Miracle-dz/UniFAR-FTUs huggingface dataset:
Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: An expert consensus document from the society for cardiovascular angiography and interventions (SCAI)

Numerous definitions have been proposed for the diagnosis of myocardial infarction (MI) after coronary revascularization. The universal definition for MI designates post procedural biomarker thresholds for defining percutaneous coronary intervention (PCI)‐related MI (type 4a) and coronary artery bypass grafting (CABG)‐related MI (type 5) which are of uncertain prognostic importance. In addition, for both MI types cTn is recommended as the biomarker of choice, the prognostic significance of which is less well validated than CK‐MB. Widespread adoption of a MI definition not clearly linked to subsequent adverse events such as mortality or heart failure may have serious consequences for the appropriate assessment of devices and therapies, may affect clinical care pathways, and may result in misinterpretation of physician competence. Rather than employing an MI definition sensitive for small degrees of myonecrosis (the occurrence of which, based on contemporary large‐scale studies, are unlikely to have important clinical consequences), it is instead recommended that a threshold level of biomarker elevation which has been strongly linked to subsequent adverse events in clinical studies be used to define a “clinically relevant MI. ” The present document introduces a new definition for "clinically relevant MI" after coronary revascularization (PCI or CABG) which is applicable for use in clinical trials, patient care, and quality outcomes assessment. © 2013 Wiley Periodicals, Inc.
Divorce and Death

Forty years of follow-up data from the Charleston Heart Study (CHS) were used to examine the risk for early mortality associated with marital separation or divorce in a sample of more than 1,300 adults assessed on several occasions between 1960 and 2000. Participants who were separated or divorced at the start of the study evidenced significantly elevated rates of early mortality, and these results held after adjusting for baseline health status and other demographic variables. Being separated or divorced throughout the CHS follow-up window was one of the strongest predictors of early mortality. However, the excess mortality risk associated with separation or divorce was completely eliminated when participants who had ever experienced a marital separation or divorce during the study were compared with all other participants. These findings suggest that a key predictor of early death is the amount of time people live as separated or divorced. It is possible that the mortality risk conferred by marital dissolution is due to dimensions of personality that predict divorce as well as a decreased likelihood of future remarriage.
Low profile vascular plugs for paravalvular leaks after TAVR

Paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) is associated with less good outcomes. The use of percutaneous plugs is among the strategies to treat PVL after TAVR. Plugs have been limited by the need to pass 4–6 F delivery sheaths between the TAVR stent frame and the native valve leaflets.
Interchain hydrophobic clustering promotes rigidity in HIV-1 protease flap dynamics: new insights from Molecular Dynamics

The dynamics of HIV-1 protease (HIV-pr), a drug target for HIV infection, has been studied extensively by both computational and experimental methods. The flap dynamics of HIV-pr is considered to be more important for better ligand binding and enzymatic actions. Moreover, it has been demonstrated that the drug-induced mutations can change the flap dynamics of HIV-pr affecting the binding affinity of the ligands. Therefore, detailed understanding of flap dynamics is essential for designing better inhibitors. Previous computational investigations observed significant variation in the flap opening in nanosecond time scale indicating that the dynamics is highly sensitive to the simulation protocols. To understand the sensitivity of the flap dynamics on the force field and simulation protocol, molecular dynamics simulations of HIV-pr have been performed with two different AMBER force fields, ff99 and ff02. Two different trajectories (20 ns each) were obtained using the ff99 and ff02 force field. The results showed polarizable force field (ff02) make the flap tighter than the nonpolarizable force field (ff99). Some polar interactions and hydrogen bonds involving flap residues were found to be stronger with ff02 force field. The formation of interchain hydrophobic cluster (between flap tip of one chain and active site wall of another chain) was found to be dominant in the semi-open structures obtained from the simulations irrespective of the force field. It is proposed that an inhibitor, which will promote this interchain hydrophobic clustering, may make the flaps more rigid, and presumably the effect of mutation would be small on ligand binding.
Non-specificity and synergy at the binding site of the carboplatin-induced DNA adduct via molecular dynamics simulations of the MutSα–DNA recognition complex

MutSα is the most abundant mismatch-binding factor of human DNA mismatch repair (MMR) proteins. MMR maintains genetic stability by recognizing and repairing DNA defects. Failure to accomplish their function may lead to cancer. In addition, MutSα recognizes at least some types of DNA damage making it a target for anticancer agents. Here, complementing scarce experimental data, we report unique hydrogen-bonding motifs associated with the recognition of the carboplatin induced DNA damage by MutSα. These data predict that carboplatin and cisplatin induced damaging DNA adducts are recognized by MutSα in a similar manner. Our simulations also indicate that loss of base pairing at the damage site results in (1) non-specific binding and (2) changes in the atomic flexibility at the lesion site and beyond. To further quantify alterations at MutSα–DNA interface in response to damage recognition, non-bonding interactions and salt bridges were investigated. These data indicate (1) possible different packing and (2) disruption of the salt bridges at the MutSα–DNA interface in the damaged complex. These findings (1) underscore the general observation of disruptions at the MutSα–DNA interface and (2) highlight the nature of the anticancer effect of the carboplatin agent. The analysis was carried out from atomistic simulations.
Nighttime Sleep and Daytime Nap Patterns in School Age Children with and Without Asthma

Objective: This research examines subjective and objective report of naps and nighttime sleep in 9- to 11-year-old children with and without asthma. Methods: This between subjects study collected prospective self-report diary and objective actigraphy measures of sleep from 27 children with and 27 without asthma during a 7-day/6-night at-home monitoring period. Results: Thirty-two percent of participants reported daytime naps. Nappers were more likely to be children with asthma (12/27 vs. 5/27, p = 0.04) even though the children with asthma did not report being more tired, sleepy, or less alert in the morning. Nappers did not differ from non-nappers on self-report measures of overall sleep quality or number of awakenings but were documented, via objective measures, to have later (clock time: 23:05 vs. 22:21, p = 0.04) and more variable (Levine’s Test for Equality of Variances: F = 10.68, p = 0.002) sleep onset times than non-nappers. Sleep offset times did not differ between the nappers vs. non-nappers, therefore, nappers had fewer total minutes of nighttime sleep than did the non-nappers (437 vs. 465, p = 0.04). Later (clock time: 23:01 vs. 22:15, p = 0.01) sleep onset times were also documented in minority vs. Caucasian children. Conclusions: Napping appears a more common behavior than expected especially in children with asthma or of minority ethnicity but the reasons are unclear. Self-report measures may not capture important sleep characteristics that objective measures can identify. Strategies to reduce late and variable bedtimes of all children are needed given our awareness of the negative cognitive, emotional, and behavioral consequences of poor sleep in children.
The Impact of Medical Comorbidity on Mental Health and Functional Health Outcomes Among Children with Anxiety Disorders

Objective: Medical comorbidity is common among children with anxiety disorders; however, little is known about the impact of such comorbidity on mental and functional health outcomes. Even less is known about these problems in high-risk samples of youth. Method: Participants in this study were youth with at least one anxiety disorder with a physical illness (N = 77) or without a physical illness (N = 73), as well as youth with at least one physical illness (but no anxiety disorder) (N = 438). These youth were recruited as part of the Patterns of Care study in which the original set of participants (N = 1715) were randomly sampled from one of five public sectors of care (e.g., juvenile justice, child welfare, mental health, alcohol and substance use services, school services for children with serious emotional disturbance) in San Diego County. Psychiatric diagnoses were assessed with a structured interview and three standardized measures were used to assess child health, emotional, and behavior functioning. Results: At least half of children with anxiety disorders had a comorbid physical illness. Allergies and asthma were the most common comorbid physical illnesses. Children with anxiety disorders who had a comorbid physical illness exhibited greater levels of emotional problems, more somatic complaints, and more functional impairment than anxious children without a physical illness as well as than children with physical illness alone. Parents of children in the comorbid group also reported greater caregiver strain than the other two groups. Conclusions: Children with anxiety disorders have high rates of chronic illnesses such as asthma and allergies. These children experience considerable impairment and likely have unique needs that may complicate usual care.
Simulating the antimicrobial mechanism of human β-defensin-3 with coarse-grained molecular dynamics

Human β-defensin-3 (HβD-3) is an endogenous antimicrobial peptide with potent and broad killing activity against various microorganisms, and thus, it is an attractive candidate for the development of novel peptide antibiotics, but its antimicrobial mechanism remains elusive. To characterize the mechanism, we used multi-microsecond coarse-grained simulations with the MARTINI force field. These simulations show HβD-3 peptides can form oligomers on the surface of bacterial membrane and make anionic lipids (POPG) clustered. Furthermore, two kinds of regions (one is composed of pure POPG lipids, and the other is enriched in POPE lipids) are formed in the membrane; on the border of them, there are some obvious defects, which result in the membrane disruption. By contrast, the simulations also reveal that the contacts between the HβD-3 peptides and mammalian membrane are not stable. These results provide biophysical insights into HβD-3 selectivity and suggest a possible antimicrobial mechanism.
Modularity in protein structures: study on all-alpha proteins

Modularity is known as one of the most important features of protein’s robust and efficient design. The architecture and topology of proteins play a vital role by providing necessary robust scaffolds to support organism’s growth and survival in constant evolutionary pressure. These complex biomolecules can be represented by several layers of modular architecture, but it is pivotal to understand and explore the smallest biologically relevant structural component. In the present study, we have developed a component-based method, using protein’s secondary structures and their arrangements (i.e. patterns) in order to investigate its structural space. Our result on all-alpha protein shows that the known structural space is highly populated with limited set of structural patterns. We have also noticed that these frequently observed structural patterns are present as modules or “building blocks” in large proteins (i.e. higher secondary structure content). From structural descriptor analysis, observed patterns are found to be within similar deviation; however, frequent patterns are found to be distinctly occurring in diverse functions e.g. in enzymatic classes and reactions. In this study, we are introducing a simple approach to explore protein structural space using combinatorial- and graph-based geometry methods, which can be used to describe modularity in protein structures. Moreover, analysis indicates that protein function seems to be the driving force that shapes the known structure space.
Ultrafast molecular dynamics of biofuel extraction for microalgae and bacteria milking: blocking membrane folding pathways to damaged lipid-bilayer conformations with nanomicelles

Cell milking is a 100% renewable green energy for CO2 by extraction of biofuels inside the cytosol of photosynthetic micro-organisms as microalgae and bacteria. The cells are exposed to a hydrophobic solvent forming holes and cracks through their membranes from which the biofuels can leak out. In protein folding, the goal would be to find pathways to the unique functional protein conformer. However, in the lipid-bilayer interaction with the solvent for milking, the objective is to block the pathways for damaged membrane conformations of low free energy with undesired nanostructures, using the solvent properties, as shown with an ab initio structural bioinformatic model. Statistical thermodynamics is used to compute the free energy (including entropy) from the molecular dynamics trajectory of the biomolecular system with many conformational changes. This model can be extended to the general problem of biomolecules folding as for proteins and nucleic acids. Using an adaptation of the Einstein diffusion law, the conformational change dynamics of the lipid bilayer depends on the two diffusion coefficients of the solvent: D1 before the irreversible folding transition time and the much smaller D2 thereafter. In contrast to the n-hexane and n-heptane hydrocarbons of smaller size, the residual D2 = 4.7 × 10−7 cm2/s of the n-decane solvent, with the highest partition coefficient among the three extractors, is the only to present a D2 value that is significantly below the critical threshold of 10−6 cm2/s. Therefore, the membrane would resist to long hydrocarbons and the exposed cells would remain viable for milking.
Molecular dynamics simulations on the interaction of the transmembrane NavAb channel with cholesterol and lipids in the membrane

Increased cholesterol levels are associated with multiple pathological conditions. In this work, molecular dynamics simulations were applied to observe the influence of membrane cholesterol levels on a voltage-gated sodium channel. Different lipid compositions are modeled around the channel to obtain information about the possible effects by which cholesterol influences NavAb channels. Cholesterol was normally not directly interacting with either the closed or inactivated conformation. Cholesterol increased lipid packing implying that it plays a crucial role in restricting lipid movement in the region around 1 nm of the channel in a 1-palmitoyl-2-oeleoyl phosphatidylcholine matrix. Our results provide the first computational indication of an indirect modulation of NavAb channels by membrane cholesterol.
A Study of the Effect of Birth Interval on the Development of 9-year-old Schoolchildren in Singapore

The effect of birth interval on some physical and mental aspects of 9-year old children was studied in Singapore between September 1974 and July 1975. Birth interval falls into 2 main categories -- B1 the interval preceding the birth of the index child and B2 the interval following the birth of the child. It was hypothesized that the shorter the interval B1 the lower the vocabulary score and general attainment of the index child would be and the shorter the interval B2 the lesser the physical growth of the index child would be. A significant difference was found in the Mill Hill vocabulary score Ravens Progressive Matrices score as well as height and weight for children born with varying birth intervals. Children with shorter B1 intervals do score lower than those with longer B1 intervals there being a gradual improvement as B1 progresses from less than 12 months to over 24 months. The relationship is linear. The effect of B2 is less marked and is inconsistent. The most striking correlation is between B1 and vocabulary score B1 accounting for about 39% of the variation in the Mill Hill test. B2 does not have as great an effect as expected on height and weight but it was significant at the 5% level for height. B1 is again more important. In both height and weight neither birth interval is as important as in the verbal and perception tests. Neither family size nor language spoken at home affect the vocabulary score to any significant extent. Income does have an association with all 4 major variables considered and is 2nd in importance to B1 as a predictor variable in the cases of vocabulary score and Ravens score.
Research Training of Developmental-Behavioral Pediatrics Fellows: A Survey of Fellowship Directors by Developmental-Behavioral Pediatrics Research Network

Objective: To describe research training in Developmental-Behavioral Pediatrics (DBP) Fellowship Programs. Methods: Thirty-five US-accredited DBP fellowships were contacted through the Developmental-Behavioral Pediatrics Research Network to complete an online survey on scholarly work and research training. Results: With an 83% response rate, responding programs represented 110 (87 filled) fellowship positions. External funding for fellowship positions was minimal (11 positions fully funded, 13 funded above 50% of cost). Structured research training included didactic lectures, web-based training, university courses, direct mentoring, journal clubs, and required reading. Of the 159 fellows described, spanning a 5-year training period, the majority chose projects relying on their own data collection (57%) rather than joining an existing research study and focused on clinical research (86%). Among 96 fellows with completed scholarly work, 29% were observational/epidemiological studies, 22% secondary analyses of large data sets, 16% community-based research, and 15% survey design. A limited number of fellows pursued basic science, meta-analysis/critical appraisal of the literature, or analysis of public policy. Barriers to successful fellow research are as follows: lack of time and money, challenges in balancing clinical demands and protected faculty research time, limited faculty research opportunities, time or expertise, and a lack of infrastructure for fellow research mentoring. Conclusions: The scholarly work of fellows in DBP fellowship programs has primarily focused on clinical research using observational/epidemiological research and secondary analysis of large data set. Barriers largely in faculty time and expertise for research mentoring and inadequate funding in programs that have high clinical demands and little resources for research efforts were noted.
Short‐ and long‐term outcomes in diabetes patients undergoing percutaneous coronary intervention with bivalirudin compared with heparin and glycoprotein IIb/IIIA inhibitors: A meta‐analysis of randomized trials

Diabetes patients undergoing percutaneous coronary intervention (PCI) have more complications than nondiabetes patients, including increased long‐term mortality. Use of bivalirudin versus heparin and glycoprotein IIb/IIIa inhibitors (GPI) in diabetes patients undergoing PCI and its effect on long‐term mortality were evaluated in few randomized trials, but with conflicting results.
Nurse Manager Residency Program: An Innovative Leadership Succession Plan

To ensure succession planning within the ranks of nurse managers meet current and projected nursing management needs and organizational goals, we developed and implemented a nurse manager residency program at our hospital. By identifying, supporting, and mentoring clinical experts who express a desire and display an aptitude for nursing leadership, we are graduating individuals who can transition to a nurse manager position with greater ease and competence.
Effect of guanidine hydrochloride and urea on the interaction of 6-thioguanine with human serum albumin: a spectroscopic and molecular dynamics based study

6-thioguanine (6-TG) is an antineoplastic, nucleobase guanine, purine analog drug belongs to thiopurine drug-family of antimetabolites. In the present study, we report an experimental approach towards interaction mechanism of 6-TG with human serum albumin (HSA) and examine the chemical stability of HSA in the presence of denaturants such as guanidine hydrochloride (GdnHCl) and urea. Interaction of 6-TG with HSA has been studied by various spectroscopic and spectropolarimeteric methods to investigate what short of binding occurs at physiological conditions. 6-TG binds in the hydrophobic cavity of subdomain IIA of HSA by static quenching mechanism which induces conformation alteration in the protein structure. That helpful for further study of denaturation process where change in secondary structures causes unfolding of protein that also responsible for severance of domain III from rest of the protein part. We have also performed molecular simulation and molecular docking study in the presence of denaturating agents to determine the binding property of 6-TG and the effect of denaturating agents on the structural activity of HSA. We had found that GdnHCl is more effective denaturating agent when compared to urea. Hence, this study provides straight evidence of the binding mechanism of 6-TG with HSA and the formation of intermediate or unfolding transition that causes unfolding of HSA. Graphical abstract 6-thioguanine bind to HSA through a static quenching procedure by ground-state complex formation and hydrogen bonds and hydrophobic interaction played a major role in the reaction process. GdnHCl and urea denature the HSA by two-state unfolding mechanisms, GdnHCl is more effective denaturant in comparison to urea.
Qualidade de vida no trabalho de profissionais do NASF no município de São Paulo

A apreensao e a analise da Qualidade de Vida no Trabalho (QVT) dos profissionais do Nucleo de Apoio a Saude da Familia (NASF) sao de extrema importância, uma vez que a implantacao dessa equipe e recente e seu processo de trabalho desenvolve-se numa logica contra-hegemonica de trabalho em saude. Este estudo procurou identificar as percepcoes acerca da QVT dos profissionais das equipes de NASF que atuam no municipio de Sao Paulo, bem como os aspectos facilitadores e dificultadores por eles identificados no cotidiano do trabalho. Trata-se de um estudo qualitativo, de natureza descritiva e exploratoria, realizado em Unidades Basicas de Saude da Familia, com uma equipe do NASF de cada uma das cinco Coordenadorias Regionais de Saude do municipio de Sao Paulo: Leste, Centro-Oeste, Norte, Sudeste e Sul. Foram realizadas 40 entrevistas, cuja analise de conteudo revelou quatro nucleos de sentido relacionados a percepcao e a avaliacao da qualidade de vida no trabalho dos profissionais: (1) infraestrutura para o trabalho; (2) sobrecarga e qualidade de vida no trabalho; (3) autonomia e identificacao com o trabalho; (4) trabalho em equipe e relacionamento interpessoal. O processo de trabalho do NASF vem sendo modificado e reestruturado desde sua implantacao, conforme as particularidades e necessidades locais. Envolve diversas questoes que afetam diretamente a QVT, podendo ate repercutir negativamente na qualidade do servico prestado. Os profissionais do NASF e seu fazer cotidiano requerem um olhar ampliado da gestao e dos demais atores envolvidos, em prol de uma melhor QTV e, consequentemente, de uma minimizacao de insatisfacao, adoecimentos, afastamentos e estresse ocupacional.