If process steam is also decoupled during the load shedding, high exhaust steam temperatures in the turbine stages can lead to plant shutdown. In addition, component damage can be expected in thick‐walled components due to high temperature and pressure amplitudes. Thus, it can be shown in this paper that the lifetime losses are highest at the high‐pressure preheater 6 and at the deheater and that the process heat coupling cannot be operated with constant mass flow under all circumstances. In order to investigate these issues, a detailed model of a lignite power plant has been created, which was developed in Modelica for simulating and comparing scenarios for a variety of applications. The model comprises the entire water‐steam cycle including turbines, preheaters and pumps, as well as a very detailed boiler model including the air supply, coal mills, heating surfaces, and piping. Furthermore, the power plants' control system has been implemented in a very precise way. In addition, the study involves a calculation of lifetime consumption for specific components to evaluate the effects. In summary, it can be stated that this study examines the thermodynamic aspects during a load‐shedding scenario for the first time. It focuses on processes within the power plant and thus differs significantly from other studies on this topic, which approach the issue from the electrical grid side.

Objetivo: O objetivo é verificar o impacto do uso da mensuração a valor justo sobre os honorários de auditoria, diferenciando-se inclusive o período pré e pós adoção do CPC 46. Metodologia: A pesquisa apresentada é quantitativa, sendo que para o teste das hipóteses levantadas foi utilizada a técnica de regressão múltipla, com dados disponíveis das empresas listadas na B3 referentes ao período entre 2010 e 2016. Resultados: As evidências indicam que a complexidade e subjetividade do valor justo é reconhecida pelas empresas de auditoria, ou seja, as firmas de auditoria consideram que a mensuração a valor justo implica mais esforços e que os riscos de auditoria associados se elevam, levando as firmas à cobrança de um prêmio de risco pela prestação do serviço. Entretanto, não foi possível confirmar que os honorários dos auditores aumentaram após a adoção da IFRS13 (CPC 46). Contribuições do estudo: Teóricas/metodológicas - o estudo contribui para a compreensão sobre os impactos da adoção de normas internacionais de contabilidade, neste caso específico, sobre honorários de auditoria. Sociais/para gestão - dada a evidência de que há maior custo de auditoria associado à maior complexidade das informações em ambiente de valor justo, as empresas podem desenvolver mecanismos de minimização de incerteza associada às informações a serem auditadas.

Until very recently, complete characterization of the megagenomes of conifers has remained elusive. The diploid genome of sugar pine (Pinus lambertiana Dougl.) has a highly repetitive, 31 billion bp genome. It is the largest genome sequenced and assembled to date, and the first from the subgenus Strobus, or white pines, a group that is notable for having the largest genomes among the pines. The genome represents a unique opportunity to investigate genome "obesity" in conifers and white pines. Comparative analysis of P. lambertiana and P. taeda L. reveals new insights on the conservation, age, and diversity of the highly abundant transposable elements, the primary factor determining genome size. Like most North American white pines, the principal pathogen of P. lambertiana is white pine blister rust (Cronartium ribicola J.C. Fischer ex Raben.). Identification of candidate genes for resistance to this pathogen is of great ecological importance. The genome sequence afforded us the opportunity to make substantial progress on locating the major dominant gene for simple resistance hypersensitive response, Cr1 We describe new markers and gene annotation that are both tightly linked to Cr1 in a mapping population, and associated with Cr1 in unrelated sugar pine individuals sampled throughout the species' range, creating a solid foundation for future mapping. This genomic variation and annotated candidate genes characterized in our study of the Cr1 region are resources for future marker-assisted breeding efforts as well as for investigations of fundamental mechanisms of invasive disease and evolutionary response.

Background: The COVID-19 vaccine candidate CVnCoV comprises sequence-optimized mRNA encoding SARS-CoV-2 S-protein encapsulated in lipid nanoparticles. In this phase 2a study, we assessed reactogenicity and immunogenicity of two or three doses in younger and older adults. Methods: Younger (18–60 years) and older (>60 years) adults were enrolled in two sites in Panama and Peru to receive either 6 or 12 µg doses of CVnCoV or licensed control vaccines 28 days apart; subsets received a 12 µg booster dose on Day 57 or Day 180. Solicited adverse events (AE) were reported for 7 days and unsolicited AEs for 4 weeks after each vaccination, and serious AEs (SAE) throughout the study. Humoral immunogenicity was measured as neutralizing and receptor binding domain (RBD) IgG antibodies and cellular immunogenicity was assessed as CD4+/CD8 + T cell responses. Results: A total of 668 participants were vaccinated (332 aged 18–60 years and 336 aged > 60 years) including 75 who received homologous booster doses. Vaccination was well tolerated with no vaccine-related SAEs. Solicited and unsolicited AEs were mainly mild to moderate and resolved spontaneously. Both age groups demonstrated robust immune responses as neutralizing antibodies or RBD-binding IgG, after two doses, with lower titers in the older age group than the younger adults. Neither group achieved levels observed in human convalescent sera (HCS), but did equal or surpass HCS levels following homologous booster doses. Following CVnCoV vaccination, robust SARS-CoV-2 S-protein-specific CD4 + T-cell responses were observed in both age groups with CD8 + T-cell responses in some individuals, consistent with observations in convalescing COVID-19 patients after natural infection. Conclusions: We confirmed that two 12 µg doses of CVnCoV had an acceptable safety profile, and induced robust immune responses. Marked humoral immune responses to homologous boosters suggest two doses had induced immune memory.

Summary: Background: Head and neck cancer (HNC) surgery remains an important component of management but is associated with a high rate of surgical site infection (SSI). We aimed to assess the safety and efficacy of a topical mucosal antiseptic bundle in preventing SSI and evaluate microbial predictors of infection through a genomic sequencing approach. Methods: This study was an open-label, single-arm, single-center, phase 2 trial of a topical mucosal antiseptic bundle in patients with HNC undergoing aerodigestive tract resection and reconstruction. Patients underwent topical preparation of the oral mucosa with povidone-iodine (PI) and chlorhexidine gluconate (CHG) pre- and intra-operatively followed by oral tetracycline ointment every 6 hours for 2 days post-operatively. The primary outcome was change in bacterial bioburden at the oral surgical site. Secondary outcomes included safety, SSI, and microbial predictors of infection. Findings: Of 27 patients screened between January 8, 2021, and May 14, 2021, 26 were enrolled and 25 completed the study. There were no antiseptic-related adverse events. The topical mucosal antiseptic bundle significantly decreased oral bacterial colony-forming units from pre-operative levels (log10 mean difference 4·03, 95%CI 3·13–4·;92). There were three SSI (12%) within 30 days. In correlative genomic studies, a distinct set of amplicon sequence variants in the post-operative microbiome was associated with SSI. Further, despite no instance of post-operative orocervical fistula, metagenomic sequence mapping revealed the oral cavity as the origin of the infectious organism in two of the three SSI. Interpretation: The bacterial strains which subsequently caused SSI were frequently identified in the pre-operative oral cavity. Accordingly, a topical antiseptic bundle decreased oral bacterial bioburden throughout the peri-operative period and was associated with a low rate of SSI, supporting further study of topical antisepsis in HNC surgery. Funding: Alliance Oncology.

Aortocaval fistulas (ACFs) are rare complications of abdominal aortic aneurysms (AAA), with an incidence of 0.22% to 6.04%, associated with a significant increase in mortality rate because of both their direct clinical repercussion and the technical difficulty involved in their treatment. Owing to technical limitations related to the open treatment of AAA with ACFs, as well as their associated morbidity and mortality rates, endovascular treatment is an important option to consider.However, under such clinical situations, the morphology of the aneurysm and the possibility of endoleak may present as limitations to an endovascular approach, as the endoleak is seen as the most frequent complication in the treatments of AAAs.Herein, we report the case of a patient who underwent endovascular treatment with an endoprosthesis for an infrarenal abdominal aortic aneurysm fistulized to the inferior vena cava, associated with a type III endoleak correction.The hemodynamic behavior of the fistula described in this case resembled that of a high-output fistula. ACF diagnosis is preferably made by contrast computed tomography, where early presence of contrast in the venous system and loss of space or abnormal communication is detected between the two vessels involved; in this case, the abdominal aorta and inferior vena cava (IVC). The treatment is surgery through ACF and aneurysm repair. We report the case of a patient who underwent endovascular correction of AAA with ACF, and presented, after 4 months, with the need for reintervention due to a type III endoleak. This case shows two complications in the same patient, a rare situation in the medical literature.

Abstract Background A subset of patients with serology suggesting celiac disease have an initially negative biopsy but subsequently develop histopathologic celiac disease. Here we characterize patients with potential celiac disease who progress to celiac disease. Methods We performed a retrospective analysis of children (0–18 years of age) with biopsy-confirmed celiac disease seen at St. Louis Children’s Hospital between 2013 and 2018. Results Three hundred sixteen of 327 (96%) children with biopsy-confirmed celiac disease were diagnosed on initial biopsy. The 11 children with potential celiac disease who progressed to celiac disease had lower anti-tissue transglutaminase (anti-TTG IgA) concentrations (2.4 (1.6–5) X upper limit of normal (ULN) vs. 6.41 (3.4–10.5) X ULN) at time of first biopsy. Their median anti-TTG IgA concentrations rose from 2.4 (1.6–5) X ULN to 3.6 (3.1–9.2) X ULN between biopsies. Conclusions Four percent of biopsy confirmed celiac patients initially had a negative biopsy, but later developed histopathologic celiac disease. This is likely an underestimate as no surveillance algorithm was in place. We recommend repeat assessment in children whose serology suggests celiac disease despite normal small bowel biopsy.

Little information is presently available regarding the frequency of the silent shedders of respiratory viruses in healthy sport horses and their impact on environmental contamination. Therefore, the aim of this study was to investigate the detection frequency of selected respiratory pathogens in nasal secretions and environmental stall samples of sport horses attending a multi-week equestrian event during the summer months. Six out of fifteen tents were randomly selected for the study with approximately 20 horse/stall pairs being sampled on a weekly basis. Following weekly collection for a total of 11 weeks, all samples were tested for the presence of common respiratory pathogens (EIV, EHV-1, EHV-4, ERAV, ERBV, and Streptococcus equi ss equi (S. equi)) using qPCR. A total of 19/682 nasal swabs (2.8%) and 28/1288 environmental stall sponges (2.2%) tested qPCR-positive for common respiratory pathogens. ERBV was the most common respiratory virus (17 nasal swabs, 28 stall sponges) detected, followed by EHV-4 (1 nasal swab) and S. equi (1 nasal swab). EIV, EHV-1, EHV-4 and ERAV were not detected in any of the study horses or stalls. Only one horse and one stall tested qPCR-positive for ERBV on two consecutive weeks. All the other qPCR-positive sample results were related to individual time points. Furthermore, only one horse/stall pair tested qPCR-positive for ERBV at a single time point. The study results showed that in a selected population of sport horses attending a multi-week equestrian event in the summer, the frequency of the shedding of respiratory viruses was low and primarily restricted to ERBV with little evidence of active transmission and environmental contamination.

Eco-friendly chemical methods using FDA-approved Pluronic F127 (PLU) block copolymer have garnered much attention for simultaneously forming and stabilizing Au nanoparticles (AuNPs). Given the remarkable properties of AuNPs for usage in various fields, especially in biomedicine, we performed a systematic study to synthesize AuNP-PLU nanocomposites under optimized conditions using UV irradiation for accelerating the reaction. The use of UV irradiation at 254 nm resulted in several advantages over the control method conducted under ambient light (control). The AuNP-PLU-UV nanocomposite was produced six times faster, lasting 10 min, and exhibited lower size dispersion than the control. A set of experimental techniques was applied to determine the structure and morphology of the produced nanocomposites as affected by the UV irradiation. The MTT assay was conducted to estimate IC50 values of AuNP-PLU-UV in NIH 3T3 mouse embryonic fibroblasts, and the results suggest that the sample is more compatible with cells than control samples. Afterward, in vivo maternal and fetal toxicity assays were performed in rats to evaluate the effect of AuNP-PLU-UV formulation during pregnancy. Under the tested conditions, the treatment was found to be safe for the mother and fetus. As a proof of concept or application, the synthesized Au:PLU were tested as contrast agents with an X-ray computed tomography scan (X-ray CT).