Publications by authors named "Benoit d"

422 Publications

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Fortschr Neurol Psychiatr 2021 Feb 26. Epub 2021 Feb 26.

Klinik für Psychiatrie und Psychotherapie, Zentralinstitut für Seelische Gesundheit Klinische Fakultät Mannheim, Universität Heidelberg.

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1362-9743DOI Listing
February 2021

Disrupted caregiving behavior as a mediator of the relation between disrupted prenatal maternal representations and toddler social-emotional functioning.

Dev Psychopathol 2021 Mar 2:1-9. Epub 2021 Mar 2.

Department of Pediatrics, Rainbow Babies & Children's Hospital, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

The development of maternal representations of the child during pregnancy guides a mother's thoughts, feelings, and behavior toward her child. The association between prenatal representations, particularly those that are disrupted, and toddler social-emotional functioning is not well understood. The present study examined associations between disrupted prenatal representations and toddler social-emotional functioning and to test disrupted maternal behavior as a mediator of this association. Data were drawn from 109 women from a larger prospective longitudinal study (N=120) of women and their young children. Prenatal disrupted maternal representations were assessed using the Working Model of the Child Interview disrupted coding scheme, while disrupted maternal behavior was coded 12-months postpartum from mother-infant interactions. Mother-reported toddler social-emotional functioning was assessed at ages 12 and 24 months. Disrupted prenatal representations significantly predicted poorer toddler social-emotional functioning at 24 months, controlling for functioning at 12 months. Further, disrupted maternal behavior mediated the relation between disrupted prenatal representations and toddler social-emotional problems. Screening for disrupted representations during pregnancy is needed to facilitate referrals to early intervention and decrease the likelihood of toddler social-emotional problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0954579420001674DOI Listing
March 2021

Unanticipated admission after ambulatory surgery in the pediatric population: a single-center retrospective analysis.

Acta Chir Belg 2021 Mar 8:1-7. Epub 2021 Mar 8.

Faculty of Medicine and Health Sciences, Department of Basic and Applied Medical Sciences, Ghent University Hospital, Ghent, Belgium.

Introduction: The incidence of adverse events in day surgery is an important quality indicator. This retrospective study investigated factors independently associated with unanticipated admission of pediatric patients after ambulatory surgery.

Patients And Methods: Ambulatory pediatric patients requiring unanticipated admission between January 2016 and December 2018 were compared to ambulatory pediatric patients who were discharged home after a planned surgery. Demographic data, organizational data, American Society of Anesthesiologists (ASA) classification, type of surgery, type of anesthesia, length of surgery, time of completion of the surgery, campus site, and season were collected in both groups. The reason for unexpected admission was classified according to four subtypes: anesthetic, medical, social/organizational and surgical reason, respectively. Multivariate logistic regression was used to identify independent factors associated with unanticipated admission.

Results: From a total of 4235 pediatric patients, 78 children (1.9%) required unanticipated admission. The reasons for admission were anesthetic  = 29 (37.3%), surgical  = 20 (25.6%), medical  = 16 (20.5%) and social/organizational  = 13 (16.6%). Age <2 years (odds ratio [OR] 3.005, 95% confidence interval (CI) 1.500-6.018; ASA class 2 (OR 2.144; 95% CI 1.193-3.852); ASA class 3 (OR 11.617; CI 5.698-23.685); length of surgery >2 h (OR 3.056; CI 1.829-5.107); completion of surgery > 2:30 PM (OR 3.507; CI 1.854-6.633) and campus site (OR 3.628; CI 1.991-6.610) were factors significantly associated with unanticipated admission.

Conclusion: Children are less likely to be admitted after ambulatory surgery when preoperatively carefully selected and when prioritized considering age, general health condition and invasiveness of the surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00015458.2021.1893579DOI Listing
March 2021

Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure.

Ann Intensive Care 2021 Jan 27;11(1):17. Epub 2021 Jan 27.

AP-HP, Hôpital Saint-Louis, Medical Intensive Care Unit and Department of Biostatistics, APHP, Hopital St-Louis, 1 avenue Claude Vellefaux, 75010, Paris, France.

Background: Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure.

Results: In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1-3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69-7.01) vs. 6.10 (4.48-8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557-0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82-0.96], p = 0.04).

Conclusion: A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13613-021-00801-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838224PMC
January 2021

Impact of the repurposed drug thonzonium bromide on host oral-gut microbiomes.

NPJ Biofilms Microbiomes 2021 01 22;7(1). Epub 2021 Jan 22.

Biofilm Research Labs, Levy Center for Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Drug repurposing is a feasible strategy for the development of novel therapeutic applications. However, its potential use for oral treatments and impact on host microbiota remain underexplored. Here, we assessed the influences of topical oral applications of a repurposed FDA-approved drug, thonzonium bromide, on gastrointestinal microbiomes and host tissues in a rat model of dental caries designed to reduce cross-contamination associated with coprophagy. Using this model, we recapitulated the body site microbiota that mirrored the human microbiome profile. Oral microbiota was perturbed by the treatments with specific disruption of Rothia and Veillonella without affecting the global composition of the fecal microbiome. However, disturbances in the oral-gut microbial interactions were identified using nestedness and machine learning, showing increased sharing of oral taxon Sutterella in the gut microbiota. Host-tissue analyses revealed caries reduction on teeth by thonzonium bromide without cytotoxic effects, indicating bioactivity and biocompatibility when used orally. Altogether, we demonstrate how an oral treatment using a repurposed drug causes localized microbial disturbances and therapeutic effects while promoting turnover of specific oral species in the lower gut in vivo.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41522-020-00181-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822857PMC
January 2021

Mental Health & Parental Concerns during COVID-19: The Experiences of New Mothers Amidst Social Isolation.

Midwifery 2021 Mar 19;94:102902. Epub 2020 Dec 19.

School of Nursing, Dalhousie University, PO Box 15000, 5869 University Avenue, Halifax, Nova Scotia, Canada, B3H 4R2. Electronic address:

Background: The COVID-19 pandemic has resulted in an unprecedented situation for new parents, with public health orders greatly affecting daily life as well as various aspects of parenting and new parent wellbeing.

Objectives: To understand the impact of the COVID-19 pandemic on mothers/parents across Nova Scotia who are caring for a child 0-12 months of age.

Design: This study utilized an online qualitative survey to collect data. Feminist poststructuralism and discourse analysis guided the analysis and discussion.

Setting: Nova Scotia, Canada PARTICIPANTS: : 68 participants were recruited from across the province of Nova Scotia.

Findings: Mental health and socialization were both major concerns for new mothers/parents, as many expressed feelings of worry, anxiety, loneliness, isolation, and stress.

Key Conclusions: Online support was sought by many new mothers/parents as a way of supporting their own mental health. Some found ways to make it meaningful for them, while others believed that it could not replace or offer the same benefits as in-person interaction and support.

Implications For Practice: Informal and formal support systems are both essential for new mothers. As public health systems and health care services learn to adapt to COVID-19, further research is required to examine how health services may best meet the needs of new mothers/parents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.midw.2020.102902DOI Listing
March 2021

Modulators of hERAP2 discovered by high-throughput screening.

Eur J Med Chem 2021 Feb 11;211:113053. Epub 2020 Dec 11.

Univ. Lille, Inserm, Institut Pasteur de Lille, U1177 - Drugs and Molecules for Living Systems, F-59000, Lille, France; Institut Universitaire de France, F- 75231, Paris, France; European Genomic Institute for Diabetes, EGID, University of Lille, F-59000, France. Electronic address:

Endoplasmic reticulum aminopeptidase 2, ERAP2, is an emerging pharmacological target in cancer immunotherapy and control of autoinflammatory diseases, as it is involved in antigen processing. It has been linked to the risk of development of spondyloarthritis, and it associates with the immune infiltration of tumours and strongly predicts the overall survival for patients receiving check-point inhibitor therapy. While some selective inhibitors of its homolog ERAP1 are available, no selective modulator of ERAP2 has been disclosed so far. In order to identify such compounds, we screened an in-house focused library of 1920 compounds designed to target metalloenzymes. Structure-Activity Relationships and docking around two hits led to the discovery of selective inhibitors of ERAP2. Amid those, some bind to yet untapped amino-acids in the S1 pocket. Importantly, we disclose also the first activator of small substrates hydrolysis by ERAP2. Inhibitors and activators identified in this study could serve as useful starting points for optimization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2020.113053DOI Listing
February 2021

Hepatic dysfunction impairs prognosis in critically ill patients with hematological malignancies: A post-hoc analysis of a prospective multicenter multinational dataset.

J Crit Care 2020 Dec 4;62:88-93. Epub 2020 Dec 4.

Intensive Care Unit, Institut Paoli Calmettes, Marseille, France.

Purpose: Hyperbilirubinemia is frequent in patients with hematological malignancies admitted to the intensive care unit (ICU). Literature about hepatic dysfunction (HD) in this context is scarce.

Methods: We investigated the prognostic impact of HD analyzing a prospective multicenter cohort of 893 critically ill hematology patients. Two groups were defined: patients with HD (total bilirubin ≥33 μmol/L at ICU admission) and patients without HD.

Results: Twenty one percent of patients were found to have HD at ICU admission. Cyclosporine, antimicrobials before ICU admission, abdominal symptoms, ascites, history of liver disease, neutropenia, increased serum creatinine and myeloma were independently associated with HD. Etiology remained undetermined in 73% of patients. Hospital mortality was 56.3% and 36.3% respectively in patients with and without HD (p < 0.0001). Prognostic factors independently associated with hospital mortality in HD group were, performance status >1 (OR = 2.07, 95% CI = 1.49-2.87, p < 0.0001), invasive mechanical ventilation (OR = 3.92, 95% CI = 2.69-5.71, p < 0.0001), renal replacement therapy (OR = 1.74, 95% CI = 1.22-2.47, p = 0.002), vasoactive drug (OR = 1.81, 95% CI = 1.21-2.71, p = 0.004) and SOFA score without bilirubin level at ICU admission (OR = 1.09, 95% CI = 1.04-1.14, p < 0.0001).

Conclusions: HD is common, underestimated, infrequently investigated, and is associated with impaired outcome in critically ill hematology patients. HD should be considered upon ICU admission and managed as other organ dysfunctions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcrc.2020.11.023DOI Listing
December 2020

Attributable Mortality of Ventilator-associated Pneumonia: Replicating Findings, Revisiting Methods.

Ann Am Thorac Soc 2020 Dec 7. Epub 2020 Dec 7.

University Hospital Ghent, 60200, Department of Intensive Care Medicine, Gent, Belgium.

Rationale: Estimating the impact of ventilator-associated pneumonia (VAP) from routinely collected ICU data is methodologically challenging.

Objectives: We aim to replicate earlier findings of limited VAP-attributable ICU mortality in an independent cohort. By refining statistical analyses, we gradually tackle different sources of bias.

Methods: Records of 2,720 adult patients admitted to Ghent University Hospital ICUs (2013-2017) and receiving mechanical ventilation within 48 hours following admission were extracted from linked ICIS and COSARA databases. The VAP-attributable fraction of ICU mortality was estimated using a competing risk analysis that is restricted to VAP-free patients (approach 1), accounts for VAP onset by treating it as either a competing (approach 2) or censoring event (approach 3), or additionally adjusts for time-dependent confounding via inverse probability weighting (approach 4).

Results: Two hundred ten patients (7.7%) acquired VAP. Based on benchmark approach 4, we estimated that (compared to current preventive measures) hypothetical eradication of VAP would lead to a relative ICU mortality reduction of 1.7% (95% confidence interval: -1.3-4.6) by day 10 and of 3.6% (95% confidence interval: 0.7-6.5) by day 60. Approaches 1-3 produced estimates ranging from -0.7 to 2.5% by day 10, and from 5.2 to 5.5% at day 60.

Conclusions: In line with previous studies using appropriate methodology, we found limited VAP-attributable ICU mortality given current state-of-the-art VAP prevention measures. Our study illustrates that inappropriate accounting of the time-dependency of exposure and confounding of its effects may misleadingly suggest protective effects of early-onset VAP and systematically overestimate attributable mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202004-385OCDOI Listing
December 2020

Functional muscle synergies to support the knee against moment specific loads while weight bearing.

J Electromyogr Kinesiol 2021 Feb 21;56:102506. Epub 2020 Nov 21.

School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada; School of Human Kinetics, University of Ottawa, 125 University Pr, Ottawa, ON K1N 1A2, Canada. Electronic address:

Objective: Externally applied abduction and rotational loads are major contributors to the knee joint injury mechanism; yet, how muscles work together to stabilize the knee against these loads remains unclear. Our study sought to evaluate lower limb functional muscle synergies in healthy young adults such that muscle activation can be directly related to internal knee joint moments.

Methods: Concatenated non-negative matrix factorization extracted muscle and moment synergies of 22 participants from electromyographic signals and joint moments elicited during a weight-bearing force matching protocol.

Results: Two synergy sets were extracted: Set 1 included four synergies, each corresponding to a general anterior, posterior, medial, or lateral force direction. Frontal and transverse moments were coupled during medial and lateral force directions. Set 2 included six synergies, each corresponding to a moment type (extension/flexion, ab/adduction, internal/external rotation). Hamstrings and quadriceps dominated synergies associated with respective flexion and extension moments while quadriceps-hamstring co-activation was associated with knee abduction. Rotation moments were associated with notable contributions from hamstrings, quadriceps, gastrocnemius, and hip ab/adductors, corresponding to a general co-activation muscle synergy.

Conclusion: Our results highlight the importance of muscular co-activation of all muscles crossing the knee to support it during injury-inducing loading conditions such as externally applied knee abduction and rotation. Functional muscle synergies can provide new insight into the relationship between neuromuscular control and knee joint stability by directly associating biomechanical variables to muscle activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jelekin.2020.102506DOI Listing
February 2021

Matrix metalloproteinase (MMP)-degradable tissue engineered periosteum coordinates allograft healing via early stage recruitment and support of host neurovasculature.

Biomaterials 2021 Jan 19;268:120535. Epub 2020 Nov 19.

Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA; Department of Orthopaedics and Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, USA; Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA; Materials Science Program, University of Rochester, Rochester, NY, USA; Department of Chemical Engineering, University of Rochester, Rochester, NY, USA; Department of Biomedical Genetics and Center for Oral Biology, University of Rochester Medical Center, Rochester, NY, USA. Electronic address:

Despite serving as the clinical "gold standard" treatment for critical size bone defects, decellularized allografts suffer from long-term failure rates of ~60% due to the absence of the periosteum. Stem and osteoprogenitor cells within the periosteum orchestrate autograft healing through host cell recruitment, which initiates the regenerative process. To emulate periosteum-mediated healing, tissue engineering approaches have been utilized with mixed outcomes. While vascularization has been widely established as critical for bone regeneration, innervation was recently identified to be spatiotemporally regulated together with vascularization and similarly indispensable to bone healing. Notwithstanding, there are no known approaches that have focused on periosteal matrix cues to coordinate host vessel and/or axon recruitment. Here, we investigated the influence of hydrogel degradation mechanism, i.e. hydrolytic or enzymatic (cell-dictated), on tissue engineered periosteum (TEP)-modified allograft healing, especially host vessel/nerve recruitment and integration. Matrix metalloproteinase (MMP)-degradable hydrogels supported endothelial cell migration from encapsulated spheroids whereas no migration was observed in hydrolytically degradable hydrogels in vitro, which correlated with increased neurovascularization in vivo. Specifically, ~2.45 and 1.84-fold, and ~3.48 and 2.58-fold greater vessel and nerve densities with high levels of vessel and nerve co-localization was observed using MMP degradable TEP (MMP-TEP) -modified allografts versus unmodified and hydrolytically degradable TEP (Hydro-TEP)-modified allografts, respectively, at 3 weeks post-surgery. MMP-TEP-modified allografts exhibited greater longitudinal graft-localized vascularization and endochondral ossification, along with 4-fold and 2-fold greater maximum torques versus unmodified and Hydro-TEP-modified allografts after 9 weeks, respectively, which was comparable to that of autografts. In summary, our results demonstrated that the MMP-TEP coordinated allograft healing via early stage recruitment and support of host neurovasculature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.120535DOI Listing
January 2021

Impact of early ICU admission for critically ill cancer patients: Post-hoc analysis of a prospective multicenter multinational dataset.

J Crit Care 2020 Oct 23;62:6-11. Epub 2020 Oct 23.

Medical ICU, Saint-Louis University Hospital, AP-HP, Paris, France; Faculté de Médecine, Université de Paris, Paris, France; ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153 (Center of Epidemiology and Biostatistics Sorbonne Paris Cité, CRESS), INSERM, Paris, France. Electronic address:

Objectives: Early intensive care unit (ICU) admission, in Critically Ill Cancer Patients (CICP), is believed to have contributed to the prognostic improvement of critically ill cancer patients. The primary objective of this study was to assess the association between early ICU admission and hospital mortality in CICP.

Design: Retrospective analysis of a prospective multicenter dataset. Early admission was defined as admission in the ICU < 24 h of hospital admission. We assessed the association between early ICU admission and hospital mortality in CICP via survival analysis and propensity score matching.

Results: Of the 1011patients in our cohort, 1005 had data available regarding ICU admission timing and were included. Overall, early ICU admission occurred in 455 patients (45.3%). Crude hospital mortality in patients with early and delayed ICU admission was 33.6% (n = 153) vs. 43.1% (n = 237), respectively (P = 0.02). After adjustment for confounders, early compared to late ICU admission was not associated with hospital mortality (HR 0.92; 95%CI 0.76-1.11). After propensity score matching, hospital mortality did not differ between patients with early (35.2%) and late (40.6%) ICU admission (P = 0.13). In the matched cohort, early ICU admission was not associated with mortality after adjustment on SOFA score (HR 0.89; 95%CI 0.71-1.12). Similar results were obtained after adjustment for center effect.

Conclusion: In this cohort, early ICU admission was not associated with a better outcome after adjustment for confounder and center effect. The uncertainty with regard to the beneficial effect of early ICU on hospital mortality suggests the need for an interventional study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcrc.2020.10.022DOI Listing
October 2020

Impact of perceived inappropiate cardiopulmonary resuscitation on emergency clinicians' intention to leave the job: Results from a cross-sectional survey in 288 centres across 24 countries.

Resuscitation 2021 Jan 20;158:41-48. Epub 2020 Nov 20.

Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.

Introduction: Cardiopulmonary resuscitation (CPR) in patients with a poor prognosis increases the risk of perception of inappropriate care leading to moral distress in clinicians. We evaluated whether perception of inappropriate CPR is associated with intention to leave the job among emergency clinicians.

Methods: A cross-sectional multi-centre survey was conducted in 24 countries. Factors associated with intention to leave the job were analysed by conditional logistic regression models. Results are expressed as odds ratios with 95% confidence intervals.

Results: Of 5099 surveyed emergency clinicians, 1836 (36.0%) were physicians, 1313 (25.7%) nurses, 1950 (38.2%) emergency medical technicians. Intention to leave the job was expressed by 1721 (33.8%) clinicians, 3403 (66.7%) often wondered about the appropriateness of a resuscitation attempt, 2955 (58.0%) reported moral distress caused by inappropriate CPR. After adjustment for other covariates, the risk of intention to leave the job was higher in clinicians often wondering about the appropriateness of a resuscitation attempt (1.43 [1.23-1.67]), experiencing associated moral distress (1.44 [1.24-1.66]) and who were between 30-44 years old (1.53 [1.21-1.92] compared to <30 years). The risk was lower when the clinician felt valued by the team (0.53 [0.42-0.66]), when the team leader acknowledged the efforts delivered by the team (0.61 [0.49-0.75]) and in teams that took time for debriefing (0.70 [0.60-0.80]).

Conclusion: Resuscitation attempts perceived as inappropriate by clinicians, and the accompanying moral distress, were associated with an increased likelihood of intention to leave the job. Interprofessional collaboration, teamwork, and regular interdisciplinary debriefing were associated with a lower risk of intention to leave the job. ClinicalTrials.gov; No.: NCT02356029.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resuscitation.2020.10.043DOI Listing
January 2021

Sex-specific landing biomechanics and energy absorption during unanticipated single-leg drop-jumps in adolescents: implications for knee injury mechanics.

J Biomech 2020 Dec 28;113:110064. Epub 2020 Sep 28.

School of Human Kinetics, University of Ottawa, 125 University, Ottawa, ON K1N 6N5, Canada; School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Ottawa Carleton Institute for Biomedical Engineering, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada. Electronic address:

Females aged between 13 and 17 years old possess the highest non-contact ACL injury incidence of any sex-age strata. Considering that energy absorption strategies have been associated with a reduced risk for sustaining an ACL injury, evaluating landing performance in youth athletes requires investigations beyond the kinematic level. The purpose of this study was to identify sex-specific energy absorption strategies in adolescent males and females, including the relationship between strength and the observed strategies. Thirty-one healthy adolescent athletes completed unanticipated single-leg drop-jump landings on their dominant limb. Sex-specific kinematics and lower-limb contributions to energy absorption were then compared over the landing phase for each jump. Pearson and Spearman correlation coefficients determined the relationship between isometric joint strength and the observed kinematics and energy absorption. Female participants absorbed a larger proportion of the landing energy at the ankle (p = 0.046, d = 0.75) and smaller proportion at the hip (p = 0.028, d = 0.85) compared to males. Females also reached larger peak negative joint power in their knee (p = 0.001, d = 1.1) and ankle (p = 0.04, d = 0.79). Hip extension strength was positively correlated with trunk flexion (r = 0.559, p = 0.001) and negatively correlated with forward pelvic tilt (r = -0.513, p = 0.003). Females adopted an energy absorption strategy which utilized the distal joints to absorb a larger portion of the landing forces and tended to absorb the forces later in the landing phase relative to males. The greater reliance on distal joints is correlated to reduced hip strength and may increase the risk for sustaining an ACL injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiomech.2020.110064DOI Listing
December 2020

Spatial frequency domain imaging for the longitudinal monitoring of vascularization during mouse femoral graft healing.

Biomed Opt Express 2020 Oct 3;11(10):5442-5455. Epub 2020 Sep 3.

Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA.

Allograft is the current gold standard for treating critical-sized bone defects. However, allograft healing is usually compromised partially due to poor host-mediated vascularization. In the efforts towards developing new methods to enhance allograft healing, a non-terminal technique for monitoring the vascularization is needed in pre-clinical mouse models. In this study, we developed a non-invasive instrument based on spatial frequency domain imaging (SFDI) for longitudinal monitoring of the mouse femoral graft healing. SFDI technique provided total hemoglobin concentration (THC) and oxygen saturation (StO) of the graft and the surrounding soft tissues. SFDI measurements were performed from 1 day before to 44 days after graft transplantation. Autograft, another type of bone graft with higher vascularization potential was also measured as a comparison to allograft. For both grafts, the overall temporal changes of the measured THC agreed with the physiological expectations of vascularization timeline during bone healing. A significantly greater increase in THC was observed in the autograft group compared to the allograft group, which agreed with the expectation that allografts have more compromised vascularization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.401472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587272PMC
October 2020

Matrix Control of Periodontal Ligament Cell Activity Via Synthetic Hydrogel Scaffolds.

Tissue Eng Part A 2020 Dec 9. Epub 2020 Dec 9.

Department of Biomedical Engineering and University of Rochester, Rochester, New York, USA.

Rebuilding the tooth-supporting tissues (periodontium) destroyed by periodontitis remains a clinical challenge. Periodontal ligament cells (PDLCs), multipotent cells within the periodontal ligament (PDL), differentiate and form new PDL and mineralized tissues (cementum and bone) during native tissue repair in response to specific extracellular matrix (ECM) cues. Thus, harnessing ECM cues to control PDLC activity , and ultimately, to design a PDLC delivery vehicle for tissue regeneration is an important goal. In this study, poly(ethylene glycol) hydrogels were used as a synthetic PDL ECM to interrogate the roles of cell-matrix interactions and cell-mediated matrix remodeling in controlling PDLC activity. Results showed that PDLCs within matrix metalloproteinase (MMP)-degradable hydrogels expressed key PDL matrix genes and showed a six to eightfold increase in alkaline phosphatase (ALP) activity compared with PDLCs in nondegradable hydrogel controls. The increase in ALP activity, commonly considered an early marker of cementogenic/osteogenic differentiation, occurred independent of the presentation of the cell-binding ligand RGD or soluble media cues and remained elevated when inhibiting PDLC-matrix binding and intracellular tension. ALP activity was further increased in softer hydrogels regardless of degradability and was accompanied by an increase in PDLC volume. However, scaffolds that fostered PDLC ALP activity did not necessarily promote hydrogel ECM mineralization. Rather, matrix mineralization was greatest in stiffer, MMP-degradable hydrogels and required the presence of soluble media cues. These divergent outcomes illustrate the complexity of the PDLC response to ECM cues and the limitations of current scaffold materials. Nevertheless, key biomaterial design principles for controlling PDLC activity were identified for incorporation into scaffolds for periodontal tissue regeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ten.TEA.2020.0278DOI Listing
December 2020

Ligand Density Controls C-Type Lectin-Like Molecule-1 Receptor-Specific Uptake of Polymer Nanoparticles.

Adv Biosyst 2020 11 19;4(11):e2000172. Epub 2020 Oct 19.

University of Rochester, Department of Biomedical Engineering, Rochester, NY, USA.

The newest generation of drug delivery systems (DDSs) exploits ligands to mediate specific targeting of cells and/or tissues. However, studies investigating the link between ligand density and nanoparticle (NP) uptake are limited to a small number of ligand-receptor systems. C-type lectin-like molecule-1 (CLL1) is uniquely expressed on myeloid cells, which enables the development of receptors specifically targeting treat various diseases. This study aims to investigate how NPs with different CLL1 targeting peptide density impact cellular uptake. To this end, poly(styrene-alt-maleic anhydride)-b-poly(styrene) NPs are functionalized with cyclized CLL1 binding peptides (cCBP) ranging from 240 ± 12 to 31 000 ± 940 peptides per NP. Unexpectedly, the percentage of cells with internalized NPs is decreased for all cCBP-NP designs regardless of ligand density compared to unmodified NPs. Internalization through CLL1 receptor-mediated processes is further investigated without confounding the effects of NP size and surface charge. Interestingly, high density cCBP-NPs (>7000 cCBP per NP) uptake is dominated by CLL1 receptor-mediated processes while low density cCBP-NPs (≈200 cCBP per NP) and untargeted NP occurred through non-specific clathrin and caveolin-mediated endocytosis. Altogether, these studies show that ligand density and uptake mechanism should be carefully investigated for specific ligand-receptor systems for the design of targeted DDSs to achieve effective drug delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adbi.202000172DOI Listing
November 2020

Decision Tree Learning Algorithm for Classifying Knee Injury Status Using Return-to-Activity Criteria.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:5494-5497

Anterior cruciate ligament (ACL) injury rates in female adolescents are increasing. Irrespective of treatment options, approximately 1/3 will suffer secondary ACL injuries following their return to activity (RTA). Despite this, there are no evidence-informed RTA guidelines to aid clinicians in deciding when this should occur. The first step towards these guidelines is to identify relevant and feasible measures to assess the functional status of these patients. The purpose of this study was therefore to evaluate tests frequently used to assess functional capacity following surgery using a Reduced Error Pruning Tree (REPT). Thirty-six healthy and forty-two ACLinjured adolescent females performed a series of functional tasks. Motion analysis along with spatiotemporal measures were used to extract thirty clinically relevant variables. The REPT reduced these variables down to two limb symmetry measures (maximum anterior hop and maximum lateral hop), capable of classifying injury status between the healthy and ACL injured participants with a 69% sensitivity, 78% specificity and kappa statistic of 0.464. We, therefore, conclude that the REPT model was able to evaluate functional capacity as it relates to injury status in adolescent females. We also recommend considering these variables when developing RTA assessments and guidelines.Clinical Relevance- Our results indicate that spatiotemporal measures may differentiate ACL-injured and healthy female adolescents with moderate confidence using a REPT. The identified tests may reasonably be added to the clinical evaluation process when evaluating functional capacity and readiness to return to activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/EMBC44109.2020.9176010DOI Listing
July 2020

Dual antibacterial drug-loaded nanoparticles synergistically improve treatment of Streptococcus mutans biofilms.

Acta Biomater 2020 10 25;115:418-431. Epub 2020 Aug 25.

University of Rochester, Department of Biomedical Engineering, Rochester, NY, United States; University of Rochester, Materials Science Program, NY, United States; University of Rochester, Department of Orthopaedics and Center for Musculoskeletal Research, NY, United States; University of Rochester, Center for Oral Biology, NY, United States; University of Rochester, Department of Chemical Engineering, NY, United States. Electronic address:

Dental caries (i.e., tooth decay), which is caused by biofilm formation on tooth surfaces, is the most prevalent oral disease worldwide. Unfortunately, many anti-biofilm drugs lack efficacy within the oral cavity due to poor solubility, retention, and penetration into biofilms. While drug delivery systems (DDS) have been developed to overcome these hurdles and improve traditional antimicrobial treatments, including farnesol, efficacy is still modest due to myriad resistance mechanisms employed by biofilms, suggesting that synergistic drug treatments may be more efficacious. Streptococcus mutans (S. mutans), a cariogenic pathogen and biofilm forming model organism, has several key virulence factors including acidogenicity and exopolysaccharide (EPS) matrix synthesis. Flavonoids, such as myricetin, can reduce both biofilm acidogenicity and EPS synthesis. Therefore, a nanoparticle carrier (NPC) DDS with flexibility to co-load farnesol in the hydrophobic core and myricetin within the cationic corona, was tested in vitro using established and developing S. mutans biofilms. Co-loaded NPC treatments effectively disrupted biofilm biomass (i.e., dry weight) and reduced biofilm viability by ~3 log CFU/mL versus single drug-only controls in developing biofilms, suggesting dual-drug delivery exhibits synergistic anti-biofilm effects. Mechanistic studies revealed that co-loaded NPCs synergistically inhibited planktonic bacterial growth compared to controls and reduced S. mutans acidogenicity due to decreased atpD expression, a gene associated with acid tolerance. Moreover, the myricetin-loaded NPC corona enhanced NPC binding to tooth-mimetic surfaces, which can increase drug efficacy through improved retention at the biofilm-apatite interface. Altogether, these findings suggest promise for co-delivery of myricetin and farnesol DDS as an alternative anti-biofilm treatment to prevent dental caries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2020.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530141PMC
October 2020

Divergence analysis of failed and successful unanticipated single-leg landings reveals the importance of the flight phase and upper body biomechanics.

J Biomech 2020 Aug 13;109:109879. Epub 2020 Jun 13.

School of Human Kinetics, University of Ottawa, 125 University, Ottawa, ON K1N 6N5, Canada; School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada; Ottawa Carleton Institute for Biomedical Engineering, University of Ottawa, 800 King Edward Ave., Ottawa, ON K1N 6N5, Canada. Electronic address:

The purpose of this study was to describe neuromuscular and kinematic differences during failed and successful drop-vertical jumps in a pediatric population. Healthy young athletes (n = 32) completed single-leg drop vertical jump landings where the required landing leg was unanticipated. Trials were categorized as failed if the participant shifted their base of support during the landing. Joint kinematics and muscle activation amplitudes were time normalized over the flight and landing phases. Statistical parametric mapping (SPM) was used to compare landings and a moving average convergence divergence oscillator was then calculated to determine where failed and successful waveforms began to diverge prior to reaching statistical significance. SPM determined that participants performed the failed trials with reduced pelvic tilt towards the landing limb during 41-69% of the flight phase, greater trunk flexion angle during 31-100% of the landing phase and greater trunk tilt away from the landing limb during 3-13% and 21-90% of the landing phase. Greater rectus femoris activation during the failed trials was identified during 88-100% of the flight phase, as well as 1-4% and 71-97% of the landing phase. Greater gluteus medius and biceps femoris activation was also identified in the failed trials during 54-72% and 76-89% of the landing phase respectively. These findings indicate that the control of proximal joints has an important role in determining if a participant will fail a landing; and that how athletes prepare for a landing may be more relevant than the kinematics following ground contact.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbiomech.2020.109879DOI Listing
August 2020

Treatment Limitation Decisions in Critically Ill Patients With a Malignancy on the Intensive Care Unit.

J Intensive Care Med 2021 Jan 13;36(1):42-50. Epub 2020 Aug 13.

Department of Intensive Care, 6993Erasmus MC-University Medical Center Rotterdam, the Netherlands.

Background: Treatment limitation decisions (TLDs) on the ICU can be challenging, especially in patients with a malignancy. Up-to-date literature regarding TLDs in critically ill patients with a malignancy admitted to the ICU is scarce. The aim was to compare the incidence of written TLDs between patients with an active malignancy, patients with a malignancy in their medical history (complete remission, CR) and patients without a malignancy admitted unplanned to the ICU.

Methods: We conducted a retrospective cohort study in a large university hospital in the Netherlands. We identified all unplanned admissions to the ICU in 2017 and categorized the patients in 3 groups: patients with an active malignancy (study population), with CR and without a malignancy. A TLD was defined as a written instruction not to perform life-saving treatments, such as CPR in case of cardiac arrest. A multivariate binary logistic regression analysis was used to identify whether having a malignancy was associated with TLDs.

Results: Of the 1046 unplanned admissions, 125 patients (12%) had an active malignancy and 76 (7.3%) patients had CR. The incidence of written TLDs in these subgroups were 37 (29.6%) and 20 (26.3%). Age (OR 1.03; 95% CI 1.01 -1.04), SOFA score at ICU admission (OR 1.11; 95% CI 1.05 -1.18) and having an active malignancy (OR 1.75; 95% CI 1.04-2.96) compared to no malignancy were independently associated with written TLDs. SOFA scores on the day of the TLD were not significantly different in patients with and without a malignancy.

Conclusions: This study shows that the presence of an underlying malignancy is independently associated with written TLDs during ICU stay. Patients with CR were not at risk of more written TLDs. Whether this higher incidence of TLDs in patients with a malignancy is justified, is at least questionable and should be evaluated in future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0885066620948453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705645PMC
January 2021

Multiple locus variable number tandem repeat analysis for the characterization of wild feline Bartonella species and subspecies.

Vet Microbiol 2020 Aug 17;247:108788. Epub 2020 Jul 17.

UMR BIPAR 956, Ecole nationale vétérinaire d'Alfort, Anses, INRA, Université Paris-Est, Maisons-Alfort, France.

Bartonella genus includes an increasing number of species and subspecies, especially among wild felids, the positioning of which, with regards to the zoonotic species Bartonella henselae, is important to determine. The aim of this study was to test the ability of a molecular typing technique to distinguish between various Bartonella isolates obtained from four different species of free-ranging and captive wild felids and to identify key profiles or markers allowing differentiating them from each other and/or from B. henselae or B. koehlerae. A molecular typing technique for B. henselae based on the polymorphism of variable number tandem repeat units (VNTR) called MLVA (Multiple Locus VNTR Analysis) was applied to 24 Bartonella isolates from free-ranging or captive wild felids, 19 of which were obtained from California and five from three countries in Southern Africa, and compared with 49 B. henselae isolates from cats, dog or humans from the United States including the human ATCC (American Type Culture Collection) reference strain, B. henselae Houston 1. MLVA allowed distinguishing Bartonella isolates from wild felids from either B. henselae or B. koehlerae. We confirmed infection of semi-captive cheetahs with an isolate similar to a Californian bobcat isolate. MLVA also confirmed the unique profile of a free-ranging cheetah isolate from Namibia. Specific profiles were observed making MVLA a useful identification/classification tool of these wild felid isolates and suggesting that they are highly adapted to a specific feline reservoir. Finally, circulation of B. henselae isolates between domestic cats, wild felids and humans is likely occurring, based on the close allelic profiles of some isolates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetmic.2020.108788DOI Listing
August 2020

The obesity paradox in critically ill patients: a causal learning approach to a casual finding.

Crit Care 2020 08 5;24(1):485. Epub 2020 Aug 5.

Department of Applied Mathematics, Computer Science and Statistics, Ghent University, Ghent, Belgium.

Background: While obesity confers an increased risk of death in the general population, numerous studies have reported an association between obesity and improved survival among critically ill patients. This contrary finding has been referred to as the obesity paradox. In this retrospective study, two causal inference approaches were used to address whether the survival of non-obese critically ill patients would have been improved if they had been obese.

Methods: The study cohort comprised 6557 adult critically ill patients hospitalized at the Intensive Care Unit of the Ghent University Hospital between 2015 and 2017. Obesity was defined as a body mass index of ≥ 30 kg/m. Two causal inference approaches were used to estimate the average effect of obesity in the non-obese (AON): a traditional approach that used regression adjustment for confounding and that assumed missingness completely at random and a robust approach that used machine learning within the targeted maximum likelihood estimation framework along with multiple imputation of missing values under the assumption of missingness at random. 1754 (26.8%) patients were discarded in the traditional approach because of at least one missing value for obesity status or confounders.

Results: Obesity was present in 18.9% of patients. The in-hospital mortality was 14.6% in non-obese patients and 13.5% in obese patients. The raw marginal risk difference for in-hospital mortality between obese and non-obese patients was - 1.06% (95% confidence interval (CI) - 3.23 to 1.11%, P = 0.337). The traditional approach resulted in an AON of - 2.48% (95% CI - 4.80 to - 0.15%, P = 0.037), whereas the robust approach yielded an AON of - 0.59% (95% CI - 2.77 to 1.60%, P = 0.599).

Conclusions: A causal inference approach that is robust to residual confounding bias due to model misspecification and selection bias due to missing (at random) data mitigates the obesity paradox observed in critically ill patients, whereas a traditional approach results in even more paradoxical findings. The robust approach does not provide evidence that the survival of non-obese critically ill patients would have been improved if they had been obese.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13054-020-03199-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405433PMC
August 2020

Oxygenation Strategy During Acute Respiratory Failure in Critically-Ill Immunocompromised Patients.

Crit Care Med 2020 Sep;48(9):e768-e775

ICU, Saint Louis Teaching Hospital, Paris, France.

Objectives: To assess the response to initial oxygenation strategy according to clinical variables available at admission.

Design: Multicenter cohort study.

Setting: Thirty French and Belgium medical ICU.

Subjects: Immunocompromised patients with hypoxemic acute respiratory failure.

Interventions: None.

Measurements And Main Results: Data were extracted from the Groupe de Recherche en Reanimation Respiratoire du patient d'Onco-Hématologie database. Need for invasive mechanical ventilation was the primary endpoint. Secondary endpoint was day-28 mortality. Six-hundred forty-nine patients were included. First oxygenation strategies included standard oxygen (n = 245, 38%), noninvasive ventilation (n = 285; 44%), high-flow nasal cannula oxygen (n = 55; 8%), and noninvasive ventilation + high-flow nasal cannula oxygen (n = 64; 10%). Bilateral alveolar pattern (odds ratio = 1.67 [1.03-2.69]; p = 0.04), bacterial (odds ratio = 1.98 [1.07-3.65]; p = 0.03) or opportunistic infection (odds ratio = 4.75 [2.23-10.1]; p < 0.001), noninvasive ventilation use (odds ratio = 2.85 [1.73-4.70]; p < 0.001), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.96 [1.27-3.02]; p = 0.0002) were independently associated with intubation rate. Day-28 mortality was independently associated with bacterial (odds ratio = 2.34 [1.10-4.97]; p = 0.03) or opportunistic infection (odds ratio = 4.96 [2.11-11.6]; p < 0.001), noninvasive ventilation use (odds ratio = 2.35 [1.35-4.09]; p = 0.003), Sequential Organ Failure Assessment score (odds ratio = 1.19 [1.10-1.28]; p < 0.001), and ratio of PaO2 and FIO2 less than 100 at ICU admission (odds ratio = 1.97 [1.26-3.09]; p = 0.003). High-flow nasal cannula oxygen use was neither associated with intubation nor mortality rates.

Conclusions: Some clinical characteristics at ICU admission including etiology and severity of acute respiratory failure enable to identify patients at high risk for intubation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004456DOI Listing
September 2020

Antiphospholipid antibodies in patients with COVID-19: A relevant observation?

J Thromb Haemost 2020 09 23;18(9):2191-2201. Epub 2020 Jul 23.

Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium.

Background: High incidence of thrombosis in COVID-19 patients indicates a hypercoagulable state. Hence, exploring the involvement of antiphospholipid antibodies (aPL) in these patients is of interest.

Objectives: To illustrate the incidence of criteria (lupus anticoagulant [LAC], anticardiolipin [aCL] immunoglobulin G [IgG]/IgM, antibeta2-glycoprotein I antibodies [aβ2GPI] IgG/IgM) and noncriteria (anti-phosphatidyl serine/prothrombin [aPS/PT], aCL, and aβ2GPI IgA) aPL in a consecutive cohort of critically ill SARS-CoV-2 patients, their association with thrombosis, antibody profile and titers of aPL.

Patients/methods: Thirty-one consecutive confirmed COVID-19 patients admitted to the intensive care unit were included. aPL were measured at one time point, with part of the aPL-positive patients retested after 1 month.

Results: Sixteen patients were single LAC-positive, two triple-positive, one double-positive, one single aCL, and three aCL IgG and LAC positive. Seven of nine thrombotic patients had at least one aPL. Sixteen of 22 patients without thrombosis were aPL positive, amongst them two triple positives. Nine of 10 retested LAC-positive patients were negative on a second occasion, as well as the double-positive patient. Seven patients were aPS/PT-positive associated to LAC. Three patients were aCL and aβ2GPI IgA-positive.

Conclusion: Our observations support the frequent single LAC positivity during (acute phase) observed in COVID-19 infection; however, not clearly related to thrombotic complications. Triple aPL positivity and high aCL/aβ2GPI titers are rare. Repeat testing suggests aPL to be mostly transient. Further studies and international registration of aPL should improve understanding the role of aPL in thrombotic COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.14994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361253PMC
September 2020

Electrostatic Interactions Enable Nanoparticle Delivery of the Flavonoid Myricetin.

ACS Omega 2020 Jun 28;5(22):12649-12659. Epub 2020 May 28.

Department of Biomedical Engineering, University of Rochester, Rochester, New York 14642, United States.

Flavonoids are natural polyphenolic compounds with myriad biological activities and potential as prophylactic and therapeutic agents. However, poor aqueous solubility and low bioavailability have limited the clinical utility of flavonoids, suggesting that drug delivery systems (DDSs) may improve their clinical relevance. Therefore, loading of a representative flavonoid (i.e., myricetin) into a diblock, polymeric nanoparticle carrier (NPC) DDS with a cationic corona and hydrophobic core was investigated. Absorbance and fluorescence spectroscopy results revealed association constants and standard Gibbs free energy values that align with previously reported values ( = ∼1-3 × 10 M; Δ° = -5.4 to -6.0 kcal mol), suggesting that NPCs load myricetin via electrostatic interactions. The zeta potential and gel electrophoresis analysis confirmed this loading mechanism and indicated that NPCs improve myricetin solubility >25-fold compared to myricetin alone. Finally, the dual-drug loading of NPCs was tested using a combination of myricetin and a hydrophobic drug (i.e., farnesol). Electrostatic loading of NPCs with myricetin at concentrations ≤1.2 mM did not affect NPC core loading and release of farnesol, thus demonstrating a novel formulation strategy for the dual-drug-loaded NPC. These findings offer key insights into the NPC DDS design that may enhance the clinical relevance of flavonoid-based therapeutic approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b04101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288370PMC
June 2020

Delivery of RNAi-Based Therapeutics for Bone Regeneration.

Curr Osteoporos Rep 2020 06;18(3):312-324

Department of Biomedical Engineering, University of Rochester, 308 Robert B. Goergen Hall, Rochester, NY, 14627, USA.

Purpose Of Review: The clinical significance, target pathways, recent successes, and challenges that preclude translation of RNAi bone regenerative approaches are overviewed.

Recent Findings: RNA interference (RNAi) is a promising new therapeutic approach for bone regeneration by stimulating or inhibiting critical signaling pathways. However, RNAi suffers from significant delivery challenges. These challenges include avoiding nuclease degradation, achieving bone tissue targeting, and reaching the cytoplasm for mRNA inhibition. Many drug delivery systems have overcome stability and intracellular localization challenges but suffer from protein adsorption that results in clearance of up to 99% of injected dosages, thus severely limiting drug delivery efficacy. While RNAi has myriad promising attributes for use in bone regenerative applications, delivery challenges continue to plague translation. Thus, a focus on drug delivery system development is critical to provide greater delivery efficiency and bone targeting to reap the promise of RNAi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11914-020-00587-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322619PMC
June 2020

The first microsolvation step for furans: New experiments and benchmarking strategies.

J Chem Phys 2020 Apr;152(16):164303

Deutsches Elektronen-Synchrotron, Notkestr. 85, 22607 Hamburg, Germany.

The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0004465DOI Listing
April 2020

Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study.

Crit Care Med 2020 Jun;48(6):822-829

Medical ICU, Saint-Louis Teaching Hospital, Paris, France.

Objectives: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades.

Data Source: Seven European ICUs.

Study Selection: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality.

Data Extraction: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994-2015).

Data Synthesis: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48-67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93-0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52-4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10-1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not.

Conclusions: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000004322DOI Listing
June 2020