bluuebunny/crossref_metadata_2025 huggingface dataset:
Individualized brain development and cognitive outcome in infants with congenital heart disease
Authors: Bonthrone Alexandra F , Dimitrova Ralica , Chew Andrew , Kelly Christopher J , Cordero-Grande Lucilio , Carney Olivia , Egloff Alexia , Hughes Emer , Vecchiato Katy , Simpson John , Hajnal Joseph V , Pushparajah Kuberan , Victor Suresh , Nosarti Chiara , Rutherford Mary A , Edwards A David , O’Muircheartaigh Jonathan , Counsell Serena J
Published: March 2021

Infants with congenital heart disease are at risk of neurodevelopmental impairments, the origins of which are currently unclear. This study aimed to characterize the relationship between neonatal brain development, cerebral oxygen delivery and neurodevelopmental outcome in infants with congenital heart disease. A cohort of infants with serious or critical congenital heart disease (N = 66; N = 62 born ≥37 weeks) underwent brain MRI before surgery on a 3T scanner situated on the neonatal unit. T2-weighted images were segmented into brain regions using a neonatal-specific algorithm. We generated normative curves of typical volumetric brain development using a data-driven technique applied to 219 healthy infants from the Developing Human Connectome Project (dHCP). Atypicality indices, representing the degree of positive or negative deviation of a regional volume from the normative mean for a given gestational age, sex and postnatal age, were calculated for each infant with congenital heart disease. Phase contrast angiography was acquired in 53 infants with congenital heart disease and cerebral oxygen delivery was calculated. Cognitive and motor abilities were assessed at 22 months (N = 46) using the Bayley scales of Infant and Toddler Development–Third Edition. We assessed the relationship between atypicality indices, cerebral oxygen delivery and cognitive and motor outcome. Additionally, we examined whether cerebral oxygen delivery was associated with neurodevelopmental outcome through the mediating effect of brain volume. Negative atypicality indices in deep grey matter were associated with both reduced neonatal cerebral oxygen delivery and poorer cognitive abilities at 22 months across the whole sample. In infants with congenital heart disease born ≥37 weeks, negative cortical grey matter and total tissue volume atypicality indices, in addition to deep grey matter structures, were associated with poorer cognition. There was a significant indirect relationship between cerebral oxygen delivery and cognition through the mediating effect of negative deep grey matter atypicality indices across the whole sample. In infants born ≥37 weeks, cortical grey matter and total tissue volume atypicality indices were also mediators of this relationship. In summary, lower cognitive abilities in toddlers with congenital heart disease were associated with smaller grey matter volumes before cardiac surgery. The aetiology of poor cognition may encompass poor cerebral oxygen delivery leading to impaired grey matter growth. Interventions to improve cerebral oxygen delivery may promote early brain growth and improve cognitive outcomes in infants with congenital heart disease.
Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome
Authors: Zhang Yun , Zhang Song , Li Bolin , Luo Yingchun , Gong Yongtai , Jin Xuexin , Zhang Jiawei , Zhou Yun , Zhuo Xiaozhen , Wang Zixi , Zhao Xinbo , Han Xuejie , Gao Yunlong , Yu Hui , Liang Desen , Zhao Shiqi , Sun Danghui , Wang Dingyu , Xu Wei , Qu Guangjin , Bo Wanlan , Li Dan , Wu Yue , Li Yue
Published: March 2021

Aims

Ageing is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-related diseases. However, whether the aged-associated dysbiosis contributes to age-related AF is still unknown. Direct demonstration that the aged gut microbiota is sufficient to transmit the enhanced AF susceptibility in a young host via microbiota-intestinal barrier-atria axis has not yet been reported. This study aimed to determine whether gut microbiota dysbiosis affects age-related AF.

Methods and results

Herein, by using a faecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Specially, we found the dramatically increased levels of circulating lipopolysaccharide (LPS) and glucose led to the up-regulated expression of NOD-like receptor protein (NLRP)-3 inflammasome, promoting the development of AF, which depended on the enhanced atrial fibrosis in recipient host. Inhibition of inflammasome by a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, resulted in a lower atrial fibrosis and AF susceptibility. Then, we conducted cross-sectional clinical studies to explore the effect of ageing on the altering trends with glucose levels and circulating LPS among clinical individuals in two China hospitals. We found that both of serum LPS and glucose levels were progressively increased in elderly patients as compared with those young. Furthermore, the ageing phenotype of circulating LPS and glucose levels, intestinal structure and atrial NLRP3-inflammasome of rats were also confirmed in clinical AF patients. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF.

Conclusions

Collectively, these studies described a novel causal role of aberrant gut microbiota in the pathogenesis of age-related AF, which indicates that the microbiota-intestinal barrier-atrial NLRP3 inflammasome axis may be a rational molecular target for the treatment of aged-related arrhythmia disease.
A case report of inappropriate inhibition of ventricular pacing due to a unique pacemaker electrogram storage feature
Authors: Khan Habib R , Chan William K , Kanawati Juliana , Yee Raymond
Published: March 2021

Background

Modern permanent pacemakers (PPMs) have individual features designed to identify cardiac rhythm abnormalities and improve their performance. Inappropriate pacing inhibition may be an undesired outcome from these features and cause symptoms in patients who require frequent pacing, leading to dizziness, and syncope. Inappropriate inhibition can be difficult to identify in circumstances that are intermittent and difficult to reproduce.

Case summary

A 57-year-old female underwent a mitral valve replacement (MVR) for severe mitral stenosis. One month following MVR, she presented with symptomatic third-degree atrioventricular block, and a dual-chamber PPM (Advisa™, Medtronic, Minneapolis, USA) was implanted and programmed DDD 50–130 b.p.m. At the 3-month follow-up, she reported frequent episodes of lightheadedness. She was found to have intermittent ventricular pacing inhibition on a 48-h Holter monitor due to an internal function of the Advisa™ series of PPMs that attempts to store an electrogram (EGM) every 1 h and 30 s. During the EGM storage, an amplified signal from the storage capacitor can result in oversensing by the ventricular channel and inappropriate pacing inhibition.

Discussion

To rectify the issue, the ventricular lead sensitivity value was increased from 0.9 mV to 1.2 mV. No instances of inappropriate ventricular pacing inhibition were noted on follow-up. To our knowledge, this is a rare case of inappropriate ventricular pacing inhibition caused by a combination of PPM self-adjusting sensitivity algorithm and oversensing every 1 h and 30 s from an amplified storage capacitor. Physicians should be aware of this possible complication and differentiate it from device or lead malfunction.
Obesity is not a contraindication to veno-arterial extracorporeal life support
Authors: Salna Michael , Fried Justin , Kaku Yuji , Brodie Daniel , Sayer Gabriel , Uriel Nir , Naka Yoshifumi , Takeda Koji
Published: March 2021

OBJECTIVES

Obesity may complicate the peripheral cannulation and delivery of veno-arterial extracorporeal life support (ECLS). With rising global body mass indices (BMI), obesity is becoming increasingly prevalent in severe cardiogenic shock yet its impact on outcomes is not well described. This study sought to examine the relationship between BMI and veno-arterial ECLS outcomes to better inform clinical decision-making.

METHODS

All cardiogenic shock patients undergoing peripheral veno-arterial ECLS at our institution from March 2008 to January 2019 were retrospectively analysed (n = 431). Patients were divided into 4 groups, BMI 17.5–24.9, 25–29.9, 30–34.9 and ≥35 kg/m2, and compared on clinical outcomes. Multivariable logistic regression was performed to identify variables associated with survival to discharge, the primary outcome of interest.

RESULTS

The median BMI was 28.3 kg/m2 (interquartile range 24.8–32.6) with a range of 17.0–69.1 kg/m2. Obese patients achieved significantly lower percentages of predicted flow rates compared with BMI < 25 kg/m2 patients though did not differ in their lactate clearances. Patients with BMI ≥35 kg/m2 had similar complication rates to the other cohorts but were more likely to require continuous veno-venous haemodialysis (51% vs 25–40% in other cohorts, P = 0.002). Overall survival to discharge was 48% (n = 207/431) with no differences between the cohorts (P = 0.92). Patients with BMI ≥35 kg/m2 had considerably lower survival (10%) in extracorporeal membrane oxygenation cardiopulmonary resuscitation compared with the other groups (P = 0.17). On multivariable logistic regression, BMI was not significantly associated with failure to survive to discharge.

CONCLUSIONS

In conclusion, with the rising global prevalence of obesity, the results of our study suggest that clinicians need not treat obesity as a negative prognostic factor in cardiogenic shock requiring ECLS.
Assessing the indirect effects of COVID-19 on healthcare delivery, utilization and health outcomes: a scoping review
Authors: Roy Charlotte M , Bollman E. Brennan , Carson Laura M , Northrop Alexander J , Jackson Elizabeth F , Moresky Rachel T
Published: March 2021

Background

The COVID-19 pandemic and global efforts to contain its spread, such as stay-at-home orders and transportation shutdowns, have created new barriers to accessing healthcare, resulting in changes in service delivery and utilization globally. The purpose of this study is to provide an overview of the literature published thus far on the indirect health effects of COVID-19 and to explore the data sources and methodologies being used to assess indirect health effects.

Methods

A scoping review of peer-reviewed literature using three search engines was performed.

Results

One hundred and seventy studies were included in the final analysis. Nearly half (46.5%) of included studies focused on cardiovascular health outcomes. The main methodologies used were observational analytic and surveys. Data were drawn from individual health facilities, multicentre networks, regional registries, and national health information systems. Most studies were conducted in high-income countries with only 35.4% of studies representing low- and middle-income countries (LMICs).

Conclusion

Healthcare utilization for non-COVID-19 conditions has decreased almost universally, across both high- and lower-income countries. The pandemic’s impact on non-COVID-19 health outcomes, particularly for chronic diseases, may take years to fully manifest and should be a topic of ongoing study. Future research should be tied to system improvement and the promotion of health equity, with researchers identifying potentially actionable findings for national, regional and local health leadership. Public health professionals must also seek to address the disparity in published data from LMICs as compared with high-income countries.
Collection and consumption of non-wood forest products in Europe
Authors: Lovrić Marko , Da Re Riccardo , Vidale Enrico , Prokofieva Irina , Wong Jennifer , Pettenella Davide , Verkerk Pieter Johannes , Mavsar Robert
Published: March 2021

Many non-wood forest products (NWFPs) such as mushrooms and berries are collected and consumed in Europe; but both national statistical and scientific data on this topic are reported only for a limited number of countries, products and case-study areas. Without an adequate quantitative basis, their importance as source of food and income, their links to recreation and cultural heritage, are all under-valued in forest-focused and forest-related policies. In this study, we aimed to address this gap by assessing the consumption and collection of NWFPs through a statistically representative survey in 28 European countries with over 17 000 respondents. Our results show that 90 per cent of households consume NWFPs and about one-quarter collects them. The consumption and collection rates, as well as the number of collected products and their contribution to household income, increase from the west to east of Europe. The vast majority of collected products are consumed fresh. Households with higher income consume a more diverse range of NWFPs, especially in Western Europe. The relation between income and collection is more ambiguous, but there is some indication that the collection rate is higher than average among higher-income households in North and Western Europe and among lower-income households in Eastern and South-Eastern Europe. Households for which NWFP collection is the main income source are predominantly located in Eastern Europe, and they focus their activities on few key products. Our results also identify recreational, hobby and professional collectors whose characteristics vary across socio-economic variables and geographical gradient. Recreational collectors in Western and Southern Europe collect 8 kg of NWFPs from five different products, while recreational collectors in Central-Eastern and North-Baltic Europe collect about four times more from 10 different products. Hobby collectors collect ~100 kg of NWFP per year and professional collectors half a ton, where both groups focus on 8–12 different products. Professional collectors are predominantly located in Eastern and South-Eastern Europe. We end the study by pointing to future research directions and with a series of policy recommendations on how NWFPs could be addressed along the geographical, income and urban–rural gradient with respect to their role in forest recreation as a food and income source.
Efficient CRISPR/Cas9 mutagenesis for neurobehavioral screening in adult zebrafish
Authors: Klatt Shaw Dana , Mokalled Mayssa H
Published: March 2021

Adult zebrafish are widely used to interrogate mechanisms of disease development and tissue regeneration. Yet, the prospect of large-scale genetics in adult zebrafish has traditionally faced a host of biological and technical challenges, including inaccessibility of adult tissues to high-throughput phenotyping and the spatial and technical demands of adult husbandry. Here, we describe an experimental pipeline that combines high-efficiency CRISPR/Cas9 mutagenesis with functional phenotypic screening to identify genes required for spinal cord repair in adult zebrafish. Using CRISPR/Cas9 dual-guide ribonucleic proteins, we show selective and combinatorial mutagenesis of 17 genes at 28 target sites with efficiencies exceeding 85% in adult F0 “crispants”. We find that capillary electrophoresis is a reliable method to measure indel frequencies. Using a quantifiable behavioral assay, we identify seven single- or duplicate-gene crispants with reduced functional recovery after spinal cord injury. To rule out off-target effects, we generate germline mutations that recapitulate the crispant regeneration phenotypes. This study provides a platform that combines high-efficiency somatic mutagenesis with a functional phenotypic readout to perform medium- to large-scale genetic studies in adult zebrafish.
Proteasome Control of [URE3] Prion Propagation by Degradation of Anti-Prion Proteins Cur1 and Btn2 in Saccharomyces cerevisiae
Authors: Edskes Herman K , Stroobant Emily E , DeWilde Morgan P , Bezsonov Evgeny E , Wickner Reed B
Published: March 2021

[URE3] is a prion of the nitrogen catabolism controller, Ure2p, and [PSI+] is a prion of the translation termination factor Sup35p in S. cerevisiae. Btn2p cures [URE3] by sequestration of Ure2p amyloid filaments. Cur1p, paralogous to Btn2p, also cures [URE3], but by a different (unknown) mechanism. We find that an array of mutations impairing proteasome assembly or MG132 inhibition of proteasome activity result in loss of [URE3]. In proportion to their prion—curing effects, each mutation affecting proteasomes elevates the cellular concentration of the anti-prion proteins Btn2 and Cur1. Of >4,600 proteins detected by SILAC, Btn2p was easily the most overexpressed in a pre9Δ (α3 core subunit) strain. Indeed, deletion of BTN2 and CUR1 prevents the prion—curing effects of proteasome impairment. Surprisingly, the 15 most unstable yeast proteins are not increased in pre9Δ cells suggesting altered proteasome specificity rather than simple inactivation. Hsp42, a chaperone that cooperates with Btn2 and Cur1 in curing [URE3], is also necessary for the curing produced by proteasome defects, although Hsp42p levels are not substantially altered by a proteasome defect. We find that pre9Δ and proteasome chaperone mutants that most efficiently lose [URE3], do not destabilize [PSI+] or alter cellular levels of Sup35p. A tof2 mutation or deletion likewise destabilizes [URE3], and elevates Btn2p, suggesting that Tof2p deficiency inactivates proteasomes. We suggest that when proteasomes are saturated with denatured/misfolded proteins, their reduced degradation of Btn2p and Cur1p automatically upregulates these aggregate-handling systems to assist in the clean-up.
De novo assembly and delivery to mouse cells of a 101 kb functional human gene
Authors: Mitchell Leslie A , McCulloch Laura H , Pinglay Sudarshan , Berger Henri , Bosco Nazario , Brosh Ran , Bulajić Milica , Huang Emily , Hogan Megan S , Martin James A , Mazzoni Esteban O , Davoli Teresa , Maurano Matthew T , Boeke Jef D
Published: March 2021

Design and large-scale synthesis of DNA has been applied to the functional study of viral and microbial genomes. New and expanded technology development is required to unlock the transformative potential of such bottom-up approaches to the study of larger mammalian genomes. Two major challenges include assembling and delivering long DNA sequences. Here, we describe a workflow for de novo DNA assembly and delivery that enables functional evaluation of mammalian genes on the length scale of 100 kilobase pairs (kb). The DNA assembly step is supported by an integrated robotic workcell. We demonstrate assembly of the 101 kb human HPRT1 gene in yeast from 3 kb building blocks, precision delivery of the resulting construct to mouse embryonic stem cells, and subsequent expression of the human protein from its full-length human gene in mouse cells. This workflow provides a framework for mammalian genome writing. We envision utility in producing designer variants of human genes linked to disease and their delivery and functional analysis in cell culture or animal models.
Flexibility of joint production in mixed fisheries and implications for management
Authors: Briton Florence , Thébaud Olivier , Macher Claire , Gardner Caleb , Little Lorne Richard
Published: March 2021

Over the past decade, efforts have been made to factor technical interactions into management recommendations for mixed fisheries. Yet, the dynamics underlying joint production in mixed fisheries are generally poorly captured in operational mixed fisheries models supporting total allowable catch advice. Using an integrated ecological–economic simulation model, we explore the extent to which fishers are likely to alter the species composition of their landings in a mixed fishery managed with individual transferable quotas, the Australian Southern and Eastern Scalefish and Shark Fishery. Our simulations capture three different types of joint production problems, highlighting the flexibility that exists in terms of achievable catch compositions when quota markets provide the economic incentives to adapt fishing practices to quota availability. These results highlight the importance of capturing the drivers of fishing choices when advising TAC decisions in mixed fisheries. We also identify a hierarchy of species in this fishery, with harvest targets set for primary commercial species determining most of its socio-economic performance.
Simultaneous Determination of Nine Residual Solvents in Sorafenib Tosylate by Gas Chromatography
Authors: Sun Rong , Hu Chengran , Dou Qian , Luan Libiao
Published: March 2021

Background

Direct injection gas chromatography is convenient and quick. The residual solvent with a higher boiling point can be measured by using direct inhection gas chromatography. This method could be developed for residual solvents analysis of sorafenible tosylate.

Objective

In the present investigation, the injection method was developed and validated for the detection and quantification of residual solvents in sorafenib tosylate.

Method

The nine kinds of residual solvents were separated using direct injection gas chromatographic technology, and a quantitative analysis was performed. Analytical performance of the proposed injection method was validated as per the defined guidelines with respect to linearity, accuracy, precision, robustness, and specificity.

Results

Under the optimized conditions, simultaneous separation and determination of nine kinds of residual solvents, including methanol, acetonitrile, ethyl acetate, tetrahydrofuran, chlorobenzene, toluene, acetone, dichloromethane, and N, N-dimethylformamide were carried out using a DB-WAXETR polyethylene glycol Inertap Pure-WAX column (30 m × 0. 32 mm × 0.25 µm) for separation. The calibration plot was found to be linear, accurate, precise, robust, and specific for direct injection gas chromatography. The residual solvents in sorafenib tosylate were quantified by the developed method.

Conclusions

The present method was successfully applied for analysis of residual solvents in sorafenib tosylate. Similarly, the method can be used for quality control and stability testing of other medicines.

Highlights

A validated GC assay for the combined analysis of the nine solutions which offered a reference method for the detection of residual solvents in other medicines.
Investigation of the Conditions for Preconcentration of Cadmium Ions by Solid Phase Extraction Method Using Modified Juglans regia L. Shells
Authors: Özkalkan Hüsna , Saygili Canlidinç Rukiye
Published: March 2021

Background

Juglans regia L. shells as agricultural waste can be considered as alternative sorbents to minimize the problems associated with heavy metal pollution.

Objective

In this study, J. regia shells (JRS) and JRS modified with hydrazine hydrate (JRS-HH) were used as sorbents and compared for the preconcentration of Cd(II) ions from aqueous solution.

Methods

For the characterization of sorbents, scanning electron microscopy and energy dispersive X-ray (SEM/EDX) analysis and Fourier transform infrared (FTIR) spectroscopy were used. For preconcentration, the solid phase extraction (SPE) technique was used. Preconcentration studies were performed by column method and pH, eluent type and concentration, sample volume, flow rate, and interfering ions effect were studied to determine the optimum column parameters.

Results

The limit of detection (LOD) of the sorbents (JRS and JRS-HH) are 0.31 and 0.18 µg/L, respectively. According to the Langmuir isotherm model for both sorbents, for JRS KL = 0.030 L/mg, R2 = 0.992, 0.016 L/mg, and for JRS-HH KL = 0.016 L/mg, R2 = 0.998 and maximum adsorption capacities of the sorbents were found to be as 29.6 and 65.7 mg/g, respectively. The mean recoveries and RSD values at a 95% confidence level (N = 6) for Cd(II) were 100.9% and 3.42, and 100.6% and 3.79, for the JRS and JRS-HH sorbents, respectively.

Conclusions

Using this method good results were obtained when compared with those in the literature and the proposed method was successfully applied to the analysis of the certificated reference material (NIST 1640).

Highlights

JRS are an effective and inexpensive sorbent for the preconcentration of metal ions when modified. Thus, low-cost agricultural wastes are both recovered and have an economic value.
Pharmacovigilance of COVID-19 vaccines in the context of Nepal: an assessment based on early adverse drug reaction reports
Authors: Jha Nisha , Palaian Subish , Shankar Pathiyil R , Dangal Ganesh
Published: March 2021

Objective

The objective of this study was to assess the ongoing pharmacovigilance of coronavirus disease-19 (COVID-19) vaccines in the Nepalese context based on the available preliminary adverse drug reaction (ADR) reports and suggest approaches for strengthening pharmacovigilance mechanisms.

Methods

Currently, many COVID-19 vaccines are under advanced development and some have begun to be administered. In Nepal, the vaccination programme was initiated with Oxford/AstraZeneca COVID-19 AZD1222 (Covishield) vaccine on January 27th targeting frontline healthcare professionals, sanitary staff and security workers. Newspaper reports and ADR reports received at a regional pharmacovigilance centre in Nepal were analysed. Nepal initiated a national pharmacovigilance programme 15 years back and has 14 functioning regional pharmacovigilance centres. The authors examine the strengths and challenges facing the current pharmacovigilance system in ensuring the safety of COVID-19 vaccines.

Key findings

The news coverage has not mentioned any deaths till date with COVID-19 vaccination. Some patients reported vomiting, urticaria and sudden increase in blood pressure. Few people suffered from headache, fever and myalgia after being vaccinated. A vaccine, approved in an accelerated manner may have safety concerns. The vaccine may cause several types of reactions, but serious reactions have not been reported. Occurrence of adverse effects due to the vaccine is being studied.

Conclusions

Involving key stake holders, training health professionals and strengthening existing reporting procedures are important. Developing a system of reporting and analysing ADRs daily can help generate actionable intelligence to improve the safety of the vaccination programme. Establishing functioning communication channels between regulatory authorities and other stakeholders is crucial.
Enhancing Military Field Hospitals: World Health Organization Emergency Medical Team Verification
Authors: Licina Derek , DeHaai Brian , Slattery Andrea
Published: March 2021

Despite the significant investment in the U.S. and partner nation military field hospital capability, the DoD has not pursued WHO Emergency Medical Team verification. Doing so would reinforce the DoD as an international leader, uphold the DoD as a partner of choice for response when requested, and enable the DoD to assist other nations in achieving the same.
Fast radio burst detection in the presence of coloured noise
Authors: Zhang C F , Xu J W , Men Y P , Deng X H , Xu Heng , Jiang J C , Wang B J , Lee K J , Li J , Yuan J P , Liu Z Y , Huang Y X , Xu Y H , Li Z X , Hao L F , Luo J T , Dai S , Luo R , Zakie Hassan , Ma Z Y
Published: March 2021

In this paper, we investigate the impact of correlated noise on fast radio burst (FRB) searching. We found that (1) the correlated noise significantly increases the false alarm probability; (2) the signal-to-noise ratios (S/N) of the false positives become higher; (3) the correlated noise also affects the pulse width distribution of false positives, and there will be more false positives with wider pulse width. We use 55-h observation for M82 galaxy carried out at Nanshan 26m radio telescope to demonstrate the application of the correlated noise modelling. The number of candidates and parameter distribution of the false positives can be reproduced with the modelling of correlated noise. We will also discuss a low S/N candidate detected in the observation, for which we demonstrate the method to evaluate the false alarm probability in the presence of correlated noise. Possible origins of the candidate are discussed, where two possible pictures, an M82-harboured giant pulse and a cosmological FRB, are both compatible with the observation.
Inflammatory Markers During Early Treatment of Seroconverters in a Randomized Placebo-Controlled Trial of PrEP (ANRS-IPERGAY)
Authors: Chawki Sylvain , Charreau Isabelle , Gabassi Audrey , Carette Diane , Cua Eric , Cotte Laurent , Pialoux Gilles , Pintado Claire , Meyer Laurence , Chaix Marie-Laure , Delaugerre Constance , Molina Jean-Michel
Published: March 2021

HIV-related inflammation is associated with poor outcomes. We describe inflammatory biomarkers in 17 participants in a pre-exposure prophylaxis trial who seroconverted with very early initiation of antiretroviral therapy. Inflammation peaked at the time of HIV infection and returned to baseline within 6–12 months. Starting antiretroviral therapy very early could help mitigate long-lasting HIV-related inflammation.
Coronavirus Disease 2019 Mitigation Strategies Were Associated With Decreases in Other Respiratory Virus Infections
Authors: Sinha Pranay , Reifler Katherine , Rossi Michael , Sagar Manish
Published: March 2021

Detection of diverse respiratory viruses in Boston was approximately 80% lower after practices were instituted to limit coronavirus disease 2019 (COVID-19) spread compared with the same time period during the previous 5 years. Continuing the strategies that lower COVID-19 dissemination may be useful in decreasing the incidence of other viral respiratory infections.
Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-, Cefiderocol-Resistant ST-512 Klebsiella pneumoniae–Producing KPC-31, a D179Y Variant of KPC-3
Authors: Tiseo Giusy , Falcone Marco , Leonildi Alessandro , Giordano Cesira , Barnini Simona , Arcari Gabriele , Carattoli Alessandra , Menichetti Francesco
Published: March 2021

A 68-year-old man had recurrent bacteremia by Klebsiella pneumoniae carbapenemase (KPC)–producing K. pneumoniae resistant to ceftazidime-avibactam and cefiderocol. The sequencing of a target region showed that it harbored a KPC-3 variant enzyme (D179Y; KPC-31), which confers resistance to ceftazidime-avibactam and restores meropenem susceptibility. The patient was successfully treated with meropenem-vaborbactam.
The era of virtual care: Perspectives of youth on virtual appointments in COVID-19 and beyond
Authors: Fletcher Sarah E , Tsang Vivian W L
Published: March 2021

In response to COVID-19, paediatric providers have shifted to providing outpatient health care appointments through telehealth. Youth perspectives on changes to health care access during the pandemic are important to consider when optimizing care for paediatric patients. Youth who contributed to this commentary reported that major benefits of virtual care included time savings, ease of access, continuity of care, and ability to participate in health appointments from the comfort of one’s own home without a risk of COVID-19 exposure. These youth also recognized limitations to virtual care, including the inability to complete laboratory or imaging tests, and the lack of physical examination capabilities. Additionally, they stressed the importance of visual components of virtual appointments and health care providers needing to consider privacy restrictions youth may have. Overall, our cohort of youth feel positive about virtual care and hope care providers can work with youth individually to determine the best solution for them.
What remains of the evidence for auxin feedback on PIN polarity patterns?
Authors: ten Tusscher Kirsten H
Published: March 2021

In light of recent findings, the feedback between auxin and PIN that plays a major role in models for self-organized auxin patterning requires revisiting.
Climate Change and Long-Run Discount Rates: Evidence from Real Estate
Authors: Giglio Stefano , Maggiori Matteo , Rao Krishna , Stroebel Johannes , Weber Andreas
Published: March 2021

We show that housing markets provide information about the appropriate discount rates for valuing investments in climate change abatement. Real estate is exposed to both consumption and climate risk and its term structure of discount rates is downward sloping, reaching 2.6% for payoffs beyond 100 years. We use a tractable asset pricing model that incorporates features of climate change to show that the term structure of discount rates for climate-hedging investments is thus upward sloping but bounded above by the risk-free rate. At horizons at which risk-free rates are unavailable, the estimated housing discount rates provide an upper bound.
Occipital sleep spindles predict sequence learning in a visuo-motor task
Authors: Lutz Nicolas D , Admard Marie , Genzoni Elsa , Born Jan , Rauss Karsten
Published: March 2021

Study Objectives

The brain appears to use internal models to successfully interact with its environment via active predictions of future events. Both internal models and the predictions derived from them are based on previous experience. However, it remains unclear how previously encoded information is maintained to support this function, especially in the visual domain. In the present study, we hypothesized that sleep consolidates newly encoded spatio-temporal regularities to improve predictions afterwards.

Methods

We tested this hypothesis using a novel sequence-learning paradigm that aimed to dissociate perceptual from motor learning. We recorded behavioral performance and high-density electroencephalography (EEG) in male human participants during initial training and during testing two days later, following an experimental night of sleep (n = 16, including high-density EEG recordings) or wakefulness (n = 17).

Results

Our results show sleep-dependent behavioral improvements correlated with sleep-spindle activity specifically over occipital cortices. Moreover, event-related potential (ERP) responses indicate a shift of attention away from predictable to unpredictable sequences after sleep, consistent with enhanced automaticity in the processing of predictable sequences.

Conclusions

These findings suggest a sleep-dependent improvement in the prediction of visual sequences, likely related to visual cortex reactivation during sleep spindles. Considering that controls in our experiments did not fully exclude oculomotor contributions, future studies will need to address the extent to which these effects depend on purely perceptual versus oculomotor sequence learning.
Interictal Epileptiform Discharges are Task Dependent and are Associated with Lasting Electrocorticographic Changes
Authors: Meisenhelter Stephen , Quon Robert J , Steimel Sarah A , Testorf Markus E , Camp Edward J , Moein Payam , Culler George W , Gross Robert E , Lega Bradley C , Sperling Michael R , Kahana Michael J , Jobst Barbara C
Published: March 2021

The factors that control the occurrence of interictal epileptiform discharges (IEDs) are not well understood. We suspected that this phenomenon reflects an attention-dependent suppression of interictal epileptiform activity. We hypothesized that IEDs would occur less frequently when a subject viewed a task-relevant stimulus compared with viewing a blank screen. Furthermore, IEDs have been shown to impair memory when they occur in certain regions during the encoding or recall phases of a memory task. Although these discharges have a short duration, their impact on memory suggests that they have longer lasting electrophysiological effects. We found that IEDs were associated with an increase in low-frequency power and a change in the balance between low- and high-frequency oscillations for several seconds. We found that the occurrence of IEDs is modified by whether a subject is attending to a word displayed on screen or is observing a blank screen. In addition, we found that discharges in brain regions in every lobe impair memory. These findings elucidate the relationship between IEDs and memory impairment and reveal the task dependence of the occurrence of IEDs.
Microtubule‐targeting agents impair kinesin‐2‐dependent nuclear transport of β‐catenin: Evidence of inhibition of Wnt/β‐catenin signaling as an important antitumor mechanism of microtubule‐targeting agents
Authors: Kumari Anuradha , Shriwas Omprakash , Sisodiya Shailendra , Santra Manas K. , Guchhait Sankar K. , Dash Rupesh , Panda Dulal
Published: March 2021

An aberrant accumulation of nuclear β‐catenin is closely associated with the augmentation of cancer malignancy. In this work, we report that several microtubule‐targeting agents (MTAs) such as vinblastine, taxol, and C12 (combretastatin‐2‐aminoimidazole analog) inhibit Wnt/β‐catenin signaling in oral squamous cell carcinoma (OSCC). We showed that the inhibition of microtubule dynamics by MTAs decreased the level of β‐catenin by increasing Axin and adenomatous polyposis coli levels and reducing the level of dishevelled. Furthermore, MTAs strongly reduced the localization of β‐catenin in the nucleus. The reduction in the level of nuclear β‐catenin was neither due to the degradation of β‐catenin in the nucleus nor due to an increase in the export of nuclear β‐catenin from the nucleus. A motor protein kinesin‐2 was found to assist the nuclear transportation of β‐catenin. Interestingly, Wnt/β‐catenin signaling antagonist treatment synergized with MTAs and the activators of Wnt/β‐catenin signaling antagonized with the MTAs. C12 potently suppressed the growth of 4‐Nitroquinoline 1‐oxide‐induced OSCC in the tongue of C57 black 6 mice and also abrogated Wnt/β‐catenin signaling pathway in the tumor. Our results provide evidence that the decrease in Wnt/β‐catenin signaling is an important antitumor effect of MTAs and the combined use of MTAs with Wnt/β‐catenin signaling antagonists could be a promising strategy for cancer chemotherapy.
Starvation induces an increase in intracellular calcium and potentiates the progesterone‐induced mouse sperm acrosome reaction
Authors: Sánchez‐Cárdenas Claudia , Romarowski Ana , Orta Gerardo , De la Vega‐Beltrán José Luis , Martín‐Hidalgo David , Hernández‐Cruz Arturo , Visconti Pablo E. , Darszon Alberto
Published: March 2021

We have recently reported two different methodologies that improve sperm functionality. The first method involved transient exposure to the Ca2+ ionophore A23187, and the second required sperm incubation in the absence of energy nutrients (starvation). Both methods were associated with an initial loss of motility followed by a rescue step involving ionophore removal or addition of energy metabolites, respectively. In this work, we show that starvation is accompanied by an increase in intracellular Ca2+ ([Ca2+]i). Additionally, the starved cells acquire a significantly enhanced capacity to undergo a progesterone‐induced acrosome reaction. Electrophysiological measurements show that CatSper channel remains active in starvation conditions. However, the increase in [Ca2+]i was also observed in sperm from CatSper null mice. Upon starvation, addition of energy nutrients reversed the effects on [Ca2+]i and decreased the effect of progesterone on the acrosome reaction to control levels. These data indicate that both methods have common molecular features.
Telerheumatology: before, during, and after a global pandemic
Authors: Matsumoto Rachel A. , Barton Jennifer L.
Published: March 2021

Purpose of review

In early 2020, the COVID-19 global pandemic shifted most healthcare to remote delivery methods to protect patients, clinicians, and hospital staff. Such remote care delivery methods include the use of telehealth technologies including clinical video telehealth or telephone visits. Prior to this, research on the acceptability, feasibility, and efficacy of telehealth applied to rheumatology, or telerheumatology, has been limited.

Recent findings

Telerheumatology visits were found to be noninferior to in-person visits and are often more time and cost effective for patients. Clinicians and patients both noted the lack of a physical exam in telehealth visits and patients missed the opportunity to have lab work done or other diagnostic tests they are afforded with in-person visits. Overall, patients and clinicians had positive attitudes toward the use of telerheumatology and agreed on its usefulness, even beyond the pandemic.

Although telerheumatology has the potential to expand the reach of rheumatology practice, some of the most vulnerable patients still lack the most basic resources required for a telehealth visit. As the literature on telerheumatology continues to expand, attention should be paid to health equity, the digital divide, as well as patient preferences in order to foster true shared decision-making over telehealth.
Recent advances in the treatment of neuromyelitis optica spectrum disorders
Authors: Romeo Andrew R.
Published: March 2021

Purpose of review

This review examines recently published randomized placebo-controlled trials for the treatment of neuromyelitis optica spectrum disorders (NMOSD).

Recent findings

Until recently, treatments for NMOSD were used-off label and had not been subjected to randomized placebo-controlled trials. Increased understanding of the pathophysiology of NMOSD, particularly aquaporin-4-IgG seropositive NMOSD, lead to the investigation of eculizumab, inebilizumab, and satralizumab for maintenance therapy. Eculizumab inhibits the cleavage of the terminal complement protein C5, inebilizumab depletes immune cells of B-lymphocyte lineage, and satralizumab inhibits interleukin-6 receptors. International, phase 3, randomized, placebo-controlled trials have demonstrated that each of these therapies reduces the risk of NMOSD relapse. In some cases, the studied therapies were administered in conjunction with other immunosuppressants. Each therapy has important safety considerations, notably risk of meningococcal infection with eculizumab and risks of infection and hypogammaglobulinemia with inebilizumab. Reviewing trial design highlights future areas of inquiry for the treatment of NMOSD.

Eculizumab, inebilizumab, and satralizumab are effective maintenance therapies approved for the treatment of AQP-4 seropositive NMOSD.
Treatment for systemic sclerosis-associated interstitial lung disease
Authors: Roofeh David , Lescoat Alain , Khanna Dinesh
Published: March 2021

Purpose of review

This review provides an overview of the current treatments for systemic sclerosis-interstitial lung disease (SSc-ILD) and proposes a conceptual framework for disease management with case scenarios.

Recent findings

Broad treatment categories include traditional cytotoxic therapies, biologic disease-modifying rheumatic drugs, antifibrotic agents, autologous hematopoietic stem cell transplant, and lung transplantation. The optimal use of each option varies depending on SSc-ILD severity, progression, and comorbidities of individual patients. A high-quality randomized controlled trial demonstrated nintedanib's ability to retard decline of lung function in patients with limited and diffuse cutaneous disease, with established ILD. Tocilizumab, recently approved by the FDA, provides a unique intervention in those with early SSc associated with ILD with elevated acute-phase reactants: two well designed trials showed lung function preservation in phase 2 and phase 3 trials.

Stratifying patients based on key SSc-ILD characteristics (e.g. severity, risk of progression, comorbid disease presentation) may provide a useful guide for practitioners treating SSc-ILD.
Practical management strategies for benign hypermobility syndromes
Authors: Minhas Deeba
Published: March 2021

Purpose of review

Patients with symptomatic hypermobility syndrome such as hypermobile Ehlers-Danlos syndromes (hEDS) and hypermobility spectrum disorders (HSD) commonly present to rheumatologists with joint pain and functional disability. Providers often have difficulty with diagnosis due to a lack of knowledge on the range of associated manifestations and the available therapeutic modalities. This review will discuss recent updates on diagnostic measures and treatment options for rheumatologists to help patients navigate hEDS/HSD.

Recent findings

This article describes newer diagnostic measures and assessment of hEDS/HSD manifestations. Evidence supporting physical therapy and occupational therapy is provided, as well as recent updates on assistive devices, compressive garments, orthoses, and surgical interventions. Given patient heterogeneity specific guidance about the amount and type of therapies required to produce a beneficial effect is lacking. Treatment should be individualized, and many of the studies focus on regional joint complaints rather than a whole-body approach.

Physical therapy and occupational therapy remain the cornerstone of treatment.
The relationship between atlas hypoplasia and os odontoideum in children with Down syndrome: a preliminary case report
Authors: Fujimoto Yoh , Miyoshi Kota , Oshima Yasushi , Takikawa Kazuharu , Takeshita Yujiro , Nakamura Takeomi , Tanaka Sakae
Published: March 2021

The purpose of this study was to evaluate the relationship of os odontoideum and the size of atlas among children with Down syndrome. Understanding the risk of developing myelopathy in asymptomatic cases is important in children with Down syndrome. Children with os odontoideum are considered to be at high risk of developing myelopathy because of instability; however, in cases that are complicated by atlas hypoplasia, the risk remains the same, regardless of instability. This retrospective case-control study assessed atlas hypoplasia in children with Down syndrome with or without os odontoideum. We retrospectively assessed the records of 59 patients (36 males and 23 females) with Down syndrome who underwent spinal X-ray evaluations at our hospital. The average age at examination was 5.0 years (range, 4–7). We evaluated the following radiologically: the presence of os odontoideum; atlas-dens interval; space available for the spinal cord at the atlas level (C1SAC); instability index; sagittal atlas diameter (SAD) as an index of atlas hypoplasia and C5 level SAC (C5SAC), adjusted for child growth. Os odontoideum was present in seven cases (12%). Between the groups with and without os odontoideum, there was no significant difference in age (mean, 5.2 vs. 5.0 years) or male/female ratio (57 vs. 62% males). The SAD/C5SAC (mean, 1.6 vs. 1.9) was significantly smaller in the group with os odontoideum than in those without os odontoideum. The instability index was not significantly different between the two groups. Children with Down syndrome and os odontoideum have small SAD. Evaluations for atlas hypoplasia are necessary.
Controversies in the Treatment of Hallux Valgus
Authors: Nedwicki Matthew , Nemec Scott A.
Published: March 2021

Hallux valgus is a common deformity encountered by the foot and ankle specialist. The treatment options are many for this deformity. Both single and double corrective osteotomies as well as arthrodesis procedures are commonly utilized to obtain correction. The approach to management, procedures as well as outcomes are reviewed and compared highlighting the optimal treatment for the hallux valgus deformity.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Conversion of Tibiotalocalcaneal Arthrodesis to Total Ankle Arthroplasty in the Setting of Fibular Deficiency
Authors: Posner Andrew D. , Haddad Stefanos F. , Harrington Michael , Angelicola-Richardson Kyle , Rosenbaum Andrew J.
Published: March 2021

Conversion of symptomatic ankle arthrodesis to total ankle arthroplasty is becoming more common. Lateral fibula insufficiency has historically been considered a contraindication for arthrodesis takedown and conversion arthroplasty. Studies have described several methods for restoring an adequate lateral buttress but reported mixed results. The authors describe a novel technique tip for a single-procedure conversion of tibiotalocalcaneal arthrodesis to total ankle arthroplasty in the setting of fibular deficiency. The described technique uses unique templating and bone cuts and can be successfully replicated in these challenging cases.

Level of Evidence: Level V—expert opinion.