bluuebunny/crossref_metadata_2025 huggingface dataset:
0974 Family-Based Study Of Sleep In Autism Spectrum Disorder Without Intellectual Disability
Authors: Elkhatib Smidt S D , Ghorai A , Gehringer B , Dow H C , Smernoff Z , Taylor S C , Zhang J , Rader D J , Almasy L , Brodkin E S , Bucan M
Published: May 2020

Introduction

Sleep problems are a common concern in children with autism spectrum disorder (ASD) that can persist into adulthood. This study aims to further explore sleep in ASD without intellectual disability (ASD w/o ID).

Methods

We recruited individuals with ASD w/o ID (probands) and relatives as part of the Autism Spectrum Program of Excellence (ASPE) at the University of Pennsylvania. Actimetry data were collected via a wrist-worn tri-axial accelerometer for 21 days. Data from 212 participants were considered. We analyzed sleep data using the algorithms GGIR, ChronoSapiens, and PennZzz. The sleep traits of proband and sibling pairs were compared using paired t-test or Wilcoxon signed-rank test. We used the Social Responsiveness Scale, Second Edition (SRS-2) to assess social impairment and restricted/repetitive traits. We compared SRS-2 scores to sleep traits using partial Spearman or Pearson correlations adjusting for age (171 participants).

Results

Probands demonstrated later sleep onset (p = 0.03), decreased M10 average (10-hour period of highest activity/day; p = 0.006), decreased relative amplitude (measure of rest-activity rhythm; p<0.001), and decreased total daytime activity (p = 0.005) compared to siblings. Regarding social function and restricted/repetitive traits, adult males showed an inverse correlation between SRS-2 total score and sleep efficiency (r = -0.2, p= 0.04) and a positive correlation between SRS-2 total score and intradaily variability (r = 0.3, p = 0.02). Adult females showed an inverse correlation between SRS-2 total score and M10 average (r = -0.3, p = 0.02) and between SRS-2 total score and relative amplitude (self-report r = -0.4, p = 0.001; informant r = -0.3, p = 0.005).

Conclusion

This study focuses on the analysis of sleep traits in ASD including the relationship between social function and sleep. Thus far, the most robust findings are decreased daytime activity and relative amplitude in individuals with ASD w/o ID compared to siblings. We have also shown that ASD social impairment may be related to sleep dysfunction.

Support

NIH T32HL07713, anonymous donor, and the Institute for Translational Medicine and Therapeutics of the Perelman School of Medicine at the University of Pennsylvania.
0977 Risk Factors For Developing Sleep Disorders In Children
Authors: Johnson A K , Santos A A , Araujo L G , Gonsalves V S , Walker B L , Santos A B , Ajayi A O
Published: May 2020

Introduction

Unidentified sleep disorders can affect emotional, cognitive and social development in children. Screening for sleep disorders within the pediatric population is not common practice during medical visits. The objective of this study is to identify specific questions related to behavioral and physiological factors having potential to screen and detect those at risk for sleep disorders in a general pediatric clinic.

Methods

A retrospective archive from electronic medical records was analyzed from 1,361 children patients, 0-18 years old, that visited a pediatric clinic from March-November of 2019. Children or their parents reported on the presence of eight objective behavioral and physiological factors on the Kids Sleep Screener Questionnaire (KSSQ), which were used as potential risk factors for sleep disorders. Propensity of daytime sleepiness was measured through the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD). Scores higher than 11 were considered a positive indicator of potential sleep disorders because of excessive daytime sleepiness. Positive scores from the ESS-CHAD were used for comparison with the KSSQ factors using chi-square test of SAS software.

Results

Among the eight factors, snoring was the strongest risk factor and increased sleep duration was the weakest risk factor associated with a positive ESS-CHAD. Relationships among risk factors and the increased likelihood for developing sleep disorders were statistically significant (p<0.05-p<0.0001) and identified as following: snoring by 2.46 times, restless sleeper by 2.03 times, behavioral or learning difficulties by 1.43 times, nocturnal awakenings by 1.16 times, excessive sleepiness during the day by 1.10 times. Sleep onset latency and increased sleep duration were weak indicators due to a likeliness of less than one time (p<0.05) to be associated with a positive ESS-CHAD. Abnormal sleep behavior was not a statistically significant risk factor (p≥0.05) for potential sleep disorders in children.

Conclusion

There were associations between seven behavioral and physiological risk factors with overall sleep propensity in children. These results exhibit that the KSSQ is an important tool to identify potential sleep disorders in children and the need for follow up with a sleep specialist. The KSSQ is under validation for becoming a standard sleep screener in pediatrics.

Support

N/A
0981 Sleep Practices In Pediatric Cancer—Does Sleep Hygiene Matter For Reducing Cancer Symptom Burden?
Authors: Daniel L C , Gross Y , Meltzer L , Forrest C , Barakat L
Published: May 2020

Introduction

Sleep disturbances are common during pediatric cancer treatment and recent evidence suggests a correlation between sleep and symptom burden. Improving nighttime sleep may impact patients’ ability to cope with symptoms. The current study tests the interaction between sleep hygiene and sleep disturbances in predicting cancer-related symptoms to determine if the relationship between sleep and symptoms is different for patients with better sleep hygiene.

Methods

102 caregivers of children with cancer (ages 5-17, M=10.12, SD=4.02; 58% female) completed parent-proxy Pediatric Sleep Practices Questionnaire (yielding routine consistency and sleep opportunity scores) and measures of cancer-related symptoms (PROMIS Sleep Disturbance, Fatigue, and Pain Interference; PedsQL—Cancer Module-Nausea subscale). The interaction between sleep disturbances and sleep hygiene (consistency, opportunity) on each symptom (pain, nausea, fatigue) were tested using PROCESS moderation.

Results

81% of caregivers report that their child receives sufficient sleep but only 12% reported regular consistent sleep patterns/routines. Sleep opportunity was not related to sleep disturbances or cancer-related symptoms, but more routine consistency was related to fewer sleep disturbances (r=.30, p=.003). The interaction between sleep disturbances and routine consistency significantly predicted pain interference [R2=.16, F(3, 98)=6.37, p<.001; Bint =-0.17, p=.028] and nausea [R2=.16, F(3, 98)=6.47, p<.001; Bint=0.46, p=.004]. The interaction between sleep disturbances and sleep opportunity significantly predicted nausea [R2=.15, F(3, 98)=5.76, p=.001; Bint =0.68, p=.016] but not pain interference. Both interaction models predicting fatigue were not significant.

Conclusion

The sleep/pain and sleep/nausea relationships are stronger in patients with more consistent sleep routines and the sleep/nausea relationship is also stronger in patients with sufficient/well-timed sleep opportunities. Sleep and fatigue were moderately related across all levels of both sleep hygiene components. Clinical interventions that target sleep hygiene together with sleep disturbances such as nighttime awakenings and poor sleep quality may be more effective in addressing cancer-related symptoms such as pain and nausea.

Support

This work was supported in part by funding from the Patient-Centered Outcomes Research Institute (PCORI-D-17-00187; PI Christopher Forrest).
0984 Less Consistent Bedtimes Explains The Relationship Between Household Poverty And BMI In Toddlers
Authors: Covington L B , Armstrong B , Black M M
Published: May 2020

Introduction

Consistent bedtimes, in conjunction with physical activity and diet have been linked to healthy weight in childhood. Young children living in impoverished families are at risk for obesity, and the mechanisms of obesity etiology are not fully understood. This study compares the role of bedtime consistency, physical activity and diet quality as mediators between household poverty and toddler weight gain.

Methods

207 toddlers participating in an obesity prevention trial wore Actical accelerometers for up to 7 consecutive days, at 3 time points over 12 months. At each assessment, gender-specific BMI-for-age z-scores (zBMI) were calculated from toddlers’ weight/length according to WHO standards. Household poverty ratio was calculated based on the number of household members and annual income. Diet quality was assessed using Healthy Eating Index (HEI-2015) from 24-hour dietary recall. Physical activity and sleep were measured using ankle accelerometry (Actical; Sadeh algorithm used for sleep). Bedtime consistency was defined as SD of sleep onset across 7 days. A multi-level mediation model was conducted in the SPSS macro MLmed examining toddler bedtime consistency, physical activity and diet quality as mediators between household poverty and toddler zBMI. The analysis adjusted for toddler age, gender, total sleep time and intervention group.

Results

Between-person effects revealed that less household poverty was associated with more consistent bedtimes. Children with less consistent bedtimes, but not poor diet quality or physical activity, had higher zBMI. Bedtime consistency indirectly explained the association between average household poverty and average toddler zBMI over 12 months.

Conclusion

Children who generally have less bedtime consistency, above and beyond physical activity and diet quality, had higher zBMI. This link uniquely indirectly explained the association between household poverty and zBMI. Inconsistent bedtimes may indicate lack of structure in other health behaviors, and therefore, continued longitudinal research examining family routines may inform obesity prevention strategies.

Support

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), R01HD056099
0994 Assessment Of Sleep-wake And Circadian Rhythm Disruption In Children And Adolescents Diagnosed With Craniopharyngioma
Authors: LaRosa K N , Crowley S J , Hancock D , Caples M , Merchant T E , Crabtree V M , Mandrell B
Published: May 2020

Introduction

Patients with craniopharyngioma are at increased risk for hypersomnia/narcolepsy and circadian rhythm disruption, secondary to hypothalamic-pituitary involvement of the tumor. We assessed youth with craniopharyngioma to determine presence of the dim light melatonin onset (DLMO) and concurrent sleep disturbance.

Methods

Fifty-two patients (7-21 years; 51% female) enrolled on our institutional protocol for craniopharyngioma that included surgery, proton therapy, or both. In-home salivary melatonin was collected after surgery and hourly beginning 3 h before to 1 h after habitual bedtime to determine the DLMO, which was defined as the time that melatonin exceeded a 4 pg/mL threshold. Polysomnography and a next day multiple sleep latency test (MSLT) were also conducted.

Results

Hypersomnia/narcolepsy was indicated in 86% of patients. DLMO was detected in 29 (56%) patients and averaged 21:04 (±1:14). All but 2 patients with a DLMO had a concurrent sleep diagnosis (18 hypersomnia, 8 narcolepsy, 1 insomnia). In those we could not compute a DLMO, melatonin was above the 4 pg/mL threshold in 19 (37%), suggesting that the DLMO was likely earlier than the sampling window. Two (4%) did not reach threshold, suggesting that the DLMO was later than the window. For patients in which DLMO was not computed, all but 4 had a concurrent sleep diagnosis (7 hypersomnia, 9 narcolepsy, 1 MSLT not completed). Three (6%) participants showed a pattern of melatonin decreasing before bedtime (2 hypersomnia, 1 narcolepsy). Sleep disorder diagnosis was not associated with whether a DLMO was detected or not.

Conclusion

DLMO did not occur within the sampling window in 44% of patients with the majority due to the DLMO likely occurring before sampling started. Simultaneous assessment of both sleep-wake disturbance and circadian phase could provide more informed sleep interventions for excessive sleepiness and circadian misalignment in this patient population.

Support

This study was supported by cancer center grant (CA21765) from the National Cancer Institute, and ALSAC.
Disparities in Burnout and Satisfaction With Work–Life Integration in U.S. Physicians by Gender and Practice Setting
Authors: Marshall Ariela L. , Dyrbye Liselotte N. , Shanafelt Tait D. , Sinsky Christine A. , Satele Daniel , Trockel Mickey , Tutty Michael , West Colin P.
Published: May 2020

Purpose

To explore the interaction between practice setting (academic practice [AP], private practice [PP]) and gender in relation to physician burnout and satisfaction with work–life integration (WLI).

Method

In 2017, the authors administered a cross-sectional survey of U.S. physicians and characterized rates of burnout and satisfaction with WLI using previously validated and/or standardized tools. They conducted multivariable logistic regression to determine the interaction between the included variables.

Results

Of the 3,603 participants in the final analysis, female physicians reported a higher prevalence of burnout than male physicians in both AP (50.7% vs 38.2%, P < .0001) and PP (48.1% vs 40.7%, P = .001). However, the multivariable analysis found no statistically significant gender-based differences in burnout (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.76–1.17, P = .60). Women and men in AP were less likely to report burnout than men in PP (OR 0.70, 95% CI 0.52–0.94, P = .01 and OR 0.69, 95% CI 0.53–0.90, P < .01, respectively); women in PP did not report different burnout rates from men in PP (OR 0.89, 95% CI 0.68–1.16, P = .38). Women in both AP and PP were less likely to be satisfied with WLI than men in PP (OR 0.62, 95% CI 0.47–0.83, P < .01 and OR 0.75, 95% CI 0.58–0.97, P = .03, respectively); men in AP did not report different satisfaction with WLI than men in PP (OR 1.05, 95% CI 0.82–1.33, P = .71).

Conclusions

Gender differences in rates of burnout are related to practice setting and other differences in physicians’ personal and professional lives. These results highlight the complex relationships among gender, practice setting, and other personal and professional factors in their influence on burnout and satisfaction with WLI.
Routine Venous Thromboembolism Prophylaxis May Be Inadequate in the Hypercoagulable State of Severe Coronavirus Disease 2019
Authors: Maatman Thomas K. , Jalali Farid , Feizpour Cyrus , Douglas Anthony , McGuire Sean P. , Kinnaman Gabriel , Hartwell Jennifer L. , Maatman Benjamin T. , Kreutz Rolf P. , Kapoor Rajat , Rahman Omar , Zyromski Nicholas J. , Meagher Ashley D.
Published: May 2020

Objectives:

The aim of this study was to determine the frequency of venous thromboembolism in critically ill coronavirus disease 2019 patients and associate a degree of inflammatory marker elevation to venous thromboembolism development.

Design:

An observational study that identified patients with severe coronavirus disease 2019 between March 12, 2020, and March 31, 2020. Data reported are those available through May 6, 2020.

Setting:

A multicenter study including three Indianapolis area academic hospitals.

Patients:

Two-hundred forty consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection were admitted to one of three hospitals. One-hundred nine critically ill coronavirus disease 2019 patients admitted to the ICU were included in the analysis.

Interventions:

All patients received routine subcutaneous chemical venous thromboembolism prophylaxis.

Measurements and Main Results:

The primary outcome of this study was to determine the frequency of venous thromboembolism and the degree of inflammatory and coagulation marker elevation associated with venous thromboembolism development. Descriptive statistics outlined the frequency of venous thromboembolism at any time during severe coronavirus disease 2019. Clinical course and laboratory metrics were compared between patients that developed venous thromboembolism and patients that did not develop venous thromboembolism. Hypercoagulable thromboelastography was defined as two or more hypercoagulable parameters.

Main Results:

One-hundred nine patients developed severe coronavirus disease 2019 requiring ICU care. The mean (± sd) age was 61 ± 16 years and 57% were male. Seventy-five patients (69%) were discharged home, 7 patients (6%) remain in the hospital, and 27 patients (25%) died. Venous thromboembolism was diagnosed in 31 patients (28%) 8 ± 7 days after hospital admission, including two patients diagnosed with venous thromboembolism at presentation to the hospital. Elevated admission d-dimer and peak d-dimer were associated with venous thromboembolism development (p < 0.05). d-dimer greater than 2,600 ng/mL predicted venous thromboembolism with an area under the receiver operating characteristic curve of 0.760 (95% CI, 0.661–0.858; p < 0.0001), sensitivity of 89.7%, and specificity of 59.5%. Twelve patients (11%) had thromboelastography performed and 58% of these patients had a hypercoagulable study. The calculated coagulation index was hypercoagulable in 50% of patients with thromboelastography.

Conclusions:

These data show that coronavirus disease 2019 results in a hypercoagulable state. Routine chemical venous thromboembolism prophylaxis may be inadequate in preventing venous thromboembolism in severe coronavirus disease 2019.
A Comparison of Common Plastic Surgery Operations Using the NSQIP and TOPS Databases
Authors: Veith Jacob , Collier Willem , Simpson Andrew , Magno-Padron David , Mast Bruce , Murphy Robert X. , Agarwal Jayant , Kwok Alvin
Published: May 2020

Background:

Both the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and the American Society of Plastic Surgeons Tracking Operations and Outcomes for Plastic Surgeons (TOPS) databases track 30-day outcomes.

Methods:

Using the 2008–2016 TOPS and NSQIP databases, we compared patient characteristics and postoperative outcomes for 5 common plastic surgery procedures. A weighted TOPS population was used to mirror the NSQIP population in clinical and demographic characteristics to compare postoperative outcomes.

Results:

We identified 154,181 cases. Compared with NSQIP patients, TOPS patients were more likely to be younger (47.9 versus 50.0 years), have American Society of Anesthesiologists class I-II (92.1% versus 74.6%), be outpatient (66.0% versus 49.3%), and be smokers (18.7% versus 11.7%). TOPS had extensive missing data: body mass index (40.6%), American Society of Anesthesiologists class (34.9%), diabetes (39.3%), and smoking status (37.2%). NSQIP was missing <1% of all shared categories except race (15.6%). The entire TOPS cohort versus only TOPS patients without missing data had higher rates of dehiscence (5.1% versus 3.5%) and infection (2.1% versus 1.7%). TOPS versus NSQIP patients had higher dehiscence rates (5.1% versus 1.0%) but lower rates of return to the operating room (3.1% versus 6.6%), infection (2.1% versus 3.0%), and medical complications (0.3% versus 2.2%). Nonweighted and weighted TOPS cohorts had similar 30-day outcomes.

Conclusions:

NSQIP and TOPS populations are different in characteristics and outcomes, likely due to differences in collection methodology and the types physicians using the databases. The strengths of each dataset can be used together for research and quality improvement.
Prepectoral 2-stage Breast Reconstruction with Carbon Dioxide Tissue Expansion
Authors: Kraenzlin Franca S. , Darrach Halley , Chopra Karan , Rosson Gedge D. , Broderick Kristen P. , Sacks Justin M.
Published: May 2020

Background:

Roughly 80% of patients undergoing mastectomy in the United States opt for reconstruction with implants. The introduction of acellular dermal matrices has allowed for placement of breast prostheses in the prepectoral plane, while a new carbon dioxide tissue expander (TE) (AeroForm) allows for needle-free, patient-controlled expansion. These 2 novel technologies have ushered in a new patient-centered era of breast reconstruction, with the possibility of reducing patient morbidity for the first time in decades. We hypothesize that AeroForm expanders placed in the prepectoral plane reduce time to second-stage reconstruction, reduce the number of clinic visits, and have lower complications than traditional saline TEs.

Methods:

This is a retrospective review of all patients undergoing breast mastectomy and TE placement in the prepectoral plane over a 21-month period (169 patients, 267 breasts), comparing AeroForm expanders to TEs.

Results:

The AeroForm group (n = 57) had a shorter period to second-stage reconstruction than the TE group (n = 210) (135.4 versus 181.7 days; P = 0.01) and required fewer clinic visits (5.1 versus 6.9; P < 0.01). Partial thickness (25.6% versus 12.3%, P = 0.03) and full thickness (8.7% versus 0.0%, P = 0.02) necrosis were more common in the saline cohort. The rates of infection, hematoma, and seroma requiring drainage were not statistically significant between the 2 groups.

Conclusions:

Two-staged breast reconstruction with the use of AeroForm expanders in the prepectoral space marks progress in improving care for breast cancer patients by demonstrating a reduction in some adverse events, the number of clinic visits, and the time to second-stage reconstruction.
Elective Surgery during SARS-Cov-2/COVID-19 Pandemic: Safety Protocols with Literature Review
Authors: Cárdenas-Camarena Lázaro , Bayter-Marin Jorge Enrique , Durán Héctor , Hoyos Alfredo , López-Romero César Octavio , Robles-Cervantes José Antonio , Echeagaray-Guerrero Ernesto Eduardo
Published: May 2020

Background:

Health care systems worldwide have been affected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emergence since December 2019. The coronavirus disease 2019 (COVID-19) pandemic caused a steep decrease in elective surgery scheduling, to the extent of complete cancellation without future planning of safe development.

Purpose:

We performed a review of the literature and diagnosis data analysis with the aim to reduce the risk of operating a patient infected with SARS-CoV-2/COVID-19 during the incubation period.

Methods:

We searched for specific words and phrases about SARS-CoV-2 and COVID-19 in the PubMed database (US National Library of Medicine) from December 2019 to April 2020. A detailed analysis of the clinical picture and existing diagnostic tests for COVID-19 was performed to achieve the desired objectives.

Results:

A total of 1273 out of 5930 articles about COVID-19/SARS-CoV-2 did meet the criteria for the searched terms. We reviewed 105 articles, and 60 were selected for analysis. Specific recommendations were described based on our revision.

Conclusions:

With the combination of immunoglobulin M and immunoglobulin G antibody tests + real-time polymerase chain reaction for SARS-CoV-2 implemented in different time periods by taking into account the natural history of the disease, it is possible to decrease the risk of operating a patient during the incubation period higher than 93%. Adding other security measures can further increase this percentage. As long as there is no immunity to COVID-19, these measures will help us to perform safer elective surgeries.
Current Trends in Tonometry and Tonometer Tip Disinfection
Authors: Junk Anna K. , Chang Ta Chen , Vanner Elizabeth , Chen Teresa
Published: May 2020

Precis:

A survey among members of the American Glaucoma Society (AGS) and the American Optometry Association (AOA) on tonometer preference and tonometer disinfection indicates a shift to disposable tonometer tips compared with 1987.

Purpose:

This survey’s purpose was to determine how eye care providers responded to the 2008 Centers of Disease Control (CDC) tonometer disinfection guidelines, which recommend 10% hypochlorite (dilute bleach) for reusable tonometers. Tonometers measure the eye pressure when they touch the cornea, an essential part of the eye examination.

Methods:

AGS and AOA members were surveyed on tonometer preference, tonometer use, disinfection process, disinfectants, disinfection timing, and tonometer damage.

Results:

Survey responses from 79 AOA members and 197 AGS members are included. The Goldmann tonometer is considered most accurate (70, 89% AOA and 161, 82% AGS). It is preferred by 54 (70%) AOA and 193 (98%) AGS members. Many providers (165) use reusable Goldmann tonometer tips (77, 79% AOA, 88, 45% AGS), and most clean with 70% isopropyl alcohol wipes 59 (77%) AOA and 54 (61%) AGS. In summary, 126 of 276 participants (8, 10% AOA and 118, 60% AGS) follow CDC guidelines by using disposable tips (2 AOA and 109 AGS) or disinfecting reusable tips with 10% hypochlorite (6 AOA and 9 AGS).

Conclusions:

The majority of AGS providers follow current CDC tonometer disinfection guidelines by shifting to disposable Goldmann tonometer tips. Only a minority of providers who use reusable tonometer tips disinfect with dilute bleach. Continued education on proper tonometer disinfection is critical to prevent eye-care related infection due to improper disinfection.
The Effect of Age on the Rate of Correction in Infants with Head Shape Deformities Treated with Cranial Remolding Orthoses
Authors: Weersma Lance A. , Cordial-Stout Melissa L. , Gascho Briana R. , Nolin Rachael L.
Published: May 2020

Introduction

Often, health care professionals question when the opportune time is to refer a child for cranial remolding treatment and at what age the child will have the best outcome. This study was designed to observe the rate of change of a cranial deformity when treated with a cranial remolding orthosis and how age affects that rate of correction.

Materials and Methods

A total of 670 participants with positional head deformities were included in this retrospective study. Participants were placed into three groups: plagiocephaly, brachycephaly, and asymmetrical brachycephaly. A medical record review was completed on each infant, and 200 of the 670 participants were excluded for conflicts with criteria. The STARscan for the remaining candidates (N = 470) were obtained in the office using the STARscanner™ system. Seventy-one of the remaining 470 participants were excluded for conflicts with the scan review criteria.

Results

A total of 398 participants were included in this retrospective study. Ninety-eight participants were categorized in the plagiocephaly group, 156 were categorized in the brachycephaly group, and 144 were categorized in the asymmetrical brachycephaly group. A rate of in-orthosis correction was calculated for each participant. Rate of change for plagiocephaly was calculated as initial CVAI − discharge CVAI) / length of treatment. This calculation provided an average improvement in cranial vault asymmetry index (CVAI) per day. Rate of change for brachycephaly was calculated as (initial cephalic ratio − discharge cephalic ratio) / length of treatment. This calculation provided an average decrease in cephalic ratio per day. For asymmetrical brachycephaly, rate of in-orthosis correction was obtained by finding both the average rate of change for CVAI and cephalic ratio. In addition, participants were separated into age groups and deformity type to more precisely understand the relationship and note any differences.

Conclusions

Each deformity type showed an increased rate of correction when treatment was initiated at a younger age. By quantitatively showing that the rate of correction decreases as the child age increases, we can provide valuable information on the opportune time to provide cranial remolding treatment. The results of this study show that the fastest rate of correction occurs when started at the age of 4 to 6 months and declines quickly as the child ages.
Composite Lipid Emulsion for the Infant at Risk of Intestinal Failure–associated Liver Disease
Authors: Silverman Jason A. , Turner Justine M. , Wales Paul W.
Published: May 2020

Currently, in North America we are fortunate to have a number of available options for lipid emulsions to be used in the parenteral nutrition regimens for infants and children, including for long‐term parenteral nutrition given intestinal failure. Neonates and infants in particular are at risk for intestinal failure–associated liver disease (IFALD). The choice of parenteral lipid emulsion will influence the risk and severity of IFALD. The purpose of this review is to discuss the rationale for the composite lipid emulsion SMOFlipid that includes soybean, medium‐chain triglycerides, olive and fish oils for IFALD, with focus on the Canadian practice and experience.
Latent and Overt Polyautoimmunity in Children and Adolescents With Immune Thrombocytopenia
Authors: Kamioka Priscila E. , Liphaus Bernadete L. , Beatrice Julia M. , Matsumoto Lucy C. , Reis Joyce M.A. , Lima Laila , Carneiro-Sampaio Magda M.S. , Carneiro Jorge D.A.
Published: May 2020

Autoantibodies are biomarkers for autoimmune disease diagnosis, monitoring, and prediction. Therefore, this study established the frequency of latent and overt polyautoimmunity in children and adolescents with >6 months of diagnosis of immune thrombocytopenia (ITP). Forty-seven patients with chronic or persistent disease had non–organ-specific and organ-specific autoantibodies assessed. Frequency of latent polyautoimmunity was 36.2%, and, of overt polyautoimmunity, it was 4.3%. Of ITP patients with latent polyautoimmunity, 52.9% were positive for antinuclear antibody (ANA), 47.1% for autoantibodies other than ANA, and 64.7% for multiple autoantibodies. In addition, patients with latent polyautoimmunity and those positive for ANA were significantly older at disease onset. Both ITP patients positive and negative for autoantibodies reported family members with autoimmune diseases. The autoantibodies observed were as follows: ANA, anti-dsDNA, anti-SSA/Ro, IgM aCL, anti-GAD, anti-IA2, anti-IAA, anti-TG, anti-TPO, anti-LKM1, and SMA. Of ITP patients with overt polyautoimmunity, 1 was diagnosed with type 1 diabetes mellitus and the other with thyroiditis. In conclusion, children and adolescents with ITP present high frequency of latent and overt polyautoimmunity even for autoantibodies other than ANA. Therefore, ANA and other non–organ-specific and organ-specific autoantibodies should be considered for assessment during ITP patients’ follow-up.
Improving Concussion Management by Including Driving Recommendations for Adolescents with Concussions: A Quality Improvement Project
Authors: Santana Jonathan A. , Martinie Rebecca , Gomez Jorge
Published: May 2020

Introduction:

Motor vehicle collisions are the leading cause of death in adolescents. A concussion is a common injury sustained by adolescents and may impair their driving abilities during the acute phase of recovery. Healthcare providers do not consistently perform counseling of adolescents regarding driving after a concussion. This quality improvement project’s goal was to increase the incidence of primary care sports medicine physicians providing driving recommendations to 75% of adolescents who suffered from concussions.

Methods:

Between August 2017 to August 2018, a “smart phrase” implemented in the electronic health record system reminded providers during office visits to provide driving recommendations to patients 15 years old and older who presented to the sports medicine clinic for evaluation of concussion. Performing monthly retrospective chart reviews determined the frequency of patients who received driving recommendations during the initial visit.

Results:

We achieved the goal of providing driving recommendations to 75% of concussed patients by the second month. This progress was maintained through the remainder of the year, except for 1 month (December). Forty-three percent of patients with concussions evaluated met inclusion criteria, and of those, 48% were actively driving before their concussion. The most common medical reason for restricting driving was vestibular or ocular dysfunction.

Conclusion:

This quality improvement project showed that providing driving instructions to concussion patients by implementing a smart phrase into the electronic health record system was impactful and sustainable.
The role of the gut microbiota in the pathophysiology of mental and neurological disorders
Authors: Pusceddu Matteo M. , Del Bas Josep M.
Published: May 2020

In recent decades, the concept of the gut microbiota as a potential novel therapeutic strategy for mental health has emerged. The tiny microbes inhabiting our gut communicate through a bidirectional communication signaling with the brain that influences gut physiology, brain function and behavior. Accumulating evidence suggests that perturbation of the gut microbiota contributes to the pathophysiology of mental illnesses including autism, depression and anxiety as well as neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. This review will highlight recent findings in both human and animal studies indicating how changes in the gut microbiota can impact the pathophysiology of such diseases. The current work will also provide an understanding of the efficacy of microbiota-targeted therapies on psychiatric disorders.
Novel enteric viruses in fatal enteritis of grey squirrels
Authors: Dastjerdi Akbar , Benfield Camilla , Everest David , Stidworthy Mark F. , Zell Roland
Published: May 2020

Astro- and kobuviruses infect both humans and animals. Here, we report on the disease history, detection and genomic characterization of novel astro- and kobuviruses from fatal diarrhoea of two juvenile grey squirrels. The virus particles had enterovirus-like morphology and a diameter of 28–32 nm. Next-generation sequencing confirmed astro- and kobuviruses and sequence analysis revealed typical astrovirus and picornavirus genome organizations. The astrovirus ORF2 sequence clustered with a clade of unassigned astroviruses, with marmot and rodent mamastroviruses as closest relatives. For the kobuvirus, divergences greater than 49.4 % for P1 and 43.5 % in the non-structural proteins indicated a novel species. However, phylogenetic analysis of the 3D polymerase showed that it clustered with that of the newly classified ludopivirus A1, suggesting a previous recombination event in the evolution of the kobuvirus. Our data provide further insights into the diversity of astro- and kobuviruses and broaden the spectrum of viruses infecting grey squirrels.
Simple differentiation of Salmonella Typhi, Paratyphi and Choleraesuis from Salmonella species using the eazyplex TyphiTyper LAMP assay
Authors: Rödel Jürgen , Edel Birgit , Braun Sascha D. , Ehricht Ralf , Simon Sandra , Fruth Angelika , Löffler Bettina
Published: May 2020

Introduction. Identification of typhoidal

Salmonella

(TS) serovars and their discrimination from non-typhoidal

Salmonella

(NTS) is conventionally performed by seroagglutination. This method is labour-intensive, requires technical experience and can be inconclusive in some cases. Molecular assays may be reliable alternative diagnostic tools.

Aim. This study was designed to evaluate the eazyplex TyphiTyper based on loop-mediated isothermal amplification (LAMP) for fast identification of TS and S. Choleraesuis in culture.

Methodology. A total of 121

Salmonella

strains and 33 isolates of other

Enterobacterales

species were tested by the eazyplex TyphiTyper. Simulated and clinical blood cultures (BCs) were used to examine the performance of the assay for diagnosis of systemic infection. Sample preparation took about 5 min and the test running time was 20 min. Amplification was measured by real-time fluorescence detection.

Results. All TS and S. Choleraesuis strains were correctly identified. The most common NTS S. Typhimurium (n=34) and S. Enteritidis (n=15) were detected as

Salmonella

species without any false positive result for TS targets. Cross-reactions of NTS with TS were only rarely observed. Direct testing of positive BCs gave correct results. Sensitivities and specificities of the assay were as follows: 100 and 99.3 % for S. Typhi, 100 and 98.7 % for S. Paratyphi A, 100 and 97.3 % for S. Paratyphi B, 100 and 100 % for S. Paratyphi C, 100 and 100 % for S. Choleraesuis, and 100 and 100 % for

Salmonella

species, respectively.

Conclusion. The eazyplex TyphiTyper is very easy to perform and allows the rapid identification of TS and S. Choleraesuis isolates.
A Novel Standalone Microfluidic Device for Local Control of Oxygen Tension for Intestinal-Bacteria Interactions
Authors: Wang Chengyao , Dang Thao , Baste Jasmine , Joshi Advait Anil , Bhushan Abhinav
Published: May 2020

The intestinal environment is unique because it supports the intestinal epithelial cells under a normal oxygen environment and the microbiota under an anoxic environment. Due to importance of understanding the interactions between the epithelium and the microbiota, there is a strong need for developing representative and simple experimental models. Current approaches do not capture the dual-oxygen environment, require external anaerobic chambers, or are complex. Another major limitation is that in the solutions that can mimic the dual-oxygen environment, the oxygenation level of the epithelial cells is not known, raising the question whether the cells are hypoxic. We report standalone microfluidic devices that form a dual-oxygen environment without the use of an external anaerobic chamber or oxygen scavengers to coculture intestinal epithelial and bacterial cells. By changing the thickness of the device cover, the oxygen tension in the chamber could be modulated. We verified the oxygen levels using several tests: microscale oxygen sensitive sensors incorporated within the devices, hypoxic immunostaining of Caco-2 cells, and genetically encoded bacteria. Collectively, these methods monitored oxygen concentrations in devices more comprehensively than previous reports and allowed for control of oxygen tension to match the requirements of both intestinal cells and anaerobic bacteria. Our experimental model is supported by the mathematical model that considers diffusion of oxygen into the top chamber and the cellular oxygen consumption rate. This allowed us to experimentally determine the oxygen consumption rate of the epithelial cells more precisely.
OptiMol : Optimization of binding affinities in chemical space for drug discovery
Authors: Boitreaud Jacques , Oliver Carlos , Mallet Vincent , Waldispühl Jerome
Published: May 2020

Ligand-based drug design has recently benefited from the boost of deep generative models. These models enable extensive explorations of the chemical space, and provide a platform for molecular optimization. However, current state of the art methods do not leverage the structure of the target, which is known to play a key role in the interaction.

We propose an optimization pipeline that leverages complementary structure-based and ligand-based methods. Instead of performing docking on a fixed drug bank, we iteratively select promising compounds in the whole chemical space using a ligand-centered generative model. Molecular docking is then used as an oracle to guide compound optimization. This allows to iteratively generate leads that better fit the target structure, in a closed optimization loop, without prior knowledge about bio-actives. For this purpose, we introduce a new graph to selfies VAE which benefits from a seventeen times faster decoding than graph to graph methods while being competitive with the state of the art. We then successfully optimize the generation of molecules towards high docking scores, enabling a ten-fold augmentation of high-scoring compounds found with a fixed computational budget.

Availability

Code is available on GitHub

Contact

jeromew@mcgill.ca
Autism genetics perturb prenatal neurodevelopment through a hierarchy of broadly-expressed and brain-specific genes
Authors: Gazestani Vahid H. , Chiang Austin WT , Courchesne Eric , Lewis Nathan E.
Published: May 2020

Numerous genes are associated with autism spectrum disorder (ASD); however, it remains unclear how most ASD risk genes influence neurodevelopment and result in similar traits. Recent genetic models of complex traits suggest non-tissue-specific genes converge on core disease genes; so we analyzed ASD genetics in this context. We found ASD risk genes partition cleanly into broadly-expressed and brain-specific genes. The two groups show sequential roles during neurodevelopment with broadly-expressed genes modulating chromatin remodeling, proliferation, and cell fate, while brain-specific risk genes are involved in neural maturation and synapse functioning. Broadly-expressed risk genes converge onto brain-specific risk genes and core neurodevelopmental genes through regulatory networks including PI3K/AKT, RAS/ERK, and WNT/β-catenin signaling pathways. Broadly-expressed and brain-specific risk genes show unique properties, wherein the broadly-expressed risk gene network is expressed prenatally and conserved in non-neuronal cells like microglia. However, the brain-specific gene network expression is limited to excitatory and inhibitory neurons, spanning prenatal to adulthood. Furthermore, the two groups are linked differently to comorbidities associated with ASD. Collectively, we describe here the organization of the genetic architecture of ASD as a hierarchy of broadly-expressed and brain-specific genes that disrupt successive stages of core neurodevelopmental processes.
TLR9-activated B cells improve their regulatory function by endogenously produced catecholamines
Authors: Honke Nadine , Lowin Torsten , Opgenoorth Birgit , Shaabani Namir , Lautwein Alexander , Teijaro John R. , Schneider Matthias , Pongratz Georg
Published: May 2020

The sympathetic nervous system (SNS) contributes to immune balance by promoting anti-inflammatory B cells. However, whether B cells possess a self-regulating mechanism by which they modulate regulatory B cell (Breg) function is not well understood. In this study, we investigated the ability of B cells to synthesize catecholamines upon stimulation with different B cell activators. We found, that expression of the enzymes required to generate catecholamines, is upregulated by TLR9. TLR-9-specific expression of tyrosine hydroxylase (TH) correlated with upregulation of adrenergic receptors, enhanced IL-10 production, and with an overexpression of the co-inhibitory ligands PD-L1 and FasL. Moreover, concomitant stimulation of ß1-3-adrenergic receptors together with a BCR/TLR9 stimulus enhances the anti-inflammatory potential of Bregs to suppress CD4 T cells, a crucial population in the pathogenesis of autoimmune diseases, like rheumatoid arthritis. In conclusion, our data show that B cells possess autonomous mechanisms to modulate their regulatory function. These findings help to better understand the function of Bregs in autoimmune diseases and the interplay of sympathetic nervous system and B cell function.
Moyamoya Disease-AssociatedRNF213Alleles Encode Dominant Negative Alleles That Globally Impair Ubiquitylation
Authors: Bhardwaj Abhishek , Banh Robert S. , Zhang Wei , Sidhu Sachdev S. , Neel Benjamin G.
Published: May 2020

Single nucleotide polymorphisms (SNPs) inRNF213, which encodes a 591kDa protein with AAA+ ATPase and RING E3 domains, are associated with a rare, autosomal dominant cerebrovascular disorder, Moyamoya disease (MMD). MMD-associated SNPs primarily localize to the C-terminal region of RNF213, and some affect conserved residues in the RING domain. Although the autosomal dominant inheritance of MMD could most easily be explained by RNF213 gain-of-function, the type of ubiquitylation catalyzed by RNF213 and the effects of MMD-associated SNPs on its E3-ligase activity have remained unclear. We found that the RING domain of RNF213 uses the E2-conjugating enzyme UBE2D2 to catalyze predominantly K6-dependent poly-ubiquitination events comprising a mixture of typical and atypical ubiquitin linkages. MMD-associated SNPs encode proteins with decreased E3-ligase activity and the most frequent MMD allele,RNF213R4810K, is a dominant negative mutant that decreases ubiquitylation globally. By contrast, MMD-associatedRNF213SNPs do not affect ATPase activity. We propose that decreased RNF213 E3-ligase activity is central to MMD pathogenesis.
Short distance non-autonomy and intercellular transfer of chitin synthase in Drosophila
Authors: Adler Paul N.
Published: May 2020

The complex structure of insect exoskeleton has inspired material scientists and engineers. Chitin is a major component of the cuticle and it is synthesized by the enzyme chitin synthase. There is a single chitin synthase gene (kkv) in Drosophila facilitating research on the function of chitin. Previous editing ofkkvlead to the recovery of a viable hypomorphic allele. Experiments described in this paper argue that a reduction in chitin synthase leads to the shafts of sensory bristles becoming fragile and frequently breaking off as the animals age. This is likely due to reduced chitin levels and further suggests that chitin plays a role in resilience of insect cuticle. The different layers in cuticle are continuous across the many epidermal cells that secrete the cuticle that covers the body. Little is known about the mechanisms responsible for this continuity. Using genetic mosaics and scanning electron microscopy this paper establishes thatkkvshows short range cell non-autonomy. It also provides evidence for 2 possible mechanisms. One is the intercellular transfer of Kkv protein from one cell to its neighbors and the second is the deposition of cuticular material across the boundaries of neighboring cells.
Tolerance induction in memory CD4 T cells is partial and reversible
Authors: Gray Joshua I , Al-Khabouri Shaima , Morton Fraser , Clambey Eric T , Gapin Laurent , Matsuda Jennifer L , Kappler John W , Marrack Philippa , Garside Paul , Otto Thomas D , MacLeod Megan KL
Published: May 2020

Memory T cells respond rapidly in part because they are less reliant on heightened levels of costimulatory molecules. This presents challenges to silencing memory T cells in tolerance strategies for autoimmunity or allergy. We find that memory CD4 T cells generated by infection or immunisation survive secondary activation with antigen delivered without adjuvant, regardless of their location in secondary lymphoid organs or peripheral tissues. These cells were, however, functionally altered following a tertiary immunisation with antigen and adjuvant, proliferating poorly but maintaining their ability to produce inflammatory cytokines. Transcriptional and cell cycle analysis of these memory CD4 T cells suggest they are unable to commit fully to cell division potentially because of low expression of DNA repair enzymes. In contrast, these memory CD4 T cells could proliferate following tertiary reactivation by viral re-infection. These data suggest that tolerance induction in memory CD4 T cells is partial and can be reversed.