Momentary mechanisms of binge-eating symptoms using ecological momentary assessment: The moderating role of food addiction.

OBJECTIVE: Food addiction (FA) shows phenotypic and diagnostic overlap with eating disorders characterised by binge eating, though it is unknown how momentary processes driving binge-eating symptoms differ by FA. The present study examined the possible moderating influence of FA severity on momentary mechanisms underlying binge-eating symptomatology using ecological momentary assessment (EMA). METHOD: Adults (N = 49, mean age = 34.9 ± 12.1, cis-gender female = 77.1%) who met criteria for FA and/or binge-eating disorder completed baseline measures including the Yale Food Addiction Scale (YFAS) followed by a 10-day EMA protocol. Generalised linear mixed models assessed main effects of YFAS, momentary antecedents (affect, impulsivity, food cue exposure, appetite, and eating expectancies) and two-way interactions between YFAS and within-person antecedents. RESULTS: FA severity moderated momentary associations between food cue exposure and subsequent binge-eating symptoms: the association was stronger among participants with lower but not higher YFAS scores. No other interactions were significant. CONCLUSIONS: Some functional associations underlying binge-eating symptoms vary based on individuals' level of FA symptoms. Future research to further understand how observed associations may differ amongst diverse populations and over course of illness may also inform future prevention and interventions.

The ecological validity of the Yale Food Addiction Scale 2.0 and momentary food addiction symptoms.

OBJECTIVE: This study assessed the ecological validity of the Yale Food Addiction Scale (YFAS 2.0) with ecological momentary assessment (EMA) and explored the internal consistency and convergent validity of a momentary food addiction scale. METHOD: Adults (N = 49) who met criteria for binge-eating disorder and/or food addiction (age = 34.9 ± 12.1 years; 77.1% cisgender female; 55.1% non-Hispanic White) completed online questionnaires and a 10-day EMA protocol. Analyses examined (a) associations between the YFAS 2.0 and EMA-measured variables corresponding to food addiction criteria, (b) reliability of a momentary food addiction scale (EMA-FA), and (c) concurrent associations between EMA-FA and EMA-measured negative affect, impulsivity, eating expectancies, body satisfaction, consumption of palatable food, and taste response to palatable food. RESULTS: YFAS scores were associated with EMA-reported variables corresponding to food addiction criteria (ps < .045). The multilevel reliability for EMA-FA was adequate (ω = .75-.94). Individuals with higher EMA-FA scores reported greater negative affect, impulsivity, appetite, palatable food consumption, taste response to palatable food, and contrary to expectations, greater body satisfaction (ps < .01). Within-person effects emerged for EMA-FA predicting higher negative affect, impulsivity, likelihood of palatable food consumption, more pleasurable taste responses after consuming palatable foods, yet lower body satisfaction, appetite, and eating expectancies (ps < .01). CONCLUSIONS: Results support the ecological validity of the YFAS 2.0, and additional evidence of convergent validity and internal consistency was demonstrated for a momentary food addiction scale. This assessment of the psychometric properties of the YFAS will ultimately further its utility and relevance in the study and diagnosis of food addiction. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Global impacts of marine heatwaves on coastal foundation species.

With increasingly intense marine heatwaves affecting nearshore regions, foundation species are coming under increasing stress. To better understand their impacts, we examine responses of critical, habitat-forming foundation species (macroalgae, seagrass, corals) to marine heatwaves in 1322 shallow coastal areas located across 85 marine ecoregions. We find compelling evidence that intense, summer marine heatwaves play a significant role in the decline of foundation species globally. Critically, detrimental effects increase towards species warm-range edges and over time. We also identify several ecoregions where foundation species don't respond to marine heatwaves, suggestive of some resilience to warming events. Cumulative marine heatwave intensity, absolute temperature, and location within a species' range are key factors mediating impacts. Our results suggest many coastal ecosystems are losing foundation species, potentially impacting associated biodiversity, ecological function, and ecosystem services provision. Understanding relationships between marine heatwaves and foundation species offers the potential to predict impacts that are critical for developing management and adaptation approaches.

Ciprofloxacin-Loaded Inhalable Formulations against Lower Respiratory Tract Infections: Challenges, Recent Advances, and Future Perspectives.

Inhaled ciprofloxacin (CFX) has been investigated as a treatment for lower respiratory tract infections (LRTIs) associated with cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis. The challenges in CFX effectiveness for LRTI treatment include poor aqueous solubility and therapy resistance. CFX dry powder for inhalation (DPI) formulations were well-tolerated, showing a remarkable decline in overall bacterial burden compared to a placebo in bronchiectasis patients. Recent research using an inhalable powder combining Pseudomonas phage PEV20 with CFX exhibited a substantial reduction in bacterial density in mouse lungs infected with clinical P. aeruginosa strains and reduced inflammation. Currently, studies suggest that elevated biosynthesis of fatty acids could serve as a potential biomarker for detecting CFX resistance in LRTIs. Furthermore, inhaled CFX has successfully addressed various challenges associated with traditional CFX, including the incapacity to eliminate the pathogen, the recurrence of colonization, and the development of resistance. However, further exploration is needed to address three key unresolved issues: identifying the right patient group, determining the optimal treatment duration, and accurately assessing the risk of antibiotic resistance, with additional multicenter randomized controlled trials suggested to tackle these challenges. Importantly, future investigations will focus on the effectiveness of CFX DPI in bronchiectasis and COPD, aiming to differentiate prognoses between these two conditions. This review underscores the importance of CFX inhalable formulations against LRTIs in preclinical and clinical sectors, their challenges, recent advancements, and future perspectives.

"Should We Phenobarb-it-All?" A Phenobarbital-Based Protocol for Non-Intensive Care Unit Trauma Patients at High Risk of or Experiencing Alcohol Withdrawal.

BACKGROUND: Alcohol use is frequent in trauma patients and alcohol withdrawal syndrome (AWS) is associated with significant morbidity. Benzodiazepines are commonly used for AWS, but may cause neurologic and respiratory adverse events (AEs). The objective was to evaluate the effectiveness and safety of a phenobarbital-based protocol for the treatment of AWS in non-intensive care unit (ICU) trauma patients. METHODS: Adult non-ICU trauma patients at high risk of or experiencing AWS PRE and POST implementation of a phenobarbital-based protocol were included. Outcomes were AWS-related complications (AWS-RC), benzodiazepine use, adjunctive medication use, hospital length of stay (HLOS), and medication-related AEs. Subgroup analyses were performed on patients with traumatic brain injury (TBI), rib fractures, and at high risk of severe AWS. RESULTS: Overall, 110 patients were included (51 PRE, 59 POST). AWS-RC developed in 17 PRE patients compared to 10 POST patients (33% vs 17%; P = .05). PRE patients were more likely to receive benzodiazepines (88% vs 42%, P < .0001) and higher total dose (11 vs 4 mg lorazepam equivalent; P = .001). No difference noted in HLOS (8 vs 8 days, P = .27), adjunctive medication use (49% vs 54%, P = .60), or AEs (57% vs 39%, P = .06). There was no difference in AWS-RC in the TBI subgroup (P = .19), less AEs in the rib fracture POST subgroup (P = .04), and less AWS-RC in the high risk of severe AWS POST subgroup (P = .03). DISCUSSION: A phenobarbital-based protocol in trauma patients is effective in preventing AWS-RC and decreasing benzodiazepine use without increasing AEs.

Factor Structure, Reliability, and Convergent Validity of an Ecological Momentary Assessment Binge-Eating Symptoms Scale.

Ecological momentary assessment (EMA) of binge-eating symptoms has deepened our understanding of eating disorders. However, there has been a lack of attention on the psychometrics of EMA binge-eating symptom measures. This paper focused on evaluating the psychometric properties of a four-item binge-eating symptom measure, including multilevel factor structure, reliability, and convergent validity. Forty-nine adults with binge-eating disorder and/or food addiction completed baseline questionnaires and a 10-day EMA protocol. During EMA, participants completed assessments of eating episodes, including four binge-eating symptom items. Analyses included multilevel exploratory factor analysis, computation of omega and intraclass correlation coefficients, and multilevel structural equation models of associations between contextual factors and binge-eating symptoms. A one within-subject factor solution fit the data and showed good multilevel reliability and adequate within-subjects variability. EMA binge-eating symptoms were associated with baseline binge-eating measures as well as relevant EMA eating characteristics: including greater unhealthful food and drink intake; higher perceived taste of food; lower likelihood to be planned eating; and lower likelihood of eating to occur at work/school and other locations and greater likelihood to occur at restaurants compared to home. In conclusion, the study findings support the psychometrics of a 4-item one-factor EMA measure of binge-eating symptoms.

Associations between affect dynamics and eating regulation in daily life: a preliminary ecological momentary assessment study.

Disordered eating behaviors consistently associated with emotion regulation difficulties. However, most studies have focused on affect intensity without considering dynamic affective patterns. We examined these patterns in relation to daily overeating, loss of control eating (LOCE), dietary restraint, and food craving in young adults using ecological momentary assessment (EMA).Adults (N = 24) completed a 10-day EMA protocol during which they reported momentary affect and eating patterns. Generalized linear mixed-models examined each index in relation to eating variable.Higher PA instability (within-person) was associated with higher ratings of binge-eating symptoms (B = 0.15, SE = 0.06, p = 0.007). Lower NA differentiation (within-person) was associated with higher levels of food craving (B = -10.11, SE = 4.74, p = 0.033).Our results support previous findings suggesting that acute fluctuations in PA may increase risk of binge-eating symptoms. Further, inability to differentiate between momentary states of NA was associated with cravings. This study highlights the importance of examining multiple facets of NA and PA in relation to eating regulation.Trial registration: ClinicalTrials.gov identifier: NCT02945475.

Liposomal drug delivery strategies to eradicate bacterial biofilms: Challenges, recent advances, and future perspectives.

Typical antibiotic treatments are often ineffectual against biofilm-related infections since bacteria residing within biofilms have developed various mechanisms to resist antibiotics. To overcome these limitations, antimicrobial-loaded liposomal nanoparticles are a promising anti-biofilm strategy as they have demonstrated improved antibiotic delivery and eradication of bacteria residing in biofilms. Antibiotic-loaded liposomal nanoparticles revealed remarkably higher antibacterial and anti-biofilm activities than free drugs in experimental settings. Moreover, liposomal nanoparticles can be used efficaciously for the combinational delivery of antibiotics and other antimicrobial compounds/peptide which facilitate, for instance, significant breakdown of the biofilm matrix, increased bacterial elimination from biofilms and depletion of metabolic activity of various pathogens. Drug-loaded liposomes have mitigated recurrent infections and are considered a promising tool to address challenges associated to antibiotic resistance. Furthermore, it has been demonstrated that surface charge and polyethylene glycol modification of liposomes have a notable impact on their antibacterial biofilm activity. Future investigations should tackle the persistent hurdles associated with development of safe and effective liposomes for clinical application and investigate novel antibacterial treatments, including CRISPR-Cas gene editing, natural compounds, phages, and nano-mediated approaches. Herein, we emphasize the significance of liposomes in inhibition and eradication of various bacterial biofilms, their challenges, recent advances, and future perspectives.

Treatment of Binge-Eating Disorder Across the Lifespan: An Updated Review of the Literature and Considerations for Future Research.

PURPOSE OF REVIEW: The present review describes the recent literature on treatment for binge-eating disorder (BED) in adults and youth, with a particular focus on research gaps, emerging treatments, and future research directions. RECENT FINDINGS: Evidence supports the efficacy of several treatment modalities in adults, including self-help treatment, clinician-led psychotherapy, and pharmacotherapy; the largest effect sizes have been found for psychotherapies, most of which were cognitive-behavioral in orientation. Adapted psychotherapies for youth also show promise but lack a robust body of evidence. Predictors, moderators, and mediators of treatment outcome remain poorly understood; individuals with BED continue to experience significant barriers to treatment; and research is needed to address suboptimal treatment response. Recent work has highlighted the potential of adaptive interventions and investigation of novel mechanisms to address these gaps. Research on BED treatment continues to grow, though critical questions must be answered to improve treatment efficacy across the lifespan.

Associations of daily weight management-focused social support with weight loss, activity behaviors, and eating regulation in the context of metabolic and bariatric surgery.

Objective: Greater perceived social support (PSS) is associated with more favorable changes in weight loss, activity behaviors, and eating regulation after metabolic and bariatric surgery (MBS). However, studies have relied on generic, retrospective PSS measures, and stability of PSS levels and relations with weight loss and weight-related behaviors over time is unknown. Using smartphone-based Ecological Momentary Assessment, this study evaluated pre-to 1-year post-MBS changes in daily weight management-focused PSS and associations with weight loss, device-measured activity behaviors, and eating regulation before and during the initial year after MBS. Method: Adult MBS patients (n = 71) received (1) an accelerometer to measure daily moderate-to-vigorous intensity physical activity (MVPA) and sedentary time (ST) minutes/day, and (2) a smartphone to complete morning weight-focused PSS ratings and eating regulation (dietary restraint/disinhibition) ratings at four semi-random times daily for 10 days at pre- and 3, 6, and 12-month postoperative. Generalized linear mixed models analyzed the associations of PSS with total weight loss (%TWL) and activity/eating outcomes. Results: Participants on average reported relatively stable moderate-to-high PSS (3.98 on one to five scale) across assessments. Perceived social support was not related to %TWL, MVPA, or ST. Participants with higher PSS reported lower disinhibition and higher restraint than those with lower PSS (ps < 0.05); however, participants reported higher restraint on days that PSS was lower than their usual levels (p = 0.009). Conclusions: MBS patients on average had stable PSS levels across time. Higher PSS levels were associated with greater resistance to overeating cues (disinhibition) and cognitive control to restrict food intake (restraint) over time. Additionally, participants reported higher restraint when PSS levels were lower than usual. Overall, weight-focused PSS appeared to hold greater importance in relation to regulating eating behavior than engaging in activity behaviors or weight loss among MBS patients during the initial postoperative year. Clinical Trial Registration: NCT02777177.

Independent associations of food addiction and binge eating measures with real-time eating behaviors and contextual factors: An exploratory ecological momentary assessment study.

Food addiction (FA) is a concept centered around the addictive potential of highly palatable processed foods, though there is debate over the discriminative validity of FA as a distinct construct from binge-eating symptomatology. This study explored how trait measures of FA and binge-eating symptoms independently and interactively predicted eating behaviors and posited correlates of FA and binge eating measured via ecological momentary assessment (EMA). Adult participants (N = 49) who met the criteria for FA and/or binge-eating disorder completed baseline measures of FA (Yale Food Addiction Scale [YFAS 2.0]) and binge-eating symptoms (Eating Pathology Symptom Inventory [EPSI] binge eating scale) followed by a 10-day EMA protocol. Generalized linear mixed models examined the independent effects of YFAS 2.0, EPSI, and their interaction predicting EMA outcomes. Higher YFAS 2.0 symptom count scores were uniquely related to greater EMA-measured overeating, loss of control eating, negative and positive affect, and impulsivity when controlling for EPSI scores. Conversely, higher EPSI scores were uniquely related to greater EMA-measured eagerness and urge to eat, and expectancies that eating would improve mood. No interaction effects were significant. These results highlight potential distinctions between phenomena captured by FA and other measures of binge eating, in that FA symptoms may be a marker of heightened binge-eating severity, emotional arousal, and impulsivity.

In Vitro Activities of Oxazolidinone Antibiotics Alone and in Combination with C-TEMPO against Methicillin-Resistant Staphylococcus aureus Biofilms.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a global health concern. The propensity of MRSA to form biofilms is a significant contributor to its pathogenicity. Strategies to treat biofilms often involve small molecules that disperse the biofilm into planktonic cells. Linezolid and, by extension, theoxazolidinones have been developed to treat infections caused by Gram-positive bacteria such as MRSA. However, the clinical development of these antibiotics has mainly assessed the susceptibility of planktonic cells to the drug. Previous studies evaluating the anti-biofilm activity of theoxazolidinones have mainly focused on the biofilm inhibition of Enterococcus faecalis and methicillin-sensitive Staphylococcus aureus, with only a few studies investigating the activity of oxazolidinones for eradicating established biofilms for these species. Very little is known about the ability of oxazolidinones to eradicate MRSA biofilms. In this work, five oxazolidinones were assessed against MRSA biofilms using a minimum biofilm eradication concentration (MBEC) assay. All oxazolidinones had inherent antibiofilm activity. However, only ranbezolid could completely eradicate MRSA biofilms at clinically relevant concentrations. The susceptibility of the MRSA biofilms to ranbezolid was synergistically enhanced by coadministration with the nitroxide biofilm dispersal agent C-TEMPO. We presume that ranbezolid acts as a dual warhead drug, which combines the mechanism of action of the oxazolidinones with a nitric oxide donor or cytotoxic drug.

Using Nitroxides to Enhance Carbon Fiber Interfacial Adhesion and as an Anchor for "Graft to" Surface Modification Strategies.

Nitroxide groups covalently grafted to carbon fibers are used as anchoring sites for TEMPO-terminated polymers (poly-n-butylacrylate and polystyrene) in a "graft to" surface modification strategy. All surface-modified fibers are evaluated for their physical properties, showing that several treatments have enhanced the tensile strength and Young's modulus compared to the control fibers. Up to an 18% increase in tensile strength and 12% in Young's modulus are observed. Similarly, the evaluation of interfacial shear strength in an epoxy polymer shows improvements of up to 144% relative to the control sample. Interestingly, the polymer-grafted surfaces show smaller increases in interfacial shear strength compared to surfaces modified with a small molecule only. This counterintuitive result is attributed to the incompatibility, both chemical and physical, of the grafted polymers to the surrounding epoxy matrix. Molecular dynamics simulations of the interface suggest that the diminished increase in mechanical shear strength observed for the polymer grafted surfaces may be due to the lack of exposed chain ends, whereas the small molecule grafted interface exclusively presents chain ends to the resin interface, resulting in good improvements in mechanical properties.

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

Daily ovarian hormone exposure and loss of control eating in adolescent girls: A registered report.

OBJECTIVE: The daily biobehavioral factors that precipitate loss of control eating (LOCE) in adolescent girls are not well known. Ovarian hormone levels are key biological factors associated with the etiology of eating disorders in adolescent girls. Yet, models on how daily ovarian hormone exposure predicts LOCE in adolescent girls are underdeveloped. The goal of this study is to examine the daily patterns and mechanisms of ovarian hormone levels on LOCE across the menstrual cycle in adolescent girls and the mediating roles of food-related reward anticipation and response inhibition. Ecological momentary assessment (EMA) paired with daily hormonal sampling will be used to examine (1) daily associations between within-person hormones and LOCE, and (2) the mediating role of within-person food-related reward anticipation and response inhibition. METHODS: Normally cycling adolescent girls who have reached menarche will provide daily saliva samples for hormone analysis and complete EMA for 35 days. During EMA, girls will report LOCE and will complete task-based and self-report measures of food-related response inhibition and reward anticipation. DISCUSSION: This work has implications for the development of new real-world biobehavioral models of LOCE in adolescent girls, which will guide theory improvements and treatment for LOCE. Results will provide preliminary evidence for treatment targets for novel interventions for adolescent girls-for example, a response inhibition intervention. PUBLIC SIGNIFICANCE: Adolescent eating disorders are severe mental health conditions, often marked by loss of control eating. Estrogen and progesterone play a role in the development and persistence of loss of control eating. The current study will examine how daily exposure to estrogen and progesterone predicts loss of control eating in adolescent girls and identify possible daily mechanisms linking estrogen and progesterone exposure and loss of control eating.

Simple and Efficient Synthesis of 3-Aryl-2-oxazolidinone Scaffolds Enabling Increased Potency toward Biofilms.

Infectious diseases caused by bacterial pathogens are a leading cause of mortality worldwide. In particular, recalcitrant bacterial communities known as biofilms are implicated in persistent and difficult to treat infections. With a diminishing antibiotic pipeline, new treatments are urgently required to combat biofilm infections. An emerging strategy to develop new treatments is the hybridization of antibiotics. The benefit of this approach is the extension of the useful lifetime of existing antibiotics. The oxazolidinones, which include the last resort antibiotic linezolid, are an attractive target for improving antibiofilm efficacy as they present one of the most recently discovered classes of antibiotics. A key step in the synthesis of new 3-aryl-2-oxazolidinone derivatives is the challenging formation of the oxazolidinone ring. Herein we report a direct synthetic route to the piperazinyl functionalized 3-aryl-2-oxazolidinone 17. We also demonstrate an application of these piperazine molecules by functionalizing them with a nitroxide moiety as a strategy to extend the useful lifetime of oxazolidinones and improve their potency against Methicillin-resistant Staphylococcus aureus (MRSA) biofilms. The antimicrobial susceptibility of the linezolid-nitroxide conjugate 11 and its corresponding methoxyamine derivative 12 (a control for biofilm dispersal) was assessed against planktonic cells and biofilms of MRSA. In comparison to linezolid and our lead compound 10 (a piperazinyl oxazolidinone derivative), the linezolid-nitroxide conjugate 11 displayed a minimum inhibitory concentration that was 4-16-fold higher. The opposite effect was seen in biofilms where the linezolid-nitroxide hybrid 11 was >2-fold more effective (160 µg/mL versus >320 µg/mL) in eradicating MRSA biofilms. The methoxyamine derivative 12 performed on par with linezolid. The drug-likeness of the compounds was also assessed, and all compounds were predicted to have good oral bioavailability. Our piperazinyl oxazolidinone derivative 10 was confirmed to be lead-like and would be a good lead candidate for future functionalized oxazolidinones. The modification of antibiotics with a dispersal agent appears to be a promising approach for eradicating MRSA biofilms and overcoming the antibiotic resistance associated with the biofilm mode of growth.

Outcomes of Protocol-Driven Venous Thromboembolic Chemo-Prophylaxis in Trauma Patients: A Trauma Quality Improvement Project Analysis.

INTRODUCTION: Low molecular weight heparin (LMWH) is the standard for venous thromboembolic (VTE) chemo-prophylaxis in trauma patients; however, inconsistencies in the use of LMWH exist. The objective of this study was to assess VTE outcomes in response to a chemo-prophylaxis protocol guided by patient physiology (eg, creatinine clearance) and comorbidities. METHODS: ACS TQIP Benchmark Reports at a level 1 trauma center using a patient physiology and comorbidity directed VTE chemo-prophylaxis protocol were analyzed for Spring 2019 to Fall 2021. Patient demographics, VTE rates and pharmacologic VTE prophylaxis type were collected for "All Patients" and "Elderly" (TQIP: age ≥ 55 years) cohorts. RESULTS: Data was analyzed for 1919183 "All Hospitals" (AH) and 5843 patients single institution (SI) using the physiologic and comorbidity guided VTE chemo-prophylaxis protocol. Elderly subgroup had 701965 (AH) and 2939 (SI) patients. Use of non-LMWH chemo-prophylaxis was significantly higher at SI: All patients = 62.6% SI vs 22.1% (P < .01); Elderly = 68.8% SI vs 28.1% AH (P < .01). VTE, DVT, and PE rates for All Patients and Elderly subgroup were significantly reduced at SI, except Elderly PE which was statistically equivalent. CONCLUSIONS: Protocol-driven VTE chemo-prophylaxis was associated with significantly lower LMWH use accompanied by significant reductions in All VTE, DVT, PE, and Elderly VTE and DVT with no difference in Elderly PE rates. These results may imply that adherence to a physiologic and comorbidity directed chemo-prophylaxis protocol, rather than LMWH, reduces VTE events in trauma patients. Further investigation to elucidate best practice is warranted.

Comparative Assessment of Docking Programs for Docking and Virtual Screening of Ribosomal Oxazolidinone Antibacterial Agents.

Oxazolidinones are a broad-spectrum class of synthetic antibiotics that bind to the 50S ribosomal subunit of Gram-positive and Gram-negative bacteria. Many crystal structures of the ribosomes with oxazolidinone ligands have been reported in the literature, facilitating structure-based design using methods such as molecular docking. It would be of great interest to know in advance how well docking methods can reproduce the correct ligand binding modes and rank these correctly. We examined the performance of five molecular docking programs (AutoDock 4, AutoDock Vina, DOCK 6, rDock, and RLDock) for their ability to model ribosomal-ligand interactions with oxazolidinones. Eleven ribosomal crystal structures with oxazolidinones as the ligands were docked. The accuracy was evaluated by calculating the docked complexes' root-mean-square deviation (RMSD) and the program's internal scoring function. The rankings for each program based on the median RMSD between the native and predicted were DOCK 6 > AD4 > Vina > RDOCK >> RLDOCK. Results demonstrate that the top-performing program, DOCK 6, could accurately replicate the ligand binding in only four of the eleven ribosomes due to the poor electron density of said ribosomal structures. In this study, we have further benchmarked the performance of the DOCK 6 docking algorithm and scoring in improving virtual screening (VS) enrichment using the dataset of 285 oxazolidinone derivatives against oxazolidinone binding sites in the S. aureus ribosome. However, there was no clear trend between the structure and activity of the oxazolidinones in VS. Overall, the docking performance indicates that the RNA pocket's high flexibility does not allow for accurate docking prediction, highlighting the need to validate VS. protocols for ligand-RNA before future use. Later, we developed a re-scoring method incorporating absolute docking scores and molecular descriptors, and the results indicate that the descriptors greatly improve the correlation of docking scores and pMIC values. Morgan fingerprint analysis was also used, suggesting that DOCK 6 underpredicted molecules with tail modifications with acetamide, n-methylacetamide, or n-ethylacetamide and over-predicted molecule derivatives with methylamino bits. Alternatively, a ligand-based approach similar to a field template was taken, indicating that each derivative's tail groups have strong positive and negative electrostatic potential contributing to microbial activity. These results indicate that one should perform VS. campaigns of ribosomal antibiotics with care and that more comprehensive strategies, including molecular dynamics simulations and relative free energy calculations, might be necessary in conjunction with VS. and docking.

Facets of impulsivity and reward in relation to binge-eating disorder course of illness among children: findings from the Adolescent Brain Cognitive Development study.

BACKGROUND: The present study examined facets of impulsivity and reward sensitivity [as measured by the UPPS-P Impulsive Behavior Scale and Behavioral Activation and Behavioral Inhibition Scales (BIS/BAS)] as multivariable predictors of subsequent binge-eating disorder (BED) course of illness in middle childhood. METHODS: The current sample included children aged 9-10 years (N = 9,438) who took part in the baseline and 1-year follow-up assessments of the Adolescent Brain Cognitive Development (ABCD) study. BED course was operationalized as those who never developed BED or subthreshold BED (SBED) ('control'), were diagnosed with BED/SBED at year 1 but not baseline ('developers'), were diagnosed with BED/SBED at baseline but not year 1 ('remitters'), or were diagnosed with BED/SBED at both times ('maintainers'). RESULTS: Higher baseline BIS/BAS reward responsivity scores were related to the greater likelihood of belonging to the maintainer group relative to the control and remitter groups (ORs1.12-1.19). Regarding covariates, higher baseline body mass index percentile and internalizing symptoms were related to the greater likelihood of BED development, remittance, and maintenance compared to the control group (ORs = 1.04-1.14); no variables were uniquely related to BED development. Exploratory analyses showed that the likelihood of belonging to the maintainer group compared to the control group was greatest at higher levels of negative urgency in combination with high reward responsivity. CONCLUSIONS: Heightened reward responsivity may convey risk for poorer BED course in children, while emotional disorder symptomatology may act as a more general risk and maintenance factor for BED.