bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrathecal Morphine for Analgesia in Minimally Invasive Cardiac Surgery: A Randomized, Placebo-controlled, Double-blinded Clinical Trial
Authors: Dhawan Richa , Daubenspeck Danisa , Wroblewski Kristen E. , Harrison John-Henry , McCrorey Mackenzie , Balkhy Husam H. , Chaney Mark A.
Published: September 2021

Background

Intrathecal morphine decreases postoperative pain in standard cardiac surgery. Its safety and effectiveness have not been adequately evaluated in minimally invasive cardiac surgery. The authors hypothesized that intrathecal morphine would decrease postoperative morphine consumption after minimally invasive cardiac surgery.

Methods

In this randomized, placebo-controlled, double-blinded clinical trial, patients undergoing robotic totally endoscopic coronary artery bypass received either intrathecal morphine (5 mcg/kg) or intrathecal saline before surgery. The primary outcome was postoperative morphine equivalent consumption in the first 24 h after surgery; secondary outcomes included pain scores, side effects, and patient satisfaction. Pain was assessed via visual analog scale at 1, 2, 6, 12, 24, and 48 h after intensive care unit arrival. Opioid-related side effects (nausea/vomiting, pruritus, urinary retention, respiratory depression) were assessed daily. Patient satisfaction was evaluated with the Revised American Pain Society Outcome Questionnaire.

Results

Seventy-nine patients were randomized to receive intrathecal morphine (n = 37) or intrathecal placebo (n = 42), with 70 analyzed (morphine 33, placebo 37). Intrathecal morphine patients required significantly less median (25th to 75th percentile) morphine equivalents compared to placebo during first postoperative 24 h (28 [16 to 46] mg vs. 59 [41 to 79] mg; difference, –28 [95% CI, –40 to –18]; P < 0.001) and second postoperative 24 h (0 [0 to 2] mg vs. 5 [0 to 6] mg; difference, –3.3 [95% CI, –5 to 0]; P < 0.001), exhibited significantly lower visual analog scale pain scores at rest and cough at all postoperative timepoints (overall treatment effect, –4.1 [95% CI, –4.9 to –3.3] and –4.7 [95% CI, –5.5 to –3.9], respectively; P < 0.001), and percent time in severe pain (10 [0 to 40] vs. 40 [20 to 70]; P = 0.003) during the postoperative period. Mild nausea was more common in the intrathecal morphine group (36% vs. 8%; P = 0.004).

Conclusions

When given before induction of anesthesia for totally endoscopic coronary artery bypass, intrathecal morphine decreases use of postoperative opioids and produces significant postoperative analgesia for 48 h.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Tobacco use is associated with increased postoperative pain and opioid use after reverse total shoulder arthroplasty: a retrospective cohort study
Authors: Hartline Jacob T. , Nelson Clay G. , Eads Ryan B. , Smith Richard A. , Azar Frederick M. , Brolin Tyler J. , Throckmorton Thomas W.
Published: September 2021

Background:

Tobacco use has been associated with negative outcomes in various orthopaedic procedures. To determine its effect on reverse total shoulder arthroplasty (rTSA), this study evaluated postoperative pain, opioid use, length of stay, complications, reoperations, and readmissions in the global 90-day episode of care after primary rTSA.

Methods:

A retrospective database search identified 279 patients with primary rTSA for multiple diagnoses. Patients were divided into current tobacco users (23), nonusers (150), and former users (106). All surgeries were performed with the same technique, implants, and primary surgeon. Gender, body mass index, preoperative diagnosis, laterality, and multiple comorbidities were analyzed as potential confounders.

Results:

Tobacco users reported significantly more pain at the preoperative (P=0.013) and 12-week postoperative (P=0.0068) visits; there were no differences in improvement of pain scores from preoperative to postoperative visits between groups (P=0.58). Tobacco users also showed increased postoperative opioid use (2643 mg oral morphine equivalents) compared to nonusers (2121 mg) and former users (2015 mg; P=0.04). There were no significant differences in length of stay, complications, reoperations, or readmissions between groups (P>0.05).

Conclusions:

Although no significant differences were noted in complications, reoperations, or readmissions, tobacco users reported higher levels of pain and required more opioid pain medication in the 90 days after rTSA compared with both nonusers and former users. Tobacco users experienced similar improvements in pain from the procedure as the other groups. Former users had similar postoperative outcomes as nonusers, suggesting that tobacco cessation can improve a patient’s postoperative episode of care.

Level of Evidence:

Level III.
Assess, Prevent, and Manage Pain; Both Spontaneous Awakening and Breathing Trials; Choice of Analgesia/Sedation; Delirium: Assess, Prevent, and Manage; Early Mobility; Family Engagement and Empowerment Bundle Implementation: Quantifying the Association of Access to Bundle-Enhancing Supplies and Equipment
Authors: Jeffery Alvin D. , Werthman Jennifer A. , Danesh Valerie , Dietrich Mary S. , Mion Lorraine C. , Boehm Leanne M.
Published: September 2021

OBJECTIVES:

Describe the physical environment factors (i.e., availability, accessibility) of bundle-enhancing items and the association of physical environment with bundle adherence.

DESIGN:

This multicenter, exploratory, cross-sectional study used data from two ICU-based randomized controlled trials that measured daily bundle adherence. Unit- and patient-level data collection occurred between 2011 and 2016. We developed hierarchical logistic regression models using Frequentist and Bayesian frameworks.

SETTING:

The study included 10 medical and surgical ICUs in six academic medical centers in the United States.

PATIENTS:

Adults with qualifying respiratory failure and/or septic shock (e.g., mechanical ventilation, vasopressor use) were included in the randomized controlled trials.

INTERVENTIONS:

The Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility bundle was recommended standard of care for randomized controlled trial patients and adherence tracked daily.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was adherence to the full bundle and the early mobility bundle component as identified from daily adherence documentation (n = 751 patient observations). Models included unit-level measures such as minimum and maximum distances to bundle-enhancing items and patient-level age, body mass index, and daily mechanical ventilation status. Some models suggested the following variables were influential: unit size (larger associated with decreased adherence), a standard walker (presence associated with increased adherence), and age (older associated with decreased adherence). In all cases, mechanical ventilation was associated with decreased bundle adherence.

CONCLUSIONS:

Both unit- and patient-level factors were associated with full bundle and early mobility adherence. There is potential benefit of physical proximity to essential items for Awakening and Breathing trial Coordination, Delirium assessment/management, Early mobility bundle and early mobility adherence. Future studies with larger sample sizes should explore how equipment location and availability influence practice.
Clusters Across Multiple Domains of Health-Related Quality of Life Reveal Complex Patient Outcomes After Subarachnoid Hemorrhage
Authors: Murphy Julianne , Shin Hye Jung , Wang Hanyin , Luo Yuan , Jahromi Babak , Bleck Thomas P. , Cella David , Naidech Andrew M.
Published: September 2021

OBJECTIVES:

Patients with aneurysmal subarachnoid hemorrhage (ruptured brain aneurysm) often have reduced health-related quality of life at follow-up in multiple domains (e.g., cognitive function and social function). We tested the hypothesis that there are distinct patterns of patient outcomes across domains of health-related quality of life, “complex patient outcomes,” in survivors of subarachnoid hemorrhage.

DESIGN:

Patients with subarachnoid hemorrhage were prospectively identified. Clinical data were prospectively recorded. Health-related quality of life was prospectively assessed at 3-month follow-up using the National Institutes of Health Patient Reported Outcomes Measurement Information System and neuro-quality of life in the domains of mobility, cognitive function, satisfaction with social roles, and depression. We used k-means clustering to analyze prospectively recorded health-related quality of life data, identifying clusters of complex patient outcomes. Decision tree analysis identified index hospital stay factors predictive of a patient having a particular complex patient outcome at follow-up.

SETTING:

Academic medical center.

PATIENTS:

One hundred three survivors of subarachnoid hemorrhage.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

We analyzed 103 patients, of whom 75 (72.8%) were female, and mean age was 53.6 ± 13.4 years. There were three complex patient outcomes: health-related quality of life greater than 1 sd better than the U.S. mean across all domains (n = 23, 22.3%), health-related quality of life greater than 1 sd worse than U.S. mean across all domains (n = 26, 25.2%), and satisfaction with social roles greater than 0.5 sd worse than U.S. mean with cognitive function, depression, and mobility scores near the U.S. mean (n = 54, 52.4%). In decision tree analysis, hospital disposition and Hunt and Hess Grade were associated with complex patient outcome.

CONCLUSIONS:

Complex patient outcomes across multiple domains of health-related quality of life at follow-up after subarachnoid hemorrhage are distinct and may be predictable.
Virtual Reality to Improve Sequelae of the Postintensive Care Syndrome: A Multicenter, Randomized Controlled Feasibility Study
Authors: Vlake Johan H. , Van Bommel Jasper , Wils Evert-Jan , Korevaar Tim I. M. , Bienvenu O. Joseph , Klijn Eva , Gommers Diederik , van Genderen Michel E.
Published: September 2021

OBJECTIVES:

Psychologic sequelae after critical illness, part of the postintensive care syndrome, significantly decrease quality of life. A robustly effective treatment intervention is currently lacking. Virtual reality has beneficial effects on several non-ICU–related psychologic disorders. The aim of this study was to explore patient-related determinants of ICU-specific virtual reality, such as the timing of patients’ self-reported readiness to initiate virtual reality and the number of desired sessions and safety, and to explore the effects of ICU-specific virtual reality on mental health.

DESIGN:

A multicenter, randomized controlled feasibility study.

SETTING:

ICU at a university teaching hospital and a secondary care hospital in Rotterdam, The Netherlands.

PATIENTS:

Consecutive mechanically ventilated patients with sepsis or septic shock.

INTERVENTIONS:

Patients were randomly assigned (1:1) to receive ICU-specific virtual reality (ICU-specific virtual reality group) or exposure to a nature virtual reality environment (control virtual reality group).

MEASUREMENT AND MAIN RESULTS:

Explorative outcomes were feasibility, in terms of patient-related determinants, and safety. The effects of ICU-specific virtual reality on the psychologic components of postintensive care syndrome and quality of life were additionally studied. Fifty patients (median age: 61 yr; 21 [42%] female) were included. Patients in the ICU-specific virtual reality group felt ready to initiate the virtual reality intervention 10 days (median, 95% range, 5–21 d) after ICU discharge, and one session (median, 95% range, 1–6) was desired. ICU-specific virtual reality patients experienced higher immersion, cybersickness scores were low, and no changes in vital signs were observed. They also reported reduced posttraumatic stress disorder and depression scores and better mental health from 2 days until 1 month after initial exposure (Short Form-12 Mental Component Scale: ICU-specific virtual reality, 57 [36–67] vs control virtual reality, 47 [26–63]; p < 0.01). Six months after exposure, this effect was still present for posttraumatic stress disorder and depression, but not for mental quality of life.

CONCLUSIONS:

ICU-specific virtual reality is a feasible and acceptable novel intervention that could be used during recovery from an episode of critical illness in the ICU. A future, adequately powered study should confirm whether virtual reality is able to improve mental health and quality of life.
Sleep-disordered breathing and risk of lung cancer: a meta-analysis longitudinal follow-up studies
Authors: Ma Hongfu , Zhang Xuefeng , Han Jin , Li Fenghuan
Published: September 2021

Consensus remains lack regarding whether sleep-disordered breathing (SDB) is an independent risk factor for lung cancer. We therefore conducted a meta-analysis to clarify the relationship of SDB and lung cancer. Longitudinal follow-up studies investigating the association between SDB and incidence of lung cancer were included by search of electronic databases including PubMed, Embase, and Cochrane’s Library. A random-effects model was adopted to combine the results. Seven studies were included. Pooled results showed that presence of SDB was independently associated with higher incidence of lung cancer [adjusted risk ratio (RR): 1.28; 95% confidence interval (CI), 1.11–1.47; P < 0.001; I
2 = 37%]. Sensitivity analysis limited to studies with adjustment of smoking showed consistent results (three studies, RR: 1.34; 95% CI, 1.22–1.48; P < 0.001; I
2 = 8%). Subgroup analysis suggested that the association between SDB and higher risk of lung cancer was not significantly affected by study characteristics such as study design, source of population, sample size, evaluation methods for SDB, follow-up duration, methods for validation of lung cancer, or score of study quality (P values for subgroup difference all >0.05). No significant publication bias was observed (P for Egger’s regression test = 0.258). These results suggested that SDB may be an independent risk factor of lung cancer in adult population. Intensive screening and prevention of lung cancer in subjects with SDB should be considered.
Estrogens influence differentially on the pelvic floor muscles activation at somatovisceral reflexes involved in micturition of rabbits
Authors: Sánchez-García Octavio , López-Juárez Rhode , Corona-Quintanilla Dora Luz , Ruiz Ángeles Carrasco , Martínez-Gómez Margarita , Cuevas-Romero Estela , Castelán Francisco
Published: September 2021

Objective:

To determine the estrogen-dependency of the bladder and urethral function and the coordinated activation of pelvic floor muscles (PFM) during micturition.

Methods:

We allocated age-matched female rabbits to control, 1-month ovariectomized (OVX), and OVX plus 2-week estradiol benzoate (EB) groups to record cystometry, urethral pressure, and electromyograms of bulbospongiosus (Bsm), and pubococcygeus muscles (Pcm) simultaneously. We also measured serum estradiol levels and myofiber cross-sectional area. We assessed urodynamic and urethral variables, categorized the Bsm-Pcm activation patterns at storage and voiding phases, and obtained the power spectrum density of muscle activation around the voiding phase. We investigated the influence of ovarian hormones, in general, and the contribution of estrogen, particularly on the functions of the bladder, urethra, and PFM. Statistical significance was set at P < 0.05.

Results:

Ovarian hormones influence the bladder, urethral, and PFM functions. The urodynamics analyses indicated estrogens contribute to voiding duration and, to a lesser extent, to the time between bladder contractions. Urethral pressure at closure (maximal pressure-to-maximal urethral pressure ratio) improved partially (8%, P < 0.05) in the OVX plus 2-week estradiol benzoate compared with OVX, but urethral resistance increased (∼1.9-fold, P < 0.05) compared with control rabbits. Our findings support that Pcm activity at voiding is estrogen-sensitive, albeit EB administration reduced it at storage resume, which relates to high urethral resistance.

Conclusions:

Ovariectomy impairs bladder and urethral pressures and Bsm and Pcm activation at micturition in anesthetized rabbits. Estrogen administration partially reverts some of these effects and influences Pcm activation.
Natural menopausal age and cardiovascular disease risk factors in older Chinese women: Guangzhou Biobank Cohort Study
Authors: Su Huimin , Jiang Chaoqiang , Zhang Weisen , Zhu Feng , Jin Yali , Cheng Karkeung , Lam Taihing , Xu Lin
Published: September 2021

Objective:

To examine the associations of natural menopausal age with cardiovascular disease risk factors and whether the associations varied by parity in older Chinese women.

Methods:

Information of demographic characteristics, lifestyles, and reproductive factors was collected by face-to-face interview. Framingham Risk Score was used as an indicator of cardiovascular disease risk, with a score ≥ 10% considered as high cardiovascular disease risk (vs low, dichotomous). Multivariable logistic and linear regressions were used to examine the associations of menopausal age with cardiovascular disease risk factors.

Results:

Of 18,339 women aged 50+ years, the average (standard deviation) age was 61.8 (6.9) years. Compared with women with menopausal age of 45 to 54 years, after adjustment for multiple potential confounders, women with menopausal age <45 years or ≥55 years had higher Framingham Risk Score (0.93%, 95% confidence interval: 0.40-1.46, and 0.69%, 95% confidence interval: 0.18-1.20, respectively). Women with menopausal age <45 or ≥55 years had higher odds of high cardiovascular disease risk (vs low) (odds ratio [95% confidence interval]:1.26 (1.10-1.44) and 1.17 (1.02-1.33), respectively). The associations of menopausal age with the Framingham Risk Score varied by parity (P for interaction ≤0.001). The Framingham Risk Score was higher in those with one to three parity (<45 y: 1.01 [0.43-1.59]; ≥55 y: 1.14 [0.60-1.68]) and lower for parity ≥4 (<45 y: −0.33 [−1.84 to 1.18]; ≥55 y: −2.02 [−3.82 to −0.22]). In nulliparous women, the Framingham Risk Score was highest in menopausal age <45 years (3.97 [1.67-6.26]), but the differences were nonsignificant in menopausal age ≥55 years (0.66 [−1.38 to 2.71]).

Conclusions:

Both early and late natural menopausal ages were associated with a higher cardiovascular disease risk, and the associations were stronger in those with lower parity.

Video Summary:

http://links.lww.com/MENO/A813.
The impact of the COVID-19 pandemic on infant and toddler development
Authors: Imboden Annie , Sobczak Bernadette K. , Griffin Valerie
Published: September 2021

Background:

The COVID-19 pandemic has created new cultural norms with pervasive societal implications. Families have experienced a heightened amount of physical, psychological, emotional, and financial stress. Infants and children living with stress have the potential for delayed developmental milestones, difficulty with emotional regulation, and social or behavioral issues.

Purpose:

This study aims to determine if the pandemic has affected developmental outcomes in infants and toddlers.

Methodology:

Prepandemic and postpandemic developmental (ASQ-3) scores were obtained from charts of 1,024 patients (6, 12, 18, 24, and 36 months) from two pediatric practices.

Results:

There were no significant differences in prepandemic and postpandemic ASQ-3 scores for the overall sample. Age-group analysis showed statistically significant differences in domain scores. Postpandemic problem-solving scores decreased among 6-month-olds while increasing among 24-month-olds. Categorization by score interpretation categories showed a slight decrease in postpandemic scores in the communication domain among 6- and 12-month-olds.

Conclusions:

The pandemic has the potential to affect childhood development. However, the results of this study are reassuring, showing only slight differences in developmental scores prepandemic versus postpandemic. More studies are needed to establish causation and possible trends in future developmental trajectories.

Implications:

An increased focus on communication screening and promotion of language and communication skills in young children postpandemic is needed. Education about the importance of parent–child engagement, nurturing relationships, opportunities for free-play and exploration, and caregiver support and stress reduction will continue to be of paramount importance.
Alcohol-Based Hand Rub Consumption and World Health Organization Hand Hygiene Self-Assessment Framework: A Comparison Between the 2 Surveillances in a 4-Year Region-Wide Experience
Authors: Garlasco Jacopo , Vicentini Costanza , Emelurumonye Ifeoma Nneka , D’Alessandro Giulia , Quattrocolo Francesca , Zotti Carla Maria
Published: September 2021

Objectives

Hand hygiene is essential for infection prevention. In Piedmont (Northwest Italy), hand hygiene is routinely monitored through 2 surveillance systems, the World Health Organization Hand Hygiene Self-Assessment Framework (HHSAF) and alcohol-based hand rub (ABHR) consumption. This study was aimed at (1) comparing the results of these surveillances, investigating the consistence of the 2 systems and (2) inquiring whether organizational differences among healthcare facilities significantly affected hand hygiene performances.

Methods

A retrospective analysis was performed on data collected annually from 2015 to 2018 for both surveillances from 40 hospitals of the region: HHSAF score (500 points maximum) and ABHR consumption in milliliters per patient-day (mL/PD) were considered. Logistic regression models were built to evaluate possible correlations between these variables, and observations were clustered considering both variables to identify whether groups with significant differences could be discerned. A tree-structured partitioning model was used to confirm the obtained results.

Results

A positive correlation was observed between HHSAF score and odds of belonging to the high ABHR consumption group, particularly for cutoffs set to 19 to 23 mL/PD (P = 0.033 for 23 mL/PD). Two ABHR consumption peaks were identified at approximately 10 and 22 mL/PD, corresponding to median HHSAF scores of 353.75 and 375 points, respectively. The group with better performances was mainly composed of hub hospitals (with single-hospital management).

Conclusions

The 2 surveillance systems are consistent, and the HHSAF score could work as a reasonable predictor of hand hygiene compliance in healthcare settings. Different management characteristics are crucial in creating a more/less favorable environment for hand hygiene compliance and infection prevention.
COVID-19 Vaccine Hesitancy Among PLWH in South India: Implications for Vaccination Campaigns
Authors: Ekstrand Maria L. , Heylen Elsa , Gandhi Monica , Steward Wayne T. , Pereira Matilda , Srinivasan Krishnamachari
Published: September 2021

Background:

The global effort to end the Severe Acute Respiratory Syndrome - Coronavirus 2 pandemic will depend on our ability to achieve a high uptake of the highly efficacious vaccines in all countries. India recently experienced an unprecedented transmission surge, likely fueled by a premature reopening, the highly transmissible delta variant, and low vaccination rates. Indian media have reported high degrees of vaccine hesitancy, which could interfere with efforts to prevent future surges, making it crucial to better understand the reasons for such reluctance in vulnerable populations, such as people living with HIV.

Methods:

We conducted telephone interviews with 438 people living with HIV who were participants in a longitudinal cohort, designed to examine and validate novel antiretroviral therapy ART adherence measures. Interviews were conducted in January and February 2021 and covered COVID-19–related questions on confidence in vaccine safety and efficacy, worries of vaccine side effects, trust in COVID-19 information from specific sources, and intent to get vaccinated.

Results:

Over one-third of participants (38.4%, n = 168) met our definition of “vaccine hesitant” by reporting being either unlikely to get vaccinated at all or wanting to wait. Vaccine hesitancy was associated with lack of confidence in vaccine safety, concerns about side effects and efficacy, and distrust in common sources of vaccine-related information.

Discussion:

These results highlight several challenges for vaccination efforts. Campaigns may benefit from using trusted sources, including antiretroviral therapy center staff, providing clear information about safety and efficacy and emphasizing the role of vaccines in preventing severe disease, hospitalizations and death, and the reduction of forward transmission to unvaccinated household members.
High-Density Fat Grafting Assisted Stromal Vascular Fraction Gel in Facial Deformities
Authors: Cao Zhe , Li Hui , Wang Zhen Hua , Liang Xiao-Qin
Published: September 2021

Autologous fat grafting is commonly used for soft tissue augmentation and reconstruction, this technique is limited by a high rate of graft absorption. The stromal vascular fraction gel (SVF-gel) grafting for facial volume augmentation can exert a positive effect on skin rejuvenation, but its major limitation is the low rate of conversion of Coleman fat. The purpose of our study was to investigate a novel surgery using performing high-density fat in combination with SVF-gel in the treatment of hemifacial atrophy, or Romberg diseases. From October 2017 to October 2019, 13 patients with hemifacial atrophy underwent high-density fat transfer with SVF-gel injection. The outcome was determined by the difference in presurgery and postsurgery FACE-Q modules (FACE-Q conceptual framework: 1, Satisfaction with Facial Appearance; 2, Health-Related Quality of Life; 3, Negative Sequelae; 4, Satisfaction with Process of Care), which were designed as patient-reported outcome instrument to evaluate the unique outcomes of patients undergoing facial cosmetic procedures.

The excellent cosmetic results were observed during follow-up periods, with no adverse events was seen in the treatment group. All patients showed improvements in facial augmentation and contour. In patients with facial volume loss, high-density fat transfer with SVF-gel facial injection resulted in significantly higher improvement scores and better patient satisfaction. The patient-reported FACE-Q modules presurgery and postsurgery results showed statistically significant improvement (P < 0.05). This high-density fat in combination with SVF-gel is an effective method of correcting the facial volume loss that leave no complications during follow-up, having a satisfactory volumization effect. This could largely facilitate the clinical utilization of fat.
Muscle Flap Reconstruction Based on Muscle Tension Line Groups to Repair the Philtrum of Patients With Microform Cleft Lip or Secondary Cleft Lip
Authors: Jiang Chanyuan , Zheng Yilue , Ma Hengyuan , Yin Ningbei
Published: September 2021

The muscle flap reconstruction technique was developed based on the concept of muscle tension line groups, which elucidates how nasolabial muscle tension helps maintain the shape of the philtrum. To investigate the operative effect, we reviewed 43 patients with microform cleft lip and 102 patients with secondary cleft lip treated with muscle flap reconstruction between January 2018 and June 2020. The patients were scanned using the digital three-dimensional stereophotogrammetry face system pre- and post-operatively, and comparative analysis of three-dimensional (3D) images was used to highlight variations of the philtrum. Visual analog scales were used to assess surgical outcomes. More than 6 months after the surgery, comparative 3D images of 37 patients (86.04%) with microform cleft lip and 86 patients (84.31%) with secondary cleft lip showed visible improvement in the prominence of the affected column. In addition, visual analog scale scores showed that 38 microform cleft lip patients (88.37%) and 89 secondary cleft lip patients (87.25%) had a good appearance. The postoperative prominence of the philtral column in both groups improved significantly compared to before surgery (P < 0.001 and P < 0.001, respectively). There was no significant difference in scores for philtrum prominence pre- and post-operatively between the 2 groups (P > 0.05). Muscle flap reconstruction is an effective means to create the 3D configuration of the philtrum. The biomechanical properties of muscles play a vital role in the morphological maintenance of the philtrum.
Standard Setting in Simulation-based Training of Surgical Procedures
Authors: Pietersen Pia Iben , Bjerrum Flemming , Tolsgaard Martin Grønnebæk , Konge Lars , Andersen Steven Arild Wuyts
Published: September 2021

Objective:

This systematic review aims to examine the use of standard-setting methods in the context of simulation-based training of surgical procedures.

Summary of background:

Simulation-based training is increasingly used in surgical education. However, it is important to determine which level of competency trainees must reach during simulation-based training before operating on patients. Therefore, pass/fail standards must be established using systematic, transparent, and valid methods.

Methods:

Systematic literature search was done in 4 databases (Ovid MEDLINE, Embase, Web of Science, and Cochrane Library). Original studies investigating simulation-based assessment of surgical procedures with the application of a standard setting were included. Quality of evidence was appraised using GRADE.

Results:

Of 24,299 studies identified by searches, 232 studies met the inclusion criteria. Publications using already established standard settings were excluded (N = 70), resulting in 162 original studies included in the final analyses. Most studies described how the standard setting was determined (N = 147, 91%) and most used the mean or median performance score of experienced surgeons (n = 65, 40%) for standard setting. We found considerable differences across most of the studies regarding study design, setup, and expert level classification. The studies were appraised as having low and moderate evidence.

Conclusion:

Surgical education is shifting toward competency-based education, and simulation-based training is increasingly used for acquiring skills and assessment. Most studies consider and describe how standard settings are established using more or less structured methods but for current and future educational programs, a critical approach is needed so that the learners receive a fair, valid, and reliable assessment.
Back to the basics? Transcriptomics offers integrative insights into the role of space, time and the environment for gene expression and behaviour
Authors: Fischer Eva K. , Hauber Mark E. , Bell Alison M.
Published: September 2021

Fuelled by the ongoing genomic revolution, broadscale RNA expression surveys are fast replacing studies targeting one or a few genes to understand the molecular basis of behaviour. Yet, the timescale of RNA-sequencing experiments and the dynamics of neural gene activation are insufficient to drive real-time switches between behavioural states. Moreover, the spatial, functional and transcriptional complexity of the brain (the most commonly targeted tissue in studies of behaviour) further complicates inference. We argue that a Central Dogma-like ‘back-to-basics’ assumption that gene expression changes cause behaviour leaves some of the most important aspects of gene–behaviour relationships unexplored, including the roles of environmental influences, timing and feedback from behaviour—and the environmental shifts it causes—to neural gene expression. No perfect experimental solutions exist but we advocate that explicit consideration, exploration and discussion of these factors will pave the way toward a richer understanding of the complicated relationships between genes, environments, brain gene expression and behaviour over developmental and evolutionary timescales.
Referential alarm calling elicits future vigilance in a host of an avian brood parasite
Authors: Lawson Shelby L. , Enos Janice K. , Wolf Caroline S. , Stenstrom Katharine , Winnicki Sarah K. , Benson Thomas J. , Hauber Mark E. , Gill Sharon A.
Published: September 2021

Yellow warblers (
Setophaga petechia
) use referential ‘seet’ calls to warn mates of brood parasitic brown-headed cowbirds (
Molothrus ater
). In response to seet calls during the day, female warblers swiftly move to sit tightly on their nests, which may prevent parasitism by physically blocking female cowbirds from inspecting and laying in the nest. However, cowbirds lay their eggs just prior to sunrise, not during daytime. We experimentally tested whether female warblers, warned by seet calls on one day, extend their anti-parasitic responses into the future by engaging in vigilance at sunrise on the next day, when parasitism may occur. As predicted, daytime seet call playbacks caused female warblers to leave their nests less often on the following morning, relative to playbacks of both their generic anti-predator calls and silent controls. Thus, referential calls do not only convey the identity or the type of threat at present but also elicit vigilance in the future to provide protection from threats during periods of heightened vulnerability.
Hyperendemicity associated with increased dengue burden
Authors: Lim Jue Tao , Dickens Borame Sue , Tan Ken Wei , Koo Joel Ruihan , Seah Annabel , Ho Soon Hoe , Ong Janet , Rajarethinam Jayanthi , Soh Stacy , Cook Alex R. , Ng Lee Ching
Published: September 2021

Over 105 million dengue infections are estimated to occur annually. Understanding the disease dynamics of dengue is often difficult due to multiple strains circulating within a population. Interactions between dengue serotype dynamics may result in complex cross-immunity dynamics at the population level and create difficulties in terms of formulating intervention strategies for the disease. In this study, a nationally representative 16-year time series with over 43 000 serotyped dengue infections was used to infer the long-run effects of between and within strain interactions and their impacts on past outbreaks. We used a novel identification strategy incorporating sign-identified Bayesian vector autoregressions, using structural impulse responses, historical decompositions and counterfactual analysis to conduct inference on dengue dynamics post-estimation. We found that on the population level: (i) across-serotype interactions on the population level were highly persistent, with a one time increase in any other serotype associated with long run decreases in the serotype of interest (range: 0.5–2.5 years) and (ii) over 38.7% of dengue cases of any serotype were associated with across-serotype interactions. The findings in this paper will substantially impact public health policy interventions with respect to dengue.
Black box of phage–bacterium interactions: exploring alternative phage infection strategies
Authors: Mäntynen Sari , Laanto Elina , Oksanen Hanna M. , Poranen Minna M. , Díaz-Muñoz Samuel L.
Published: September 2021

The canonical lytic–lysogenic binary has been challenged in recent years, as more evidence has emerged on alternative bacteriophage infection strategies. These infection modes are little studied, and yet they appear to be more abundant and ubiquitous in nature than previously recognized, and can play a significant role in the ecology and evolution of their bacterial hosts. In this review, we discuss the extent, causes and consequences of alternative phage lifestyles, and clarify conceptual and terminological confusion to facilitate research progress. We propose distinct definitions for the terms ‘pseudolysogeny’ and ‘productive or non-productive chronic infection’, and distinguish them from the carrier state life cycle, which describes a population-level phenomenon. Our review also finds that phages may change their infection modes in response to environmental conditions or the physiological state of the host cell. We outline known molecular mechanisms underlying the alternative phage–host interactions, including specific genetic pathways and their considerable biotechnological potential. Moreover, we discuss potential implications of the alternative phage lifestyles for microbial biology and ecosystem functioning, as well as applied topics such as phage therapy.
Open Biology: overview for special issue on dynamics of protein fatty acylation
Authors: Resh Marilyn D.
Published: September 2021

Fatty acylation is a widespread form of protein modification that occurs on specific intracellular and secreted proteins. Beyond increasing hydrophobicity and the affinity of the modified protein for lipid bilayers, covalent attachment of a fatty acid exerts effects on protein localization, inter- and intramolecular interactions and signal transduction. As such, research into protein fatty acylation has been embraced by an extensive community of biologists. This special issue highlights advances at the forefront of the field, by focusing on two families of enzymes that catalyse post-translational protein fatty acylation, zDHHC palmitoyl acyltransferases and membrane-bound O-acyl transferases, and signalling pathways regulated by their fatty acylated protein substrates. The collected contributions catalogue the tremendous progress that has been made in enzyme and substrate identification. In addition, articles in this special issue provide insights into the pivotal functions of fatty acylated proteins in immune cell, insulin and EGF receptor-mediated signalling pathways. As selective inhibitors of protein fatty acyltransferases are generated, the future holds great promise for therapeutic targeting of fatty acyltransferases that play key roles in human disease.
ADataViewer: Exploring Semantically Harmonized Alzheimer’s Disease Cohort Datasets
Authors: Salimi Yasamin , Domingo-Fernándéz Daniel , Bobis-Álvarez Carlos , Hofmann-Apitius Martin ,   for the Alzheimer’s Disease Neuroimaging Initiative,   the Japanese Alzheimer’s Disease Neuroimaging Initiative,   for the Aging Brain: Vasculature, Ischemia, and Behavior Study,   the Alzheimer’s Disease Repository Without Borders Investigators,   for the European Prevention of Alzheimer’s Disease (EPAD) Consortium, Birkenbihl Colin
Published: September 2021

INTRODUCTION

Currently, AD cohort datasets are difficult to find, lack across-cohort interoperability, and the content of the shared datasets often only becomes clear to third-party researchers once data access has been granted.

METHODS

We accessed and systematically investigated the content of 20 major AD cohort datasets on data-level. A medical professional and a data specialist manually curated and semantically harmonized the acquired datasets. We developed a platform that facilitates data exploration.

RESULTS

We present ADataViewer, an interactive platform that facilitates the exploration of 20 cohort datasets with respect to longitudinal follow-up, demographics, ethnoracial diversity, measured modalities, and statistical properties of individual variables. Additionally, we publish a variable mapping catalog harmonizing 1,196 variables across the 20 cohorts. The platform is available underhttps://adata.scai.fraunhofer.de/.

DISCUSSION

ADataViewer supports robust data-driven research by transparently displaying cohort dataset content and suggesting datasets suited for discovery and validation studies based on selected variables of interest.
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
Authors: Fallerini Chiara , Picchiotti Nicola , Baldassarri Margherita , Zguro Kristina , Daga Sergio , Fava Francesca , Benetti Elisa , Amitrano Sara , Bruttini Mirella , Palmieri Maria , Croci Susanna , Lista Mirjam , Beligni Giada , Valentino Floriana , Meloni Ilaria , Tanfoni Marco , Colombo Francesca , Cabri Enrico , Fratelli Maddalena , Gabbi Chiara , Mantovani Stefania , Frullanti Elisa , Gori Marco , Crawley Francis P. , Butler-Laporte Guillaume , Richards Brent , Zeberg Hugo , Lipcsey Miklos , Hultstrom Michael , Ludwig Kerstin U. , Schulte Eva C. , Pairo-Castineira Erola , Baillie John Kenneth , Schmidt Axel , Frithiof Robert ,   WES/WGS working group within the HGI,   GenOMICC Consortium,   GEN-COVID Multicenter Study, Mari Francesca , Renieri Alessandra , Furini Simone
Published: September 2021

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole exome sequencing data of about 4,000 SARS-CoV-2-positive individuals were used to define an interpretable machine learning model for predicting COVID-19 severity. Firstly, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthly, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management.
Asymptomatic SARS-CoV-2 infection and the demography of COVID-19
Authors: Wang Zengmiao , Wu Peiyi , Wang Jingyuan , Lourenço José , Li Bingying , Rader Benjamin , Laine Marko , Miao Hui , Wang Ligui , Song Hongbin , Bharti Nita , Brownstein John S. , Bjornstad Ottar N. , Dye Christopher , Tian Huaiyu
Published: September 2021

Asymptomatic individuals carrying SARS-CoV-2 can transmit the virus and contribute to outbreaks of COVID-19, but it is not yet clear how the proportion of asymptomatic infections varies by age and geographic location. Here we use detailed surveillance data gathered during COVID-19 resurgences in six cities of China at the beginning of 2021 to investigate this question. Data were collected by multiple rounds of city-wide PCR test with detailed contact tracing, where each patient was monitored for symptoms through the whole course of infection. We find that the proportion of asymptomatic infections declines with age (coefficient =-0.006, P<0.01), falling from 56% in age group 0–9 years to 12% in age group >60 years. Using an age-stratified compartment model, we show that this age-dependent asymptomatic pattern together with the age distribution of overall cases can explain most of the geographic differences in reported asymptomatic proportions. Combined with demography and contact matrices from other countries worldwide, we estimate that a maximum of 22%–55% of SARS-CoV-2 infections would come from asymptomatic cases in an uncontrolled epidemic based on asymptomatic proportions in China. Our analysis suggests that flare-ups of COVID-19 are likely if only adults are vaccinated and that surveillance and possibly control measures among children will be still needed in the future to contain epidemic resurgence.
COVID-19 Bimodal Clinical and Pathological Phenotypes
Authors: Batah Sabrina S , Benatti Maíra N , Siyuan Li , Telini Wagner M , Barbosa Jamile , Menezes Marcelo B , Nadai Tales R , Sá Keyla S G , Vaswani Chirag M. , Gupta Sahil , Zamboni Dario S , Wada Danilo T , Calado Rodrigo T , Oliveira Renê D R , Louzada-Junior Paulo , Auxiliadora-Martins Maria , Veras Flávio P , Cunha Larissa D , Cunha Thiago M , Luppino-Assad Rodrigo , Balancin Marcelo L , Morais Sirlei S , Martins Ronaldo B , Arruda Eurico , Chahud Fernando , Koenigkam-Santos Marcel , Cetlin Andrea A , Cunha Fernando Q , Santos Claudia dos , Capelozzi Vera L , Fukuoka Junya , Duarte-Achcar Rosane , Fabro Alexandre T
Published: September 2021

Background

Patients with coronavirus disease-2019 (COVID-19) present varying clinical complications. Different viral load and host response related to genetic and immune background are probably the reasons for these differences. We aimed to sought clinical and pathological correlation that justifies the different clinical outcomes among COVID-19 autopsies cases.

Methods

Minimally invasive autopsy was performed on forty-seven confirmed COVID-19 patients from May-July, 2020. Electronic medical record of all patients was collected and a comprehensive histopathological evaluation was performed. Immunohistochemistry, immunofluorescence, special stain, western blotting and post-mortem real-time reverse transcriptase polymerase chain reaction on fresh lung tissue were performed.

Results

We show that 5/47 (10,6%) patients present a progressive decline in oxygenation index for acute respiratory distress syndrome (PaO2/FiO2ratio), low compliance levels, interstitial fibrosis, high α-SMA+ cells/protein expression, high collagens I/III deposition and NETs(P<0.05), named as fibrotic phenotype (N=5). Conversely, 10/47 (21,2%) patients demonstrated progressive increase in PaO2/FiO2ratio, high pulmonary compliance levels, preserved elastic framework, increase thrombus formation and high platelets and D-dimer levels at admission (P<0.05), named as thrombotic phenotype. While 32/47 (68,1%) had a mixed phenotypes between both ones.

Conclusions

We believe that categorization of patients based on these two phenotypes can be used to develop prognostic tools and potential therapies since the PaO2/FiO2ratio variation and D-dimer levels correlate with the underlying fibrotic or thrombotic pathologic process, respectively; which may indicate possible clinical outcome of the patient.
Development of a novel startle response task in Duchenne muscular dystrophy
Authors: Maresh Kate E. , Papageorgiou Andriani , Ridout Deborah , Harrison Neil A. , Mandy William , Skuse David , Muntoni Francesco
Published: September 2021

Duchenne muscular dystrophy (DMD), an X-linked childhood-onset muscular dystrophy caused by loss of the protein dystrophin, can be associated with neurodevelopmental, emotional and behavioural problems. A DMD mouse model also displays a neuropsychiatric phenotype, including increased startle responses to threat which normalise when dystrophin is restored in the brain.

We hypothesised that startle responses may also be increased in humans with DMD, which would have potential translational therapeutic implications. To investigate this, we first designed a novel discrimination fear-conditioning task and tested it in six healthy volunteers, followed by male DMD (n=11) and Control (n=9) participants aged 7-12 years. The aims of this methodological task development study were to: i) confirm the task efficacy; ii) optimise data processing procedures; iii) determine the most appropriate outcome measures.

In the task, two neutral visual stimuli were presented: one ‘safe’ cue presented alone; one ‘threat’ cue paired with a threat stimulus (aversive noise) to enable conditioning of physiological startle responses (skin conductance response, SCR, and heart rate). Outcomes were the unconditioned physiological startle responses to the initial threat, and retention of conditioned responses in the absence of the threat stimulus.

We present the protocol development and optimisation of data processing methods based on empirical data. We found that the task was effective in producing significantly higher physiological startle SCR in reinforced ‘threat’ trials compared to ‘safe’ trials (P<.001). Different data extraction methods were compared and optimised, and the optimal sampling window was derived empirically. SCR amplitude was the most effective physiological outcome measure when compared to SCR area and change in heart rate, with the best profile on data processing, the least variance, successful conditioned response retention (P=.01) and reliability assessment in test-retest analysis (rho=.86). The definition of this novel outcome will allow us to study this response in a DMD population.