bluuebunny/crossref_metadata_2025 huggingface dataset:
Can the carbon and nitrogen isotope values of offspring be used as a proxy for their mother’s diet? Using foetal physiology to interpret bulk tissue and amino acid δ15N values
Authors: Lübcker Nico , Whiteman John P , Newsome Seth D , Millar Robert P , de Bruyn P J Nico
Published: July 2020

The measurement of bulk tissue nitrogen (δ15N) and carbon isotope values (δ13C) chronologically along biologically inert tissues sampled from offspring can provide a longitudinal record of their mothers’ foraging habits. This study tested the important assumption that mother–offspring stable isotope values are positively and linearly correlated. In addition, any change in the mother–offspring bulk tissues and individual amino acids that occurred during gestation was investigated. Whiskers sampled from southern elephant seal pups (Mirounga leonina) and temporally overlapping whiskers from their mothers were analyzed. This included n = 1895 chronologically subsampled whisker segments for bulk tissue δ15N and δ13C in total and n = 20 whisker segments for amino acid δ15N values, sampled from recently weaned pups (n = 17), juvenile southern elephant seals (SES) < 2 years old (n = 23) and adult female SES (n = 17), which included nine mother–offspring pairs. In contrast to previous studies, the mother–offspring pairs were not in isotopic equilibrium or linearly correlated during gestation: the Δ15N and Δ13C mother–offspring offsets increased by 0.8 and 1.2‰, respectively, during gestation. The foetal bulk δ15N values were 1.7 ± 0.5‰ (0.9–2.7‰) higher than mothers’ δ15N values before birth, while the foetal δ13C increased by ~1.7‰ during gestation and were 1.0 ± 0.5‰ (0.0–1.9‰) higher than their mothers’ δ13C at the end of pregnancy. The mother–offspring serine and glycine Δ15N differed by ~4.3‰, while the foetal alanine δ15N values were 1.4‰ lower than that of their mothers during the third trimester of pregnancy. The observed mother–offspring δ15N differences are likely explained by shuttling of glutamate–glutamine and glycine–serine amongst skeletal muscle, liver, placenta and foetal tissue. Foetal development relies primarily on remobilized endogenous maternal proteinaceous sources. Researchers should consider foetal physiology when using offspring bulk tissue isotope values as biomarkers for the mother’s isotopic composition as part of monitoring programmes.
Nerve at risk: anatomical variations of the left recurrent laryngeal nerve and implications for thoracic surgeons
Authors: Ng Caecilia , Woess Claudia , Maier Herbert , Schmidt Verena-Maria , Lucciarini Paolo , Öfner Dietmar , Rabl Walter , Augustin Florian
Published: July 2020

OBJECTIVES

Recurrent laryngeal nerve (RLN) injury during thoracic surgery may result in life-threatening postoperative complications including recurrent aspiration and pneumonia. Anatomical details of the intrathoracic course are scarce. However, only an in-depth understanding of the anatomy will help reduce nerve injury. The aim of this study was to assess the anatomic variations of the intrathoracic left RLN.

METHODS

Left-sided vagal nerves and RLN were dissected in 100 consecutive Caucasian cadavers during routine autopsy. Anatomical details were documented. Available demographic data were assessed for possible correlations.

RESULTS

All nerves were identified during dissection. Variant courses were classified in 3 different groups according to the level at which the RLN separated from the vagal nerve: above the aortic arch, level with the aortic arch and below the aortic arch. We found 11% of RLN separating above the aortic arch and crossing the aortic arch at a considerable distance to the vagal nerve. In 48% of the RLN, the nerve split off when it was level with the aortic arch, and 41% of the RLN leave the vagal nerve in a perpendicular direction below the aortic arch. All nerves crossed the ligamentum arteriosum on the posterior side. No gender-specific differences were observed.

CONCLUSIONS

Mediastinal lymph node dissection in left-sided lung cancer patients puts the RLN at risk. With more detailed anatomical knowledge about its course, it is possible to avoid risking the nerve. Visualization will help protect the nerve.
Unique Transcriptome Changes in Peripheral B Cells Revealed by Comparing Age Groups From Naive or Vaccinated Mice, Including snoRNA and Cdkn2a
Authors: Baudier Robin L , Zwezdaryk Kevin J , Czarny-Ratajczak Malwina , Kodroff Lauren H , Sullivan Deborah E , Norton Elizabeth B
Published: July 2020

Aging is associated with a decline in immune function that is not fully understood including vaccine failure. Here we report transcriptomic analysis on B cells from naive or influenza-vaccinated mice of 3 ages: young (15–23 weeks), middle-aged (63–81 weeks), and old mice (103–119 weeks). Our goal was expression profiling of B cells by age and history of vaccination to identify novel changes at the transcriptome level. We observed waning vaccine responses with age. In B cell transcripts, age and vaccination history were both important with notable differences observed in conducted analyses (eg, principal component, gene set enrichment, differentially expressed [DE] genes, and canonical pathways). Only 39 genes were significantly DE with age irrespective of vaccine history. This included age-related changes to box C/D small nucleolar (sno) RNAs, Snord123 and Snord1a. Box C/D snoRNAs regulate rRNAs through methylation and are linked to neurodegenerative, inflammatory, and cancer diseases but not specifically B cells or age. Canonical pathway changes implicated with age irrespective of vaccination history included EIF2, mTOR signaling, p53, Paxillin, and Tec kinase signaling pathways as well as cell cycle checkpoint. Importantly, we identified DE genes and pathways that were progressively altered starting in middle-age (eg, signaling by Rho family GTPases) or only altered in middle-age (eg, sphingosine-1-phosphate signaling), despite minimal differences in the ability of these mice to respond to vaccination compared to younger mice. Our results indicate the importance of vaccination or immune stimulation and analyses of multiple age ranges for aging B cell studies and validate an experimental model for future studies.
Who Conducts Health Economic Evaluations of Laboratory Tests? A Scoping Review
Authors: Giusepi Isabella , John Andrew St , Jülicher Paul
Published: July 2020

Background

Health economic evaluations (HEEs) are effectively used to inform decision making in healthcare. We sought to assess the level of involvement of laboratory professionals (LPs) in HEEs of laboratory tests.

Methods

A systematic literature search was conducted in Medline (2013 to November 28, 2018) for original articles reporting HEEs of medical laboratory tests. Eligible studies were characterized by indication, utilization, region, setting, study design, primary outcome measures, and sponsorship. Authors were classified based on stated affiliation as clinician, scientist, public health expert, or LP.

Results

In total, 140 HEEs were included in the study, of which 24 (17.1%) had contributions from LPs. Studies were primarily focused on infectious disease (n = 68), oncology (n = 23), and cardiovascular disease (n = 16). Cost-utility or cost-effectiveness analyses (n = 117) were the most frequent study types, with effectiveness measured mainly in terms of quality-adjusted life-years (n = 57) and detected cases (n = 41). Overall, 76% of HEEs followed a social or health system perspective, whereas 15% took a hospital viewpoint. Partial or full funding was received from public health organizations or industry in 39% and 16% of studies, respectively. The involvement of LPs was associated with test utilization, secondary care, analytic perspective, and an immediate time horizon (all P < 0.05). Quality of studies was found to be lower in HEEs coauthored by LPs.

Conclusion

Multidisciplinary collaboration is essential to understanding the complexity of clinical pathways. HEEs are used effectively to inform healthcare decision making. The involvement of LPs in HEEs is low. This implies that laboratory expertise is frequently not considered in decision processes.
Costing Methods as a Means to Measure the Costs of Pharmacogenomics Testing
Authors: Siamoglou Stavroula , Karamperis Kariofyllis , Mitropoulou Christina , Patrinos George P
Published: July 2020

Clinical implementation of pharmacogenomics and personalized medicine interventions relies on addressing important financial aspects of the delivery of genetic testing to the patients, be it from public or private providers. Details on how to determine the cost items of the genetic testing are often limited. The goal of this study is to present a costing methodology in order to estimate and measure the costs as far as the technical process of pharmacogenomics testing is concerned. Moreover, an overall cost mindset strategy based on the selective genotyping workflow to guide specialized laboratories of interest effectively is provided. We particularly accounted for the resources consumed within the laboratory premises such as cost of reagents for DNA isolation, cost of consumables, cost of personnel, while costs associated with patient recruitment, blood sample collection and maintenance, administration costs in the hospital, and costs of blood sample shipment were not taken into consideration. Our article presents the first-time detailed information on a costing framework for pharmacogenomic testing that could be employed to laboratories involved in routine clinical implementation of pharmacogenomics.
Beware the band adhesion: an unexpected cause of double obstruction following intraperitoneal kidney transplantation
Authors: Tovmassian David , Tang Linda , Hameed Ahmer M , Yao Jinna , Yoon Peter Daechul , Lee Taina , Laurence Jerome M , Yuen Lawrence P K , Allen Richard D M , Lau Howard , Pleass Henry C C
Published: July 2020

Small bowel obstruction (SBO) following intraperitoneal renal transplantation, either solitary or due to simultaneous pancreas-kidney transplantation, is a known complication. While SBO is most commonly due to adhesions, there have been documented cases of internal herniation following simultaneous pancreas-kidney transplantation with enteric drainage due to the formation of a mesenteric defect. We present a unique complication in which the transplant ureter has caused strangulation and necrosis of a length of small intestine. The transplant ureter was mistaken for a band adhesion and divided. Post-operative anuria signalled this difficult diagnosis. Subsequent re-look laparotomy and ureteric reimplantation with Boari flap were required. Therefore, it is important to consider the ureter as a cause of internal herniation in kidney transplant patients and recognize that a band adhesion within the pelvis may in fact be the transplant ureter, obstructing a loop of small intestine beneath its course.
Photogenerated-hole-induced rapid elimination of solid tumors by the supramolecular porphyrin photocatalyst
Authors: Zhang Zijian , Wang Li , Liu Weixu , Yan Zihe , Zhu Yongfa , Zhou Shuyun , Guan Shanyue
Published: July 2020

The rapid, complete, targeted and safe treatment for tumors remains a key issue in cancer therapy. A novel treatment of solid tumors by supramolecular photocatalyst Nano-SA-TCPP with the irradiation of 600–700 nm wavelength is established. Solid tumors (100 mm3) can be eliminated within 10 min. The 50-day mouse survival rate was increased from 0% to 100% after the photocatalytic therapy. The breakthrough was owing to the cell membrane rupture and the cytoplasmic loss caused by photogenerated holes inside cancer cells. The porphyrin-based photocatalysts can be internalized in a targeted manner by cancer cells due to the size selection effect, without entering the normal cells. The therapy has no toxicity or side effects for normal cells and organisms. Moreover, the photocatalytic therapy is effective for a variety of cancer cell lines. Because of its high efficiency, safety and universality, the photocatalytic therapy provides us with a new lancet to conquer the tumor.
Aging well: an update
Authors: Akiyama Hiroko
Published: July 2020

Population aging is a global phenomenon, and Japan is one of the front-runners of rapidly aging societies. In 2030, one-third of the Japanese population will be at least 65 years of age and 20% will be at least 75 years of age. The working age population is shrinking. Healthy aging is a crucial issue for both individual well-being and the sustainability of society. Along with biomedical research, the importance of the living environment and lifestyle has been long recognized and extensively studied. The issues have been identified and now it is time to establish solutions and actions – action-targeted research.

The Institute of Gerontology at the University of Tokyo launched a social experiment, redesigning existing communities where people could live for 100 years and remain healthy, active, and connected, while still maintaining a sense of security. This requires co-creation by citizens, researchers, government, and industry. The ultimate goal is to make linkages among longevity, health, and wealth, and to build a sustainable society.
Field-Based Tests of Strength and Anaerobic Capacity Used in Children With Developmental Coordination Disorder: A Systematic Review
Authors: Aertssen Wendy , Jelsma Dorothee , Smits-Engelsman Bouwien
Published: July 2020

Objective

Children with developmental coordination disorder (DCD) are reported to have lower levels of strength and anaerobic capacity. The purpose of this study was to (1) identify field-based tests for strength and anaerobic capacity used in studies comparing children with DCD and children who were typically developing (TD), (2) examine the methodological quality of studies reporting psychometric properties and rate the psychometric properties of the examined test, and (3) summarize available evidence by combining the methodological quality of the studies and the quality of the psychometric properties of the test.

Methods

An electronic search was conducted in July 2019 in 4 electronic databases. For purpose 1, primary studies were included with no exclusion of study design in which children aged 4 to 18 years with DCD were compared with children who were TD on strength and/or anaerobic capacity measures. For purpose 2, primary studies were included with no exclusion of study design in which a psychometric property was investigated. The Consensus-Based Standards for Selection of Health Measurement Instruments (COSMIN) was used to evaluate the methodological quality of the 34 studies and rate the psychometric properties of the tests used.

Results

Hand-held dynamometer, bent knee push-up, vertical jump, standing long-jump, functional strength measurement, fitness test, and test battery can be recommended for TD, and the shuttle run item of the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition and 10 m × 5 m sprints (straight and slalom) can be recommended for DCD.

Conclusion

Information regarding psychometric properties of field-based tests for strength and anaerobic capacity in children with DCD is lacking.

Impact

Information about the psychometric properties of field-based tests for strength and anaerobic capacity in children with DCD is lacking. More information is available on TD children, but it is also not complete; information regarding validity and responsiveness, especially, is missing. When using measures in children with DCD, it is important to keep in mind this lack of evidence for the validity and reliability of the outcomes for this target group.
Cost-effectiveness of a proportionate universal offer of free exercise: Leeds Let’s Get Active
Authors: Candio Paolo , Meads David , Hill Andrew J , Bojke Laura
Published: July 2020

Background

The purpose of this paper is to assess the cost-effectiveness of a proportionate universal programme to reduce physical inactivity (Leeds Let us Get Active (LLGA)) in adults.

Methods

A continuous-time Markov chain model was developed to assess the cost implications and QALY gains associated with increases in physical activity levels across the adult population. A parametric survival analysis approach was applied to estimate the decay of intervention effect over time. Baseline model data were obtained from previous economic models, population-based surveys and other published literature. A cost-utility analysis was conducted from a health care sector perspective over the programme duration (39 months). Scenario and probabilistic sensitivity analyses were performed to test the robustness of cost-effectiveness results.

Results

In total, 51 874 adult residents registered to the programme and provided baseline data,19.5% of which were living in deprived areas. Under base case assumptions, LLGA was found to be likely to be cost-effective. However, variations in key structural assumptions showed sensitivity of the results.

Conclusions

Results from this study suggest a non-negligible level of uncertainty regarding the effectiveness, and therefore, cost-effectiveness of a universal offer of free leisure centre-based exercise that targets hard to reach groups. Further data collection and a shift towards prospective evaluations are needed.
Serum amyloid A1 genotype associates with adult-onset familial Mediterranean fever in patients homozygous for mutation M694V
Authors: Kriegshäuser Gernot , Hayrapetyan Hasmik , Atoyan Stepan , Oberkanins Christian , Sarkisian Tamara
Published: July 2020

Objectives

FMF shows considerable variability in severity and type of clinical manifestations by geographic region, which are attributed to Mediterranean fever (MEFV) gene allelic heterogeneity, additional genetic modifiers and environmental factors. Considering the severe impact of MEFV mutation M694V on the FMF phenotype, this work aimed at investigating a possible disease modifying role of the serum amyloid A1 (SAA1) genotype in a cohort of 386 Armenian FMF patients homozygous for MEFV mutation M694V.

Methods

A cohort of 386 Armenian patients diagnosed with FMF based on the Tel-Hashomer criteria and carrying two MEFV M694V mutant alleles were included in this study. Fifty-two (13.40%) of these patients experienced their first attack at the age of ≥20 years (i.e. adult-onset FMF). MEFV and SAA1 analyses were performed by a commercial reverse-hybridization assay, and resulting genotypes were matched against the patients’ clinicodemographic profiles.

Results

Genotypic distribution of SAA1 alleles was significantly different between patients with an age of onset <20 and ≥20 years. SAA1 genotypes α/α, α/β and β/β could be identified in 8 (15.38%), 12 (23.08%) and 32 (61.54%) adult-onset patients while this was the case for 47 (14.07%), 172 (51.50%) and 115 (34.43%) patients with a disease onset <20 years, respectively (P < 0.001). Furthermore, adult-onset disease was associated with a less severe FMF phenotype (P < 0.001).

Conclusion

We have identified a significant relationship between the SAA1β/β genotype and the age of disease onset in M694V homozygous FMF patients.
CT Imaging of Small Bowel Neoplasms
Authors: Lee Andrew , Voutsinas Nicholas , Simpson William L. , Lewis Sara C. , Rosen Ally
Published: July 2020

Primary neoplasms of the small bowel are rare, accounting for less than 3% of all gastrointestinal tumors.1 Diagnosis of SB malignancy is difficult, as signs and symptoms are typically nonspecific including anemia, abdominal pain, gastrointestinal bleeding, weight loss, diarrhea, nausea, and vomiting.2 Many patients remain asymptomatic or are not diagnosed until at an advanced stage of disease or severe complications arise, such as bowel obstruction, bleeding, or perforation.2
Comparison of Minimal Invasive Versus Biportal Endoscopic Transforaminal Lumbar Interbody Fusion for Single-level Lumbar Disease
Authors: Kim Ju-Eun , Yoo Hyun-Seung , Choi Dae-Jung , Park Eugene J. , Jee Seung-Min
Published: July 2020

Study Design:

Retrospective study.

Objective:

The authors aimed to compare the clinical outcomes of biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) with those of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) using a microscope.

Summary of Background Data:

Lumbar spinal fusion has been widely performed for various lumbar spinal pathologies. Minimally invasive transforaminal interbody fusion using a tubular retractor under a microscope is a method of achieving fusion while reducing soft tissue injury. Recently, several studies have reported minimally invasive techniques for lumbar discectomy, decompression, and interbody fusion using biportal endoscopic spinal surgery.

Materials and Methods:

This retrospective study included 87 patients who underwent single-level TLIF for degenerative or isthmic spondylolisthesis between 2015 and 2018. Thirty-two and 55 patients underwent BE-TLIF (group A) and MI-TLIF (group B), respectively. Visual Analogue Scale scores of the back and leg and Oswestry Disability Index were collected perioperatively.

Further, data regarding perioperative complications, including length of hospital stay, time to ambulation, and fusion rate, were collected.

Results:

The Visual Analogue Scale score at 2 weeks and 2 months postoperatively was significantly lower in group A (P=0.001). All other clinical scores showed improvement with no significant difference between the 2 groups (P>0.05). The difference in the fusion rates between group A (93.7%) and group B (92.7%) were not significant (P=0.43).

Conclusions:

Because BE-TLIF yieldeds lesser early postoperative back pain than did MI-TLIF, it may allow early ambulation and a shorter hospitalization period. BE-TLIF may be a viable alternative to MI-TLIF in patients with degenerative or isthmic spondylolisthesis with superior clinical results in the early postoperative period.
Transparency in Prior Authorization
Authors: Kebaish Kareem J. , Galivanche Anoop R. , Grauer Jonathan N.
Published: July 2020

Prior Authorization (PA) is an insurance policy that requires providers to obtain permission before delivery of certain medical services. The aim is to ensure appropriate utilization of health care on the basis of clinical guidelines and to minimize costly procedures. The overall impact of PAs has not been well studied; however, many arguments exist in support and opposition to this practice. The Prior Authorization Transparency Act and the Healthcare Transparency Initiative are legislations enacted by the state of Arkansas to study and mitigate the effects of PAs. These legislations are particularly relevant to orthopedic surgery, as many orthopedic procedures and services require PA. There is limited evidence regarding the effects of PAs on the field of orthopedics. Studying these effects is critical to ensuring high-quality care for patients and reducing administrative and provider burden associated with PAs.
Barrier Techniques to Reduce Aerosolization During Extubation
Authors: Patel Kinner M. , Patel Rajeev B. , Ahmad Sahar
Published: July 2020

Preventing exposure of virulent pathogens during aerosolizing procedures such as intubations has been a cause of concern during the coronavirus pandemic. As such, protocols have been adjusted and precautions implemented in order to minimize the risk to the proceduralist. As patients improve, we face another high-risk aerosolizing procedure—extubation. We illustrate a protocol to help minimize the exposure risk during extubation. We describe a barrier technique during extubation which contained aerosolized particulates into a non-rebreather mask at time of extubation. Our protocol allows providers to perform extubations while minimizing exposure to aerosolized particles.
Adjunctive Fluvoxamine for Schizophrenia: A Meta-analysis of Randomized Double-Blind, Placebo-Controlled Trials
Authors: Zheng Wei , Xiang Ying-Qiang , Cai Dong-Bin , Yang Xin-Hu , Zhang Ling , Zheng Wei , Lu Xiao-Bing , Tong Yan-Ming , Huang Xiong , Ungvari Gabor S. , Sim Kang , Ning Yu-Ping , Xiang Yu-Tao
Published: July 2020

Background

This was a meta-analysis of double-blind, randomized controlled trials that examined the therapeutic effects and tolerability of adjunctive fluvoxamine versus placebo for schizophrenia.

Methods

The Review Manager, Version 5.3, was used to analyze data.

Results

Five double-blind randomized controlled trials (N = 284) covering 145 patients on adjunctive fluvoxamine and 139 patients on placebo were included in the analyses. Meta-analyses of total psychopathology, and negative, positive, and depressive symptoms did not show significant differences between the fluvoxamine and placebo groups. Two studies examined the effects of adjunctive fluvoxamine on cognitive functioning with mixed findings. Fluvoxamine was superior over placebo in lessening weight gain and metabolic abnormalities. Although fluvoxamine led to more discontinuation, no significant group differences were found regarding adverse drug reactions.

Conclusions

There was inconsistent evidence for the therapeutic effect of adjunctive fluvoxamine on cognitive functions and preliminary evidence for alleviating metabolic syndrome caused by clozapine. More studies are needed to explore further the effectiveness of adjunctive fluvoxamine for schizophrenia.
Practical Needs in the Home Care of Latino Children With Medical Complexity
Authors: Ware Emily J. , Beveridge Mark S. , Rosado Aura I. , Nageswaran Savithri
Published: July 2020

Latino children face barriers to high-quality healthcare. Because children with medical complexity (CMC) have higher healthcare needs, Latino CMC are likely to experience greater effects of these barriers. These vulnerabilities are exacerbated when Latino CMC endure adverse social conditions, such as food insecurity and housing instability. The study objective was to describe the challenges faced by caregivers of Latino CMC in meeting the practical needs of their children when caring for them at home. In this qualitative study, 70 Latino CMC enrolled in a complex care program of a tertiary care children's hospital were followed for a median duration of 45 months. We collected care coordination notes from encounter logs and interviewed bilingual care coordinators regarding their experiences with each child. Using thematic content analysis and an iterative process, we identified recurrent themes related to practical needs. Four themes emerged. Caregivers: 1) faced financial challenges due to many reasons that were exacerbated by children's medical conditions; 2) had challenges meeting basic needs of their families, including food and shelter; 3) experienced difficulties obtaining necessary medical supplies for their children; and 4) relied on care coordinators to navigate the system. We conclude that Latino caregivers of CMC experience many challenges meeting their families' basic needs and obtaining necessary medical supplies to care for their CMC at home. Care coordinators play a major role in addressing the practical needs of Latino CMC. Future studies should determine whether addressing the practical needs of Latino CMC would improve their health outcomes.
Designing a Program to Serve Older Adult LGBTQ+ Populations in Home Healthcare
Authors: Alvarado Leslie A. , Dorsen Caroline , Jere Char , Woerner Louise , Jones Emily , Miner Sarah M.
Published: July 2020

When compared with their heterosexual cisgender (nontransgender) counterparts, LGBTQ+ older adults are more likely to delay or not seek medical care, often due to fear of real or perceived discrimination from healthcare providers. HCR Home care is a home healthcare agency in Upstate New York that has been delivering high-quality in-home healthcare services for over 40 years. We recognized that we had a unique opportunity to address the vulnerabilities of older adults in the LGBTQ+ community and to better meet their health needs as they age in place. We developed a five-step process to implement a program to better serve the home healthcare needs of the LGBTQ+ population in our community. The goal of this initiative is to provide ongoing community education on home healthcare, awareness of the social and health issues surrounding LGBTQ+ older adults, and ultimately to improve care and decrease health disparities. This article describes the five-step process, the challenges, successes, and implications for the future. Ensuring there are healthcare solutions available for vulnerable and marginalized individuals is key to changing the way home healthcare is structured and improving quality of life and health outcomes for all.
The Incidence of Central Neurological Disorders Among Patients With Isolated Dizziness and the Diagnostic Yield of Neuroimaging Studies
Authors: Idil Hasan , Ozbay Yenice Gokce , Kilic Turgay Yilmaz , Eyler Yesim , Duman Atilla Ozge
Published: July 2020

Objectives:

Dizziness is a common symptom among emergency department (ED) patients and is often associated with benign processes. The aim of this study was to investigate the incidence of severe central neurological pathologies in isolated dizziness cases and the diagnostic efficiency of neuroimaging studies.

Methods:

All applications for isolated dizziness to an academic ED between January 1, 2011, and December 31, 2017 were retrospectively reviewed. The frequency of these admissions, the demographic data of the patients, the results of cranial computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) studies, and the central neurological causes of isolated dizziness were recorded.

Results:

The percentage of patients with isolated dizziness among all ED admissions was 2.5% (29,510/1,190,857). The median age of these patients was 52 years (interquartile range: 38 to 66) and 58% were female. During the study period, the rate of neuroimaging studies for isolated dizziness increased year by year, and a total of 6406 (21.7%) cranial CTs and 2896 (9.8%) DW-MRIs were performed. The diagnostic yield of neuroimaging studies was 0.6% for cranial CT and 3.9% for DW-MRI. Central neurological disorders were detected in 143 (0.48%) patients with isolated dizziness. The most common causes were posterior circulation ischemic strokes (47.5%), other ischemic strokes (18.9%), vertebrobasilar insufficiency (10.5%), and transient ischemic attack (8.4%).

Conclusions:

Isolated dizziness is rarely associated with central neurological pathologies. Neuroimaging studies, especially cranial CT, have low diagnostic yield in isolated dizziness and should therefore not be routine in the evaluation process.
GABA-B Receptor Encephalitis Triggered by Enterovirus Encephalitis in a Patient With Small Cell Lung Cancer
Authors: Kim Seong Hoon , Kim Woojun
Published: July 2020

Introduction:

Encephalitis with gamma-aminobutyric acid (GABA)-B receptor antibodies (GABA-B receptor encephalitis) is known to have underlying neoplastic condition in half of the cases; however, there could be an additional event that could work as a trigger factor. Here, we report a patient with GABA-B receptor encephalitis associated with small cell lung cancer, which was probably triggered by enterovirus encephalitis.

Case Report:

A 53-year-old man was admitted for a seizure, following fever and headache for 3 days. Status epilepticus developed on the following day. Brain magnetic resonance imaging (MRI) was normal. Cerebrospinal fluid (CSF) study revealed lymphocyte-dominant pleocytosis, and enterovirus was detected by polymerase chain reaction test in CSF later. The patient recovered after 2 weeks of treatment. Another 2 weeks later, he showed confusion and seizure without fever. Follow-up CSF study revealed no abnormalities; however, MRI showed a lesion with vasogenic edema on the right posterior hippocampus. GABA-B receptor antibodies were found in the serum and CSF. The chest computed tomography revealed a mass on his right upper lung, which was confirmed as a small cell lung cancer. GABA-B receptor encephalitis associated with small cell lung cancer was diagnosed, and intravenous immunoglobulin and methylprednisolone were infused. Following treatment, seizures and delirium stopped, and the patient recovered to a near normal state. Follow-up MRI performed 2 months later showed that the hippocampal lesion had disappeared.

Conclusion:

In cases of infectious encephalitis with an atypical recurrent course, the possibility of newly onset autoimmune encephalitis should be considered.
Apoptosis in gonadal somatic cells of scleractinian corals: implications of structural adjustments for gamete production and release
Authors: Shikina Shinya , Chen Che-Chun , Chiu Yi-Ling , Tsai Pin-Hsuan , Chang Ching-Fong
Published: July 2020

Apoptosis is an evolutionarily conserved process of programmed cell death. Here, we show structural changes in the gonads caused by apoptosis during gametogenesis in the scleractinian coral,Euphyllia ancora. Anatomical and histological analyses revealed that from the non-spawning to the spawning season, testes and ovaries increased in size due to active proliferation, differentiation and development of germ cells. Additionally, the thickness and cell density of the gonadal somatic layer decreased significantly as the spawning season approached. Further analyses demonstrated that the changes in the gonadal somatic layer were caused by apoptosis in a subpopulation of gonadal somatic cells. The occurrence of apoptosis in the gonadal somatic layer was also confirmed in other scleractinian corals. Our findings suggest that decreases in thickness and cell density of the gonadal somatic layer are structural adjustments facilitating oocyte and spermary (male germ cell cluster) enlargement and subsequent gamete release from the gonads. In animal reproduction, apoptosis in germ cells is an important process that controls the number and quality of gametes. However, apoptosis in gonadal somatic cells has rarely been reported among metazoans. Thus, our data provide evidence for a unique use of apoptosis in animal reproduction.
Does evolution design robust food webs?
Authors: Girardot B. , Gauduchon M. , Ménard F. , Poggiale J. C.
Published: July 2020

Theoretical works that use a dynamical approach to study the ability of ecological communities to resist perturbations are largely based on randomly generated ecosystem structures. By contrast, we ask here whether the evolutionary history of food webs matters for their robustness. Using a community evolution model, we first generate trophic networks by varying the level of energy supply (richness) of the environment in which species adapt and diversify. After placing our simulation outputs in perspective with present-day food webs empirical data, we highlight the complex, structuring role of this environmental condition during the evolutionary setting up of trophic networks. We then assess the robustness of food webs by studying their short-term ecological responses to swift changes in their customary environmental richness. We reveal that the past conditions have a crucial effect on the robustness of current food webs. Moreover, directly focusing on connectance of evolved food webs, it turns out that the most connected ones appear to be the least robust to sharp depletion in the environmental energy supply. Finally, we appraise the ‘adaptation’ of food webs themselves: generally poor, except in relation to a diversity of flux property.
Superior anticoagulation strategies for renal replacement therapy in critically ill patients with COVID-19: a cohort study
Authors: Arnold Frederic , Westermann Lukas , Rieg Siegbert , Neumann-Haefelin Elke , Biever Paul , Walz Gerd , Kalbhenn Johannes , Tanriver Yakup
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) patients who are admitted to intensive care units (ICU) have a high risk of requiring renal replacement therapy (RRT) due to acute kidney injury (AKI). Concomitantly, COVID-19 patients exhibit a state of hypercoagulability that can affect circuit lifespan. An optimal anticoagulation strategy is therefore needed in order to maintain circuit patency and therapeutic efficiency of RRT.

Methods

Retrospective single-centre cohort study on 71 critically ill COVID-19 patients at the University of Freiburg Medical Center. Included were all patients aged 18 years and older with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that were admitted to ICU between February 26 and May 21, 2020. We collected data on the COVID-19 disease course, AKI, RRT, thromboembolic events and anticoagulation. Primary outcome of the study was the effect of different anticoagulation strategies during RRT on extracorporeal circuit lifespans.

Results

Anticoagulation during continuous veno-venous haemodialysis (CVVHD) was performed with unfractionated heparin (UFH) or citrate. Mean treatment time in the UFH group was 21.3h (SEM: ±5.6h). Mean treatment time in the citrate group was 45.6h (SEM: ±2.7h). Citrate anticoagulation prolonged treatment duration significantly by 24.4h (p=0.0014). Anticoagulation during sustained low-efficiency daily dialysis (SLEDD) was performed with UFH, argatroban or low molecular weight heparin (LMWH). Mean dialysis time with UFH was 8.1h (SEM: ±1.3h), argatroban 8.0h (SEM: ±0.9h) and LMWH 11.8h (SEM: ±0.5h). Compared to UFH and argatroban, LMWH significantly prolonged treatment times by 3.7h (p=0.0082) and 3.8h (p=0.0024), respectively.

Conclusions

UFH fails to prevent early clotting events in dialysis circuits. For patients, who do not require an effective systemic anticoagulation, regional citrate dialysis is the most effective strategy in our cohort. For patients, who require an effective systemic anticoagulation treatment, the usage of LMWH results in the longest circuit life spans.

Funding

Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg, Germany. Else Kröner-Fresenius-Stiftung, Bad Homburg, Germany. Deutsche Forschungsgemeinschaft, Bonn, Germany.
Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2
Authors: Mou Huihui , Quinlan Brian D. , Peng Haiyong , Guo Yan , Peng Shoujiao , Zhang Lizhou , Davis-Gardner Meredith E. , Gardner Matthew R. , Crynen Gogce , Voo Zhi Xiang , Bailey Charles C. , Alpert Michael D. , Rader Christoph , Choe Hyeryun , Farzan Michael
Published: July 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates infection of cells expressing angiotensin-converting enzyme 2 (ACE2). ACE2 is also the viral receptor of SARS-CoV (SARS-CoV-1), a related coronavirus that emerged in 2002-2003. Horseshoe bats (genus Rhinolophus) are presumed to be the original reservoir of both viruses, and a SARS-like coronavirus, RaTG13, closely related SARS-CoV-2, has been isolated from one horseshoe-bat species. Here we characterize the ability of S-protein receptor-binding domains (RBDs) of SARS-CoV-1, SARS-CoV-2, and RaTG13 to bind a range of ACE2 orthologs. We observed that the SARS-CoV-2 RBD bound human, pangolin, and horseshoe bat (R. macrotis) ACE2 more efficiently than the SARS-CoV-1 or RaTG13 RBD. Only the RaTG13 RBD bound rodent ACE2 orthologs efficiently. Five mutations drawn from ACE2 orthologs of nine Rhinolophus species enhanced human ACE2 binding to the SARS-CoV-2 RBD and neutralization of SARS-CoV-2 by an immunoadhesin form of human ACE2 (ACE2-Fc). Two of these mutations impaired neutralization of SARS-CoV-1. An ACE2-Fc variant bearing all five mutations neutralized SARS-CoV-2 five-fold more efficiently than human ACE2-Fc. These data narrow the potential SARS-CoV-2 reservoir, suggest that SARS-CoV-1 and -2 originate from distinct bat species, and identify a more potently neutralizing form of ACE2-Fc.
A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection
Authors: Herrmann Andreas , Maruyama Junki , Yue Chanyu , Lahtz Christoph , Zhou Heyue , Kerwin Lisa , Guo Whenzong , Zhang Yanliang , Hoo William Soo , Yei Soonpin , Kwon Sunkuk , Fu Yanwen , Johnson Sachi , Ledesma Arthur , Zhou Yiran , Zhuang Yingcong , Yei Elena , Adamus Tomasz , Praessler Slobodan , Ji Henry
Published: July 2020

Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcγR+ antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro. The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by FcγR+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcγR+ antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo. Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations.
Anti-frameshifting ligand active against SARS coronavirus-2 is resistant to natural mutations of the frameshift-stimulatory pseudoknot
Authors: Neupane Krishna , Munshi Sneha , Zhao Meng , Ritchie Dustin B. , Ileperuma Sandaru M. , Woodside Michael T.
Published: July 2020

The coronavirus SARS-CoV-2 causing the COVID-19 pandemic uses −1 programmed ribosomal frameshifting (−1 PRF) to control the expression levels of key viral proteins. Because modulating −1 PRF can attenuate viral propagation, ligands binding to the viral RNA pseudoknot that stimulates −1 PRF may prove useful as therapeutics. Mutations in the pseudoknot have been observed over the course of the pandemic, but how they affect −1 PRF and the activity of inhibitors is unknown. Cataloguing natural mutations in all parts of the SARS-CoV-2 pseudoknot, we studied a panel of 6 mutations in key structural regions. Most mutations left the −1 PRF efficiency unchanged, even when base-pairing was disrupted, but one led to a remarkable three-fold decrease, suggesting that SARS-CoV-2 propagation may be less sensitive to modulation of −1 PRF efficiency than some other viruses. Examining the effects of one of the few small-molecule ligands known to suppress −1 PRF significantly in SARS-CoV, we found that it did so by similar amounts in all SARS-CoV-2 mutants tested, regardless of the basal −1 PRF efficiency, indicating that the activity of anti-frameshifting ligands can be resistant to natural pseudoknot mutations. These results have important implications for therapeutic strategies targeting SARS-CoV-2 through modulation of −1 PRF.
Double-strand breaks can induce DNA replication and damage amplification in G2 phase-like oocytes of mice
Authors: Ma Jun-Yu , Feng Xie , Xie Feng-Yun , Li Sen , Chen Lei-Ning , Luo Shi-Ming , Ou Xiang-Hong
Published: July 2020

Break-induced DNA replication (BIR) have been detected not only in the genome of rare disease patients but also in cancer cells, however, the mechanisms of BIR formation haven’t been explained in details. In the late G2 phase-like mouse oocytes, we found DNA double-strand breaks (DSBs) could induce Rad51 dependent small-scale DNA replication. In addition, we also found the DSBs could be amplified in mouse oocytes, and the amplification could be inhibited by Rad51 inhibitor IBR2 and DNA replication inhibitor ddATP. Lastly, we found the DSB repair was relatively inefficiency in hybrid mouse oocytes compared with that of the purebred mouse oocytes. We found DSBs could induce BIR more easier in hybrid mouse oocytes, indicating the DNA repair in oocytes could be affected by the sequence differences between homologous chromatids. In summary, our results indicated that the condensed chromatin configuration in late G2 phase and the sequence similarity between broken DNA and template DNA are causing factors of BIR in mammalian genome, and the DNA damage could be amplified in late G2 phase cells.
T cell receptor-dependent S-acylation of ZAP-70 controls activation of T cells
Authors: Tewari Ritika , Shayahati Bieerkehazhi , Fan Ying , Akimzhanov Askar M.
Published: July 2020

ZAP-70 is a cytoplasmic tyrosine kinase essential for T cell-mediated immune responses. Upon engagement of the T cell receptor, ZAP-70 is quickly recruited to the specialized plasma membrane domains, becomes activated and released to phosphorylate its laterally segregated downstream targets. A shift in ZAP-70 distribution at the plasma membrane is recognized as a critical step in T cell receptor signal transduction and amplification. However, the molecular mechanism supporting stimulation-dependent plasma membrane compartmentalization of ZAP-70 remains poorly understood. In this study, we identified previously uncharacterized reversible lipidation (S-acylation) of ZAP-70. We found that this post-translational modification of ZAP-70 is dispensable for its enzymatic activity. However, the lipidation-deficient mutant of ZAP-70 failed to propagate the T cell receptor signaling cascade suggesting that S-acylation is essential for ZAP-70 interaction with its protein substrates. The kinetics of ZAP-70 S-acylation were consistent with early T cell signaling events indicating that agonist-induced S-acylation is a part of the signaling mechanism controlling T cell activation and function.

Significance Statement

Activation of T cells is a critical part of the adaptive immune response to pathogen exposure. We found that ZAP-70, a regulatory protein essential for T cell activation, can undergo a post-translational modification with long chain fatty acids, known as S-acylation. In this report, we show that S-acylation of ZAP-70 is T cell receptor-dependent and required for its signaling function. We found that loss of ZAP-70 S-acylation resulted in T cell unresponsiveness to T cell receptor stimulation indicating that abnormalities in protein S-acylation can potentially contribute to the T cell immunodeficiency disorders.
Mutations primarily alter the inclusion of alternatively spliced exons
Authors: Baeza-Centurion Pablo , Miñana Belén , Valcárcel Juan , Lehner Ben
Published: July 2020

Genetic analyses and systematic mutagenesis have revealed that synonymous, non-synonymous and intronic mutations frequently alter the inclusion levels of alternatively spliced exons, consistent with the concept that altered splicing might be a common mechanism by which mutations cause disease. However, most exons expressed in any cell are highly-included in mature mRNAs. Here, by performing deep mutagenesis of highly-included exons and by analysing the association between genome sequence variation and exon inclusion across the transcriptome, we report that mutations only very rarely alter the inclusion of highly-included exons. This is true for both exonic and intronic mutations as well as for perturbations intrans. Therefore, mutations that affect splicing are not evenly distributed across primary transcripts but are focussed in and around alternatively spliced exons with intermediate inclusion levels. These results provide a resource for prioritising synonymous and other variants as disease-causing mutations.
One-Step Bacterial Artificial Chromosome (BAC) Modification: Cloning of the A Homology Arm into Reporter-Shuttle Vector
Authors: Heintz Nathaniel , Gong Shiaoching
Published: July 2020

In this protocol, the homology arm sequence for one-step bacterial artificial chromosome (BAC) modification is introduced by ligation into the shuttle vector carrying the reporter sequence to provide sites for recombination within the BAC clone. Crude lysates of individual bacterial transformants serve as templates in polymerase chain reaction (PCR) analysis to confirm the presence of the homology arms in the recombinant shuttle vector. To provide further assurance that the homology box has been successfully integrated into the plasmid, the enzyme digestion pattern of the modified plasmid is compared with that of the unmodified plasmid.