bluuebunny/crossref_metadata_2025 huggingface dataset:
TBIO-26. NON-CANONICAL OPEN READING FRAMES ENCODE FUNCTIONAL PROTEINS ESSENTIAL FOR CANCER CELL SURVIVAL
Authors: Prensner John , Enache Oana , Luria Victor , Krug Karsten , Clauser Karl , Dempster Joshua , Karger Amir , Wang Li , Stumbraite Karolina , Wang Vickie , Botta Ginevra , Lyons Nicholas , Goodale Amy , Kalani Zohra , Fritchman Briana , Brown Adam , Alan Douglas , Green Thomas , Yang Xiaoping , Jaffe Jacob , Roth Jennifer , Piccioni Federica , Kirschner Marc , Ji Zhe , Root David , Golub Todd
Published: December 2020

The brain is the foremost non-gonadal tissue for expression of non-coding RNAs of unclear function. Yet, whether such transcripts are truly non-coding or rather the source of non-canonical protein translation is unknown. Here, we used functional genomic screens to establish the cellular bioactivity of non-canonical proteins located in putative non-coding RNAs or untranslated regions of protein-coding genes. We experimentally interrogated 553 open reading frames (ORFs) identified by ribosome profiling for three major phenotypes: 257 (46%) demonstrated protein translation when ectopically expressed in HEK293T cells, 401 (73%) induced gene expression changes following ectopic expression across 4 cancer cell types, and 57 (10%) induced a viability defect when the endogenous ORF was knocked out using CRISPR/Cas9 in 8 human cancer cell lines. CRISPR tiling and start codon mutagenesis indicated that the biological impact of these non-canonical ORFs required their translation as opposed to RNA-mediated effects. We functionally characterized one of these ORFs, G029442—renamed GREP1 (Glycine-Rich Extracellular Protein-1)—as a cancer-implicated gene with high expression in multiple cancer types, such as gliomas. GREP1 knockout in >200 cancer cell lines reduced cell viability in multiple cancer types, including glioblastoma, in a cell-autonomous manner and produced cell cycle arrest via single-cell RNA sequencing. Analysis of the secretome of GREP1-expressing cells showed increased abundance of the oncogenic cytokine GDF15, and GDF15 supplementation mitigated the growth inhibitory effect of GREP1 knock-out. Taken together, these experiments suggest that the non-canonical ORFeome is surprisingly rich in biologically active proteins and potential cancer therapeutic targets deserving of further study.
THER-04. IS THERE A ROLE FOR CANNABIDIOL IN THE TREATMENT OF CHILDHOOD BRAIN TUMOURS?
Authors: Lockwood George , Hatfield Amelia , Mabrouk Mohamed , O’Sullivan Saoirse E , Grundy Richard G , Storer Lisa C D
Published: December 2020

Brain tumours are the leading cause of cancer related death in children with limited treatment options and high recurrence rates. Recent evidence suggests there may be anti-tumoral properties of cannabinoids, and of cannabidiol (CBD) in particular. We evaluated the effect of CBD on paediatric brain tumour cell lines in 2D and 3D spheroids; pHGG (SF188), ependymoma (BxD-1425EPN) and human astrocytes. At the CBD EC50 concentration, astrocytic cell death was insignificant. 3D spheroids decreased in size by approximately 20% when cultured in CBD compared to cells only after 5-day exposure. Cell death increased with time after a single dose of CBD. Western Blot showed an increase in Lc3b expression (autophagy) after 24 hours incubation (early cell death) with CBD in both BxD-1425EPN and SF188 with PARP expression (apoptosis) increased after 5 days incubation (late cell death). Cell cycle analysis showed a decrease of cells in G1 and no change in G2 indicating cell cycle arrest. In hypoxia, SF188 and BxD-1425EPN cells showed decreased cell death after 24 hours and 5 days when compared to normoxia and an EC50 within acceptable limits could not be achieved. SF188 cells pre-treated with receptor antagonists indicate that CBD was not acting through CB1, CB2, GPR18, PPARα or PPARγ receptors but may act as a partial agonist of the TRPV1 and 5-HT1A receptors and a full agonist of the GPR55 receptor (resazurin assay). This provides evidence that CBD is effective at killing paediatric brain tumour cells and does not have a significant effect on normal astrocytes.
THER-05. GENETICALLY STABLE POLIOVIRUS VECTOR CARRYING H3.3K27M ANTIGEN FOR TREATMENT OF DIFFUSE MIDLINE GLIOMA BY INTRAMUSCULAR INJECTION
Authors: Mosaheb Mubeen , Landi Daniel , Dobrikova Elena , Brown Michael , Yang Yuanfan , Cable Jana , Okada Hideho , Nair Smita , Bigner Darell , Ashley David , Gromeier Matthias
Published: December 2020

BACKGROUND

H3 K27M-mutant diffuse midline glioma (DMG) is invariably lethal. Viruses naturally engage innate immunity, induce antigen presentation, and mediate CD8 T cell priming against foreign antigens. Polioviruses, in particular, are uniquely tropic for dendritic cells (DC) and potently activate DC, inducing Th1-dominant cytokine profiles, CD8 T cell immunity, and enhanced epitope presentation. Thus, poliovirus is ideally suited for vectored delivery of signature tumor neoantigens, e.g. the H3 K27M feature of DMG. However, poliovirus vector design is inherently limited by genetic instability and the underlying neuropathogenicity of poliovirus.

METHODS

We created a genetically stable, polio:rhinovirus chimera vector devoid of neuropathogenicity and modified for stable expression of the HLA-A2 restricted H3.3 K27M antigen (RIPO (H3.3)).

RESULTS

RIPO(H3.3) infects, activates, and induces H3.3K27M antigen presentation in DCs in vitro. Given intramuscularly in vivo, RIPO(H3.3) recruits and activates DCs with Th1-dominant cytokine profiles, efficiently primes H3.3K27M-specific CD8 T cells, induces antigen-specific CD8 T cell migration to the tumor site, delays tumor growth, and enhances survival in murine tumor models.

CONCLUSION

This novel approach leverages the unique ability of polioviruses to activate DCs while simultaneously introducing the H3.3 K27M antigen. In this way, DCs are activated optimally in situ, while being simultaneously infected to express/present tumor antigen. RIPO(H3.3), given by intramuscular injection, will be evaluated in a clinical trial for children with H3 K27M-mutant diffuse midline glioma.
THER-09. ONCOLYTIC ADENOVIRUS, DNX-2401, FOR NAIVE DIFFUSE INTRINSIC PONTINE GLIOMAS: A PHASE I CLINICAL TRIAL
Authors: Iñigo-Marco Ignacio , Gonzalez-Huarriz Marisol , García-Moure Marc , Tamayo Ibon , Hervas Sandra , Hernandez Ruben , Buñales Maria , DeAndrea Carlos , Villalba Maria , Jones Chris , MacKay Alan , Hulleman Esther , Van der Lugt Jasper , Aldave Guillermo , Lopez-Ibor Blanca , Patiño-Garcia Ana , Diez-Valle Ricardo , Fueyo Juan , Gomez-Manzano Candelaria , de Larraya Jaime Gallego Perez , Tejada Sonia , Alonso Marta M
Published: December 2020

The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in newly diagnosed DIPG patients (NCT03178032) followed by radiotherapy. Secondary endpoints are overall survival at 12 months, percentage of responses and induced immune response against tumor. Tumor biopsy was performed through the cerebellar peduncle, followed by intratumoral injection of DNX-2401 (N=12). Three patients were treated with 1x1010vp and given the lack of toxicity we escalated to 5x1010vp. The procedure was well tolerated and reduced tumor volume was demonstrated in all patients after combined treatment (virus + radiotherapy). We performed molecular studies (RNAseq and the Oncomine Childhood Research Panel from Thermo Fisher). The immune cell composition of the biopsies pre-virus injection was assessed using multiplexed quantitative immunofluorescence. T cells were hardly detectable in these tumors while macrophages were abundant. Using a multiplexed TCR-sequencing mRNA-based assay to analyze 18 available paired pre- and post-treatment samples from the trial, we detected increased clonal T cell diversity following treatment with the virus. We also measured pre and post treatment neutralizing antibodies and their relationship with survival. Finally, we performed functional studies using 2 cell lines isolated from patients included in this trial to assess the response to the virus (infectivity, viability, T-cell recognition). In summary, the virus has shown safety and efficacy in some patients. The information obtained in this clinical study would aid understanding the response of DIPG patients to viral therapies and, therefore, to better tailor this strategy to improve the survival of these patients.
Regulation of Root Nutrient Transporters by CIPK23: ‘One Kinase to Rule Them All’
Authors: Ródenas Reyes , Vert Grégory
Published: December 2020

Protein kinases constitute essential regulatory components in the majority of cellular processes in eukaryotic cells. The CBL-INTERACTING PROTEIN KINASE (CIPK) family of plant protein kinases functions in calcium (Ca2+)-related signaling pathways and is therefore involved in the response to a wide variety of signals in plants. By covalently linking phosphate groups to their target proteins, CIPKs regulate the activity of downstream targets, their localization, their stability and their ability to interact with other proteins. In Arabidopsis, the CIPK23 kinase has emerged as a major hub driving root responses to diverse environmental stresses, including drought, salinity and nutrient imbalances, such as potassium, nitrate and iron deficiencies, as well as ammonium, magnesium and non-iron metal toxicities. This review will chiefly report on the prominent roles of CIPK23 in the regulation of plant nutrient transporters and on the underlying molecular mechanisms. We will also discuss the different scenarios explaining how a single promiscuous kinase, such as CIPK23, may convey specific responses to a myriad of signals.
An ER–Golgi Tethering Factor SLOH4/MIP3 Is Involved in Long-Term Heat Tolerance of Arabidopsis
Authors: Isono Kazuho , Tsukimoto Ryo , Iuchi Satoshi , Shinozawa Akihisa , Yotsui Izumi , Sakata Yoichi , Taji Teruaki
Published: December 2020

Plants are often exposed not only to short-term (S-) heat stress but also to diurnal long-term (L-) heat stress over several consecutive days. To reveal the mechanisms underlying L-heat stress tolerance, we here used a forward genetic screen for sensitive to long-term heat (sloh) mutants and isolated sloh4. The mutant was hypersensitive to L-heat stress but not to S-heat stress. The causal gene of sloh4 was identical to MIP3 encoding a member of the MAIGO2 (MAG2) tethering complex, which is composed of the MAG2, MIP1, MIP2 and MIP3 subunits and is localized at the endoplasmic reticulum (ER) membrane. Although sloh4/mip3 was hypersensitive to L-heat stress, the sensitivity of the mag2-3 and mip1–1 mutants was similar to that of the wild type (WT). Under L-heat stress, the ER stress and the following unfolded protein response (UPR) were more pronounced in sloh4 than in the WT. Transcript levels of bZIP60-regulated UPR genes were strongly increased in sloh4 under L-heat stress. Two processes known to be mediated by INOSITOL REQUIRING ENZYME1 (IRE1) — accumulation of the spliced bZIP60 transcript and a decrease in the transcript levels of PR4 and PRX34, encoding secretory proteins — were observed in sloh4 in response to L-heat stress. These findings suggest that misfolded proteins generated in sloh4 under L-heat stress may be recognized by IRE1 but not by bZIP28, resulting in the initiation of the UPR via activated bZIP60. Therefore, it would be possible that only MIP3 in the MAG2 complex has an additional function in L-heat tolerance, which is not related to the ER–Golgi vesicle tethering.
Lipid accumulation product is a reliable indicator for identifying metabolic syndrome: the China Multi-Ethnic Cohort (CMEC) Study
Authors: Zhang X , Hong F , Liu L , Nie F , Du L , Guan H , Wang Z , Zeng Q , Yang J , Wang J , Li X , Zhang J , Luo P
Published: December 2020

Background

Previous studies have shown that lipid accumulation product (LAP) was associated with the risk of cardiometabolic disease. It is not clear whether LAP could be used as a marker to identify metabolic syndrome (MetS) among Chinese ethnic groups.

Aim

To assess the reliability of LAP as a maker to identify MetS among Dong adults.

Design

Population-based cross-sectional study.

Method

We included 6494 Dong individuals (1403 patients) aged 30–79 years from southwest China. MetS was established by Chinese Diabetes Society. Logistic regression model was utilized to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curve was utilized to calculate area under the ROC curve (AUC) and 95% CIs to obtain the identification ability for MetS.

Results

The risk of MetS was increased with per 5 units increase of LAP (OR 1.37 [95% CI, 1.34–1.39]). Similar results were found in subgroup analyses and sensitivity analyses. Clustered metabolic risk associated with per 5 units increase of LAP was observed for people with 1 (OR 1.59 [95% CI, 1.53–1.65]), 2 (2.15 [2.06–2.24]), 3 (2.59 [2.48–2.71]), 4 (2.81 [2.69–2.95]) and 5 (3.03 [2.87–3.21]) MetS components. LAP presented higher AUC (0.915 [95% CI, 0.907–0.923]) than other included obesity indices (P < 0.05).

Conclusion

These data support evidence that LAP was related to the risk of MetS, had a high AUC and could be a reliable index for identifying MetS patients among Dong adults in Chinese.
Climate Change Policy: Can New Actors Affect Japan’s Policy-Making in the Paris Agreement Era?
Authors: KAMEYAMA Yasuko
Published: December 2020

This article examines changes in Japan’s policies related to climate change, focusing on three notable events that could have significantly altered Japan’s decisions on climate change: (a) the hosting of the Third Conference of the Parties (COP3) to the United Nations Framework Convention on Climate Change (UNFCCC) and the adoption of the Kyoto Protocol in December 1997, (b) the Fukushima Daiichi nuclear power plant accident in March 2011, and (c) the adoption of the Paris Agreement in December 2015 and its early enforcement in November 2016. The study shows that the Japanese government’s position remained fundamentally the same throughout these events. It called for emission reduction targets that would not harm the Japanese economy, considered nuclear power to be the least costly way to reduce carbon dioxide emissions, and avoided any mention of a 2°C mean global temperature rise as the long-term target. Meanwhile, after the Paris Agreement came into effect in 2016, an increasing number of Japanese private companies and local governments started taking voluntary actions to reduce their respective emissions, independent of national policy. These changes by sub/non-state actors have begun to alter decision-making at the national government level and could be a sign of transformational changes in Japan, wherein these new actors’ voices have a greater influence on Japan’s climate change policy than those of the traditional state-based actors.
‘Unconscionability’ and the case against lumping: three case studies
Authors: Liew Ying Khai
Published: December 2020

This article argues that unconscionability provides no good basis for arguments in favour of lumping equitable doctrines in English law. It explores three areas of equity where unconscionability has most strongly divided lumpers and splitters: undue influence and unconscionable bargains; proprietary estoppel and constructive trusts; and the ‘rule in Re Rose’ and the decision in Pennington v Waine. In relation to each discussion, the paper explains how lumpers rely on the idea of unconscionability to argue in favour of merging or expanding those established doctrines, and argues against lumping, by explaining how this distorts a proper understanding of the law.
Effects of myricetin against cadmium-induced neurotoxicity in PC12 cells
Authors: Aminzadeh Azadeh , Salarinejad Ayda
Published: December 2020

Cadmium (Cd) is one of the most prevalent toxic metals widely found in the environment. Cd induces toxicity and apoptosis in various organs and cells. The nervous system is one of the primary organs targeted by Cd. Cd toxicity is correlated with induction of severe oxidative stress. Myricetin, a natural product, has been found to exert protective effects against various disease conditions. The present study aimed to evaluate the potential protective effects of myricetin on Cd-induced neurotoxicity in PC12 cells. The cells were pretreated with myricetin in the absence and presence of Cd. The viability of cells was assessed using the MTT assay. Markers of oxidative stress were investigated by the lipid peroxidation (LPO), glutathione (GSH) content, and total antioxidant capacity (TAC). Moreover, activation of caspase 3 was examined by Western blot analysis. Myricetin could significantly enhance the viability of PC12 cells. Pretreatment of the cells with myricetin, prior to Cd exposure, showed a significant decrease in the levels of LPO whereas GSH and TAC levels were increased. In addition, the activity of caspase-3 was notably prevented by myricetin. These findings revealed that myricetin has protective effects on Cd-induced neurotoxicity in PC12 cells, which can be linked to its antioxidant potential, inhibition of LPO, and prevention of caspase-3 activation.
What Mediates Treatment Effects in a Presurgery Physiotherapy Treatment in Surgical Candidates With Degenerative Lumbar Spine Disorders? A Mediation and Conditional Process Analysis of the PREPARE Randomized Controlled Trial
Authors: Fors Maria , Öberg Birgitta , Lindbäck Yvonne , Enthoven Paul , Abbott Allan
Published: December 2020

Objectives:

Treatment guidelines recommend targeting both physical and psychological factors in interventions for degenerative lumbar spine disorders. Studying the treatment mechanisms gives information on key factors explaining the outcome improvement that can refine treatments. This study explores treatment mediators in a physiotherapy treatment on disability, pain intensity, and health-related quality of life in surgical candidates with degenerative lumbar spine disorders compared with waiting-list controls. An additional aim was to evaluate patients’ expectation as a moderator of treatment outcome.

Materials and Methods:

Data collected from 197 patients in a single-blinded randomized controlled trial comparing 9 weeks of multifaceted physiotherapy with waiting-list controls were used in this conditional process analysis. Analysis was carried out on group differences for change in Oswestry Disability Index, Pain Visual Analog Scale (VAS) back pain, EuroQol-5D, and EuroQol-VAS. The putative moderation role of expectations and mediation role of change in physical variables and psychosocial variables were tested.

Results:

Change in self-efficacy mediated improvement in all outcomes. Improvement in Oswestry Disability Index was also mediated by change in depression; VAS was mediated by change in fear-avoidance beliefs; and EuroQol-VAS was mediated by change in activity level and fear avoidance beliefs. Improvements were moderated by patients’ treatment expectations.

Discussion:

Self-efficacy, fear-avoidance beliefs, physical activity level, and patients’ treatment expectations were found to be important factors explaining treatment effects. Self-efficacy was the consistent mediator for effects of the presurgical physiotherapy on disability, back pain intensity, and health-related quality of life.
Experience With Cardiology-Oriented Outcomes in Critically Ill Patients With Coronavirus Disease 2019
Authors: Connor-Schuler Randi , Wong A. Ian , Shah Anand , Fiza Babar , Lyle Melissa , Ramonell Richard , Hockstein Maxwell , Chang George , Markham David , Searles Charles , McDaniel Michael , Baer Jefferson , Powell Cindy , Daniels Lisa
Published: December 2020

Objectives:

Coronavirus disease 2019 is associated with high mortality rates and multiple organ damage. There is increasing evidence that these patients are at risk for various cardiovascular insults; however, there are currently no guidelines for the diagnosis and management of such cardiovascular complications in patients with coronavirus disease 2019. We share data and recommendations from a multidisciplinary team to highlight our institution’s clinical experiences and guidelines for managing cardiovascular complications of coronavirus disease 2019.

Design, Setting, and Patients:

This was a retrospective cohort study of patients admitted to one of six ICUs dedicated to the care of patients with coronavirus disease 2019 located in three hospitals within one academic medical center in Atlanta, Georgia.

Measurements/Interventions:

Chart review was conducted for sociodemographic, laboratory, and clinical data. Rates of specific cardiovascular complications were assessed, and data were analyzed using a chi-square or Wilcoxon rank-sum test for categorical and continuous variables. Additionally, certain cases are presented to demonstrate the sub committee’s recommendations.

Main Results:

Two-hundred eighty-eight patients were admitted to the ICU with coronavirus disease 2019. Of these, 86 died (29.9%), 242 (84.03%) had troponin elevation, 70 (24.31%) had dysrhythmias, four (1.39%) had ST-elevation myocardial infarction, eight (2.78%) developed cor pulmonale, and 190 (65.97%) with shock. There was increased mortality risk in patients with greater degrees of troponin elevation (p < 0.001) and with the development of arrhythmias (p < 0.001), cor pulmonale (p < 0.001), and shock (p < 0.001).

Conclusions:

While there are guidelines for the diagnosis and management of pulmonary complications of coronavirus disease 2019, there needs to be more information regarding the management of cardiovascular complications as well. These recommendations garnered from the coronavirus disease 2019 cardiology subcommittee from our institution will add to the existing knowledge of these potential cardiovascular insults as well as highlight suggestions for the diagnosis and management of the range of cardiovascular complications of coronavirus disease 2019. Additionally, with the spread of coronavirus disease 2019, our case-based recommendations provide a bedside resource for providers newly caring for patients with coronavirus disease 2019.
Feasibility and Safety of Prone Position Transport for Severe Hypoxemic Respiratory Failure Due to Coronavirus Disease 2019
Authors: Seethala Raghu R. , Frakes Michael A. , Cocchi Michael N. , Cohen Jason E. , Dargin James , Friedman Frank , Grant Christian , Kaye Adam , Wilcox Susan R.
Published: December 2020

Objectives:

To assess the safety and feasibility of a new protocol for interhospital critical care transport of mechanically ventilated patients in the prone position during the coronavirus disease 2019 pandemic by nurse and paramedic critical care transport teams.

Design:

Retrospective observational study.

Setting:

Single critical care transport agency serving multiple centers in the greater Boston area.

Patients:

All transports of intubated patients in the prone position with severe hypoxemic respiratory failure secondary to coronavirus disease 2019.

Interventions:

Records were reviewed for patients transported in the prone position. Major adverse events in transport, defined as severe hypoxemia (oxygen saturation < 80% or an absolute decrease in oxygen saturation > 10%), hypotension (mean arterial pressure < 65 mm Hg) not responsive to vasopressors or inotropes, endotracheal tube or vascular catheter dislodgement, and cardiac arrest, were recorded.

Measurements and Main Results:

A total of 25 patients were transported in prone position. The mean Pao
2:Fio
2 ratio in the group was 101.3 mm Hg, and 76% (n = 19) were on vasopressors. Fourteen patients (56%) had hypotension with at least one episode of mean arterial pressure less than 65 mm Hg en route, and seven (28%) had an episode of oxygen desaturation less than 88%. Only one major adverse event of severe hypoxemia (oxygen saturation < 80%) was noted.

Conclusions:

Critical care transport of severe hypoxemic respiratory failure patients with coronavirus disease 2019 in the prone position is safe when performed by a dedicated team of critical care nurse and paramedics with an established protocol.
The Future of Nursing
Authors: Sanderson Carla D.
Published: December 2020

As development of the Future of Nursing 2020-30 Report by the National Academy of Medicine is underway, the nursing profession is positioned to continue positively impacting health and health equity in the United States. Progress to date engenders hope that nurses will continue to take a significant role in reducing health disparities. The work to create a culture of health aligns with the Christian imperative to “love your neighbor as yourself.”
Improving Healthcare Access by Teaching Intercultural Communication
Authors: Chatman Sherri H. , Wynn Stephanie T.
Published: December 2020

Nonnative English speakers may hesitate or avoid accessing healthcare in the United States due to cultural and communication barriers. Role-play is effective as a method of reducing healthcare access due to inadequate communication skills. A role-play activity used with female Muslim immigrants to the United States enabled participants to develop communication skills and gain confidence for future interactions with a healthcare provider.
Selenium modifies associations between multiple metals and neurologic symptoms in Gulf states residents
Authors: Werder Emily J. , Engel Lawrence S. , Curry Matthew D. , Sandler Dale P.
Published: December 2020

Background:

Metals have been shown to have a wide range of neurologic effects across the life course, but most studies consider neurodevelopment or neurodegenerative diseases in older adults. We investigated exposure to metals during adulthood in association with subclinical neurologic endpoints, considering the metals individually and as a mixture, and potential interactions among exposures.

Methods:

We measured blood levels of cadmium, lead, mercury, manganese, and selenium in 1007 Gulf state residents and estimated cross-sectional associations between ranked levels of blood metals and the presence of self-reported neurologic symptoms. Single pollutant models were mutually adjusted for other metals and we used quantile g-computation to evaluate associations with exposure to the combined mixture. In stratified analyses, we assessed heterogeneity by smoking and blood selenium.

Results:

The highest quartile of cadmium was associated with a higher prevalence of central nervous system symptoms (prevalence ratio [PR] = 1.50; 95% confidence interval [CI] = 1.13, 1.99), with stronger associations among nonsmokers (PR = 1.63; 95% CI = 1.11, 2.38) and those with low selenium (PR = 2.29, 95% CI = 1.50, 3.49). Selenium also modified associations between lead and peripheral nervous system symptoms, with increased symptoms in the low selenium group at all quartiles of exposure (P-trend = 0.07). Conversely, those with the highest co-exposure to mercury and selenium had reduced neurologic symptoms (PR = 0.73, 95% CI = 0.55, 0.96). Results of the mixture analysis were consistent with single chemical results.

Conclusions:

Cadmium exhibited the most consistent relationship with increased neurologic symptoms, though lead was an important exposure in subgroup analyses. Selenium may modify subclinical neurotoxic effects of metals at non-occupational levels in adults.
Efficacy of intra-operative administration of iron isomaltoside for preventing postoperative anaemia after total knee arthroplasty
Authors: Yoo Seokha , Bae Jinyoung , Ro Du H. , Han Hyuk-Soo , Lee Myung C. , Park Sun-Kyung , Lim Young-Jin , Bahk Jae-Hyon , Kim Jin-Tae
Published: December 2020

BACKGROUND

Postoperative anaemia is common after total knee arthroplasty (TKA). Emerging evidence shows the beneficial effects of peri-operative iron supplementation in patients at risk of postoperative anaemia.

OBJECTIVE

To evaluate the efficacy of intra-operative administration of iron isomaltoside for the prevention of postoperative anaemia in patients undergoing TKA.

DESIGN

Randomised, controlled, double-blind, parallel-group study.

SETTING

A tertiary care teaching hospital; between 29 March 2018 and 16 April 2019.

PATIENTS

Eighty-nine patients scheduled for unilateral TKA were included.

INTERVENTION

Iron isomaltoside or placebo were administered intravenously over 30 min during surgical wound closure.

MAIN OUTCOME MEASURES

The primary outcome measure was the incidence of anaemia at 30 days after TKA: anaemia was defined as haemoglobin less than 12 g dl−1 for female and less than 13 g dl−1 for male.

RESULTS

In total, 89 patients were included in the final analysis (44 in the treatment group; 45 in the control group). The administered dose of iron isomaltoside in the treatment group was 1136 ± 225 mg. The incidence of anaemia at 30 days after TKA was significantly lower in the treatment group (34.1%, 15/44) than that in the control group (62.2%, 28/45): relative risk 0.55 (95% confidence interval, 0.34 to 0.88), P = 0.008. Haemoglobin concentration, serum ferritin concentrations, and transferrin saturation were also significantly higher in the treatment group at 30 days after TKA.

CONCLUSION

The intra-operative administration of iron isomaltoside effectively prevents postoperative anaemia in patients undergoing TKA, and thus it can be included in patient blood management protocols for reducing postoperative anaemia in these population.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT03470649.
Chronic stress indicated by hair cortisol concentration in anaesthesiologists and its relationship to work experience and emotional intelligence
Authors: van der Wal Raymond A.B. , Bijleveld Erik , Herwaarden Antonius E. van , Bucx Martin J.L. , Prins Judith B. , Scheffer GertJan
Published: December 2020

BACKGROUND

Anaesthesia is a stressful medical specialty. The reaction to stress is constituted by behavioural, psychological and physiological components. Chronic physiological stress can have negative consequences for health.

OBJECTIVES

First, we hypothesised that chronic physiological stress is higher for both beginning and late-career consultant anaesthesiologists. Second, we hypothesised that individuals high in emotional intelligence endure lower physiological stress.

DESIGN

Cross-sectional biomarker and survey study.

SETTING

Participants were recruited during the May 2019 annual meeting of the Dutch Anaesthesia Society.

PARTICIPANTS

Of the 1348 colleagues who attended the meeting, 184 (70 male/114 female) participated in the study. Of the study participants, 123 (67%) were consultant anaesthesiologists (52 male/71 female) and 61 (33%) were resident anaesthesiologists (18 male/43 female). Exclusion criteria were endocrine disorders and not having enough hair. Also, experience of a recent major life event led to exclusion from analysis of our hypotheses.

MAIN OUTCOME MEASURES

Chronic physiological stress was measured by hair cortisol concentration. Emotional intelligence was assessed using a validated Dutch version of the Trait Emotional Intelligence Questionnaire. As secondary measures, psychological sources of stress were assessed using validated Dutch versions of the home-work interference (SWING) and the effort-reward imbalance questionnaires.

RESULTS

In support of Hypothesis 1, hair cortisol concentration was highest among early and late-career consultant anaesthesiologists (quadratic effect: b = 45.5, SE = 16.1, t = 2.8, P = 0.006, R
2 = 0.14). This nonlinear pattern was not mirrored by self-reported sources of psychological stress. Our results did not support Hypothesis 2; we found no evidence for a relationship between emotional intelligence and physiological stress.

CONCLUSION

In the early and later phases of an anaesthesiologist's career, physiological chronic stress is higher than in the middle of the career. However, this physiological response could not be explained from known sources of psychological stress. We discuss these findings against the background of key differences between physiological and psychological stress.
The efficacy of high flow nasal oxygenation for maintaining maternal oxygenation during rapid sequence induction in pregnancy
Authors: Zhou Shuangqiong , Zhou Yao , Cao Xiuhong , Ni Xiu , Du Weijia , Xu Zhendong , Liu Zhiqiang
Published: December 2020

BACKGROUND

High-flow nasal oxygenation (HFNO) for pre-oxygenation in rapid sequence induction (RSI) has only been assessed in volunteer parturients without intubation.

OBJECTIVES

To evaluate the efficacy of HFNO in comparison with the conventional facemask for oxygenation during RSI for caesarean section under general anaesthesia.

SETTING

Operating room in a tertiary hospital.

DESIGN

Prospective randomised, controlled study.

PARTICIPANTS

Thirty-four healthy parturients undergoing general anaesthesia for caesarean section.

INTERVENTIONS

Parturients were randomly assigned to HFNO or standard facemask (SFM) group.

MAIN OUTCOME MEASURES

The primary outcome measure was the PaO2 immediately after intubation. Secondary outcomes included lowest saturation throughout the intubation procedure, end-tidal oxygen concentration (EtO2) on commencing ventilation, blood gas analysis (pH, PaCO2), fetal outcomes and intubation-related adverse events.

RESULTS

PaO2 in the HFNO group was significantly higher than that in SFM group (441.41 ± 46.73 mmHg versus 328.71 ± 72.80 mmHg, P < 0.0001). The EtO2 concentration in the HFNO group was higher than that in the SFM group (86.71 ± 4.12% versus 76.94 ± 7.74%, P < 0.0001). Compared to baseline, PaCO2 immediately after intubation also increased significantly in both groups (HFNO group: 30.87 ± 2.50 mmHg versus 38.28 ± 3.18 mmHg; SFM group: 29.82 ± 2.57 mmHg versus 38.05 ± 5.76 mmHg, P < 0.0001), but there was no difference in PaCO2 between the two groups. There was no difference in lowest saturation, intubation times, duration of apnoea, pH value or fetal outcomes.

CONCLUSIONS

Compared with SFM, HFNO provided a higher PaO2 and EtO2 immediately after intubation in parturients. HFNO is safe as a method of oxygenation during RSI in parturients undergoing general anaesthesia for caesarean section.

TRIAL REGISTRATION

Clinical trial ChiCTR1900023121.
Alkali Burn Over a LASIK Flap
Authors: Witsberger Emily M. , Patel Sanjay V.
Published: December 2020

Purpose:

To describe the management and outcome of an ocular surface alkali burn in the setting of previous laser in situ keratomileusis (LASIK).

Methods:

This is a case report and review of relevant literature.

Results:

A 25-year-old man with a history of LASIK presented 4 weeks after a sodium hydroxide splash to his left eye with visual acuity of 20/60 and a nonhealing epithelial defect adjacent to sectoral inferior limbal ischemia in the setting of trichiasis from upper eyelid cicatricial entropion. After topical corticosteroids were discontinued following the repair of the entropion, the patient returned 3 days later with worsening vision and severe diffuse lamellar keratitis with the melting of the LASIK flap. After promptly lifting the flap and debriding the interface, inflammation was managed with oral, instead of topical, corticosteroids. Over several weeks, the epithelium healed, and inflammation and interface edema resolved. At 10 years of follow-up, the patient had developed a localized pseudopterygium with mild corneal neovascularization but maintained 20/20 uncorrected visual acuity.

Conclusions:

A chemical burn over a LASIK flap poses a challenge for managing corticosteroids, which are required to prevent diffuse lamellar keratitis but can also contribute to keratolysis beyond the first week after an alkali injury. Oral corticosteroid therapy may be beneficial in this situation, with a low threshold to lift the LASIK flap and debride the interface if inflammation occurs.
Investigating the Geometry and Mechanical Properties of Human Round Window Membranes Using Micro-Fringe Projection
Authors: Liang Junfeng , Nakmali Don , Gan Rong Z. , Lu Hongbing , Dai Chenkai
Published: December 2020

Hypothesis:

The geometry and the mechanical property of the round window membrane (RWM) have a fundamental impact on the function of cochlea.

Background:

Understanding the mechanical behavior of RWM is important for cochlear surgery and design for the cochlear implant. Although the anatomy of RWM has been widely studied and described in the literature, argument remains regarding the true shape of RWM. The mechanical properties of RWM are also scarcely reported due to the difficulty of the measurement of the small size RWM.

Methods:

In this paper, micro-fringe projection was used to reconstruct the 3-dimensional geometries of 14 RWMs. Mechanical properties of the RWMs were subsequently measured using finite element (FE) model and an inverse method. The three-dimensional surface topographies and the curvatures of the two major directions reconstructed from the micro-fringe projection both demonstrated wide variations among samples.

Results:

The diameters of the RWMs vary from 1.65 to 2.2 mm and the curvatures vary from −0.97 to 3.76 mm−1. The nonlinear elasticity parameters in the Ogden model for each sample was measured and the average effective Young's modulus is approximately 1.98 MPa.

Conclusion:

The geometries and mechanical properties of the human RWM measured in the work could potentially be applied to surgery design and on modeling analysis for the cochlea.
High expression of microRNA 221 is a poor predictor for glioma
Authors: Song Yanlin , He Min , Zhang Jing , Xu Jianguo
Published: December 2020

Background:

MicroRNA 221 has been found to be a good marker for several cancers. Some studies also focused on the relationship between microRNA 221 and glioma. However, the results are controversial. We aimed to systematically evaluate the prognostic role of microRNA 221 in glioma through performing a meta-analysis.

Methods:

The articles which were included in our study were searched on the Web of Science, EMBASE, PubMed, Cochrane Library and China National Knowledge Infrastructure. The basic characteristics and relevant data were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to evaluate the prognostic role of microRNA 221 in glioma.

Results:

Eight studies with 1069 patients were included. We systematically evaluated the role of microRNA 221 for overall survival (OS) and disease free survival (DFS) in glioma patients (HR for OS = 1.66, 95% CI, 1.34–2.04; HR for DFS = 1.14, 95% CI, 1.02–1.26). Subgroup analyses were performed according to the nation of the studies, the origin of the samples, the stage of the tumors, the cut-off value, and the method for detecting the microRNA 221. No significant publication bias was found (P = .133).

Conclusion:

In conclusion, high expression of microRNA 221 was related to poor prognosis of glioma. These findings may assist future exploration on microRNA 221 and help predict the prognosis of glioma. However, due to the significant heterogeneity of these studies, more studies are warranted.
Breast metastasis from EGFR/ALK negative lung adenocarcinoma
Authors: Cao Liyu , Lv Liting
Published: December 2020

Introduction:

Lung adenocarcinoma is the most common type of lung cancer. Distant metastasis of lung adenocarcinoma often occurs in multiple organs. The common metastasis sites of lung cancer include the lungs, brain, bones, adrenal glands, and lymph nodes; however, breast metastasis is rare.

Patient concerns:

In this report, we describe a case of breast metastasis from lung adenocarcinoma. A 55-year-old woman reported left breast pain for more than 1 month.

Diagnosis:

Based on imaging, pathological examination, and immunohistochemical examination, the diagnosis of breast metastasis from lung adenocarcinoma was confirmed. Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement were not detected by next-generation sequencing.

Interventions:

The patient was treated with six courses of a combination of albumin-bound paclitaxel, cisplatin, and bevacizumab over 21 days.

Outcomes:

After six cycles of palliative chemotherapy, her left breast pain and swelling subsided; in addition, her serum CA12-5, CYFRA, and CEA levels normalized by April 2019. PR status was evaluated as per the RECIST 1.1 criteria. The patient developed brain metastases 3 months later and died due to multiple organ failure.

Conclusion:

The possibility of breast metastasis should be considered in patients with existing malignant tumors and breast pain. Clinical and imaging examinations are helpful for diagnosis, and pathological and immunohistochemical analyses are the most important diagnostic tools.
Application of ultrasound in a congenital cystic adenomatoid malformation in an adult
Authors: Xu Wen , Wen Qing , Zha Lijing , Liu Chunmei , Huang Pintong
Published: December 2020

Introduction:

Congenital cystic adenomatoid malformation (CCAM) is a rare developmental lung abnormality, that typically manifests in neonates and infants but rarely in adults. Ultrasound is an important method of diagnosing CCAM in neonates and infants; however, few articles have reported the value of transthoracic lung ultrasound in the diagnosis of CCAM in adults.

Patient concerns:

We present a case of a 34-year-old woman with a cavitary lesion in her left lower lobe, that suggested chronic inflammation.

Diagnosis:

The patient underwent ultrasound examination and contrast-enhanced ultrasound-guided transthoracic core biopsy; histology suggested the diagnosis of lung hamartoma. Surgical resection of the lesion followed by histopathological analysis confirmed the diagnosis of CCAM.

Interventions:

The patient underwent transthoracic core biopsy under contrast-enhanced ultrasound guidance. A left lower lobectomy was then performed subsequently.

Outcomes:

The patient had a smooth recovery and remained asymptomatic during the 12-months of postoperative follow-up.

Conclusion:

We report a rare case of CCAM to suggest that transthoracic ultrasound combined with contrast-enhanced ultrasound is a safe and effective method of diagnosing the subpleural lung malformations in adults, thereby avoiding multiple radiation exposures and associated complications.
Latent Class Analysis to Represent Social Determinant of Health Risk Groups in the Medicaid Cohort of the District of Columbia
Authors: McCarthy Melissa L. , Zheng Zhaonian , Wilder Marcee E. , Elmi Angelo , Kulie Paige , Johnson Samuel , Zeger Scott L.
Published: December 2020

Objective:

To develop distinct social risk profiles based on social determinants of health (SDH) information and to determine whether these social risk groups varied in terms of health, health care utilization, and costs.

Methods:

We prospectively enrolled 8943 beneficiaries insured by the District of Columbia Medicaid program between September 2017 and December 2018. Participants completed a SDH survey and we obtained their Medicaid claims data for a 2-year period before study enrollment. We used latent class analysis (LCA) to identify distinct social risk profiles based on their SDH responses. We assessed the relationship among different SDH as well as the relationship among the social risk classes and health, health care use and costs.

Results:

The majority of SDH were moderately to strongly correlated with one another. LCA yielded 4 distinct social risk groups. Group 1 reported the least social risks with the most employed. Group 2 was distinguished by financial strain and housing instability with fewer employed. Group 3 were mostly unemployed with limited car and internet access. Group 4 had the most social risks and most unemployed. The social risk groups demonstrated meaningful differences in health, acute care utilization, and health care costs with group 1 having the best health outcomes and group 4 the worst (P<0.05).

Conclusions:

LCA is a practical method of aggregating correlated SDH data into a finite number of distinct social risk groups. Understanding the constellation of social challenges that patients face is critical when attempting to address their social needs and improve health outcomes.
Surgical Re-entry Strategy Following COVID-19 Pandemic
Authors: Wohler Andrew D. , Kneisl Jeffrey S. , Macknet David M. , Hysong Alexander A. , Kaney Kathleen , Moroney Scott , Hsu Joseph R.
Published: December 2020

Following the Presidential declaration of a national emergency, many health care organizations adhered to recommendations from the Centers for Medicare and Medicaid (CMS) as well as the American College of Surgeons (ACS) to postpone elective surgical cases. The transition to only emergent and essential urgent surgical cases raises the question, how and when will hospitals and surgery centers resume elective cases? As a large health care system providing multispecialty tertiary/quaternary care with across the Southeast United States, a collaborative approach to resuming elective surgery is critical. Numerous surgical societies have outlined a tiered approach to resuming elective surgery. The majority of these guidelines are suggestions which place the responsibility of making decisions about re-entry strategy on individual health care systems and practitioners, taking into account the local case burden, projected case surge, and availability of resources and personnel. This paper reviews challenges and solutions related to the resumption of elective surgeries and returning to the pre-COVID-19 surgical volume within an integrated health care system that actively manages 18 facilities, 111 operating rooms, and an annual operative volume exceeding 123,000 cases. We define the impact of COVID-19 across our surgical departments and outline the staged re-entry approach that is being taken to resume surgery within the health care system.
Occult Pneumothorax Identification on Extended Focused Assessment with Sonography for Trauma Examination in Children
Authors: Malek Daniel , Santillanes Genevieve , Hsiao Victor , Mailhot Thomas , Claudius Ilene
Published: December 2020

Objective

Occult pneumothoraces (OPTXs) are defined by air within the pleural space that is not visible on conventional chest radiographs (CXR). The aim of this study was to understand how frequently the Extended Focused Assessment with Sonography for Trauma (eFAST) examination identifies occult PTX in a pediatric blunt trauma population as compared with a criterion standard of chest computed tomography (CCT).

Methods

This study is a secondary analysis of blunt trauma patients younger than 18 years who underwent CCT at Los Angeles County +USC Medical Center Emergency Department from October 2015 to April 2017. The eFAST examination was performed and documented by an emergency medicine resident with attending oversight or by an emergency medicine attending for each trauma. The eFAST results were reviewed for patients diagnosed with small or trace pneumothoraces identified on CCT.

Results

Of 168 pediatric trauma patients undergoing CCT, 16 had OPTXs not seen on CXR and 4 patients had a small/trace PTX without a corresponding CXR performed. None were identified on eFAST.

Conclusions

Although the sample size in this data set was small, our eFAST examinations identified none of 16 proven and 4 presumed OPTXs. The standard eFAST examination performed poorly in the detection of OPTXs in this single-center study of pediatric blunt trauma victims.