Implementation and evaluation of pharmacist-led heart failure diagnostic and guideline directed medication therapies clinic.

BACKGROUND: Timely diagnosis of heart failure (HF) and rapid optimisation of guideline-directed medication therapy (GDMT) improves patients qualities of life, reducing mortality and morbidity. Previous papers describe the role of pharmacists in medication optimisation, but not in the diagnosis of HF. AIM: To describe the development, implementation, and evaluation of pharmacist-led heart failure clinics with respect to time from referral to diagnosis, time from diagnosis to first review with a specialist, and the proportion receiving optimal GDMT 180 days after diagnosis. SETTING: Community outpatient clinics in rural west Wales, United Kingdom. DEVELOPMENT: Two experienced non-medical prescribing pharmacists, one of whom had additional diagnostic qualifications in cardiology, delivered the clinic. IMPLEMENTATION: Patients referred with suspected HF were risk-stratified to urgent (within 14 days of referral) or routine (within 42 days) review, based on natriuretic peptide levels. Patients attended the clinic for assessment, including physical examination, electrocardiogram, and echocardiogram. Those with HF with reduced ejection fraction were initiated on drug treatment and referred to the follow-up pharmacist-led GDMT clinic. EVALUATION: A sample of 100 patients was evaluated (50 from pre-existing and 50 from new service). Median time from referral to diagnosis reduced from 61 days (IQR 47-115) to 16 days (IQR 10.5-27.5) for urgent and 19 days (IQR 11.5-33) for routine. Median time to first appointment following diagnosis reduced from 54 days (IQR 36-60.5) to 14 days (IQR 9.75-28.75) (p value < 0.0001), and proportion of patients achieving GDMT at 180 days following diagnosis improved from 24 to 86% (p value < 0.0001). CONCLUSION: This pharmacist HF diagnostic clinic and medication optimisation clinic improved time to diagnosis, time to first specialist review, and proportion of patients' achieving GDMT optimisation in a rural healthcare setting.

Association between metabolic syndrome and salivary MMP-8, myeloperoxidase in periodontitis.

OBJECTIVE: This study investigated the effect of metabolic syndrome (MetS) on periodontal clinical parameters and salivary biomarkers' matrix metalloproteinase-8 (MMP-8) and myeloperoxidase (MPO) in patients with periodontitis. METHODS: A total of 120 participants aged 25-55 were categorized into three groups: MetS with periodontitis (n = 40); systemically healthy with periodontitis (n = 40); and systemically and periodontally healthy controls (n = 40). Data collected included systemic parameters like waist circumference (WC), blood pressure (BP), high- and low-density lipoproteins, triglycerides (TG), fasting blood sugar (FBS), and glycated hemoglobin (HbA1c). Periodontal parameters estimated included bleeding on probing score (BoP), full-mouth plaque score (FMPS), periodontal probing depth (PPD), clinical attachment loss (CAL), and the number of missing teeth. Unstimulated whole saliva was analyzed via ELISA for active MMP-8 (aMMP-8), total MMP-8 (tMMP-8), and MPO. RESULTS: Participants with MetS and periodontitis exhibited significantly higher periodontal parameters, salivary aMMP-8, and MPO (26.26 vs. 24.1 ng/mL and 13.53 vs. 11.55 ng/mL compared to systemically healthy periodontitis patients) (all p < 0.01). Positive correlations occurred between aMMP-8 and WC, TG, and FBS (p < 0.01), and between MPO and WC, BP, and TG (p < 0.01). CONCLUSIONS: The positive associations between these biomarkers and metabolic parameters indicate their potential utility for monitoring cardiovascular and glycemic risk in patients with periodontal disease.

High night temperature stress on rice (Oryza sativa) - insights from phenomics to physiology. A review.

Rice (Oryza sativa ) faces challenges to yield and quality due to urbanisation, deforestation and climate change, which has exacerbated high night temperature (HNT). This review explores the impacts of HNT on the physiological, molecular and agronomic aspects of rice growth. Rise in minimum temperature threatens a potential 41% reduction in rice yield by 2100. HNT disrupts rice growth stages, causing reduced seed germination, biomass, spikelet sterility and poor grain development. Recent findings indicate a 4.4% yield decline for every 1°C increase beyond 27°C, with japonica ecotypes exhibiting higher sensitivity than indica. We examine the relationships between elevated CO2 , nitrogen regimes and HNT, showing that the complexity of balancing positive CO2 effects on biomass with HNT challenges. Nitrogen enrichment proves crucial during the vegetative stage but causes disruption to reproductive stages, affecting grain yield and starch synthesis. Additionally, we elucidate the impact of HNT on plant respiration, emphasising mitochondrial respiration, photorespiration and antioxidant responses. Genomic techniques, including CRISPR-Cas9, offer potential for manipulating genes for HNT tolerance. Plant hormones and carbohydrate enzymatic activities are explored, revealing their intricate roles in spikelet fertility, grain size and starch metabolism under HNT. Gaps in understanding genetic factors influencing heat tolerance and potential trade-offs associated with hormone applications remain. The importance of interdisciplinary collaboration is needed to provide a holistic approach. Research priorities include the study of regulatory mechanisms, post-anthesis effects, cumulative HNT exposure and the interaction between climate variability and HNT impact to provide a research direction to enhance rice resilience in a changing climate.

Evaluation of Bony Femoral Morphological Parameters in Anterior Cruciate Ligament Injury Using Magnetic Resonance Imaging: A Retrospective Unmatched Case-Control Study.

Background Over time, there has been a noticeable increase in anterior cruciate ligament (ACL) injuries. The current imperative is to anticipate predisposing factors and proactively prevent ACL injuries. The occurrence of ACL injuries has been linked to diverse factors associated with the morphology of the distal femur. Objectives Through this study, we aim to compare the anatomic variables of distal femur morphology such as notch width (NW), bicondylar width (BW), notch entrance width (NEW), and notch width index (NWI) between patients with ACL injuries and non-injured patients using MRI. We also aim to make a comparison of these factors between male and female genders to assess the gender variability. Material and methods A retrospective case-control study was conducted amongst patients who underwent MRI Knee scan for clinical suspicion of internal derangement during the study period. We selected the first 125 individuals who were found to have ACL injury in the MRI scans and selected another 125 individuals who had an intact ACL in the scans, to serve as controls in the study. Demographic information was retrieved from the hospital's electronic records, and the assessment of NW, NWI, BW, and NEW was conducted through a review of MRI sequences. They were then compared between the cases and control groups, as well as between male and female genders. Results The ACL-injured group exhibited statistically significant reductions in NW and NWI. While 17.39 mm was the mean NW among cases, 17.86 was the mean value among controls. Similarly, the mean NWI was 0.25 among patients with ACL injuries and 0.27 among controls. Gender-based comparisons also revealed statistically significant differences in NW and NWI measurements, where females were reported to have comparatively lower measurements. The mean NW for males and females in the injured group were 18.26 mm and 15.40 mm, respectively, while it was 18.71 mm and 16.90 mm, respectively, in the control group. In the case of NEW, males in the injured group had a slightly higher value (21.33 mm) than the controls (20.65). Females on the other hand exhibited a lower mean value of NEW in ACL-injured group (18.51 mm) in comparison to the non-injured (18.79 mm). BW did not seem to show a significant difference between the two groups. Conclusions In the studied population, ACL injuries demonstrated a higher occurrence in individuals with a narrow femoral intercondylar NWI. If any of these characteristics are identified in an MRI, it may be helpful to identify individuals who are at a higher risk of developing ACL injuries and may thereby help in planning preventative strategies.

Levels of the HtrA1 Protein in Serum and Vitreous Humor Are Independent of Genetic Risk for Age-Related Macular Degeneration at the 10q26 Locus.

Purpose: The purpose of this study was to determine if levels of the HtrA1 protein in serum or vitreous humor are influenced by genetic risk for age-related macular degeneration (AMD) at the 10q26 locus, age, sex, AMD status, and/or AMD disease severity, and, therefore, to determine the contribution of systemic and ocular HtrA1 to the AMD disease process. Methods: A custom-made sandwich ELISA assay (SCTM ELISA) for detection of the HtrA1 protein was designed and compared with three commercial assays (R&D Systems, MyBiosource 1 and MyBiosource 2) using 65 serum samples. Concentrations of HtrA1 were thereafter determined in serum and vitreous samples collected from 248 individuals and 145 human donor eyes, respectively. Results: The SCTM ELISA demonstrated high specificity, good recovery, and parallelism within its linear detection range and performed comparably to the R&D Systems assay. In contrast, we were unable to demonstrate the specificity of the two assays from MyBioSource using either recombinant or native HtrA1. Analyses of concentrations obtained using the validated SCTM assay revealed that genetic risk at the 10q26 locus, age, sex, or AMD status are not significantly associated with altered levels of the HtrA1 protein in serum or in vitreous humor (P > 0.05). Conclusions: HtrA1 levels in serum and vitreous do not reflect the risk for AMD associated with the 10q26 locus or disease status. Localized alteration in HTRA1 expression in the retinal pigment epithelium, rather than systemic changes in HtrA1, is the most likely driver of elevated risk for developing AMD among individuals with risk variants at the 10q26 locus.

Association between Gingival Phenotype and Periodontal Disease Severity-A Comparative Longitudinal Study among Patients Undergoing Fixed Orthodontic Therapy and Invisalign Treatment.

This longitudinal study aimed to compare the association between gingival phenotype (thin vs. thick) and periodontal disease severity in patients undergoing fixed orthodontic therapy (FOT) and Invisalign treatment over a six-month follow-up period. Clinical periodontal parameters, including full mouth plaque score (FMPS), full mouth bleeding score (FMBS), gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), gingival recession (GR), keratinized tissue width (KTW), transgingival probing, and gingival biotype assessment, were recorded at baseline and 6 months into treatment for both orthodontic groups and a control group. Statistical analysis evaluated differences in parameters between groups and across time points. In the thick phenotype, both Invisalign and FOT groups showed a significant mean reduction in FMPS (baseline to 6 months) by -24.8707 and -12.3489, respectively (p < 0.05). The gingival index decreased significantly for both groups, with Invisalign and FOT showing reductions of -0.83355 and -1.10409, respectively (p < 0.05). FMBS (baseline to 6 months) decreased significantly for Invisalign and FOT, with mean differences of -9.10298 and -12.6579 (p < 0.05). Probing pocket depth (baseline to 6 months) was also significantly reduced for both Invisalign and FOT groups while CAL showed non-significant differences in both groups (p > 0.05). Similar changes were seen in the thin phenotype too. This study highlights the positive influence of both Invisalign and fixed orthodontic therapy on periodontal health, particularly in patients with thin and thick gingival biotypes. These findings, with significant reductions in key periodontal parameters, offer valuable insights to guide orthodontic treatment decisions and enhance patient outcomes.

Assessment of the Nonlinear Electrophoretic Migration of Nanoparticles and Bacteriophages.

Bacteriophage therapy presents a promising avenue for combating antibiotic-resistant bacterial infections. Yet, challenges exist, particularly, the lack of a straightforward purification pipeline suitable for widespread application to many phage types, as some phages are known to undergo significant titer loss when purified via current techniques. Electrokinetic methods offer a potential solution to this hurdle, with nonlinear electrophoresis emerging as a particularly appealing approach due to its ability to discern both the size and shape of the target phage particles. Presented herein is the electrokinetic characterization of the mobility of nonlinear electrophoresis for two phages (SPN3US and ϕKZ) and three types of polystyrene nanoparticles. The latter served as controls and were selected based on their sizes and surface charge magnitude. Particle tracking velocimetry experiments were conducted to characterize the mobility of all five particles included in this study. The results indicated that the selected nanoparticles effectively replicate the migration behavior of the two phages under electric fields. Further, it was found that there is a significant difference in the nonlinear electrophoretic response of phages and that of host cells, as first characterized in a previous report, illustrating that electrokinetic-based separations are feasible. The findings from this work are the first characterization of the behavior of phages under nonlinear electrophoresis effects and illustrate the potential for the development of electrokinetic-based phage purification techniques that could aid the advancement of bacteriophage therapy.

Mechanism of Viral DNA Packaging in Phage T4 Using Single-Molecule Fluorescence Approaches.

In all tailed phages, the packaging of the double-stranded genome into the head by a terminase motor complex is an essential step in virion formation. Despite extensive research, there are still major gaps in the understanding of this highly dynamic process and the mechanisms responsible for DNA translocation. Over the last fifteen years, single-molecule fluorescence technologies have been applied to study viral nucleic acid packaging using the robust and flexible T4 in vitro packaging system in conjunction with genetic, biochemical, and structural analyses. In this review, we discuss the novel findings from these studies, including that the T4 genome was determined to be packaged as an elongated loop via the colocalization of dye-labeled DNA termini above the portal structure. Packaging efficiency of the TerL motor was shown to be inherently linked to substrate structure, with packaging stalling at DNA branches. The latter led to the design of multiple experiments whose results all support a proposed torsional compression translocation model to explain substrate packaging. Evidence of substrate compression was derived from FRET and/or smFRET measurements of stalled versus resolvase released dye-labeled Y-DNAs and other dye-labeled substrates relative to motor components. Additionally, active in vivo T4 TerS fluorescent fusion proteins facilitated the application of advanced super-resolution optical microscopy toward the visualization of the initiation of packaging. The formation of twin TerS ring complexes, each expected to be ~15 nm in diameter, supports a double protein ring-DNA synapsis model for the control of packaging initiation, a model that may help explain the variety of ring structures reported among pac site phages. The examination of the dynamics of the T4 packaging motor at the single-molecule level in these studies demonstrates the value of state-of-the-art fluorescent tools for future studies of complex viral replication mechanisms.

"What's Next in My Arc of Development?": An Exploratory Study of What Medical Students Need to Care for Patients of Different Backgrounds.

PHENOMENON: Medical schools must equip future physicians to provide equitable patient care. The best approach, however, is mainly dependent on a medical school's context. Graduating students from our institution have reported feeling ill-equipped to care for patients from "different backgrounds" on the Association of American Medical Colleges' Graduation Questionnaire. We explored how medical students interpret "different patient backgrounds" and what they need to feel prepared to care for diverse patients. APPROACH: We conducted an exploratory qualitative case study using focus groups with 11, Year 2 (MS2) and Year 4 (MS4) medical students at our institution. Focus groups were recorded, transcribed, and coded using thematic analysis. We used Bobbie Harro's cycles of socialization and liberation to understand how the entire medical school experience, not solely the curriculum, informs how medical students learn to interact with all patients. FINDINGS: We organized our findings into four major themes to characterize students' medical education experience when learning to care for patients of different backgrounds: (1) Understandings of different backgrounds (prior to medical school); (2) Admissions process; (3) Curricular socialization; and (4) Co-curricular (or environmental) socialization. We further divided themes 2, 3, and 4 into two subthemes when learning how to care for patients of different backgrounds: (a) the current state and (b) proposed changes. We anticipate that following the proposed changes will help students feel more prepared to care for patients of differing backgrounds. INSIGHTS: Our findings show that preparing medical students to care for diverse patient populations requires a multitude of intentional changes throughout medical students' education. Using Harro's cycles of socialization and liberation as an analytic lens, we identified multiple places throughout medical students' educational experience that are barriers to learning how to care for diverse populations. We propose changes within medical students' education that build upon each other to adequately prepare students to care for patients of diverse backgrounds. Each proposed change culminates into a systemic shift within an academic institution and requires an intentional commitment by administration, faculty, admissions, curriculum, and student affairs.

The Association of Biomolecular Resource Facilities Proteome Informatics Research Group Study on Metaproteomics (iPRG-2020).

Metaproteomics research using mass spectrometry data has emerged as a powerful strategy to understand the mechanisms underlying microbiome dynamics and the interaction of microbiomes with their immediate environment. Recent advances in sample preparation, data acquisition, and bioinformatics workflows have greatly contributed to progress in this field. In 2020, the Association of Biomolecular Research Facilities Proteome Informatics Research Group launched a collaborative study to assess the bioinformatics options available for metaproteomics research. The study was conducted in 2 phases. In the first phase, participants were provided with mass spectrometry data files and were asked to identify the taxonomic composition and relative taxa abundances in the samples without supplying any protein sequence databases. The most challenging question asked of the participants was to postulate the nature of any biological phenomena that may have taken place in the samples, such as interactions among taxonomic species. In the second phase, participants were provided a protein sequence database composed of the species present in the sample and were asked to answer the same set of questions as for phase 1. In this report, we summarize the data processing methods and tools used by participants, including database searching and software tools used for taxonomic and functional analysis. This study provides insights into the status of metaproteomics bioinformatics in participating laboratories and core facilities.

QTLs and Candidate Loci Associated with Drought Tolerance Traits of Kaybonnet x ZHE733 Recombinant Inbred Lines Rice Population.

Rice is the most important staple crop for the sustenance of the world's population, and drought is a major factor limiting rice production. Quantitative trait locus (QTL) analysis of drought-resistance-related traits was conducted on a recombinant inbred line (RIL) population derived from the self-fed progeny of a cross between the drought-resistant tropical japonica U.S. adapted cultivar Kaybonnet and the drought-sensitive indica cultivar ZHE733. K/Z RIL population of 198 lines was screened in the field at Fayetteville (AR) for three consecutive years under controlled drought stress (DS) and well-watered (WW) treatment during the reproductive stage. The effects of DS were quantified by measuring morphological traits, grain yield components, and root architectural traits. A QTL analysis using a set of 4133 single nucleotide polymorphism (SNP) markers and the QTL IciMapping identified 41 QTLs and 184 candidate genes for drought-related traits within the DR-QTL regions. RT-qPCR in parental lines was used to confirm the putative candidate genes. The comparison between the drought-resistant parent (Kaybonnet) and the drought-sensitive parent (ZHE733) under DS conditions revealed that the gene expression of 15 candidate DR genes with known annotations and two candidate DR genes with unknown annotations within the DR-QTL regions was up-regulated in the drought-resistant parent (Kaybonnet). The outcomes of this research provide essential information that can be utilized in developing drought-resistant rice cultivars that have higher productivity when DS conditions are prevalent.

Expression of advanced glycation end products and their receptors in diabetic periodontitis patients.

AIM: The systematic review aimed to compare the levels of advanced glycation end products (AGEs) and RAGE (AGE receptors) expression in diabetic periodontitis patients with non-diabetic periodontitis patients and to identify the relationship of AGE and RAGE levels with periodontal disease severity. MATERIALS AND METHODS: The literature search was carried out according to PRISMA guidelines by two independent researchers using four online databases: PubMed, Scopus, Web of Science Core Collection, and Pro-Quest. Relevant studies published between 2000 and March 2023 were included in this review. The association of diabetes and AGE/RAGE levels on periodontal health, periodontal pocket depth (PPD), and clinical attachment loss (CAL) was studied. RESULTS: Sixteen cross-sectional studies, including 2794 patients (age range 15-75 years), were identified in the final stage. An elevated AGE level was observed among patients with diabetes and chronic periodontal disease compared to the non-diabetic group. Furthermore, the levels of AGE and RAGE are associated with CAL and PPD. Potential confounding factors like genetic and methodological differences were also responsible for AGE and RAGE variation. CONCLUSION: Levels of AGEs and RAGE expressions in diabetic periodontitis patients differ from non-diabetic periodontitis patients. The differences may impact the course and severity of periodontal disease.

High Daytime Temperature Responsive MicroRNA Profiles in Developing Grains of Rice Varieties with Contrasting Chalkiness.

High temperature impairs starch biosynthesis in developing rice grains and thereby increases chalkiness, affecting the grain quality. Genome encoded microRNAs (miRNAs) fine-tune target transcript abundances in a spatio-temporal specific manner, and this mode of gene regulation is critical for a myriad of developmental processes as well as stress responses. However, the role of miRNAs in maintaining rice grain quality/chalkiness during high daytime temperature (HDT) stress is relatively unknown. To uncover the role of miRNAs in this process, we used five contrasting rice genotypes (low chalky lines Cyp, Ben, and KB and high chalky lines LaGrue and NB) and compared the miRNA profiles in the R6 stage caryopsis samples from plants subjected to prolonged HDT (from the onset of fertilization through R6 stage of caryopsis development). Our small RNA analysis has identified approximately 744 miRNAs that can be grouped into 291 families. Of these, 186 miRNAs belonging to 103 families are differentially regulated under HDT. Only two miRNAs, Osa-miR444f and Osa-miR1866-5p, were upregulated in all genotypes, implying that the regulations greatly varied between the genotypes. Furthermore, not even a single miRNA was commonly up/down regulated specifically in the three tolerant genotypes. However, three miRNAs (Osa-miR1866-3p, Osa-miR5150-3p and canH-miR9774a,b-3p) were commonly upregulated and onemiRNA (Osa-miR393b-5p) was commonly downregulated specifically in the sensitive genotypes (LaGrue and NB). These observations suggest that few similarities exist within the low chalky or high chalky genotypes, possibly due to high genetic variation. Among the five genotypes used, Cypress and LaGrue are genetically closely related, but exhibit contrasting chalkiness under HDT, and thus, a comparison between them is most relevant. This comparison revealed a general tendency for Cypress to display miRNA regulations that could decrease chalkiness under HDT compared with LaGrue. This study suggests that miRNAs could play an important role in maintaining grain quality in HDT-stressed rice.

CONQUER Scleroderma: association of gastrointestinal tract symptoms in early disease with resource utilization.

OBJECTIVES: SSc is associated with increased health-care resource utilization and economic burden. The Collaborative National Quality and Efficacy Registry (CONQUER) is a US-based collaborative that collects longitudinal follow-up data on SSc patients with <5 years of disease duration enrolled at scleroderma centres in the USA. The objective of this study was to investigate the relationship between gastrointestinal tract symptoms and self-reported resource utilization in CONQUER participants. METHODS: CONQUER participants who had completed a baseline and 12-month Gastrointestinal Tract Questionnaire (GIT 2.0) and a Resource Utilization Questionnaire (RUQ) were included in this analysis. Patients were categorized by total GIT 2.0 severity: none-to-mild (0-0.49); moderate (0.50-1.00), and severe-to-very severe (1.01-3.00). Clinical features and medication exposures were examined in each of these categories. The 12-month RUQ responses were summarized by GIT 2.0 score categories at 12 months. RESULTS: Among the 211 CONQUER participants who met the inclusion criteria, most (64%) had mild GIT symptoms, 26% had moderate symptoms, and 10% severe GIT symptoms at 12 months. The categorization of GIT total severity score by RUQ showed that more upper endoscopy procedures and inpatient hospitalization occurred in the CONQUER participants with severe GIT symptoms. These patients with severe GIT symptoms also reported the use of more adaptive equipment. CONCLUSION: This report from the CONQUER cohort suggests that severe GIT symptoms result in more resource utilization. It is especially important to understand resource utilization in early disease cohorts when disease activity, rather than damage, primarily contributes to health-related costs of SSc.

Antenatal ultrasound features of isolated recurrent copy number variation in 7q11.23 (Williams syndrome and 7q11.23 duplication syndrome).

OBJECTIVE: We aimed to gather fetal cases carrying a 7q11.23 copy number variation (CNV) and collect precise clinical data to broaden knowledge of antenatal features in these syndromes. METHODS: We retrospectively recruited unrelated cases with 7q11.23 deletion, known as Williams-Beuren syndrome (WBS), or 7q11.23 duplication who had prenatal ultrasound findings. We collected laboratory and clinical data, fetal ultrasound, cardiac ultrasound and fetal autopsy reports from 18 prenatal diagnostic centers throughout France. RESULTS: 40 fetuses with WBS were collected and the most common features were intra-uterine growth retardation (IUGR) (70.0%, 28/40), cardiovascular defects (30.0%, 12/40), polyhydramnios (17.5%, 7/40) and protruding tongue (15.0%, 6/40). Fetal autopsy reports were available for 11 cases and were compared with ultrasound prenatal features. Four cases of fetuses with 7q11.23 microduplication were collected and prenatal ultrasound signs were variable and often isolated. CONCLUSION: This work strengthens the fact that 7q11.23 CNVs are associated with a broad spectrum of antenatal presentations. IUGR and cardiovascular defects were the most frequent ultrasound signs. By reporting the biggest series of antenatal WBS, we aim to better delineate distinctive signs in fetuses with 7q11.23 CNVs.

Correlation between three-dimensional echocardiography and cardiopulmonary fitness in patients with univentricular heart: A cross-sectional multicentre prospective study.

BACKGROUND: The prognosis of patients with a functional single ventricle has improved, with better cardiopulmonary fitness, health-related quality of life and survival. Conventional echocardiography remains the first-line technique in single ventricle follow-up. Three-dimensional (3D) echocardiography has shown recent value in congenital cardiology, but its ability to predict functional status in patients with a single ventricle remains unknown. AIM: To evaluate, in patients with a single ventricle, the association between 3D echocardiography variables and functional status determined by cardiopulmonary fitness. METHODS: Children and adults with a functional single ventricle were prospectively enrolled in this multicentre study. Cardiopulmonary fitness was assessed by cardiopulmonary exercise test, with measures of maximum oxygen uptake (VO2max) and ventilatory efficiency (VE/VCO2 slope). 3D echocardiography was performed with off-line reproducibility analyses, using TomTec Arena™ software. Health-related quality of life was assessed using the SF-36 questionnaire. RESULTS: A total of 33 patients were screened, and 3D echocardiography analyses were feasible in 22 subjects (mean age 28±9years). 3D echocardiography ejection fraction correlated with percent-predicted VO2max (r=0.64, P<0.01), VE/VCO2 slope (r=-0.41, P=0.05), two-dimensional echocardiography ejection fraction (r=0.55, P<0.01) and health-related quality of life physical functioning dimension (r=0.56, P=0.04). 3D echocardiography indexed end-systolic volume correlated with percent-predicted VO2max (r=-0.45, P=0.03) and VE/VCO2 slope (r=0.65, P<0.01). 3D echocardiography reproducibility was good. CONCLUSIONS: Single ventricle ejection fraction and volumes measured by 3D echocardiography correlated with cardiopulmonary fitness, as determined by two main prognostic cardiopulmonary exercise test variables: VO2max and VE/VCO2 slope. Despite good reproducibility, 3D echocardiography feasibility remained limited. 3D echocardiography may be of value in single ventricle follow-up, provided that the technique and analysis software are improved.

Molecular mapping and characterization of QTLs for grain quality traits in a RIL population of US rice under high nighttime temperature stress.

Elevated nighttime temperatures resulting from climate change significantly impact the rice crop worldwide. The rice (Oryza sativa L.) plant is highly sensitive to high nighttime temperature (HNT) during grain-filling (reproductive stage). HNT stress negatively affects grain quality traits and has a major impact on the value of the harvested rice crop. In addition, along with grain dimensions determining rice grain market classes, the grain appearance and quality traits determine the rice grain market value. During the last few years, there has been a major concern for rice growers and the rice industry over the prevalence of rice grains opacity and the reduction of grain dimensions affected by HNT stress. Hence, the improvement of heat-stress tolerance to maintain grain quality of the rice crop under HNT stress will bolster future rice value in the market. In this study, 185 F12-recombinant inbred lines (RILs) derived from two US rice cultivars, Cypress (HNT-tolerant) and LaGrue (HNT-sensitive) were screened for the grain quality traits grain length (GL), grain width (GW), and percent chalkiness (%chalk) under control and HNT stress conditions and evaluated to identify the genomic regions associated with the grain quality traits. In total, there were 15 QTLs identified; 6 QTLs represented under control condition explaining 3.33% to 8.27% of the phenotypic variation, with additive effects ranging from - 0.99 to 0.0267 on six chromosomes and 9 QTLs represented under HNT stress elucidating 6.39 to 51.53% of the phenotypic variation, with additive effects ranging from - 8.8 to 0.028 on nine chromosomes for GL, GW, and % chalk. These 15 QTLs were further characterized and scanned for natural genetic variation in a japonica diversity panel (JDP) to identify candidate genes for GL, GW, and %chalk. We found 6160 high impact single nucleotide polymorphisms (SNPs) characterized as such depending on their type, region, functional class, position, and proximity to the gene and/or gene features, and 149 differentially expressed genes (DEGs) in the 51 Mbp genomic region comprising of the 15 QTLs. Out of which, 11 potential candidate genes showed high impact SNP associations. Therefore, the analysis of the mapped QTLs and their genetic dissection in the US grown Japonica rice genotypes at genomic and transcriptomic levels provide deep insights into genetic variation beneficial to rice breeders and geneticists for understanding the mechanisms related to grain quality under heat stress in rice.

Mass Spectral Analyses of Salmonella Myovirus SPN3US Reveal Conserved and Divergent Themes in Proteolytic Maturation of Large Icosahedral Capsids.

Salmonella myovirus SPN3US has a T = 27 capsid composed of >50 different gene products, including many that are packaged along with the 240 kb genome and ejected into the host cell. Recently, we showed that an essential phage-encoded prohead protease gp245 is responsible for cleavage of proteins during SPN3US head assembly. This proteolytic maturation step induces major changes in precursor head particles, enabling them to expand and undergo genome packaging. To comprehensively define the composition of the mature SPN3US head and elucidate how it is modified by proteolysis during assembly, we conducted tandem mass spectrometry analysis of purified virions and tailless heads. Fourteen protease cleavage sites were identified in nine proteins, including eight sites not previously identified in head proteins in vivo. Among these was the maturation cleavage site of gp245 which was identical to the autocleavage site we had previously identified in purified recombinant gp245. Our findings underscore the value of employing multiple mass spectrometry-based experimental strategies as a way to enhance the detection of head protein cleavage sites in tailed phages. In addition, our results have identified a conserved set of head proteins in related giant phages that are similarly cleaved by their respective prohead proteases, suggesting that these proteins have important roles in governing the formation and function of large icosahedral capsids.

Feasibility and Diagnostic Value of Recording Smartwatch Electrocardiograms in Neonates and Children.

OBJECTIVE: The objective of this study was to evaluate the agreement of smartwatch-derived single-lead electrocardiogram (ECG) recordings with 12-lead ECGs for diagnosing electrocardiographic abnormalities. STUDY DESIGN: A 12-lead ECG and an ECG using Apple Watch were obtained in 110 children (aged 1 week to 16 years) with normal (n = 75) or abnormal (n = 35) 12-lead ECGs (atrioventricular block [7], supraventricular tachycardia [SVT] {5}, bundle branch block [12], ventricular preexcitation [6], long QT [5]). In children aged <6 years, the ECG recording was performed with the active participation of an adult who applied the neonate or child's finger to the crown of the watch. In older children, tracings were obtained after brief teaching without adult guidance. All 12-lead ECGs were independently evaluated by 2 blinded cardiologists. Apple Watch ECGs were independently evaluated by another blinded cardiologist. RESULTS: In 109 children (99.1%), the smartwatch tracing was of sufficient quality for evaluation. Smartwatch tracings were 84% sensitive and 100% specific for the detection of an abnormal ECG. All 75 normal tracings were correctly identified. Of the 35 children with abnormalities on 12-lead ECGs, 5 (14%) were missed, most often because of baseline wander and artifacts. Rhythm disorders (atrioventricular block or SVT) and bundle branch blocks were correctly detected in most cases (11 of 12 and 11 of 12, respectively); preexcitation and long QT was detected in 4 of 6 and 4 of 5, respectively. CONCLUSION: Smartwatch ECGs recorded with parental assistance in children aged up to 6 years and independently in older children have the potential to detect clinically relevant conditions.

Outcome of long gap esophageal atresia at 6 years: A prospective case control cohort study.

BACKGROUND DATA: EA is the most frequent congenital esophageal malformation. Long gap EA remains a therapeutic challenge for pediatric surgeons. A case case-control prospective study from a multi-institutional national French data base was performed to assess the outcome, at age of 1 and 6 years, of long gap esophageal atresia (EA) compared with non-long gap EA/tracheo-esophageal fistula (TEF). The secondary aim was to assess whether initial treatment (delayed primary anastomosis of native esophagus vs. esophageal replacement) influenced mortality and morbidity at ages 1 and 6 years. METHODS: A multicentric population-based prospective study was performed and included all patients who underwent EA surgery in France from January 1, 2008 to December 31, 2010. A comparative study was performed with non-long gap EA/TEF patients. Morbidity at birth, 1 year, and 6 years was assessed. RESULTS: Thirty-one patients with long gap EA were compared with 62 non-long gap EA/TEF patients. At age 1 year, the long gap EA group had longer parenteral nutrition support and longer hospital stay and were significantly more likely to have complications both early post-operatively and before age 1 year compared with the non-long gap EA/TEF group. At 6 years, digestive complications were more frequent in long gap compared to non-long gap EA/TEF patients. Tracheomalacia was the only respiratory complication that differed between the groups. Spine deformation was less frequent in the long gap group. There were no differences between conservative and replacement groups at ages 1 and 6 years except feeding difficulties that were more common in the native esophagus group. CONCLUSIONS: Long gap strongly influenced digestive morbidity at age 6 years.