bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor sleep correlates with biomarkers of neurodegeneration in mild traumatic brain injury patients: a CENC study
Authors: Werner J Kent , Shahim Pashtun , Pucci Josephine U , Lai Chen , Raiciulescu Sorana , Gill Jessica M , Nakase-Richardson Risa , Diaz-Arrastia Ramon , Kenney Kimbra
Published: December 2020

Study Objectives

Sleep disorders affect over half of mild traumatic brain injury (mTBI) patients. Despite evidence linking sleep and neurodegeneration, longitudinal TBI-related dementia studies have not considered sleep. We hypothesized that poor sleepers with mTBI would have elevated markers of neurodegeneration and lower cognitive function compared to mTBI good sleepers and controls. Our objective was to compare biomarkers of neurodegeneration and cognitive function with sleep quality in warfighters with chronic mTBI.

Methods

In an observational warfighters cohort (n = 138 mTBI, 44 controls), the Pittsburgh Sleep Quality Index (PSQI) was compared with plasma biomarkers of neurodegeneration and cognitive scores collected an average of 8 years after injury.

Results

In the mTBI cohort, poor sleepers (PSQI ≥ 10, n = 86) had elevated plasma neurofilament light (NfL, x̅ = 11.86 vs 7.91 pg/mL, p = 0.0007, d = 0.63) and lower executive function scores by the categorical fluency (x̅ = 18.0 vs 21.0, p = 0.0005, d = –0.65) and stop-go tests (x̅ = 30.1 vs 31.1, p = 0.024, d = –0.37). These findings were not observed in controls (n = 44). PSQI predicted NfL (beta = 0.22, p = 0.00002) and tau (beta = 0.14, p = 0.007), but not amyloid β42. Poor sleepers showed higher obstructive sleep apnea (OSA) risk by STOP-BANG scores (x̅ = 3.8 vs 2.7, p = 0.0005), raising the possibility that the PSQI might be partly secondary to OSA.

Conclusions

Poor sleep is linked to neurodegeneration and select measures of executive function in mTBI patients. This supports implementation of validated sleep measures in longitudinal studies investigating pathobiological mechanisms of TBI related neurodegeneration, which could have therapeutic implications.
Evaluation of immunoglobulin-Y in place of tylosin phosphate in the diets fed to Holstein Steers and preliminary analysis of liver abscess duration on animal growth performance
Authors: Stotz Miranda K , Henry Darren D , Crossland Whitney L
Published: December 2020

Despite the regular use of feed-grade macrolide-antibiotics, bovine liver abscesses persist, representing a financial burden to pre- and post-mortem sectors of the beef industry. An immunoglobulin-Y (IGY) additive developed to target Fusobacterium necrophorum and Trueperella pyogenes, was evaluated for the control of liver abscesses. Research is needed for the impact of liver abscess severity as well as abscess duration on steer performance and carcass characteristics. Holstein steers (n = 64; initial body weight (BW) = 372.5 ± 2.41 kg) consuming a finishing diet for 188 d were used in a completely randomized design where treatments included: TYL (tylosin phosphate 90 mg/d; n = 32) or IGY (2.5 g/d; n = 32) and steer was the experimental unit. Feed intake was recorded daily while BW and liver ultrasound outcome (normal or abnormal) was recorded every 28 d until slaughter to estimate duration of abscess presence (DUR). Continuous variables of animal growth performance and carcass characteristics were analyzed using the MIXED procedure of SAS. Categorical quality grade and liver data were analyzed using the GLIMMIX procedure of SAS. Treatment did not affect live or carcass-adjusted growth performance (P ≥ 0.131). However, steers fed TYL had greater (P = 0.042) empty body fat (EBF) % and a greater proportion of carcasses grading premium choice than steers fed IGY (P = 0.030). Treatment did not affect prevalence of abscessed livers, abscess severity or estimated abscess duration (P ≥ 0.213) but datasets with greater experimental units are needed to substantiate this outcome. Increasing abscess severity tended (P ≤ 0.10) to linearly reduce carcass-adjusted gain to feed (G:F), fat thickness, and EBF. Carcass dressing % was only affected by severe (A+ and A+AD) abscess scores (P = 0.010). Carcass-adjusted final BW, average daily gain, G:F, and hot carcass weight was decreased only when the estimated DUR was ≥140 d (P ≤ 0.05). Carcass dressing %, however, was linearly affected by estimated liver abscess DUR (P ≤ 0.005), regardless of abscess severity. Preliminary evidence suggests that measuring the duration of liver abscess affliction during the feeding period may also give insight to the degree of performance reduction.
Subjective SES is Associated with Children’s Neurophysiological Response to Auditory Oddballs
Authors: Anwyl-Irvine Alexander L , Dalmaijer Edwin S , Quinn Andrew J , Johnson Amy , Astle Duncan E
Published: December 2020

Language and reading acquisitions are strongly associated with a child’s socioeconomic status (SES). There are a number of potential explanations for this relationship. We explore one potential explanation—a child’s SES is associated with how children discriminate word-like sounds (i.e., phonological processing), a foundational skill for reading acquisition. Magnetoencephalography data from a sample of 71 children (aged 6 years and 11 months–12 years and 3 months), during a passive auditory oddball task containing word and nonword deviants, were used to test “where” (which sensors) and “when” (at what time) any association may occur. We also investigated associations between cognition, education, and this neurophysiological response. We report differences in the neural processing of word and nonword deviant tones at an early N200 component (likely representing early sensory processing) and a later P300 component (likely representing attentional and/or semantic processing). More interestingly we found “parental subjective” SES (the parents rating of their own relative affluence) was convincingly associated with later responses, but there were no significant associations with equivalized income. This suggests that the SES as rated by their parents is associated with underlying phonological detection skills. Furthermore, this correlation likely occurs at a later time point in information processing, associated with semantic and attentional processes. In contrast, household income is not significantly associated with these skills. One possibility is that the subjective assessment of SES is more impactful on neural mechanisms of phonological processing than the less complex and more objective measure of household income.
Effects of Excessive Choline Administration on Cardiovascular Risk Factors and Hepatic Cholesterol Metabolism in Female SD Rats
Authors: Lim Taehwan , Ryu Juhee , Lee Kiuk , Hwang Keum Taek
Published: December 2020

Choline has been considered to be linked to an increase of cardiovascular risk. It can be metabolized to trimethylamine by gut microbiota and further converted by hepatic flavin monooxygenase 3 (FMO3) to trimethylamine‐N‐oxide (TMAO) which is known to be a putative promoter of cardiovascular disease. However, the effects of excessive choline administration on the cardiovascular risk, especially in SD rats, have been little studied. The purpose of this study was to evaluate the effects of excessive choline administration on serum TMAO level, aortic wall thickness, and expression of hepatic genes responsible for cholesterol metabolism in female SD rats. Twenty female SD rats were fed AIN93‐G diet with or without various concentrations of choline chloride (1.5%, 2.25%, 3%) (w/w) in autoclaved water for 8 weeks. Aortic wall section of the rat was stained by hematoxylin and eosin. Serum TMAO and choline levels were determined by UPLC‐Synapt G2‐Si. Hepatic mRNA expression of FMO3, farnesoid X receptor (FXR), liver X receptor α (LXRα), sterol regulatory element‐binding protein 2 (SREBP‐2), cholesterol 7 alpha‐hydroxylase (CYP7A1), and low‐density lipoprotein receptor (LDLR) was determined by quantitative PCR. Serum TMAO level was significantly (p<0.05) higher in the rat fed 1.5% choline‐containing water (1.5C) than control group (25.03 ± 14.27 vs. 0.34 ± 0.35 μM). However, serum choline levels were not significantly (p>0.05) different (18.01 ± 7.15 vs. 23.13 ± 11.89 μM). Aortic wall of the 1.5C seemed to be thicker than the control group. Relative mRNA expression of CYP7A1 was down‐regulated in the 1.5C compared to the control group (0.32 ± 0.24 vs. 1.00 ± 0.56, p<0.05), whereas that of FXR was up‐regulated (1.59 ± 0.60 vs. 1.00 ± 0.39, p<0.05). However, mRNA expressions of hepatic FMO3, LDLR, LXRα, and SREBP‐2 were not significantly (p>0.05) different. Excessive choline administration seemed to be able to affect cardiovascular system in female SD rats via production of TMAO and regulation of CYP7A1 and FXR. Additional research about secondary bile acid produced by gut bacteria is needed.

Support or Funding Information

This research has been supported by National Research Foundation of Korea (NRF‐ 2017R1D1A1B03028407) funded by the Ministry of Education of Korea.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ang‐1 and MCP‐1 cooperate in pericyte recruitment during angiogenesis
Authors: Aplin Alfred C , Fogel Eric , Nicosia Roberto F
Published: December 2020

Rat and mouse aortic rings produced angiogenic outgrowths in collagen gel cultures in response to the injury of the dissection procedure. Neovessels were composed of endothelial cells and surrounding pericytes. Pericyte recruitment along endothelial sprouts was enhanced by treating cultures with angiopoeitin‐1 (Ang‐1). Analysis of gene expression in Ang‐1 stimulated cultures revealed upregulated expression of several inflammatory cytokines, including monocyte chemotactic protein‐1 (MCP‐1). Recombinant MCP‐1 dose‐dependently increased pericyte number while anti‐MCP‐1 antibody depleted vessels of pericytes and abrogated Ang‐1 mediated pericyte recruitment. Mouse aortas deficient for MCP‐1 or its receptor CCR2 had fewer pericytes than controls. MCP‐1 deficiency also impaired the pericyte recruitment activity of Ang‐1. These results implicate MCP‐1 as a mediator of Ang‐1 effects on the development and maturation of the vessel wall during angiogenesis following injury. Supported by NHLBI‐HL52585, and a Merit Review Grant from the Department of Veterans Affairs.
Epigenetic changes in human cells exposed to X‐rays
Authors: Chaudhry M. Ahmad , Omaruddin Romaica A
Published: December 2020

An understanding of cellular processes that determine the response to ionizing radiation (IR) treatment is essential to improve radiotherapy. We investigated the DNA methylation changes in X‐ray‐irradiated TK6 and WTK1 cells that differ in sensitivity to IR. The global DNA methylation alterations as measured by an ELISA showed hypomethylation. Using AP‐PCR we observed time dependent dynamic changes in the regional genomic DNA methylation patterns. The AP‐PCR profiles were different between these cells indicating the involvement of differential genomic DNA responses to radiation treatment. The analysis of the components of the DNA methylation machinery showed the modulation of maintenance and de novo methyltransferases in irradiated cells. DNMT1 mRNA levels were increased in TK6 cells but were repressed in WTK1 cells. DNMT3A and DNMT3B were induced in both cells. TET1, involved in the conversion of 5‐methylcytosine to 5‐hydroxymethylcytosine was induced in both cells. This study demonstrates that irradiated cells acquire epigenetic changes in the DNA methylation patterns and the associated cellular machinery are involved in the response to radiation exposure. This study also shows that DNA methylation patterns are changed at different genomic regions and are dependent upon time after irradiation and the genetic background of the cell.
A single‐dose, microtracer study to determine the mass balance of orally administered, 14C‐labeled sweetener in healthy adult men (LB450)
Authors: Williamson Patricia , Schunk Tim , Woodyer Ryan , Chiuu Daisie , Song Qi , Atiee George , Unger Steve
Published: December 2020

The objective of this study was to determine the mass balance recovery of a rare sugar, through measurement of absorption, metabolism, and elimination using 14C radio‐labeled tracer with quantification via liquid scintillation counting and accelerator mass spectrometry (AMS). AMS measures isotope ratios to achieve low detection limits, providing quantification of 14C labeled compounds to low attomole levels. Eight healthy male subjects were housed within a metabolic ward for 1 week. The orally administered 776 nCi [14C(U)]‐rare sugar (99% purity), in a beverage containing 15g of unlabeled sweetener was consumed following a light breakfast. Blood, urine, fecal and expired air samples were collected at baseline and at various time points through168 hr for detection of the radiotracer and potential metabolites. Plasma Cmax occurred ~1.5 hours after dosing. Urinary total radioactivity (TRA) was 48.02‐90.25 % of dose over 168hr of collection. There was one subject with a low urine recovery (48.02%) within the first 12hr, possibly due to a missed collection. Fecal TRA (0‐120hr) was 1.79‐5.65 % of dose. Expired air 14C detection over 6hrs was only 0‐0.05% of dose and considered negligible. Overall, TRA 14C recovery was approximately 90%. High performance liquid chromatographic fractions analyzed with AMS showed the majority of the radiotracer was intact (TRA 80.3% plasma; 83.6% urine; 16% fecal). The 14C‐rare sugar was the most abundant compound in the plasma and excreta, demonstrating that this novel sugar is absorbed, but not metabolized.

Grant Funding Source: Research supported by Tate & Lyle, Health and Nutrition Sciences.
Supportive Interventions to Reduce Pain and Stress During Ophthalmic Examinations for Retinopathy of Prematurity in Premature Infants
Authors: Pollaci Mikayla , Schlenk Elizabeth A. , Baum Caitlyn , Godfrey Kathleen
Published: December 2020

Background:

Ophthalmic examinations are a frequent source of pain and stress in premature infants. There is evidence for the use of supportive interventions during infant ophthalmic examinations to reduce pain and stress, but there are no standard recommendations for their implementation.

Purpose:

The purpose of this quality improvement project was to implement evidence-based, supportive interventions during ophthalmic examinations in premature infants and evaluate the impact on pain, oxygen saturation, heart rate, bradycardic events, and neonatal stress cues.

Methods:

A preintervention and intervention group design was used. Primary outcomes were pain and oxygen saturation. Secondary outcomes were heart rate, number of bradycardic events, and number of neonatal stress cues. Independent-sample t tests were used to compare means of the measures in the preintervention and intervention groups.

Results:

Supportive interventions during ophthalmic examinations significantly reduced infant pain (during and after the examination), number of bradycardic events (during and after the examination), and number of neonatal stress cues (before, during, and after the examination). There was also a trend for supportive interventions to decrease pain before the examination.

Implications for Practice:

Supportive interventions during ophthalmic examinations are effective in reducing pain, bradycardic events, and neonatal stress cues in premature infants and can be successfully implemented as part of a unit-based protocol.

Implications for Research:

Future research is needed to determine the long-term outcomes associated with supportive interventions during ophthalmic examinations in premature infants.
Reliability and Validity of the Arabic Version of the Parental Stressor Scale and Nurse Parental Support Tool
Authors: Rabie Dina , Provenzi Livio , Matta Nashwa , Montirosso Rosario
Published: December 2020

Background:

The admission of a newborn infant to a neonatal intensive care unit (NICU) due to preterm birth or high-risk conditions, such as perinatal injury, sepsis, hypoxia, congenital malformation, or brain injury, is a stressful experience for mothers. There is currently a lack of research on maternal perceived stress and support in Egyptian NICUs and no validated Arabic tool to investigate this further.

Purpose:

To determine the reliability and validity of the Arabic language versions of the Parental Stressor Scale: NICU (PSS:NICU) and the Nurse Parental Support Tool (NPST).

Methods:

Egyptian mothers completed the PSS:NICU and the NPST at the time of their infants' discharge from the NICU. Reliability was assessed with Cronbach α and Spearman-Brown coefficient. The multifactorial structure of the PSS:NICU Arabic version was tested. Associations with sociodemographic and clinical variables were explored with bivariate correlations and t tests.

Results:

Sixty-eight mothers of preterm (PT) infants and 52 mothers of ill full-term (IFT) infants completed the study. Mothers of PT and IFT infants did not differ for sociodemographic variables. High internal consistency (α range between .93 and .96) emerged for both tools. Spearman-Brown coefficients ranged between 0.86 and 0.94. The multidimensional structure of the PSS:NICU was confirmed and 3 core dimensions explained up to 71.48% of the variance. Perceived nursing support did not diminish the effects of stress in mothers of infants admitted to the NICU, regardless of PT or IFT infants' status. A longer NICU stay was associated with greater stress in mothers of PT infants. The presence of comorbidities was significantly associated with stress of mothers of IFT infants.

Implications for Research:

Future research is needed to develop evidence-based support for mothers whose infants are admitted to a NICU in Egypt. The availability of validated and reliable PSS:NICU and NPST scales in Arabic will facilitate cross-country and cross-cultural research on maternal stress in the NICU.

Implications for Practice:

Neonatal care nurses in Egypt will be able to increase their understanding of the stressors experienced by mothers of infants admitted to the NICU. This will in turn enable the introduction of neonatal care policies aimed at reducing specific stressors and provide improved maternal support.
Using a Systems Engineering Approach to Design an Interactive Mobile Health Application for Improving Asthma Self-management
Authors: Li Xueping , Wyatt Tami H. , Velur Rajashekaran Pradeep , Bayless Adaya Kirk , Odom Laura
Published: December 2020

Mobile health applications are in demand. According to the Grand Review Research group, there were US $12.4 billion in mobile health app sales in 2018. Increasingly, providers are seeking new ways to engage their pediatric patients. One approach is through mobile health apps. Nearly 10 000 mobile health apps target youth and teens, especially for children with conditions that require complex treatment and self-management. One such chronic illness is asthma. Children with asthma who lack social support are particularly vulnerable to exacerbations because they often are not focused on self-care. For this reason, successful asthma programs for children engage family members, encouraging them to play an active role on the healthcare team. The Just-in-Time Asthma Self-management Intervention is unique in several ways compared to other asthma management mobile applications. The app uses gold standard, evidence-based asthma care practices and extends the support infrastructure beyond family and healthcare providers to engage the child, their peers, and school personnel. Further, the app was built using a systems engineering approach. This article reviews the basis for developing an asthma care mobile application including the conceptual framework supporting a systems model, how the Just-in-Time Asthma Self-management Intervention is unique, and how it was built using a systems engineering design.
Is Spironolactone the Preferred Renin–Angiotensin–Aldosterone Inhibitor for Protection Against COVID-19?
Authors: Wilcox Christopher S. , Pitt Bertram
Published: December 2020

The high mortality of specific groups from COVID-19 highlights the importance of host–viral interactions and the potential benefits from enhancing host defenses. SARS-CoV-2 requires angiotensin-converting enzyme (ACE) 2 as a receptor for cell entry and infection. Although both ACE inhibitors and spironolactone can upregulate tissue ACE2, there are important points of discrimination between these approaches. The virus requires proteolytic processing of its spike protein by transmembrane protease receptor serine type 2 (TMPRSS2) to enable binding to cellular ACE2. Because TMPRSS2 contains an androgen promoter, it may be downregulated by the antiandrogenic actions of spironolactone. Furin and plasmin also process the spike protein. They are inhibited by protease nexin 1 or serpin E2 (PN1) that is upregulated by angiotensin II but downregulated by aldosterone. Therefore, spironolactone should selectively downregulate furin and plasmin. Furin also promotes pulmonary edema, whereas plasmin promotes hemovascular dysfunction. Thus, a downregulation of furin and plasmin by PN1 could be a further benefit of MRAs beyond their well-established organ protection. We review the evidence that spironolactone may be the preferred RASSi to increase PN1 and decrease TMPRSS2, furin, and plasmin activities and thereby reduce viral cell binding, entry, infectivity, and bad outcomes. This hypothesis requires direct investigation.
Do Vancomycin Pharmacokinetics Differ Between Obese and Non-obese Patients? Comparison of a General-Purpose and Four Obesity-Specific Pharmacokinetic Models
Authors: Colin Pieter J. , Eleveld Douglas J. , Hart Andrew , Thomson Alison H.
Published: December 2020

Background:

Over the past decade, numerous obesity-specific pharmacokinetic (PK) models and dosage regimens have been developed. However, it is unclear whether vancomycin PKs differ between obese and other patients after accounting for weight, age, and kidney function. In this study, the authors investigated whether using obesity-specific population PK models for vancomycin offers any advantage in accuracy and precision over using a recently developed general-purpose model.

Methods:

Vancomycin plasma concentrations in a cohort of 49 obese patients (body mass index [BMI] >30 kg/m2), not previously used in the development of any of the evaluated models, were used to validate the performance of 4 obesity-specific models and a general model. Bias and imprecision were calculated for the a priori and a posteriori predictive performance.

Results:

The bias of the a priori prediction was lowest for one of the obesity-specific models (−1.40%) and that of the general model was a close second (−7.0%). The imprecision was lowest for the general model (4.34 mg/L). The predictive performance for the a posteriori predictions was best for the general model, both for bias (1.96%) and imprecision (2.75 mg/L).

Conclusions:

The results of the external validation of vancomycin PK in obese patients showed that currently available obesity-specific models do not necessarily outperform a broadly supported general-purpose model. Based on these results, the authors conclude that there is no advantage in using vancomycin PK models specifically tailored to obese patients over the general-purpose model reported by Colin et al.
High Intrapatient Variability in Tacrolimus Exposure Calculated Over a Long Period Is Associated With De Novo Donor-Specific Antibody Development and/or Late Rejection in Thai Kidney Transplant Patients Receiving Concomitant CYP3A4/5 Inhibitors
Authors: Larpparisuth Nuttasith , Pongnatcha Tanapon , Panprom Pera , Promraj Ratchawat , Premasathian Nalinee , Vongwiwatana Attapong
Published: December 2020

Background:

High intrapatient variability in tacrolimus trough levels (Tac IPV) is associated with poor allograft outcomes. Tac IPV was previously calculated using trough levels 6–12 months after kidney transplantation (KT). Data on the accuracy of Tac IPV calculation over a longer period, the association between high Tac IPV and donor-specific antibody (DSA) development after KT in Asian patients, and the role of IPV in patients receiving concomitant cytochrome P450 (CYP)3A4/5 inhibitors (CYPinh) are limited.

Methods:

A retrospective review of patients who underwent KT at our center in 2005–2015, and who received Tac with mycophenolate during the first 2 years after KT was performed. IPV was calculated using Tac levels adjusted by dosage. DSA was monitored annually after KT using a Luminex microbead assay.

Results:

In total, 236 patients were enrolled. CYPinh were prescribed to 189 patients (80.1%): 145 (61.4%), 31 (13.1%), and 13 (5.5%) received diltiazem, fluconazole, and ketoconazole, respectively. Mean IPV calculated from adjusted Tac levels for 6–12 months (IPV6–12) and 6–24 months (IPV6–24) after KT were 20.64% ± 11.68% and 23.53% ± 10.39%, respectively. Twenty-six patients (11%) showed late rejection and/or DSA occurrence, and had significantly higher IPV6–24 (29.42% ± 13.78%) than others (22.77% ± 9.64%; P = 0.02). There was no difference in IPV6–12 (24.31% ± 14.98% versus 20.17% ± 10.90%; P = 0.18). IPV6–12 and IPV6–24 were comparable in patients who did and did not receive CYPinh. When using mean IPV6–24 as a cutoff, patients with higher IPV6–24 had a higher probability of developing DSA and/or late rejection (P = 0.048).

Conclusions:

Tac IPV6–24 was higher and more significantly associated with DSA development and/or late rejection than Tac IPV6–12, independent of Tac trough level. This is the first study to demonstrate the impact of high IPV on DSA development in Asian patients, and that Tac IPV is comparable between patients with and without CYPinh.
Rheological behavior of commercial artificial tear solutions
Authors: Arshinoff Steve , Hofmann Ilan , Nae Hemi
Published: December 2020

Purpose:

To measure the rheological behavior of artificial tears to gain insight into the potential role of rheology in predicting the efficacy of artificial tear solutions for the treatment of dry-eye disease (DED).

Setting:

Research laboratories of I-MED Pharma, Canada, Rohn and Associates, Inc., New Jersey, and Hydan Technologies, New Jersey.

Design:

Laboratory investigation.

Methods:

Twenty commercially available artificial tear drops were purchased in Canada and the United Kingdom. Rheological measurements of viscosity and normal stress as a function of shear rate were performed at 25°C.

Results:

For comparison of the rheological behavior, the various artificial tears were sorted into 3 groups: group A, which exhibit significant non-Newtonian shear-thinning behavior; group B, which exhibit moderate non-Newtonian shear-thinning behavior; and group C, which exhibit Newtonian behavior throughout the shear rate range. Results of normal stress difference, N1, as a function of shear rate were concordant with the rheological testing, indicated the viscoelastic nature of the samples in groups A and B, whereas members of group C did not exhibit any elasticity.

Conclusions:

The various artificial tear solutions were sorted into groups based on their Newtonian or non-Newtonian behaviors. The results suggest that non-Newtonian solutions should provide better comfort and longer-lasting symptomatic relief for DED. It remains to be confirmed clinically if there is a direct correlation between the rheological behavior of artificial tears and their ability to provide prolonged relief in DED, or if other factors are more important.
Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study
Authors: Fan Song , Zhen Qi , Chen Cheng , Wang Wenjun , Wu Qibing , Ma Huihui , Zhang Chengyuan , Zhang Li , Lu Baojing , Ge Huiyao , Yong Liang , Li Bao , Yu Yafen , Chen Weiwei , Mao Yiwen , Qu Guangbo , Su Li , Wang Aoli , Ding Zhen , Li Haiwen , Zhang Jin , Wang Yonglian , Gao Yufeng , Xu Xihai , Zhu Zhongming , Chen Jun , Zhang Long , Liang Hongqiang , Wu Song , Huang Meng , Xia Quan , Li Ping , Sun Yehuan , Liang Chaozhao , Wei Wei , Liu Qingsong , Sun Liangdan
Published: December 2020

Objective:

Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19).

Methods:

In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022).

Results:

The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.

Conclusion:

Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.
Mendelian randomization as a tool for causal inference in human nutrition and metabolism
Authors: Larsson Susanna C.
Published: December 2020

Purpose of review

The current review describes the fundamentals of the Mendelian randomization framework and its current application for causal inference in human nutrition and metabolism.

Recent findings

In the Mendelian randomization framework, genetic variants that are strongly associated with the potential risk factor are used as instrumental variables to determine whether the risk factor is a cause of the disease. Mendelian randomization studies are less susceptible to confounding and reverse causality compared with traditional observational studies. The Mendelian randomization study design has been increasingly used in recent years to appraise the causal associations of various nutritional factors, such as milk and alcohol intake, circulating levels of micronutrients and metabolites, and obesity with risk of different health outcomes. Mendelian randomization studies have confirmed some but challenged other nutrition-disease associations recognized by traditional observational studies. Yet, the causal role of many nutritional factors and intermediate metabolic changes for health and disease remains unresolved.

Mendelian randomization can be used as a tool to improve causal inference in observational studies assessing the role of nutritional factors and metabolites in health and disease. There is a need for more large-scale genome-wide association studies to identify more genetic variants for nutritional factors that can be utilized for Mendelian randomization analyses.
The use of grafts in frontal sinus drill-outs
Authors: Yin Tary , Douglas Richard
Published: December 2020

Purpose of review

A significant complication of the frontal sinus drill-out procedure is restenosis of the frontal neo-ostium. To improve postoperative healing in this region, various mucosal grafts and pedicled flaps have been designed to reconstruct the mucosal lining of the frontal neo-ostium. We provide an overview of the types of grafts described for reconstruction and discuss the latest evidence on their efficacy.

Recent findings

Frontal neo-ostium mucosal reconstruction may be performed using free, pedicled, or a combination of grafts. There are several case series that report good outcomes and low revision rates following the use of grafts in frontal sinus drill-outs, and one randomized controlled study demonstrating increased ostial patency. However, the use of grafts did not alter the rate of revision surgery and only one study reported an improvement in Sino-Nasal Outcome Test-22 scores after one year.

Studies have suggested that frontal sinus drill-out grafts result in favorable restenosis and graft success rates. However, larger randomized control trials will be required to determine whether frontal sinus drill-out grafts contribute to a tangible clinical benefit for patients.
Multisystem inflammatory syndrome in children
Authors: Soma Vijaya L. , Shust Gail F. , Ratner Adam J.
Published: December 2020

Purpose of review

Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases.

Recent findings

Clinical presentation of MIS-C is dominated by significant inflammation. Fever, gastrointestinal symptoms, cardiac dysfunction, and hypotension are common features. Kawasaki disease-like findings are common, but epidemiologic data and recent mechanistic studies suggest that distinct inflammatory pathways mediate Kawasaki disease and MIS-C. A broad diagnostic approach is recommended, given overlapping presentations between MIS-C and many other disease processes. Current management of MIS-C is highly variable, depending on illness severity, and can range from supportive care to aggressive immune modulation. A multidisciplinary approach with early involvement of multiple pediatric subspecialists is recommended for complicated cases.

Several studies have described the clinical manifestations of MIS-C, but definitive diagnosis remains challenging. Robust information about long-term outcomes awaits further study, as do immunologic data to refine diagnostic and therapeutic strategies.
Heart transplantation candidacy
Authors: Vieira Jefferson L. , Mehra Mandeep R.
Published: December 2020

Purpose of review

Timely referral of eligible candidates for consideration of advanced therapies, such as a heart transplantation or mechanical circulatory support is essential. The characteristics of heart transplantation candidates have changed significantly over the years, leading to a more complex evaluation process. The present review summarizes recent advances in the evaluation process for heart transplantation eligibility.

Recent findings

The heart transplantation allocation policy was recently reviewed in the USA in an effort to reduce waitlist mortality and to ensure fair geographic allocation of organs to the sickest patients. Moreover, patients with chronic infectious diseases, as well as malignancies, are being currently considered acceptable candidates for transplantation. Listing practices for heart transplantation vary between programmes, with a greater willingness to consider high-risk candidates at higher-volume centres.

The ultimate decision to place high-risk candidates on the heart transplantation waitlist should be based on a combination of quantitative and qualitative data analysis informed by clinical judgement, and the chronic shortage of organ donors makes this process an important ethical concern for any society. Future guidelines should discuss approaches to achieve fair organ allocation while preserving improved outcomes after transplantation.
MicroRNAs: small molecules, big effects
Authors: Tinel Claire , Lamarthée Baptiste , Anglicheau Dany
Published: December 2020

Purpose of review

In kidney transplantation, microRNAs (miRNAs) have been extensively studied over the past decade, and panels of differentially expressed miRNAs have been identified from various body fluids/tissues, including blood, plasma, urine, or allograft biopsies, and in various conditions, such as acute T-cell-mediated and antibody-mediated rejections, chronic allograft rejection, interstitial fibrosis and tubular atrophy, acute tubular necrosis or BKV nephropathy.

Recent findings

This review outlines our current knowledge regarding the complexity of miRNA regulation in fine-tuning expression of two-thirds of the human genome and the potential of miRNAs as biomarkers, based on an increasing number of case--control studies with, however, no evidence of short-term clinical development. Instead, a progressive change in study objectives is reported, with the most recent literature using miRNA-targeted genes as entry points for studying disease pathways.

Our nascent understanding of their presumed roles in alloimmunity suggests that miRNAs are key regulators in many allograft injuries. Future directions should investigate how the integration of miRNAs with other layers of molecular data, such as genomic, transcriptomic, or proteomic data, could help to characterize the cellular interactions involved in allograft rejection and whether miRNA-based therapy could be of relevance for transplant medicine.
Congenital Symmastia
Authors: Kraft Casey T. , Chandawarkar Rajiv , Chetta Matthew D. , Poteet Stephen J.
Published: December 2020

Congenital symmastia is a relatively uncommon condition and poorly described in the literature. Although numerous studies have evaluated iatrogenic symmastia including its prevention and treatment, considerably less has been studied with regard to congenital symmastia. In this review, the authors seek to consolidate the literature published thus far and provide techniques and principles of management that may guide surgeons treating patients with this condition.
Abdominoplasty
Authors: Ramirez Alejandro E. , Hsieh Tung-Ying , Cardenas Juan P. , Lao William W.
Published: December 2020

Background

Abdominoplasty has been evolving since the 1960s with many technical innovations throughout the years. It has become one of the most frequent and common procedures done in aesthetic plastic surgery, with the ultimate goal of not only to remove the excess tissue in the abdominal area but also to achieve an aesthetic trunk silhouette.

Objective

The prime objective of this article was to describe our preferred approach for a full cosmetic abdominoplasty.

Methods

We summarized all the key technical aspects from our shared surgical approach for abdominoplasty. The article describes collective experiences from authors performing the surgery in South America, North America, and Asia.

Results

The key technical aspects identified were conservative muscle plication, customized excess tissue resection, and ultrasound-assisted liposuction to improve definition in the abdominal lines and body curves, combined with lipofilling. The aesthetic results are presented.

Conclusions

Abdominoplasty should be customized to every patient's anatomy and desired cosmetic outcome, taking into consideration all the anatomical areas surrounding the abdominal wall.
Stroke epidemiology and COVID-19 pandemic
Authors: Logroscino Giancarlo , Beghi Ettore
Published: December 2020

Purpose of review

The aim of this study was to describe the impact of the COVID-19 outbreak on the epidemiology, cause and clinical characteristics of incident stroke in different settings and populations.

Recent findings

Several studies have shown that there are three main themes in the epidemiology of stroke during the COVID-19 pandemic: COVID-19 seems to be associated with stroke in a significant number of patients. This association has been reported in several clinical series, mainly from China. There is a consistent trend towards a decreased number of hospital admissions of stroke patients during the pandemic. There are no population-based data available on incident stroke in individuals with COVID-19.

In this review, we report on increased rates and severe prognosis of ischemic stroke among individuals with COVID-19, probably explained by hypercoagulability and inflammation, documented since the early phase of disease.

We confirm the presence of falling rates of new ischemic stroke admissions in hospitals, probably due to social consequences of the pandemic: fear to be infected or not adequately treated in the hospital. This phenomenon is restricted to mild stroke and transient ischemic attacks.

Short and long-term consequences of this trend of new strokes in the pandemic need to be evaluated.
Facial and vocal markers of schizophrenia measured using remote smartphone assessments
Authors: Galatzer-Levy Isaac R. , Abbas Anzar , Koesmahargyo Vidya , Yadav Vijay , Perez-Rodriguez M. Mercedes , Rosenfield Paul , Patil Omkar , Dockendorf Marissa F. , Moyer Matthew , Shipley Lisa A. , Hansen Bryan J.
Published: December 2020

Background

Machine learning-based facial and vocal measurements have demonstrated relationships with schizophrenia diagnosis and severity. Here, we determine their accuracy of when acquired through automated assessments conducted remotely through smartphones. Demonstrating utility and validity of remote and automated assessments conducted outside of controlled experimental settings can facilitate scaling such measurement tools to aid in risk assessment and tracking of treatment response in difficult to engage populations.

Methods

Measurements of facial and vocal characteristics including facial expressivity, vocal acoustics, and speech prevalence were assessed in 20 schizophrenia patients over the course of 2 weeks in response to two classes of prompts previously utilized in experimental laboratory assessments: evoked prompts, where subjects are guided to produce specific facial expressions and phonations, and spontaneous prompts, where subjects are presented stimuli in the form of emotionally evocative imagery and asked to freely respond. Facial and vocal measurements were assessed in relation to schizophrenia symptom severity using the Positive and Negative Syndrome Scale.

Results

Vocal markers including speech prevalence, vocal jitter, fundamental frequency, and vocal intensity demonstrated specificity as markers of negative symptom severity while measurement of facial expressivity demonstrated itself as a robust marker of overall schizophrenia severity.

Conclusion

Established facial and vocal measurements, collected remotely in schizophrenia patients via smartphones in response to automated task prompts, demonstrated accuracy as markers of schizophrenia severity. Clinical implications are discussed.
Identifying US Counties with High Cumulative COVID-19 Burden and Their Characteristics
Authors: Li Daniel , Gaynor Sheila M. , Quick Corbin , Chen Jarvis T. , Stephenson Briana J.K. , Coull Brent A. , Lin Xihong
Published: December 2020

Identifying areas with high COVID-19 burden and their characteristics can help improve vaccine distribution and uptake, reduce burdens on health care systems, and allow for better allocation of public health intervention resources. Synthesizing data from various government and nonprofit institutions of 3,142 United States (US) counties as of 12/21/2020, we studied county-level characteristics that are associated with cumulative case and death rates using regression analyses. Our results showed counties that are more rural, counties with more White/non-White segregation, and counties with higher percentages of people of color, in poverty, with no high school diploma, and with medical comorbidities such as diabetes and hypertension are associated with higher cumulative COVID-19 case and death rates. We identify the hardest hit counties in US using model-estimated case and death rates, which provide more reliable estimates of cumulative COVID-19 burdens than those using raw observed county-specific rates. Identification of counties with high disease burdens and understanding the characteristics of these counties can help inform policies to improve vaccine distribution, deployment and uptake, prevent overwhelming health care systems, and enhance testing access, personal protection equipment access, and other resource allocation efforts, all of which can help save more lives for vulnerable communities.

Significance statement

We found counties that are more rural, counties with more White/non-White segregation, and counties with higher percentages of people of color, in poverty, with no high school diploma, and with medical comorbidities such as diabetes and hypertension are associated with higher cumulative COVID-19 case and death rates. We also identified individual counties with high cumulative COVID-19 burden. Identification of counties with high disease burdens and understanding the characteristics of these counties can help inform policies to improve vaccine distribution, deployment and uptake, prevent overwhelming health care systems, and enhance testing access, personal protection equipment access, and other resource allocation efforts, all of which can help save more lives for vulnerable communities.
Celecoxib Colorectal Bioavailability and Chemopreventive Response in Familial Adenomatous Polyposis Patients
Authors: Yang Peiying , Zuo Xiangsheng , Advani Shailesh , Wei Bo , Malek Jessica , Day R. Sue , Shureiqi Imad
Published: December 2020

The chemopreventive activity of celecoxib against colorectal cancer is limited to a proportion of familial adenomatous polyposis (FAP) patients who experience a response. The cause of this response variability and the potential mechanisms underlying these responses remain poorly understood. Preclinical studies showed that celecoxib increases the production of main oxidative metabolism product of linoleic acid, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), to suppress colorectal tumorigenesis. We conducted a phase II clinical study to determine whether celecoxib increases 13-S-HODE production in colonic adenomas from FAP patients. Twenty seven FAP patients completed a 6-month oral course of 400 mg of celecoxib twice a day and had colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and obtain colorectal normal and polyp biopsies to measure celecoxib, 13-HODE, 15-HETE, 12-HETE, and LTB4 levels by LC/MS. Celecoxib levels in sera from those patients were also measured before treatment and 2, 4, and 6 months of treatment. Seventeen of the 27 patients experienced a response to celecoxib, with a more than 30% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in FAP patients.