Polyaromatic Radical Anions: Utilization of a Harmonic Model in Simulating Radical Vibrational Structure and Gas-Phase Acidity Determination

Through their diverse molecular structure, charge and protonation states, polyaromatic hydrocarbons (PAHs) play a central role in the field of Biochemistry, combustion chemistry, and Astrochemistry. In this poster, a harmonic model was utilized in the Franck–Condon (FC) analysis of the vibrational structure of negative radical anions of PAHs such as naphthalene and anthracene, following the ultra violet (UV) photodetachment of the initially prepared deprotonated anionic species. The two PAHs are utilized as a prototype for the vibronic analysis of the ground-state and lowest lying excited states of similar gas-phase isomers that contain a rigid, ring structure. The spectra are interpreted based on the comparison with quantum-mechanical data obtained from ab initio calculations as well as the Franck-Condon (FC) calculations. The geometric and frequency of the optimized structures of the anion and the neutral radical are calculated using the GAUSSIAN 09 software package. The FC factors of the anion PES are simulated using the PESCAL program. PESCAL obtains the FC factors using molecular geometry, normal mode vectors, and normal mode harmonic vibrational frequencies of the anion and neutral states. These FC simulations are based on a harmonic oscillator approximation model that utilizes the Duschinsky rotation between the normal mode vectors of the anion and neutral radical species. The calculated adiabatic electron affinity is utilized in the negative ion thermochemical cycle to determine gas-phase acidity values of neutral PAH molecules

The clinical and behavioral cardiometabolic risk of children and young people on mental health inpatient units: A systematic review and meta-analysis

Objective: Serious mental illness is associated with physical health comorbidities, however most research has focused on adults. We aimed to synthesise existing literature on clinical and behavioral cardiometabolic risk factors of young people on mental health inpatient units. Methods: A systematic review and meta-analysis was conducted, using electronic searches of PsycINFO, EMBASE, AMED, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE. Eligible studies included child/adolescent mental health inpatient units for 25) was 32.4% (95% CI 26.1%–39.5%; n = 2789), and who were obese (BMI > 30) was 15.5% (95% CI 4.5%–41.6%; n = 2612). Pooled prevalence rates for tobacco use was 51.5% (95% CI 32.2–70.2; N = 804,018). Early signs of metabolic risk were observed; elevated blood cholesterol, presence of physical health conditions, and behavioral risk factors (e.g. physical inactivity). Conclusions: This review highlights the vulnerability of young people admitted to inpatient units and emphasises the opportunity to efficiently monitor, treat and intervene to target physical and mental health

Social cognition in multiple sclerosis:A systematic review and meta-analysis

Objective: To quantify the magnitude of deficits in theory of mind (ToM) and facial emotion recognition among patients with multiple sclerosis (MS) relative to healthy controls. Methods: An electronic database search of Ovid MEDLINE, PsycINFO, and Embase was conducted from inception to April 1, 2016. Eligible studies were original research articles published in peer-reviewed journals that examined ToM or facial emotion recognition among patients with a diagnosis of MS and a healthy control comparison group. Data were independently extracted by 2 authors. Effect sizes were calculated using Hedges g. Results: Twenty-one eligible studies were identified assessing ToM (12 studies) and/or facial emotion recognition (13 studies) among 722 patients with MS and 635 controls. Deficits in both ToM (g -0.71, 95% confidence interval [CI] -0.88 to -0.55, p < 0.001) and facial emotion recognition (g -0.64, 95% CI -0.81 to -0.47, p < 0.001) were identified among patients with MS relative to healthy controls. The largest deficits were observed for visual ToM tasks and for the recognition of negative facial emotional expressions. Older age predicted larger emotion recognition deficits. Other cognitive domains were inconsistently associated with social cognitive performance. Conclusions: Social cognitive deficits are an overlooked but potentially important aspect of cognitive impairment in MS with potential prognostic significance for social functioning and quality of life. Further research is required to clarify the longitudinal course of social cognitive dysfunction, its association with MS disease characteristics and neurocognitive impairment, and the MS-specific neurologic damage underlying these deficits

Can high-intensity interval training improve mental health outcomes in the general population and those with physical illnesses? A systematic review and meta-analysis

Objective: High-intensity interval training (HIIT) is a safe and feasible form of exercise. The aim of this meta-analysis was to investigate the mental health effects of HIIT, in healthy populations and those with physical illnesses, and to compare the mental health effects to non-active controls and other forms of exercise. Design Random effects meta-analyses were undertaken for randomised controlled trials (RCTs) comparing HIIT with non-active and/or active (exercise) control conditions for the following coprimary outcomes: mental well-being, symptoms of depression, anxiety and psychological stress. Positive and negative affect, distress and sleep outcomes were summarised narratively. Data sources: Medline, PsycINFO, Embase and CENTRAL databases were searched from inception to 7 July 2020. Eligibility criteria for selecting studies RCTs that investigated HIIT in healthy populations and/or those with physical illnesses and reported change in mental well-being, depression, anxiety, psychological stress, positive/negative affect, distress and/or sleep quality. Results: Fifty-eight RCTs were retrieved. HIIT led to moderate improvements in mental well-being (standardised mean difference (SMD): 0.418; 95% CI: 0.135 to 0.701; n=12 studies), depression severity (SMD: –0.496; 95% CI: −0.973 to −0.020; n=10) and perceived stress (SMD: −0.474; 95% CI: −0.796 to −0.152; n=4) compared with non-active controls, and small improvements in mental well-being compared with active controls (SMD:0.229; 95% CI: 0.054 to 0.403; n=12). There was a suggestion that HIIT may improve sleep and psychological distress compared with non-active controls: however, these findings were based on a small number of RCTs. Conclusion: These findings support the use of HIIT for mental health in the general population. Level of evidence The quality of evidence was moderate-to-high according to the Grading of Recommendations Assessment, Development and Evaluation) criteria

Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study

<p>Abstract</p> <p>Background</p> <p>Continuous complete clinical remission in T-cell acute lymphoblastic leukemia (T-ALL) is now approaching 80% due to the implementation of aggressive chemotherapy protocols but patients that relapse continue to have a poor prognosis. Such patients could benefit from augmented therapy if their clinical outcome could be more accurately predicted at the time of diagnosis. Gene expression profiling offers the potential to identify additional prognostic markers but has had limited success in generating robust signatures that predict outcome across multiple patient cohorts. This study aimed to identify robust gene classifiers that could be used for the accurate prediction of relapse in independent cohorts and across different experimental platforms.</p> <p>Results</p> <p>Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (<it>IL-7R</it>), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low <it>IL-7R </it>expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-κB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort.</p> <p>Conclusions</p> <p>We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.</p

Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci

ABSTRACT Antimicrobial resistance in Staphylococcus aureus presents an increasing threat to human health. This resistance is often encoded on mobile plasmids, such as pSK41; however, the mechanism of transfer of these plasmids is not well understood. In this study, we first examine key protein-DNA interactions formed by the relaxase enzyme, NES, which initiates and terminates the transfer of the multidrug resistance plasmid pSK41. Two loops on the NES protein, hairpin loops 1 and 2, form extensive contacts with the DNA hairpin formed at the oriT region of pSK41, and here we establish that these contacts are essential for proper DNA cleavage and religation by the full 665-residue NES protein in vitro . Second, pSK156 and pCA347 are nonconjugative Staphylococcus aureus plasmids that contain sequences similar to the oriT region of pSK41 but differ in the sequence predicted to form a DNA hairpin. We show that pSK41-encoded NES is able to bind, cleave, and religate the oriT sequences of these nonconjugative plasmids in vitro . Although pSK41 could mobilize a coresident plasmid harboring its cognate oriT , it was unable to mobilize plasmids containing the pSK156 and pCA347 variant oriT mimics, suggesting that an accessory protein like that previously shown to confer specificity in the pWBG749 system may also be involved in transmission of plasmids containing a pSK41-like oriT . These data indicate that the conjugative relaxase in trans mechanism recently described for the pWBG749 family of plasmids also applies to the pSK41 family of plasmids, further heightening the potential significance of this mechanism in the horizontal transfer of staphylococcal plasmids. IMPORTANCE Understanding the mechanism of antimicrobial resistance transfer in bacteria such as Staphylococcus aureus is an important step toward potentially slowing the spread of antimicrobial-resistant infections. This work establishes protein-DNA interactions essential for the transfer of the Staphylococcus aureus multiresistance plasmid pSK41 by its relaxase, NES. This enzyme also processed variant oriT -like sequences found on numerous plasmids previously considered nontransmissible, suggesting that in conjunction with an uncharacterized accessory protein, these plasmids may be transferred horizontally via a relaxase in trans mechanism. These findings have important implications for our understanding of staphylococcal resistance plasmid evolution

Correlatos del índice de masa corporal en los pacientes moderados y graves con el síndrome del intestino irritable

Irritable bowel syndrome (IBS) is a common and potentially disabling gastrointestinal (GI) disorder that is subject to strong psychological influences particularly among more severe IBS patients. Little is known about the role of actionable lifestyle factors (e.g., obesity) that influence the trajectory of other chronic diseases. This study examined the associations between obesity and different aspects of illness experience among more severe IBS patients. We hypothesized that Body Mass Index (BMI) would positively correlate with worse health outcomes including more severe IBS symptoms, extraintestinal complaints, and emotional distress. At pretreatment baseline in a National Institutes of Health (NIH)-funded behavioral trial, 448 Rome-diagnosed IBS patients (MAGE  = 41; MBMI = 26, Female = 8%) were administered a test battery that included a variety of clinical (IBS symptom severity, fear of GI symptoms, BMI, etc.), and sociodemographic (e.g. age, etc.) variables. BMI was positively and significantly correlated with somatization (unexplained somatic complaints) but not IBS symptom severity or emotional distress. A series of moderated multiple regression analyses showed that the associations between BMI and somatization were moderated by the interaction between BMI and age, and fear of GI symptoms. Older patients with higher BMI reported higher levels of somatization and patients who were more fearful of GI symptoms were more likely to experience somatization if they also had a high BMI. These data highlight the relationship between lifestyle factors and extraintestinal symptoms among more severe IBS patients and the impact of both sociodemographic (age) and psychosocial (fear of GI symptoms) factors on this relationship.SII es un trastorno gastrointestinal común y potencialmente incapacitante, susceptible a las influencias psicológicas fuertes, especialmente entre los pacientes más graves. Se sabe poco sobre el papel de los factores del estilo de vida (p.ej. obesidad) que influyen en la trayectoria de otras enfermedades crónicas. Este estudio ha examinado la correlación entre la obesidad y los diferentes aspectos de la experiencia de enfermedad en los pacientes más graves con el SII. Nuestra hipótesis fue que el SII se podría correlacionar positivamente con peores resultados de salud, incluyendo síntomas más graves del SII, molestias extraintestinales y angustia emocional. Durante el pretratamiento, en una prueba de comportamiento basada en NIH, 448 pacientes con el SII diagnosticados mediante los criterios de Roma (MEDAD = 41, MIMC = 26, F = 8%) fueron sometidos a una batería de prueba que incluía una variedad de variables clínicas (gravedad del SII, miedo de síntomas gastrointestinales, IMC etc.) y sociodemográficas (p. ej. edad etc.) El IMC fue positiva y significativamente correlacionado con la somatización (molestias somáticas inexplicadas), pero no con la gravedad de los síntomas del SII o angustia emocional. Una serie de múltiples análisis regresivos moderados demostró que la relación entre el IMC y la somatización fue moderada por la interacción entre el IMC, la edad y el miedo de los síntomas gastrointestinales. Los pacientes mayores con el IMC más alto mostraron niveles de somatización más altos, y los pacientes que tenían más miedo de los síntomas gastrointestinales tenían más posibilidad de sufrir la somatización si tenían también el IMC alto. Estos datos subrayan la relación entre los factores de estilo de vida y los síntomas extraintestinales entre los pacientes más graves con el SII, tanto como el impacto que tienen factores sociodemográficos (edad) y psicosociales (miedo de los síntomas gastrointestinales) en su relación

Phylodynamic Inference of Bacterial Outbreak Parameters Using Nanopore Sequencing

Nanopore sequencing and phylodynamic modeling have been used to reconstruct the transmission dynamics of viral epidemics, but their application to bacterial pathogens has remained challenging. Cost-effective bacterial genome sequencing and variant calling on nanopore platforms would greatly enhance surveillance and outbreak response in communities without access to sequencing infrastructure. Here, we adapt random forest models for single nucleotide polymorphism (SNP) polishing developed by Sanderson and colleagues (2020. High precision Neisseria gonorrhoeae variant and antimicrobial resistance calling from metagenomic nanopore sequencing. Genome Res. 30(9):1354–1363) to estimate divergence and effective reproduction numbers (Re) of two methicillin-resistant Staphylococcus aureus (MRSA) outbreaks from remote communities in Far North Queensland and Papua New Guinea (PNG; n = 159). Successive barcoded panels of S. aureus isolates (2 × 12 per MinION) sequenced at low coverage (>5× to 10×) provided sufficient data to accurately infer genotypes with high recall when compared with Illumina references. Random forest models achieved high resolution on ST93 outbreak sequence types (>90% accuracy and precision) and enabled phylodynamic inference of epidemiological parameters using birth–death skyline models. Our method reproduced phylogenetic topology, origin of the outbreaks, and indications of epidemic growth (Re > 1). Nextflow pipelines implement SNP polisher training, evaluation, and outbreak alignments, enabling reconstruction of within-lineage transmission dynamics for infection control of bacterial disease outbreaks on portable nanopore platforms. Our study shows that nanopore technology can be used for bacterial outbreak reconstruction at competitive costs, providing opportunities for infection control in hospitals and communities without access to sequencing infrastructure, such as in remote northern Australia and PNG