The role of time to positive blood cultures in enhancing the predictive capability of DENOVA score for diagnosing infective endocarditis in patients with Enterococcus faecalis bacteremia.

DENOVA-score is useful to stratify the risk of infective endocarditis (IE) in Enterococcus faecalis bacteremia. Recently, time to positive (TTP) of blood cultures has also been related with a higher risk of IE. The objective was to evaluate DENOVA- score with TTP to improve its specificity. We performed a retrospective, case-control study in adult patients with E. faecalis bacteremia. Thirty-nine patients with definite E. faecalis IE and 82 with E. faecalis bacteremia were included. The addition of a TTP ≤ 8 h to DENOVA-score did not improve the diagnostic accuracy of this score.

Upper storage-capacity limit and multiple occupancy phenomena in H2-hydroquinone clathrates using Monte Carlo and DFT simulations.

The upper hydrogen-storage capacity limit of the ß-hydroquinone clathrate has been investigated using hybrid Grand-Canonical Monte Carlo/Molecular Dynamics simulations, for temperatures ranging from 77 K to 300 K. The evolution with pressure of the cage occupancies has been monitored in detail, describing the progressive nature of the uptake process. It is found that the storage capacity of the pure ß-HQ + H2 clathrate could reach 0.6 wt% (weight percentage) only for pressures above 1400 bar, at ambient temperature. The enhancement of the storage capacities by the multiple occupancy phenomenom was accordingly shown to be very limited by the need for extreme conditions. Following this observation, an unmodified version of the van der Waals & Platteeuw theory was applied allowing for the prediction of experimentally accessible formation pressures. Density functional theory calculations were addittionnaly performed to comprehensively characterize the hydrogen diffusion process within the clathrate crystalline structure, considering different occupancy scenarios.

Functional neuroimaging of resilience to trauma: convergent evidence and challenges for future research.

Resilience is broadly defined as the ability to adapt successfully following stressful life events. Here, we review functional MRI studies that investigated key psychological factors that have been consistently linked to resilience to severe adversity and trauma exposure. These domains include emotion regulation (including cognitive reappraisal), reward responsivity, and cognitive control. Further, we briefly review functional imaging evidence related to emerging areas of study that may potentially facilitate resilience: namely social cognition, active coping, and successful fear extinction. Finally, we also touch upon ongoing issues in neuroimaging study design that will need to be addressed to enable us to harness insight from such studies to improve treatments for - or, ideally, guard against the development of - debilitating post-traumatic stress syndromes.

Carbapenem alternatives for treatment of bloodstream infections due to AmpC producing enterobacterales.

INTRODUCTION: Carbapenems (CR) have traditionally been the first line treatment for bacteremia caused by AmpC-producing Enterobacterales. However, CR have a high ecological impact, and carbapenem-resistant strains continue rising. Thus, other treatment alternatives like Piperacillin-Tazobactam (P-T) or Cefepime (CEF) and oral sequential therapy (OST) are being evaluated. METHODS: We conducted a retrospective, single-centre observational study. All adult patients with AmpC-producing Enterobacterales bacteremia were included. The primary endpoint was clinical success defined as a composite of clinical cure, 14-day survival, and no adverse events. We evaluated the evolution of patients in whom OST was performed. RESULTS: Seventy-seven patients were included, 22 patients in the CR group and 55 in the P-T/CEF group (37 patients received CEF and 18 P-T). The mean age of the patients was higher in the P-T/CEF group (71 years in CR group vs. 76 years in P-T/CEF group, p = 0.053). In the multivariate analysis, age ≥ 70 years (OR 0.08, 95% CI [0.007-0.966], p = 0.047) and a Charlson index ≥ 3 (OR 0.16, 95% CI [0.026-0.984], p = 0.048), were associated with a lower clinical success. Treatment with P-T/CEF was associated with higher clinical success (OR 7.75, 95% CI [1.273-47.223], p = 0.026). OST was performed in 47% of patients. This was related with a shorter in-hospital stay (OST 14 days [7-22] vs. non-OST 18 days [13-38], p = 0.005) without difference in recurrence (OST 3% vs. non-OST 5%, p = 0.999). CONCLUSIONS: Targeted treatment with P-T/CEF and OST could be safe and effective treatments for patients with AmpC-producing Enterobacterales bacteremia.

C-reactive protein is associated with cognitive performance in a large cohort of euthymic patients with bipolar disorder.

Data support the notion that 40-60% of patients with bipolar disorder (BD) have neurocognitive deficits. It is increasingly accepted that functioning in BD is negatively impacted by these deficits, yet they have not been a successful target for treatment. The biomarkers that predict cognitive deficits in BD are largely unknown, however recent evidence suggests that inflammation may be associated with poorer cognitive outcomes in BD. We measured C-reactive protein (CRP), a marker of systemic inflammation and risk of inflammatory disease, in 222 euthymic BD patients and 52 healthy controls. Within the patient sample, using multivariate analyses of covariance (MANCOVA) we compared cognitive performance of those with high CRP (≥5 mg/L) versus the remaining subjects (<5 mg/L) on a battery of cognitive tests. We evaluated relationships with several other relevant clinical features. We also examined the role of CRP in cognitive decline using a proxy cognitive decline metric, defined as the difference between premorbid and current IQ estimates, in a logistic regression analysis. Approximately 80% of our sample were BD-I, and the remainder were BD-II and 42.6% of our sample had a history of psychosis. We found a statistically significant effect of CRP on cognitive performance on a broad range of tests; participants with CRP ≥ 5 mg/L had worse performance on several measures of executive functioning, MATRICS processing speed and MATRICS reasoning and problem solving relative to those with lower CRP. We also identified CRP as a significant positive predictor of proxy cognitive decline. Our results indicate that elevated CRP is associated with a broad cognitive dysfunction in affectively remitted BD patients. These results may point to a subgroup of patients who might benefit from treatments to reduce inflammation.

Social media and smartphone app use predicts maintenance of physical activity during Covid-19 enforced isolation in psychiatric outpatients.

There is growing concern that the social and physical distancing measures implemented in response to the Covid-19 pandemic may negatively impact health in other areas, via both decreased physical activity and increased social isolation. Here, we investigated whether increased engagement with digital social tools may help mitigate effects of enforced isolation on physical activity and mood, in a naturalistic study of at-risk individuals. Passively sensed smartphone app use and actigraphy data were collected from a group of psychiatric outpatients before and during imposition of strict Covid-19 lockdown measures. Data were analysed using Gaussian graphical models: a form of network analysis which gives insight into the predictive relationships between measures across timepoints. Within-individuals, we found evidence of a positive predictive path between digital social engagement, general smartphone use, and physical activity-selectively under lockdown conditions (N = 127 individual users, M = 6201 daily observations). Further, we observed a positive relationship between social media use and total daily steps across individuals during (but not prior to) lockdown. Although there are important limitations on the validity of drawing causal conclusions from observational data, a plausible explanation for our findings is that, during lockdown, individuals use their smartphones to access social support, which may help guard against negative effects of in-person social deprivation and other pandemic-related stress. Importantly, passive monitoring of smartphone app usage is low burden and non-intrusive. Given appropriate consent, this could help identify people who are failing to engage in usual patterns of digital social interaction, providing a route to early intervention.

Gastrointestinal colonization by OXA-48-producing Enterobacterales: risk factors for persistent carriage.

Carbapenem-resistant Enterobacterales (CRE) infections are a major health problem. Intestinal colonization is a key factor in developing infection. However, factors associated with persistent colonization by CRE are unknown. The aim of the study was to identify factors associated with persistent CRE gut colonization. This is a retrospective, single-centre, observational study of adult patients with CRE gut colonization between January 2015 and January 2020. Epidemiologic characteristics, comorbidities, infectious events, duration of hospitalization and antimicrobial treatment received in the follow-up period were collected. Colonization was defined as isolation in at least 2 rectal swab culture samples of CRE. Decolonization was defined as 3 negative rectal swab cultures or 2 negative cultures and a negative molecular test. A cohort of 86 patients with CRE gut colonization was selected: 44 patients with spontaneous decolonization (DC) and 42 patients with persistent colonization (PC). The mean follow-up period was 24 months (IQR 14-33) in the DC group vs. 25 months (IQR 16-36) in the PC group (p = 0.478). Patient characteristics were similar between both groups. Colonization by other MDR microorganisms was high (44 patients, 51%) and slightly more common in the PC group (PC 60% vs. DC 43%, p = 0.139). The use of ceftazidime-avibactam was more common among the PC group (PC 33% vs. DC 14%, p = 0.041). We observed a higher percentage of antimicrobial therapy in the previous 30 days (PC 68% vs. DC 57%, p = 0.371) and 90 days (PC 81% vs. DC 82%, p = 0.353) in the PC group. Multivariable analysis showed that patients that have received ceftazidime-avibactam therapy (OR 4.9 95% CI [1.45-16.39], p = 0.010), and those colonized by other MDR microorganisms (OR 2.5, 95% CI [0.96-6.25], p = 0.060) presented a higher risk of PC. Ceftazidime-avibactam use and colonization by other MDR microorganisms might be associated with CRE persistent gut colonization.

Ceftazidime-avibactam treatment in bacteremia caused by OXA-48 carbapenemase-producing Klebsiella pneumoniae.

Therapeutic options for bacteremia caused by carbapenem-resistant Enterobacterales (CRE) OXA-48-type are limited. The objective of this study was to analyze clinical success of CAZ-AVI compared with best available therapy (BAT) in patients with Klebsiella pneumoniae carbapenemase-producing OXA-48-type bacteremia (CRKp-OXA-48). We conducted a retrospective, single-center observational study in adult patients with CRKp-OXA-48 between December 2015 and May 2019. We collected the patients' clinical and epidemiological characteristics, antibiotic treatment (CAZ-AVI vs. BAT), and evolution. Factors associated with clinical success were analyzed using binary logistic regression. The study included 76 patients with CRKp-OXA-48-type bacteremia 33 received CAZ-AVI and 43 BAT. CAZ-AVI was mainly used in monotherapy (91%). Clinical success was more common in patients < 70-year-old (OR 4.79, 95% CI [1.435-16.002], p = 0.011) and CAZ-AVI treatment (OR 6.69, 95% CI [1.68-26.604], p = 0.007). Kaplan-Meier survival curve of 14-day mortality showed a lower mortality in patients who received CAZ-AVI (log rank 0.013). However, CAZ-AVI did not achieve statistical difference in IPTW for 14- and 30-day mortality (aOR 0.1, 95% CI [0.02-1.22], p = 0.076 and aOR 1.7, 95% CI [0.48-5.98], p = 0.413, respectively). CAZ-AVI treatment might be associated with a greater clinical success in CRKp-OXA-48 bacteremia.

Pramipexole to Improve Cognition in Bipolar Disorder: A Randomized Controlled Trial.

BACKGROUND: Adults with bipolar disorder (BD) often experience neurocognitive impairment that negatively impacts functioning and quality of life. Previous trials have found that dopamine agonist agents improve cognition in healthy volunteers and that adults with BD who have stable mood and mild cognitive deficits may also benefit. We hypothesized that pramipexole, a dopamine agonist, would improve neurocognitive function in patients with BD. METHODS: We recruited 60 adults (aged 18-65 years) with a diagnosis of BD I or II for an 8-week, double-blind, placebo-controlled trial (NCT02397837). All had stable mood and clinically significant neurocognitive impairment at baseline. Participants were randomized to receive pramipexole (n = 31) or a placebo (n = 29), dose was initiated at 0.125 mg 2 times a day and increased to a target of 4.5 mg/d. RESULTS: At trial end, the primary outcome, MATRICS Consensus Cognitive Battery composite score, had not improved more in the pramipexole group (mean [SD] = 1.15 [5.4]) than in the placebo group (mean [SD] = 4.12 [5.2], Cohen's d = 0.56, P = 0.049), and mixed models, controlling for symptoms, showed no association between treatment group and MATRICS Consensus Cognitive Battery scores. No serious adverse events were reported. CONCLUSIONS: These results suggest that pramipexole is not an efficacious cognitive enhancement agent in BD, even in a sample enriched for characteristics that were associated with a beneficial response in prior work. There are distinct cognitive subgroups among adults with BD and may be related differences in neurobiology that affect response to pramipexole. Additional research to better understand the onset and nature of the cognitive deficits in people with BD will be an important step toward a more personalized approach to treatment.

Self-reported body silhouettes: a diagnostic instrument for anthropometric parameters.

OBJECTIVE: Routine body size measurement of anthropometric values requires professionals, standardized techniques, and calibrated tools. Therefore, there is a need for easier screening tools such as the self-reported body silhouette (Self-bosi). The aim of this study was to analyze the performance of Self-bosi as a proxy of anthropometric values. STUDY DESIGN: Prospective analytic study of the Health Workers Cohort Study. METHODS: Adult participants of the Health Workers Cohort Study were included. Then, through the calculation sensitivity and specificity of Self-bosi to detect abnormal waist circumference (WC) (≥90 cm for male and ≥80 cm for female participants), elevated body fat percentage (BF%) (≥25% for male and ≥35% for female participants), as well as overweight and obesity (≥25 kg/m2) and obesity (≥30 kg/m2). RESULTS: A total of 2471 male and 5940 female participants were analyzed. Overall, Self-bosi discriminate high WC values (area under the curve [AUC]; male participants: 0.80, female participants: 0.82); increased BF% (AUC: male participants: 0.78, female participants: 0.83); overweight and obesity (AUC: male participants: 0.81, female participants: 0.86); and obesity (AUC: male participants: 0.83, female participants: 0.89). CONCLUSION: Self-bosi is an accurate method to assess increased WC, BF%, obesity, and overweight-obesity in Mexican adults. Given its simplicity and low-cost of the self-reported body silhouette, it might be considered a useful anthropometric screening instrument in large scale epidemiological research.

Severe childhood trauma and clinical and neurocognitive features in schizotypal personality disorder.

OBJECTIVE: Literature suggests that childhood trauma increases vulnerability for schizophrenia-spectrum disorders, including schizotypal personality disorder (SPD). Yet, it remains unexplored whether childhood trauma predicts symptom load and the level of neurocognitive functioning in SPD. METHOD: We included 225 individuals with SPD and 127 healthy controls. Childhood trauma was evaluated using the Childhood Trauma Questionnaire, and schizotypal traits were assessed using the Schizotypal Personality Questionnaire. Standard neurocognitive assessments covered six cognitive domains. RESULTS: All types of reported childhood trauma were significantly associated with SPD, in a linear fashion. Severe sexual abuse showed the greatest magnitude of association with higher cognitive-perceptual load (e.g., ideas of reference, odd belief or magical thinking); severe emotional neglect was associated with interpersonal scores (e.g., excessive social anxiety, constricted affect) within the SPD group. SPD individuals who reported severe trauma showed worse cognitive functioning (i.e., working memory, verbal/visual learning and memory, as well as verbal fluency). CONCLUSIONS: Particular severe childhood trauma types were associated with higher cognitive-perceptual and interpersonal symptoms in SPD, along with worse cognitive functioning. These findings highlight the need for clinicians to enquire about childhood trauma in SPD patients, since unaddressed early adverse experiences may carry long-term negative consequences.

High delayed mortality after the first episode of Clostridium difficile infection.

Clostridium difficile infection (CDI) is characterized by a high delayed and unrelated mortality. Predicting delayed mortality in CDI patients could allow the implementation of interventions that could reduce these events. A prospective multicentric study was carried out to investigate prognostic factors associated with mortality. It was based on a cohort (July 2015 to February 2016) of 295 patients presenting with CDI. Logistic regression was used and the model was calibrated using the Hosmer-Lemeshow test. The mortality rate at 75 days in our series was 18%. Age (>65 years), comorbidity (defined by heart failure, diabetes mellitus with any organ lesion, renal failure, active neoplasia or immunosuppression) and fecal incontinence at clinical presentation were associated with delayed (75-day) mortality. When present, each of the aforementioned variables added one point to the score. Mortalities with 0, 1, 2 and 3 points were 0%, 9.4%, 18.5% and 38.2%, respectively. The area under the ROC curve was 0.743, and the Hosmer-Lemeshow goodness-of-fit test p value was 0.875. Therefore, the prediction of high delayed mortality in CDI patients by our scoring system could promote measures for increasing survival in suitable cases.

Solubilization of organic matter by electrochemical treatment of sludge: Influence of operating conditions.

Sludge generated after wastewater treatment represents an important challenge due to the large amounts produced and the need to adequately treat it. Anaerobic digestion is the preferred treatment process to obtain renewable energy as well as a biosolid with the potential to be reused in land application. This process generates biogas (methane and carbon dioxide) that may be used for energy co-generation. However, anaerobic digestion is limited by the hydrolysis step since bacteria need to break down organic matter and large molecules to allow conversion into biogas. In this study, electrochemical treatment of sludge is proposed to solubilize organic matter. Boron-doped diamond electrodes were used to treat waste activated sludge under different experimental conditions (current density, flow rate, time) to evaluate their influence on the solubilization of organic matter (in terms of chemical oxygen demand). The degree of solubilization ranged between 0.31 and 1.78%. Based on the results, optimal operating conditions were current density of 19.3 mA cm-2, flow rate of 4 L min-1, and treatment time of 30 min. Furthermore, treatment flow rate was found to play a key role in solubilization, as the process is controlled by mass transfer.

Current Knowledge on Gene-Environment Interactions in Personality Disorders: an Update.

PURPOSE OF REVIEW: We review the existing literature on gene-environment interactions (G×E) and epigenetic changes primarily in borderline personality disorder (BPD) but also in antisocial, schizotypal, and avoidant personality disorders. RECENT FINDINGS: Research supports that susceptibility genes to BPD or its underlying traits may be expressed under certain environmental conditions such as physical or childhood sexual abuse. Epigenetic modifications of neurodevelopment- and stress-related genes are suggested to underlie the relationship between early life adversary and borderline personality disorder. Only limited studies have investigated the role of gene-environment interactions and epigenetic changes in the genesis of antisocial, schizotypal, and avoidant personality disorders. Considering the lack of pharmacological treatment for most personality disorders, the emerging evidence on the critical role of G×E and epigenetic changes in the genesis of personality disorders could help develop more biologically oriented therapeutic approaches. Future studies should explore the potential of this new therapeutic dimension.

A description of hydroquinone clathrates using molecular dynamics: Molecular model and crystalline structures for CH4 and CO2 guests.

The crystalline structure of hydroquinone clathrates has been studied using molecular dynamics. A flexible non-polarizable all-atom molecular model, based on the original Optimized Potentials for Liquid Simulations force field with recalculated point electric charges, has been used to describe the hydroquinone molecule, and the crystalline solid structure of the α native phase has been analyzed. Then, the ß clathrates have been studied, considering CO2 and CH4 as guest molecules, and also the empty clathrate structure. In all cases, the lattice parameters obtained through molecular simulation show excellent agreement with reported experimental values, showing that the molecular model selected is able to reproduce both the native crystalline phase and also the clathrate structures. In addition, the process of clathrate guest molecule release upon heating has been characterized, and the simulations show a good correspondence with the very recent experimental trends observed for both guest molecules analyzed.

Pharmacological risk factors associated with hospital readmission rates in a psychiatric cohort identified using prescriptome data mining.

BACKGROUND: Worldwide, over 14% of individuals hospitalized for psychiatric reasons have readmissions to hospitals within 30 days after discharge. Predicting patients at risk and leveraging accelerated interventions can reduce the rates of early readmission, a negative clinical outcome (i.e., a treatment failure) that affects the quality of life of patient. To implement individualized interventions, it is necessary to predict those individuals at highest risk for 30-day readmission. In this study, our aim was to conduct a data-driven investigation to find the pharmacological factors influencing 30-day all-cause, intra- and interdepartmental readmissions after an index psychiatric admission, using the compendium of prescription data (prescriptome) from electronic medical records (EMR). METHODS: The data scientists in the project received a deidentified database from the Mount Sinai Data Warehouse, which was used to perform all analyses. Data was stored in a secured MySQL database, normalized and indexed using a unique hexadecimal identifier associated with the data for psychiatric illness visits. We used Bayesian logistic regression models to evaluate the association of prescription data with 30-day readmission risk. We constructed individual models and compiled results after adjusting for covariates, including drug exposure, age, and gender. We also performed digital comorbidity survey using EMR data combined with the estimation of shared genetic architecture using genomic annotations to disease phenotypes. RESULTS: Using an automated, data-driven approach, we identified prescription medications, side effects (primary side effects), and drug-drug interaction-induced side effects (secondary side effects) associated with readmission risk in a cohort of 1275 patients using prescriptome analytics. In our study, we identified 28 drugs associated with risk for readmission among psychiatric patients. Based on prescription data, Pravastatin had the highest risk of readmission (OR = 13.10; 95% CI (2.82, 60.8)). We also identified enrichment of primary side effects (n = 4006) and secondary side effects (n = 36) induced by prescription drugs in the subset of readmitted patients (n = 89) compared to the non-readmitted subgroup (n = 1186). Digital comorbidity analyses and shared genetic analyses further reveals that cardiovascular disease and psychiatric conditions are comorbid and share functional gene modules (cardiomyopathy and anxiety disorder: shared genes (n = 37; P = 1.06815E-06)). CONCLUSIONS: Large scale prescriptome data is now available from EMRs and accessible for analytics that could improve healthcare outcomes. Such analyses could also drive hypothesis and data-driven research. In this study, we explored the utility of prescriptome data to identify factors driving readmission in a psychiatric cohort. Converging digital health data from EMRs and systems biology investigations reveal a subset of patient populations that have significant comorbidities with cardiovascular diseases are more likely to be readmitted. Further, the genetic architecture of psychiatric illness also suggests overlap with cardiovascular diseases. In summary, assessment of medications, side effects, and drug-drug interactions in a clinical setting as well as genomic information using a data mining approach could help to find factors that could help to lower readmission rates in patients with mental illness.

Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

BACKGROUND: Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters. METHODS: Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71). RESULTS: Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs. CONCLUSIONS: This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.

Tuning the electrical conductivity of exfoliated graphite nanosheets nanofluids by surface functionalization.

The electrical conductivity of exfoliated graphite in water nanofluids has been experimentally determined, and compared with the same property when the dispersed nanosheets have been oxidized. The effect of oxidation on this property is different if compared with the case of sintered dry nanosheets. In any case, for the sintered raw material the conduction behaves as expected in a metal, while for the nanofluid it shows values and trends typical of a weak electrolyte solution. The effect of oxidation on the electrical conductivity of exfoliated graphite can be explained as being caused by the dissociation in the fluid phase of the moieties resulting from the chemical functionalization process. This opens the possibility of designing a functionalization process to tune the nanofluid electrical conductivity.

Computational study of the interplay between intermolecular interactions and CO2 orientations in type I hydrates.

Carbon dioxide (CO2) molecules show a rich orientation landscape when they are enclathrated in type I hydrates. Previous studies have described experimentally their preferential orientations, and some theoretical works have explained, but only partially, these experimental results. In the present paper, we use classical molecular dynamics and electronic density functional theory to advance in the theoretical description of CO2 orientations within type I hydrates. Our results are fully compatible with those previously reported, both theoretical and experimental, the geometric shape of the cavities in hydrate being, and therefore, the steric constraints, responsible for some (but not all) preferential angles. In addition, our calculations also show that guest-guest interactions in neighbouring cages are a key factor to explain the remaining experimental angles. Besides the implication concerning equation of state hydrate modeling approximations, the conclusion is that these guest-guest interactions should not be neglected, contrary to the usual practice.