bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionomycin-induced mouse oocyte activation can disrupt preimplantation embryo development through increased reactive oxygen species reaction and DNA damage
Authors: Chen Chen , Sun Tingye , Yin Mingru , Yan Zhiguang , Yu Weina , Long Hui , Wang Li , Liao Xiaoyu , Yan Zheng , Li Wenzhi , Lyu Qifeng
Published: July 2020

Oocyte activation induced by calcium oscillations is an important process in normal fertilization and subsequent embryogenesis. In the clinical-assisted reproduction, artificial oocyte activation (AOA) is an effective method to improve the clinical outcome of patients with null or low fertilization rate after ICSI. However, little is known about the effect of AOA on preimplantation embryo development in cases with normal fertilization by ICSI. Here, we used ionomycin at different concentrations to activate oocytes after ICSI with normal sperm and evaluated energy metabolism and preimplantation embryo development. We found that a high concentration of ionomycin increased the frequency and amplitude of calcium oscillation patterns, affecting the balance of mitochondrial energy metabolism, leading to increased reactive oxygen species (ROS) and decreased ATP. Eventually, it increases DNA damage and decreases blastocyst formation. In addition, the addition of vitamin C to the culture medium ameliorated the increase in ROS and DNA damage and rescued the abnormal embryo development caused by excessive ionomycin activation. This study provides a perspective that the improper application of AOA may have adverse effects on preimplantation embryo development. Thus, clinical AOA treatment should be cautiously administered.
Single-molecule live-cell imaging reveals RecB-dependent function of DNA polymerase IV in double strand break repair
Authors: Henrikus Sarah S , Henry Camille , McGrath Amy E , Jergic Slobodan , McDonald John P , Hellmich Yvonne , Bruckbauer Steven T , Ritger Matthew L , Cherry Megan E , Wood Elizabeth A , Pham Phuong T , Goodman Myron F , Woodgate Roger , Cox Michael M , van Oijen Antoine M , Ghodke Harshad , Robinson Andrew
Published: July 2020

Several functions have been proposed for the Escherichia coli DNA polymerase IV (pol IV). Although much research has focused on a potential role for pol IV in assisting pol III replisomes in the bypass of lesions, pol IV is rarely found at the replication fork in vivo. Pol IV is expressed at increased levels in E. coli cells exposed to exogenous DNA damaging agents, including many commonly used antibiotics. Here we present live-cell single-molecule microscopy measurements indicating that double-strand breaks induced by antibiotics strongly stimulate pol IV activity. Exposure to the antibiotics ciprofloxacin and trimethoprim leads to the formation of double strand breaks in E. coli cells. RecA and pol IV foci increase after treatment and exhibit strong colocalization. The induction of the SOS response, the appearance of RecA foci, the appearance of pol IV foci and RecA-pol IV colocalization are all dependent on RecB function. The positioning of pol IV foci likely reflects a physical interaction with the RecA* nucleoprotein filaments that has been detected previously in vitro. Our observations provide an in vivo substantiation of a direct role for pol IV in double strand break repair in cells treated with double strand break-inducing antibiotics.
Interplay of RFX transcription factors 1, 2 and 3 in motile ciliogenesis
Authors: Lemeille Sylvain , Paschaki Marie , Baas Dominique , Morlé Laurette , Duteyrat Jean-Luc , Ait-Lounis Aouatef , Barras Emmanuèle , Soulavie Fabien , Jerber Julie , Thomas Joëlle , Zhang Yong , Holtzman Michael J , Kistler W Stephen , Reith Walter , Durand Bénédicte
Published: July 2020

Cilia assembly is under strict transcriptional control during animal development. In vertebrates, a hierarchy of transcription factors (TFs) are involved in controlling the specification, differentiation and function of multiciliated epithelia. RFX TFs play key functions in the control of ciliogenesis in animals. Whereas only one RFX factor regulates ciliogenesis in C. elegans, several distinct RFX factors have been implicated in this process in vertebrates. However, a clear understanding of the specific and redundant functions of different RFX factors in ciliated cells remains lacking. Using RNA-seq and ChIP-seq approaches we identified genes regulated directly and indirectly by RFX1, RFX2 and RFX3 in mouse ependymal cells. We show that these three TFs have both redundant and specific functions in ependymal cells. Whereas RFX1, RFX2 and RFX3 occupy many shared genomic loci, only RFX2 and RFX3 play a prominent and redundant function in the control of motile ciliogenesis in mice. Our results provide a valuable list of candidate ciliary genes. They also reveal stunning differences between compensatory processes operating in vivo and ex vivo.
The economics of the COVID-19 pandemic: an assessment
Authors: Susskind Daniel , Vines David
Published: July 2020

The COVID-19 pandemic has created both a medical crisis and an economic crisis. As others have noted, we face challenges just as big as those in the Spanish Flu Pandemic and the Great Depression—all at once. The tasks facing policy-makers are extraordinary. Many new kinds of intervention are urgently required. This issue of the Oxford Review of Economic Policy has two objectives. The first is to explore these new interventions: evaluating their use, suggesting how they might be improved, and proposing alternatives. The second is to show that the challenges facing us are global and will require international cooperation if they are to be dealt with effectively. This short introductory essay positions the papers in the issue within an overall conceptual framework, with the aim of telling an overarching story about the pandemic.
Measurements of the Ca ii infrared triplet emission lines of pre-main-sequence stars
Authors: Yamashita Mai , Itoh Yoichi , Takagi Yuhei
Published: July 2020

We investigated the chromospheric activity of 60 pre-main-sequence (PMS) stars in four molecular clouds and five moving groups. It is considered that strong chromospheric activity is driven by the dynamo processes generated by stellar rotation. In contrast, several researchers have pointed out that the chromospheres of PMS stars are activated by mass accretion from their protoplanetary disks. In this study, the Ca ii infrared triplet (IRT) emission lines were investigated utilizing medium- and high-resolution spectroscopy. The observations were conducted with Nayuta/MALLS and Subaru/HDS. Additionally, archive data obtained by Keck/HIRES, VLT/UVES, and VLT/X-Shooter were used. The small ratios of the equivalent widths indicate that Ca ii IRT emission lines arise primarily in dense chromospheric regions. Seven PMS stars show broad emission lines. Among them, four PMS stars have more than one order of magnitude brighter emission line fluxes compared to the low-mass stars in young open clusters. The four PMS stars have a high mass accretion rate, which indicates that the broad and strong emission results from a large mass accretion. However, most PMS stars exhibit narrow emission lines. No significant correlation was found between the accretion rate and flux of the emission line. The ratios of the surface flux of the Ca ii IRT lines to the stellar bolometric luminosity, $R^{\prime }_{\rm IRT}$, of the PMS stars with narrow emission lines are as large as the largest $R^{\prime }_{\rm IRT}$ of the low-mass stars in the young open clusters. This result indicates that most PMS stars, even in the classical T Tauri star stage, have chromospheric activity similar to zero-age main-sequence stars.
Late-onset versus early-onset systemic lupus: characteristics and outcome in a national multicentre register (RELESSER)
Authors: Riveros Frutos Anne , Holgado Susana , Sanvisens Bergé Arantza , Casas Irma , Olivé Alejandro , López-Longo Francisco J , Calvo-Alén Jaime , Galindo María , Fernández-Nebro Antonio , Pego-Reigosa José M , Rúa-Figueroa Iñigo ,   the RELESSER Group, García-Villanueva Jesús , Ruiz-Lucea María E , Toyos-Sáenz-de-Miera Francisco J , Andréu-Sánchez José Luis , Heras Cristina Bohórquez , Cobo-Ibáñez Tatiana , Rivas Nuria Lozano , Salgado-Pérez Eva , Ruán Jesús Ibáñez , Erausquin Celia , Tomero Eva , Horcada Loreto , Uriarte Esther , Sánchez-Atrio Ana , Rosas José , Montilla Carlos , Rodríguez–Gómez Manuel , Vela Paloma , Blanco Ricardo , Freire Mercedes , Silva Lucía , Álvarez Elvira Díez , Barceló Mónica Ibáñez , Zea Antonio , Narváez Javier , Martínez-Taboada Víctor , Marenco José Luis , de Castro Mónica Fernández , Hernández-Beriain José Ángel , Gantes Marian , Hernández-Cruz Blanca , Pérez-Venegas José J , Pecondón Ángela , Marras Carlos , Carreira Patricia , Bonilla Gema , Torrente Vicente , Castellví Iván , Alegre Juan , Moreno Mireia , Raya Enrique , de la Peña Paloma García , Vázquez Tomás , Aguirre Ángeles , Quevedo Víctor
Published: July 2020

Objective

The aim of the present study was to describe the demographic, clinical and immunological characteristics of patients with late-onset (≥50 years) SLE vs patients with early-onset SLE (<50 years).

Methods

We performed a cross-sectional retrospective study of 3619 patients from the RELESSER database (National Register of Patients with Systemic Lupus Erythematosus of the Spanish Society of Rheumatology).

Results

A total of 565 patients (15.6%) were classified as late-onset SLE and 3054 (84.4%) as early-onset SLE. The male-to-female ratio was 5:1. Mean (s.d.) age at diagnosis in the late-onset group was 57.4 (10.4) years. At diagnosis, patients with late-onset SLE had more comorbid conditions than patients with early-onset SLE; the most frequent was cardiovascular disease (P <0.005). Furthermore, diagnostic delay was longer in patients with late-onset SLE [45.3 (3.1) vs 28.1 (1.0); P <0.001]. Almost all patients with late-onset SLE (98.7%) were Caucasian. Compared with early-onset SLE and after adjustment for time since diagnosis, patients with late-onset SLE more frequently had serositis, major depression, thrombotic events, cardiac involvement and positive lupus anticoagulant values. They were also less frequently prescribed immunosuppressive agents. Mortality was greater in late-onset SLE (14.3% vs 4.7%; P <0.001).

Conclusion

Late-onset SLE is insidious, with unusual clinical manifestations that can lead to diagnostic errors. Clinical course is generally indolent. Compared with early-onset disease, activity is generally reduced and immunosuppressants are less commonly used. Long-term prospective studies are necessary to determine whether the causes of death are associated with clinical course or with age-associated comorbidities in this population.
Evaluation of the impact of a nurse-led program of patient self-assessment and self-management in axial spondyloarthritis: results of a prospective, multicentre, randomized, controlled trial (COMEDSPA)
Authors: Molto Anna , Gossec Laure , Poiraudeau Serge , Claudepierre Pascal , Soubrier Martin , Fayet Françoise , Wendling Daniel , Gaudin Philippe , Dernis Emmanuelle , Guis Sandrine , Pouplin Sophie , Ruyssen-Witrand Adeline , Chales Gerard , Mariette Xavier , Beauvais Catherine , Combe Bernard , Flipo René-Marc , Richette Pascal , Chary-Valckenaere Isabelle , Saraux Alain , Sibilia Jean , Schaeverbeke Thierry , Dougados Maxime
Published: July 2020

Objective

To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis.

Methods

Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group).

Results

A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ).

Conclusion

This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.
White Matter Microstructural Abnormalities in the Broca’s-Wernicke’s-Putamen “Hoffman Hallucination Circuit” and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations
Authors: Salisbury Dean F , Wang Yiming , Yeh Fang-Cheng , Coffman Brian A
Published: July 2020

Background

Functional connectivity abnormalities between Broca’s and Wernicke’s areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca’s and Wernicke’s areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca’s-Wernicke’s-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP.

Methods

White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI).

Results

FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different.

Conclusions

Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca’s and Wernicke’s areas. Other bilateral tracts’ gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.
Radial oxygen loss is correlated with nitrogen nutrition in mangroves
Authors: Cheng Hao , Liu Yong , Jiang Zhao-Yu , Wang You-Shao
Published: July 2020

The present study aimed to explore the possible functions of radial oxygen loss (ROL) on mangrove nutrition. A field survey was conducted to explore the relations among ROL, root anatomy and leaf N in different mangrove species along a continuous tidal gradient. Three mangroves with different ROL (Avicennia marina [A. marina], Kandelia obovata and Rhizophora stylosa) were then selected to further explore the dynamics of N at the root-soil interface. The results showed that seaward pioneer mangrove species such as A. marina appeared to exhibit higher leaf N despite growing under poorer nutrient conditions. Greater leaf N in pioneer mangroves coincided with their special root structure (e.g., high porosity together with a thin lignified/suberized exodermis) and powerful ROL. An interesting positive relation was observed between ROL and leaf N in mangroves. Moreover, rhizo-box data further showed that soil nitrification was also strongly correlated with ROL. A. marina, which had the highest ROL among the three mangrove species studied, consistently possessed the highest levels of NO3−, nitrification and ammonia-oxidizing bacteria and archaea gene copies in the rhizosphere. Besides, both NO3− and NH4+ influxes were found to be higher in the roots of A. marina when compared to those of K. obovata and R. stylosa. In summary, greater N acquisition by pioneer mangroves such as A. marina was strongly correlated with ROL which would regulate N transformation and translocation at the root-soil interface. The implications of this study may be significant in mangrove nutrition and the mechanisms involved in mangrove zonation.
Stability of Hybrid Maize Reaction to Gibberella Ear Rot and Deoxynivalenol Contamination of Grain
Authors: Lana F. Dalla , Paul P. A. , Minyo R. , Thomison P. , Madden L. V.
Published: July 2020

Trials were conducted to quantify the stability (or lack of G × E interaction) of 15 maize hybrids to Gibberella ear rot (GER; caused by Fusarium graminearum) and deoxynivalenol (DON) contamination of grain across 30 Ohio environments (3 years × 10 locations). In each environment, one plot of each hybrid was planted and 10 ears per plot were inoculated via the silk channel. GER severity (proportion of ear area diseased) and DON contamination of grain (ppm) were quantified. Multiple rank-based methods, including Kendall’s concordance coefficient (W) and Piepho’s U, were used to quantify hybrid stability. The results found insufficient evidence to suggest crossover G × E interaction of ranks, with W greater than zero for GER (W = 0.28) and DON (W = 0.26), and U not statistically significant for either variable (P > 0.20). Linear mixed models (LMMs) were also used to quantify hybrid stability, accounting for crossover or noncrossover G × E interaction of transformed observed data. Based on information criteria and likelihood ratio tests for GER and DON response variables, the models with more complex variance-covariance structures—heterogeneous compound symmetry and factor-analytic—provided a better fit than the model with the simpler compound symmetry structure, indicating that one or more hybrids differed in stability. Overall, hybrids were stable based on rank-based methods, which indicated a lack of crossover G × E interaction, but the LMMs identified a few hybrids that were sensitive to environment. Resistant hybrids were generally more stable than susceptible hybrids.
Communication during crisis
Authors: Eldridge Chad C. , Hampton Debra , Marfell Julie
Published: July 2020

The importance of leadership, messaging, and overcoming barriers
Disability Discrimination Against People With Substance Use Disorders by Postacute Care Nursing Facilities: It is Time to Stop Tolerating Civil Rights Violations
Authors: Dineen Kelly K.
Published: July 2020

People with substance use disorders (PWSUDs), including opioid use disorder (OUD), continue to face widespread discrimination, including in health care. As hospitals increasingly provide more appropriate and integrated care for PWSUDs, nursing facilities that provide postacute care are receiving more referrals for patients whose diagnosis of substance use disorders is acknowledged rather than ignored. A concerning number of these facilities refuse to admit or treat PWSUD, especially those with OUD receiving opioid agonist therapy (OAT). This practice violates multiple federal antidiscrimination laws. Postacute care nursing facilities, such a skilled nursing or rehabilitation facilities, must end discriminatory practices against PWSUDs. Legal actors, from government enforcers to public interest lawyers, should utilize existing laws to communicate that noncompliance is no longer tolerated and that the civil rights of PWSUDs matter.
Plasma Concentrations of Select Inflammatory Cytokines Predicts Pain Intensity 48 Hours Post-Shoulder Muscle Injury
Authors: Hedderson William C. , Borsa Paul A. , Fillingim Roger B. , Coombes Stephen A. , Hass Chris J. , George Steven Z.
Published: July 2020

Objectives:

The relationship between elevated inflammatory cytokine levels and peak pain intensity following acute musculoskeletal injury has not been fully elucidated in high risk subgroups. Identifying the role that these cytokines have on pain responses may help with developing tailored therapeutic approaches.

Methods:

Data were collected from 54 participants who were vulnerable to a robust pain response and delayed recovery following musculoskeletal injury. Participants completed baseline active and resting pain measurements and a blood draw before an exercised induced shoulder muscle injury. Participants returned at 24 and 48 hours postinjury for follow-up pain measurements and blood draws. Blood plasma was analyzed for interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor α. Pearson bivariate correlations were performed between cytokines and pain measurements to identify candidate variables for stepwise multiple linear regression predicting pain intensity reports.

Results:

Pearson bivariate correlation identified 13/45 correlations between inflammatory cytokines and resting pain intensity and 9/45 between inflammatory cytokines and active pain (P<0.05, r≥0.3 or r≤−0.3). This led to 5 stepwise multiple linear regression models, of which 4 met the statistical criterion (P<0.0167); including IL-10 baseline plasma concentrations predicting active pain (r
2=0.19) and resting pain (r
2=0.15) intensity 48 hours postinjury. IL-6 and IL-10 plasma concentrations at 48 hours were respectively associated with active and resting pain at 48 hours.

Discussion:

These findings suggest that elevated concentrations of inflammatory cytokines, specifically IL-10 (at baseline and 48 h) and IL-6 (at 48 h), may play a role in heightened pain responses following exercise-induced muscle injury.
Risk Factors for Delayed Extubation Following High Posterior Cervical and Occipital Fusion
Authors: Buhl Lauren K. , Mueller Ariel L. , Boone M. Dustin , Nozari Ala
Published: July 2020

Background:

Much has been written on initial airway management in patients undergoing cervical spine procedures, but comparatively less is known about extubation criteria. High cervical and occipital fusion procedures pose a particular risk for extubation given the potential for a reduced range of motion at the occiput-C1 and C1-C2 joints should reintubation be necessary.

Materials and Methods:

We performed a retrospective cohort analysis of posterior high cervical and occipital fusion cases to identify factors related to delayed extubation and postoperative airway and pulmonary complications. Using a convenience sample of all cases operated between January 2009 and April 2018, we reviewed anesthesia records and discharge summaries to compare patient characteristics, airway management, surgical factors, and postoperative complications between patients who underwent delayed extubation and those who did not.

Results:

A total of 135 patients met our inclusion criteria. Overall, 92 (68.1%) patients were extubated in the operating room (OR), and 43 (31.9%) underwent delayed extubation. Multivariate logistic regression analysis identified age, procedure length, C2 as the highest level fused, and percentage colloid administered as predictors of delayed extubation. We did not find a difference in the rate of postoperative pulmonary complications between groups (6/92 [6.5%] for OR extubation; 2/43 [4.7%] for delayed extubation). Two patients had serious airway complications, and both were extubated in the OR (2/92, 2.2%).

Conclusions:

The decision to extubate immediately postoperatively after high cervical and occipital fusion should be considered carefully as the morbidity associated with airway obstruction can be severe in this population, while negative effects of delayed extubation were not evident in our analysis.
Tracking clinical resources for coronavirus disease 2019
Authors: Duron Garret , Gelman Lauren , Dua Anisha , Putman Michael
Published: July 2020

Purpose of review

Assimilating and disseminating information during the novel coronavirus disease 2019 (COVID-19) has been challenging. The purpose of this review is to identify specific threats to the validity of the COVID-19 literature and to recommend resources for practicing rheumatologists and their patients.

Recent findings

The COVID-19 literature has rapidly expanded and includes 17 998 publications through May of 2020, 1543 of which also address rheumatic disease-related topics. Specific obstacles to acquiring high-quality information have arisen, including ‘pandemic research exceptionalism’ and a ‘parallel pandemic’ of misinformation. Unique challenges to rheumatologists include specific interest in antirheumatic disease therapies and a paucity of rheumatology-specific information. Patients with rheumatic diseases have faced shortages of critical medications and a lack of information tailored to their health conditions and medications.

We recommend rheumatologists develop a system to acquire high-quality information and offer guiding principles for triaging specific resources, which include relevance, accessibility, credibility, timeliness, and trustworthiness. The same principles can be applied to selecting patient oriented resources. Specific trustworthy resources are recommended.
CircHECTD1 up-regulates mucin 1 expression to accelerate hepatocellular carcinoma development by targeting microRNA-485-5p via a competing endogenous RNA mechanism
Authors: Jiang Qiao-Li , Feng Shu-Jiong , Yang Zhu-Ying , Xu Qi , Wang Shuang-Zhu
Published: July 2020

Background:

Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process.

Methods:

We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant.

Results:

MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ± 0.215 vs. 75.213 ± 18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ± 0.684 vs. 1.586 ± 0.398, t = 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ± 5.13% vs. 41.33% ± 3.51%, t = 8.913, P < 0.001), migration (102 ± 8 cells vs. 46 ± 8 cells, t = 8.681, P < 0.001), invasion (59 ± 7 cells vs. 28 ± 2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ± 6.97% vs. 36.33% ± 3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level.

Conclusions:

Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.
Senolytic Agent Navitoclax Inhibits Angiotensin II-Induced Heart Failure in Mice
Authors: Jia Kangni , Dai Yang , Liu Ao , Li Xiang , Wu Liqun , Lu Lin , Bao Yangyang , Jin Qi
Published: July 2020

Navitoclax, which is a type of senolytic drug, selectively eliminates senescent cells. This study aimed to evaluate the therapeutic potential of navitoclax in treatment of angiotensin II (Ang II)-induced heart failure in mice. Navitoclax or vehicle was administrated in mice with Ang II-induced heart failure. Cardiac function and electrophysiology were assessed before and after administration of navitoclax. Cardiac remodeling, including morphological changes, fibrosis, and inflammatory responses, was analyzed in myocardial tissue. Cellular effects of navitoclax were validated in isolated primary cardiomyocytes and cardiac fibroblasts in vitro. Echocardiography of mice showed that navitoclax improved cardiac dysfunction by improving the left ventricular ejection fraction (vehicle: 45.88 ± 2.19%; navitoclax: 54.70 ± 1.65%, P < 0.01). In cardiac electrophysiological testing, navitoclax increased conduction velocity (vehicle: 1.37 ± 0.05 mm/ms; navitoclax: 1.69 ± 0.08 mm/ms, P < 0.05) and decreased susceptibility to ventricular tachyarrhythmia induced by programmed electrical stimulation. Histopathological staining, immunofluorescence, and western blotting examinations showed that navitoclax ameliorated Ang II-induced cardiac fibrosis, hypertrophy, and the inflammatory response. Moreover, navitoclax eliminated senescent cells by inducing apoptosis. Therefore, navitoclax improved cardiac function and electrophysiological characteristics through decreasing cardiac fibrosis, hypertrophy, and inflammation in mice with heart failure. Pharmacological clearance of senescent cells may be a potential therapeutic approach in heart failure with reduced ejection fraction.
Sulfur Dioxide: An Endogenous Protector Against Myocardial Injury
Authors: Zhou Dan , Zhang Yong , Du Junbao , Jin Hongfang , Tang Chaoshu , Huang Yaqian
Published: July 2020

Sulfur dioxide (SO2) was previously known as a harmful gas in air pollution. Recently, it was reported that SO2can be endogenously generated in cardiovascular tissues. Many studies have revealed that endogenous SO2has important physiological and pathophysiological significance and pharmacological potential. As a novel gasotransmitter, SO2has important regulatory effects on the heart. It has a dose-dependent negative inotropic effect on cardiac function, in which L-type calcium channels are involved. SO2can also attenuate myocardial injury caused by various harmful stimuli and play an important role in myocardial ischemia-reperfusion injury and myocardial hypertrophy. These effects are thought to be linked to its ability to reduce inflammation and as an antioxidant. In addition, SO2regulates cardiomyocyte apoptosis and autophagy. Therefore, endogenous SO2plays an important role in maintaining cardiovascular system homeostasis. In the present review, the literature concerning the metabolism of endogenous SO2, its cardiac toxicological effects and physiological regulatory effects, mechanisms for SO2-mediated myocardial protection and its pharmacological applications are summarized and discussed.
Hydroxychloroquine and antiphospholipid antibody-related pregnancy morbidity: a systematic review and meta-analysis
Authors: Frishman Margreta , Radin Massimo , Schreiber Karen
Published: July 2020

Purpose of review

Pregnancies in women with antiphospholipid antibodies (aPL) are associated with several pregnancy complications. The current treatment to prevent obstetric aPL-mediated morbidity is largely based on low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH). Alternative treatment regimens to prevent obstetric aPL-related morbidity include the addition of the antimalarial hydroxychloroquine (HCQ). The aim of this systematic review is to identify the currently available evidence on the efficacy of HCQ to prevent aPL-related obstetric morbidity.

Recent findings

We identified four retrospective observational studies. No definite signal of harm was identified as none of the studies reported adverse outcomes. When comparing a total of 214 aPL-positive women with a total of 250 HCQ-exposed aPL-positive pregnancies and 521 pregnancies not exposed to HCQ, we found that HCQ exposure was not associated with an increased rate of live births [pooled OR 1.33; 95% confidence interval (CI) 0.62--2.86]). There was considerable heterogeneity in the analysis (I
2 = 59%).

HCQ seems well tolerated in pregnancy. However, because of the heterogeneity of available studies, the questions whether women with aPL (or some subpopulation of those) might benefit from this agent during pregnancy remains unanswered. Randomized controlled data are needed.
Progress Towards Parity: Female Representation in the American Society of Ophthalmic Plastic and Reconstructive Surgery
Authors: Azad Amee D. , Rosenblatt Tatiana R. , Chandramohan Arthika , Fountain Tamara R. , Kossler Andrea L.
Published: July 2020

Purpose:

To report female representation within the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) at all levels of career achievement over 50 years.

Methods:

Data were extrapolated from published ASOPRS directories and the 50th anniversary booklet. Fellowship, membership, leadership, and awards data were evaluated over 5 decades. Comparisons were made between the first and second 25 years, proportions of early and late career achievements, and time to career progression between males and females.

Results:

During the first decade, 5.6% of ASOPRS fellows were female (n = 2), which rose to 6.6% (n = 8), 17.6% (n = 32), 22.4% (n = 35), and 39.4% (n = 97) in the second, third, fourth, and fifth decades, respectively. These patterns were echoed in ASOPRS membership. When comparing the first half (1969–1994) to the second half (1995–2018), fellowship (10.5% vs. 30.0%, p < 0.001), membership (8.0% vs. 30.3%, p < 0.001), early career awards (5.6% vs. 28.9%, p = 0.047), program directorship (0.0% vs. 15.7%, p = 0.017), and executive committee female representation (4.5% vs. 16.8%, p < 0.001) increased significantly. However, females were proportionally underrepresented as program directors (p = 0.003), late career award winners (p = 0.001), executive committee members (p < 0.001), and presidents (p = 0.020). Among those reaching leadership positions, females took longer than males to become program directors by a median of 4 years (p = 0.025).

Conclusions:

There has been a steady increase in female representation in ASOPRS fellowship training and membership. While significant progress has been made, growth in female leadership and award recognition is still needed.
The forceps-needle: Combining needle and grasping functions in a single instrument
Authors: Amon Michael , Bernhart Clemens , Geitzenauer Wolfgang , Kahraman Guenal
Published: July 2020

A new forceps-needle to facilitate intrascleral haptic fixation surgery is described. In an initial series of 10 cases, the forceps-needle was used to grasp and externalize the haptic of a 3-piece intraocular lens (IOL) for transscleral fixation. The site of perforation was marked at 180 degrees 2.0 mm away from the limbus. Then, the IOL with polypropylene haptics was folded and implanted partially into the anterior chamber. A transconjunctival, scleral tunnel of about 2.0 mm length parallel to the limbus was prepared with the forceps-needle on 1 side, with the second hand holding the leading haptic through a side-port incision. The end of the first haptic was grasped and externalized after which the end of the haptic was flanged. Subsequently, a second scleral tunnel was prepared with the forceps-needle, and the second haptic was externalized and flanged. All procedures could be performed without any intraoperative complication.
The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises
Authors: Raja Srinivasa N. , Carr Daniel B. , Cohen Milton , Finnerup Nanna B. , Flor Herta , Gibson Stephen , Keefe Francis J. , Mogil Jeffrey S. , Ringkamp Matthias , Sluka Kathleen A. , Song Xue-Jun , Stevens Bonnie , Sullivan Mark D. , Tutelman Perri R. , Ushida Takahiro , Vader Kyle
Published: July 2020

The current International Association for the Study of Pain (IASP) definition of pain as “An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” was recommended by the Subcommittee on Taxonomy and adopted by the IASP Council in 1979. This definition has become accepted widely by health care professionals and researchers in the pain field and adopted by several professional, governmental, and nongovernmental organizations, including the World Health Organization. In recent years, some in the field have reasoned that advances in our understanding of pain warrant a reevaluation of the definition and have proposed modifications. Therefore, in 2018, the IASP formed a 14-member, multinational Presidential Task Force comprising individuals with broad expertise in clinical and basic science related to pain, to evaluate the current definition and accompanying note and recommend whether they should be retained or changed. This review provides a synopsis of the critical concepts, the analysis of comments from the IASP membership and public, and the committee's final recommendations for revisions to the definition and notes, which were discussed over a 2-year period. The task force ultimately recommended that the definition of pain be revised to “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage,” and that the accompanying notes be updated to a bulleted list that included the etymology. The revised definition and notes were unanimously accepted by the IASP Council early this year.
Navigator Role for Promoting Adaptive Sports and Recreation Participation in Individuals With Disabilities
Authors: Iverson Moriah , Ng Alexander V. , Yan Alice F. , Zvara Kim , Bonk Michael , Falk-Palec Deb , Sylla Cherri , Strickland Maurine , Preston Rachel , Braza Diane W.
Published: July 2020

Objective

The aims of the study were to gain a better understanding of the resources, barriers, and facilitators of participation in adaptive sport and recreational activities as a means of achieving physical activity recommendations in individuals with disability and to understand preferences for a patient navigator service to help mitigate the barriers.

Design

Clinical, academic, and community stakeholders applied a community-engaged research approach to develop online surveys and focus group questions for adults with a disability or parents of a child with a disability to meet study objectives.

Results

One hundred ninety-eight adults and 146 parents completed the online surveys. Sixteen adults and 18 parents took part in focus groups. Many participants lacked knowledge of available adaptive sport and recreational resources; other barriers were expense, limited number of trained volunteers, and need for instruction. Conversely, persons were facilitated by community, socialization, and words of encouragement/motivation. Participants strongly preferred a patient navigator to be a person active in adaptive sport and recreational or an informative resource-filled website.

Conclusions

Our findings suggest that physical activity programs including adaptive sport and recreational should be designed to offer people with disabilities opportunities to build social networks and strengthen social support. A patient navigator service could help increase participation in adaptive sport and recreational and physical activity within a community context.
Mendelian Randomization analysis of the causal impact of body mass index and waist-hip ratio on rates of hospital admission
Authors: Hazewinkel Audinga-Dea , Richmond Rebecca C. , Wade Kaitlin H. , Dixon Padraig
Published: July 2020

We analyze how measures of adiposity – body mass index (BMI) and waist-hip ratio (WHR) – causally influence rates of hospital admission. Conventional analyses of this relationship are susceptible to omitted variable bias from variables that jointly influence both hospital admission and adipose status. We implement a novel quasi-Poisson instrumental variable modelsin a Mendelian Randomization framework, identifying causal effects from random perturbations to germline genetic variation. We estimate the individual and joint effects of BMI, WHR, and WHR adjusted for BMI. We also implement multivariable instrumental variable methods in which the causal effect of one exposure is estimated conditionally on the causal effect of another exposure. Data on 310,471 participants and over 550,000 inpatient admissions in the UK Biobank were used to perform one-sample and two-sample Mendelian Randomization analyses. The results supported a causal role of adiposity on hospital admissions, with consistency across all estimates and sensitivity analyses. Point estimates were generally larger than estimates from comparable observational specifications. We observe an attenuation of the BMI effect when adjusting for WHR in the multivariable Mendelian Randomization analyses, suggesting that an adverse fat distribution, rather than a higher BMI itself, may drive the relationship between adiposity and risk of hospital admission.
A sensitive and affordable multiplex RT-qPCR assay for SARS-CoV-2 detection
Authors: Reijns Martin A.M. , Thompson Louise , Acosta Juan Carlos , Black Holly A. , Sanchez-Luque Francisco J. , Diamond Austin , Parry David A. , Daniels Alison , O’Shea Marie , Uggenti Carolina , Sanchez Maria C. , O’Callaghan Alan , McNab Michelle L.L. , Adamowicz Martyna , Friman Elias T. , Hurd Toby , Jarman Edward J. , Mow Chee Frederic Li , Rainger Jacqueline K. , Walker Marion , Drake Camilla , Longman Dasa , Mordstein Christine , Warlow Sophie J. , McKay Stewart , Slater Louise , Ansari Morad , Tomlinson Ian P.M. , Moore David , Wilkinson Nadine , Shepherd Jill , Templeton Kate , Johannessen Ingolfur , Tait-Burkard Christine , Haas Jürgen G. , Gilbert Nick , Adams Ian R. , Jackson Andrew P.
Published: July 2020

With the ongoing COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, there is need for sensitive, specific and affordable diagnostic tests to identify infected individuals, not all of whom are symptomatic. The most sensitive test involves the detection of viral RNA using RT-qPCR, with many commercial kits now available for this purpose. However, these are expensive and supply of such kits in sufficient numbers cannot always be guaranteed. We therefore developed a multiplex assay using well-established SARS-CoV-2 targets alongside a human cellular control (RPP30) and a viral spike-in control (PhHV-1), which monitor sample quality and nucleic acid extraction efficiency respectively. Here, we establish that this test performs as well as widely used commercial assays, but at substantially reduced cost. Furthermore, we demonstrate >1,000-fold variability in material routinely collected by nose-and-throat swabbing, and establish a statistically significant correlation between the detected level of human and SARS-CoV-2 nucleic acids. The inclusion of the human control probe in our assay therefore provides a quantitative measure of sample quality that could help reduce false negative rates. We demonstrate feasibility of establishing a robust RT-qPCR assay at ∼10% of the cost of equivalent commercial assays, which could benefit low resource environments and make high volume testing more affordable.
Plasticenta: Microplastics in Human Placenta
Authors: Ragusa Antonio , Svelato Alessandro , Santacroce Criselda , Catalano Piera , Notarstefano Valentina , Carnevali Oliana , Papa Fabrizio , Rongioletti Mauro Ciro Antonio , Baiocco Federico , Draghi Simonetta , D’Amore Elisabetta , Rinaldo Denise , Matta Maria , Giorgini Elisabetta
Published: July 2020

Summary paragraph

Microplastics are particles smaller than five millimetres obtained from the degradation of plastic objects abandoned in the environment. Microplastics can move from the environment to living organisms and, in fact, they have been found in fishes and mammals.

Six human placentas, prospectively collected from consenting women with uneventful pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microparticles. Detected microparticles were characterized in terms of morphology and chemical composition.

12 microparticles, ranging from 5 to 10 μm in size, were found in 4 out of 6 placentas: 5 in the foetal side, 4 in the maternal side and 3 in the chorioamniotic membranes. All the analyzed microparticles were pigmented: three of them were identified as stained polypropylene, while for the other nine it was possible to identify only the pigments, which are all used for man-made coatings, paints and dyes.

Here we show, for the first time, the presence of microparticles and microplastics in human placenta. This sheds new light on the impact of plastic on human health. Microparticles and microplastics in the placenta, together with the endocrine disruptors transported by them, could have long-term effects on human health.
Cas9 fusions for precisionin vivoediting
Authors: Richardson Ryan R. , Steyert Marilyn , Khim Saovleak N. , Romanowski Andrea J. , Inen Jeffrey , Altas Bekir , Poulopoulos Alexandros
Published: July 2020

Cas9 targets genomic loci with high specificity. When used for knockin, however, Cas9 often leads to unintended on-target knockout rather than intended edits. This imprecision is a barrier for directin vivoediting where clonal selection is not feasible. Here we demonstrate a high-throughput workflow to ratiometrically assess on-target efficiency and precision of editing outcomes. Using this workflow, we screened combinations of donor DNA and Cas9 variants, as well as fusions to DNA repair proteins. This yielded novel high-performance double-strand break repair editing agents and combinatorial optimizations with orders-of-magnitude increases in knockin precision. Cas9-RC, a novel Cas9 fusion to eRad18 and CtIP, increased knockin performance over 3-foldin vitroandin vivoin the developing mouse brain. Continued comparative assessment of existing and novel editing agents with this ratiometric framework of efficiency and precision will further the development of directin vivoknockin and future genetic therapies.