bluuebunny/crossref_metadata_2025 huggingface dataset:
Covid-19 survivors may have deterioration in frontal plane qrs-t angle and the other electrocardiogram parameters
Authors: Kuyumcu M S , Ulusan S
Published: May 2022

Funding Acknowledgements

Type of funding sources: None.

Background

COVID-19 infection is known to damage myocardial tissue and increase arrhythmic events. However, the data in the literature on permanent attachments are limited. In our study, we planned to investigate possible arrhythmic damages in COVID-19 survivors using the frontal plane QRS-T [f(QRS)-T] angle and some other ECG parameters.

Patients & Methods

269 patients who recovered from COVID-19 between April 2020 and January 2021 were included into the study. Pre-admission electrocardiograms and first-month outpatient clinic control ECGs of the patients were compared.

Results

After COVID-19, left bundle branch block (p<0.001), right bundle branch block (p<0.001), right bundle branch block (p<0.001), atrial fibrillation (p<0.001) rates had increased. Prolongation was detected in QRS duration (p<0.001), QT interval (p=0.014), adjusted QT interval (p =0.007) and Tpe interval (p=0.012). F(QRS)-T angle (p<0.001) and fragmented QRS rate (p<0.001) were increased.

Conclusions

It was observed in our study that; even if patients survive after COVID-19, permanent deterioration in ECG parameters may occur.
Pleiotropic Enhancers are Ubiquitous Regulatory Elements in the Human Genome
Authors: Laiker Ian , Frankel Nicolás
Published: May 2022

Enhancers are regulatory elements of genomes that determine spatio-temporal patterns of gene expression. The human genome contains a vast number of enhancers, which largely outnumber protein-coding genes. Historically, enhancers have been regarded as highly tissue-specific. However, recent evidence has demonstrated that many enhancers are pleiotropic, with activity in multiple developmental contexts. Yet, the extent and impact of pleiotropy remain largely unexplored. In this study we analyzed active enhancers across human organs based on the analysis of both eRNA transcription (FANTOM5 consortium data sets) and chromatin architecture (ENCODE consortium data sets). We show that pleiotropic enhancers are pervasive in the human genome and that most enhancers active in a particular organ are also active in other organs. In addition, our analysis suggests that the proportion of context-specific enhancers of a given organ is explained, at least in part, by the proportion of context-specific genes in that same organ. The notion that such a high proportion of human enhancers can be pleiotropic suggests that small regions of regulatory DNA contain abundant regulatory information and that these regions evolve under important evolutionary constraints.
Enhanced Taste Recognition Following Subacute Treatment With The Dopamine D2/D3 Receptor Agonist Pramipexole in Healthy Volunteers
Authors: Kaltenboeck Alexander , Halahakoon Don Chamith , Harmer Catherine J , Cowen Philip , Browning Michael
Published: May 2022

Background

Patients with Parkinson’s disease (PD) show impaired performance in taste recognition tests, which suggests a possible dopaminergic influence on gustatory functioning. To experimentally test this hypothesis, we assessed whether pharmacological manipulation of dopaminergic signaling in healthy volunteers can affect performance in a standardized taste recognition test.

Methods

Physically and mentally healthy volunteers (n = 40, age 18–43 years) were randomly allocated to treatment with either pramipexole or placebo using a double-blind, parallel-group design. After 12 to 15 days of treatment (dose titrated up from 0.25 mg/d of pramipexole salt to 1.0 mg/d), taste recognition performance was assessed using a standardized and validated assay (taste strip test). Additionally, visual analogue scale ratings of subjective pleasantness and disgustingness of taste samples were obtained.

Results

Compared with the placebo group, participants receiving pramipexole showed significantly higher total recognition accuracy (medianpramipexole = 14.0, medianplacebo = 13.0, U = 264.5, P = .04). This was driven by a higher sensitivity for taste in the pramipexole group. Exploratory analysis of pleasantness and disgustingness ratings of appetitive (sweet) vs aversive (bitter) stimuli suggested that pramipexole treatment was associated with overall blunted hedonic responses, but this effect did not survive the inclusion of nausea (a side effect of treatment) as a covariate in the analysis.

Conclusions

Healthy volunteers who received subacute pramipexole treatment exhibited higher taste recognition performance compared with the placebo group. This finding is consistent with a proposed role of the dopaminergic system in gustatory functioning and could have important theoretical and clinical implications.
Specific Components Associated With the Endothelial Glycocalyx Are Lost From Brain Capillaries in Cerebral Malaria
Authors: Hempel Casper , Milner Dan , Seydel Karl , Taylor Terrie
Published: May 2022

Background

Cerebral malaria (CM) is a rare, but severe and frequently fatal outcome of infection with Plasmodium falciparum. Pathogenetic mechanisms include endothelial activation and sequestration of parasitized erythrocytes in the cerebral microvessels. Increased concentrations of glycosaminoglycans in urine and plasma of malaria patients have been described, suggesting involvement of endothelial glycocalyx.

Methods

We used lectin histochemistry on postmortem samples to compare the distribution of multiple sugar epitopes on cerebral capillaries in children who died from CM and from nonmalarial comas.

Results

N-acetyl glucosamine residues detected by tomato lectin are generally reduced in children with CM compared to controls. We used the vascular expression of intercellular adhesion molecule 1 and mannose residues on brain capillaries of CM as evidence of local vascular inflammation, and both were expressed more highly in CM patients than controls. Sialic acid residues were found to be significantly reduced in patients with CM. By contrast, the levels of other sugar epitopes regularly detected on the cerebral vasculature were unchanged, and this suggests specific remodeling of cerebral microvessels in CM patients.

Conclusions

Our findings support and expand upon earlier reports of disruptions of the endothelial glycocalyx in children with severe malaria.
Funding Precarity and Women's Peace Work in Colombia, Nepal, and Northern Ireland
Authors: Boer Cueva Alba , Giri Keshab , Hamilton Caitlin , Shepherd Laura J
Published: May 2022

Civil society supports peace work in many ways, including through education, advocacy, health outreach, data gathering, expertise- and experience-sharing, event-running, community mobilization, conflict prevention, and peacebuilding. However, there are limited funds available to support this work, even though key development, peace, and security actors, including the United Nations Secretary-General, have acknowledged that developing the capacity of civil society to support peacebuilding efforts required increased investment. Scarcity of funding has created important political dynamics that affect the work that civil society can do. This study uses a qualitative semi-structured interview design to elicit information about donor funding dynamics and imperatives from expert research informants across three conflict-affected countries: Colombia, Nepal, and Northern Ireland. We explore funding dynamics, various organizational features that influence mobilization strategies, and the impact of COVID-19 on women's civil society groups working on peacebuilding. We argue that, while it is an ongoing concern, scarcity of funding is not the only inhibitor to effective peace work. Donor priorities, and embedded assumptions about the value of peace work—largely undertaken by women and women-led organizations—also challenge the viability of continued efforts toward sustainable peace.
Short- and Long-Term Biological Variability of Small Dense LDL, HDL3, and Triglyceride-Rich Lipoprotein Cholesterol
Authors: Fatica Erica M , Jenkins Sarah M , Scott Renee J , Block Darci R , Meeusen Jeffrey W , Baumann Nikola A , Saenger Amy K , Donato Leslie J
Published: May 2022

Background

Measurement of cholesterol within lipoprotein subfractions may aid in cardiovascular disease prediction. Simple, homogenous enzymatic assays for the direct measurement of lipoprotein subfractions have been developed to measure small dense low-density lipoprotein cholesterol (sdLDL-C), high-density lipoprotein-3 cholesterol (HDL3-C), and triglyceride-rich lipoprotein (TRL-C) cholesterol. The objective of this study was to determine biological variability for sdLDL-C, HDL3-C, and TRL-C in a healthy reference population to facilitate interpretation of these analytes.

Methods

Serum samples were collected from 24 healthy subjects (n = 14 female/10 male) daily for 3 days while non-fasting, and daily for 5 days, weekly for 4 weeks, and monthly for 6 months after overnight fasting. sdLDL-C, HDL3-C, and TRL-C cholesterol were measured by homogenous enzymatic assays. Sources of variability (between-subject, within-subject, and analytical) were calculated using random-effects regression models. Reference change value (RCV) and index of individuality (II) for each time period were determined from the variance components.

Results

Analytic variability (daily, weekly, and monthly CVA) was <3% for each analyte. Monthly within-subject variability (CVI) was 17.1% for sdLDL-C, 7.4% for HDL3-C, and 25.7% for TRL-C. Most of the monthly variation was attributed to between-subject variation for all 3 analytes. Overall RCVs for monthly measurements were 18.1 mg/dL for sdLDL-C, 6.1 mg/dL for HDL3-C, and 16.0 mg/dL for TRL-C. IIs were <0.6 for sdLDL-C and HDL3-C, and 0.81 for TRL-C.

Conclusions

sdLDL-C, HDL3-C, and TRL-C showed moderate within-subject variability, but high between-subject variability, in a healthy reference population. Given the high individuality of each analyte, population-based reference intervals may be inadequate to detect clinically significant changes.
Molecular Mechanisms of ARID5B-Mediated Genetic Susceptibility to Acute Lymphoblastic Leukemia
Authors: Zhao Xujie , Qian Maoxiang , Goodings Charnise , Zhang Yang , Yang Wenjian , Wang Ping , Xu Beisi , Tian Cheng , Pui Ching-Hon , Hunger Stephen P , Raetz Elizabeth A , Devidas Meenakshi , Relling Mary V , Loh Mignon L , Savic Daniel , Li Chunliang , Yang Jun J
Published: May 2022

Background

There is growing evidence for the inherited basis of susceptibility to childhood acute lymphoblastic leukemia (ALL). Genome-wide association studies have identified non-coding ALL risk variants at the ARID5B gene locus, but their exact functional effects and the molecular mechanism linking ARID5B to B-cell ALL leukemogenesis remain largely unknown.

Methods

We performed targeted sequencing of ARID5B in germline DNA of 5008 children with ALL. Variants were evaluated for association with ALL susceptibility using 3644 patients from the UK10K cohort as non-ALL controls, under an additive model. Cis-regulatory elements in ARID5B were systematically identified using dCas9-KRAB–mediated enhancer interference system enhancer screen in ALL cells. Disruption of transcription factor binding by ARID5B variant was predicted informatically and then confirmed using chromatin immunoprecipitation and coimmunoprecipitation. ARID5B variant association with hematological traits was examined using UK Biobank dataset. All statistical tests were 2-sided.

Results

We identified 54 common variants in ARID5B statistically significantly associated with leukemia risk, all of which were noncoding. Six cis-regulatory elements at the ARID5B locus were discovered using CRISPR-based high-throughput enhancer screening. Strikingly, the top ALL risk variant (rs7090445, P = 5.57 × 10–45) is located precisely within the strongest enhancer element, which is also distally tethered to the ARID5B promoter. The variant allele disrupts the MEF2C binding motif sequence, resulting in reduced MEF2C affinity and decreased local chromosome accessibility. MEF2C influences ARID5B expression in ALL, likely via a transcription factor complex with RUNX1. Using the UK Biobank dataset (n = 349 861), we showed that rs7090445 was also associated with lymphocyte percentage and count in the general population (P = 8.6 × 10–22 and 2.1 × 10–18, respectively).

Conclusions

Our results indicate that ALL risk variants in ARID5B function by modulating cis-regulatory elements at this locus.
Temporal effects of climatic factors on vegetation phenology on the Loess Plateau, China
Authors: Liu Ning , Shi Yufeng , Ding Yongxia , Liu Li , Peng Shouzhang
Published: May 2022

Studying the start (SOS) and end (EOS) of the vegetation growing season can improve vegetation prediction under climate change. Climatic factors have temporal effects on vegetation growth, including the no time effect (no), time-lag effect (lag), time-accumulation effect (acc), and both time-lag and -accumulation effects (lagacc). The linear regression equations between SOS/EOS and climatic factors were constructed for the Loess Plateau (LP). Subsequently, we analyzed the effects of single and multiple climatic factors on vegetation phenology under four temporal effect scenarios and investigated the response of vegetation phenology to the time-lag and time-accumulation effects of climatic factors, under the lagacc scenario. Among the four temporal effects, lagacc explained the effects of climate on vegetation phenology to the greatest degree, and it is the optimal temporal effect for simulating the relationship between vegetation phenology and climate on the LP. Moreover, the explanation degrees of multiple climatic factors were higher than those of single climatic factors across different temporal effects and vegetation types. Simultaneously considering multiple climatic factors improved predictability of their impact on vegetation phenology. Under lagacc, responses of SOS to temperature (TMP) and precipitation (PRE) exhibited 1.44 ± 0.43/3.49 ± 0.85 and 1.38 ± 0.30/3.38 ± 0.71 months lag/accumulation, respectively, and responses of EOS to TMP and PRE exhibited 1.35 ± 0.17/2.37 ± 0.34 and 1.59 ± 0.19/4.16 ± 0.50 months lag/accumulation, respectively, across the entire LP. The results show that both lagacc and multiple climatic factors require consideration when establishing relationships between climatic factors and vegetation phenology.
Future of professional work: evidence from legal jobs in Britain and the United States
Authors: Sako Mari , Qian Matthias , Attolini Jacopo
Published: May 2022

What is the impact of digital technology on professional work? This paper addresses this question by developing a theory on professional jurisdictional control, which we define as a profession’s power to maintain or shift from existing jurisdictional settlements in the face of external disturbances. Digital technology is a disturbance, and who ends up undertaking digital tasks depends on the nature of professional jurisdictional control. With protective jurisdictional control, the profession engages in full or subordinate jurisdiction, delegating new tasks to subordinate semiprofessionals. By contrast, with connective jurisdictional control, the profession prefers settlements by division of labor or advisory links, enabling equal-status professions to work together. Using a large and representative database of online job postings, we find evidence for this hypothesis. Empirically, we deploy three ways to gauge the nature of professional jurisdictional control: first, by comparing traditional law firms and alternative business structure firms in the UK; second, by contrasting the US (with protective jurisdictional control) and the UK; and third, by examining the legal sector (in which the legal profession dominates) and non-legal sectors. We also find that protective (connective) jurisdictional control is associated with lower (higher) pay premia for digital skills, consistent with theory. Our findings highlight the mediating role of professional jurisdictional control to inform the future of work debate.
Minimal invasive resurfacing: an innovative technique for the superior semicircular canal dehiscence. A case series
Authors: Salvinelli Fabrizio , Bonifacio Francesca , Beccaria Claudia , Greco Fabio , Frari Valeria , Iafrati Francesco , Trivelli Maurizio
Published: May 2022

The superior semicircular canal dehiscence is a vestibular disease recognized condition in recent years, and surgical therapy has been modeling itself over the years to ensure the control of vestibular symptoms and auditory symptoms. In this case series, the authors have experienced an intervention aimed at closing the superior semicircular canal dehiscence through the insertion of bone paté between the meninx and the residual middle cranial fossa bone wall. Seven patients underwent this intervention, they reported an improvement in all vestibular and auditory symptoms, and hearing threshold remained stable. Despite the small sample size, the difference was significant in the control of dizziness and the reduction of pulsatile tinnitus. The technique described in this article allows the control of symptoms in superior semicircular canal dehiscence, and it is a type of surgery familiar to the otosurgeon and easily replicable as it involves a modified mastoidectomy. More data are needed.
The evolving properties of the corona of GRS 1915+105: a spectral-timing perspective through variable-Comptonization modelling
Authors: García Federico , Karpouzas Konstantinos , Méndez Mariano , Zhang Liang , Zhang Yuexin , Belloni Tomaso , Altamirano Diego
Published: May 2022

The inverse Compton process by which soft photons are up-scattered by hot electrons in a corona plays a fundamental role in shaping the X-ray spectra of black hole (BH) low-mass X-ray binaries (LMXBs), particularly in the hard and hard-intermediate states. In these states, the power-density spectra of these sources typically show Type-C low-frequency quasi-periodic oscillations (QPOs). Although several models have been proposed to explain the dynamical origin of their frequency, only a few of those models predict the spectral-timing radiative properties of the QPOs. Here, we study the physical and geometrical properties of the corona of the BH-LMXB GRS 1915+105 based on a large sample of observations available in the RXTE archive. We use a recently developed spectral-timing Comptonization model to fit simultaneously the energy-dependent fractional rms amplitude and phase-lag spectra of the Type-C QPO in 398 observations. For this, we include spectral information gathered from fitting a Comptonization model to the corresponding time-averaged spectra. We analyse the dependence of the physical and geometrical properties of the corona upon the QPO frequency and spectral state of the source, the latter characterized by the hardness ratio. We find consistent trends in the evolution of the corona size, temperature, and feedback (the fraction of the corona photons that impinge back on to the disc) that persist for roughly 15 yr. By correlating our observations with simultaneous radio-monitoring of the source at 15 GHz, we propose a scenario in which the disc–corona interactions connect with the launching mechanism of the radio jet in this source.
Fluorodeoxyglucose-positron emission tomography/computed tomography-positive ear lesions responsive to immunosuppressive therapy in a patient with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Murao Yuki , Yoshida Yusuke , Oka Naoya , Yorishima Ai , Masuda Sho , Sugimoto Tomohiro , Ono Rina , Hirokawa Yutaka , Hirata Shintaro
Published: May 2022

A 74-year-old woman presented with vertigo, left-beating nystagmus, and auditory disturbance 4 months prior, in whom a former physician suspected Meniere’s disease. Her signs and symptoms mildly improved with a moderate dose of glucocorticoids, which was eventually tapered. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) was performed 12 days prior to routine examination. Remarkable FDG uptake was observed in the surrounding areas of the bilateral Eustachian tubes and left middle ear, which was only partially detected on magnetic resonance imaging. The patient also tested positive for myeloperoxidase–antineutrophil cytoplasmic antibody (ANCA). She was admitted to our hospital and diagnosed with otitis media with ANCA-associated vasculitis (OMAAV) based on the classification criteria. Four months after immunosuppressive therapy, the abnormal ear findings were not observed on follow-up FDG-PET/CT. The clinical course of this case suggests that FDG-PET/CT can detect occult ear involvement better than do other modalities in patients with OMAAV. In addition, FDG-PET/CT-positive ear lesions responded to immunosuppressive therapy. Therefore, FDG-PET/CT can help distinguish OMAAV from other ear diseases with non-inflammatory aetiologies and detect occult treatment-responsive OMAAV lesions in the clinical setting.
Successful treatment of bullous lupus with corticosteroids and belimumab: A case report
Authors: Keshavamurthy Chandana , Fibeger Emily , Virata Andrew , Bansal Pankaj
Published: May 2022

Cutaneous lupus erythematosus (CLE) is one of the most common manifestations of systemic lupus erythematosus (SLE), although it can manifest as an independent entity as well. Bullous systemic lupus erythematosus (BSLE) is a rare cutaneous manifestation of SLE presenting as tense vesiculobullous eruptions in a photosensitive distribution. Pathophysiology is secondary to autoantibodies against noncollagenous domain 1 and 2 (NC1 and NC2) type VII collagen, and histopathology reveals dense neutrophilic infiltration of the dermis with direct immunofluorescence showing IgG deposition at dermoepidermal junction. There is lack of data on available therapeutic options to treat BSLE, and varying responses to dapsone, methotrexate, azathioprine and corticosteroids have been reported. Belimumab, a fully humanised Change to Immunoglobulin G1λ (IgG1λ) monoclonal antibody targeting soluble B lymphocyte stimulator protein, was the first Food and Drug Administration-approved drug for SLE and has been reported to be effective for CLE. We present the case of a 41-year-old black female with SLE presenting with BSLE, who was successfully treated with corticosteroids and belimumab and did not experience disease relapse even after discontinuation of corticosteroids. To our knowledge, this is the first reported case of successful treatment of BSLE with belimumab, and further research can help determine the role of belimumab in the treatment of BSLE.
Possible role for rareTRPM7variants in patients with hypomagnesaemia with secondary hypocalcaemia
Authors: Vargas-Poussou Rosa , Claverie-Martin Felix , Prot-Bertoye Caroline , Carotti Valentina , van der Wijst Jenny , Perdomo-Ramirez Ana , Fraga-Rodriguez Gloria M , Hureaux Marguerite , Bos Caro , Latta Femke , Houillier Pascal , Hoenderop Joost G J , de Baaij Jeroen H F
Published: May 2022

Background

Hypomagnesaemia with secondary hypocal-caemia (HSH) is a rare autosomal recessive disorder caused by pathogenic variants in TRPM6, encoding the channel-kinase transient receptor potential melastatin type 6. Patients have very low serum magnesium (Mg2+) levels and suffer from muscle cramps and seizures. Despite genetic testing, a subgroup of HSH patients remains without a diagnosis.

Methods

In this study, two families with an HSH phenotype but negative for TRPM6 pathogenic variants were subjected to whole exome sequencing. Using a complementary combination of biochemical and functional analyses in overexpression systems and patient-derived fibroblasts, the effect of the TRPM7-identified variants on Mg2+ transport was examined.

Results

For the first time, variants in TRPM7 were identified in two families as a potential cause for hereditary HSH. Patients suffer from seizures and muscle cramps due to magnesium deficiency and episodes of hypocalcaemia. In the first family, a splice site variant caused the incorporation of intron 1 sequences into the TRPM7 messenger RNA and generated a premature stop codon. As a consequence, patient-derived fibroblasts exhibit decreased cell growth. In the second family, a heterozygous missense variant in the pore domain resulted in decreased TRPM7 channel activity.

Conclusions

We establish TRPM7 as a prime candidate gene for autosomal dominant hypomagnesaemia and secondary hypocalcaemia. Screening of unresolved patients with hypocalcaemia and secondary hypocalcaemia may further establish TRPM7 pathogenic variants as a novel Mendelian disorder.
The Role of Diagnostics-Driven Antifungal Stewardship in the Management of Invasive Fungal Infections: A Systematic Literature Review
Authors: Chakrabarti Arunaloke , Mohamed Naglaa , Capparella Maria Rita , Townsend Andy , Sung Anita H , Yura Renee , Muñoz Patricia
Published: May 2022

Antifungal stewardship (AFS) programs are key to optimizing antifungal use and improving outcomes in patients with invasive fungal infections. Our systematic literature review evaluated the impact of diagnostics in AFS programs by assessing performance and clinical measures. Most eligible studies were from Europe and the United States (n = 12/17). Diagnostic approaches included serum β-1–3-D-glucan test (n/N studies, 7/17), galactomannan test (4/17), computed tomography scan (3/17), magnetic resonance (2/17), matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS; 2/17), polymerase chain reaction (1/17), peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) assay (1/17), and other routine methods (9/17). Time to species identification decreased significantly using MALDI-TOF and PNA-FISH (n = 2). Time to targeted therapy and length of empiric therapy also decreased (n = 3). Antifungal consumption decreased by 11.6%–59.0% (7/13). Cost-savings ranged from 13.5% to 50.6% (5/10). Mortality rate (13/16) and length of stay (6/7) also decreased. No negative impact was reported on patient outcomes. Diagnostics-driven interventions can potentially improve AFS measures (antifungal consumption, cost, mortality, and length of stay); therefore, AFS implementation should be encouraged.
MAPKs trigger antiviral immunity by directly phosphorylating a rhabdovirus nucleoprotein in plants and insect vectors
Authors: Ding Zhi-Hang , Gao Qiang , Tong Xin , Xu Wen-Ya , Ma Lulu , Zhang Zhen-Jia , Wang Ying , Wang Xian-Bing
Published: May 2022

Signaling by the evolutionarily conserved mitogen-activated protein kinase or extracellular signal-regulated kinase (MAPK/ERK) plays critical roles in converting extracellular stimuli into immune responses. However, whether MAPK/ERK signaling induces virus immunity by directly phosphorylating viral effectors remains largely unknown. Barley yellow striate mosaic virus (BYSMV) is an economically important plant cytorhabdovirus that is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus) in a propagative manner. Here, we found that the barley (Hordeum vulgare) MAPK MPK3 (HvMPK3) and the planthopper ERK (LsERK) proteins interact with the BYSMV nucleoprotein (N) and directly phosphorylate N protein primarily on serine 290. The overexpression of HvMPK3 inhibited BYSMV infection, whereas barley plants treated with the MAPK pathway inhibitor U0126 displayed greater susceptibility to BYSMV. Moreover, knockdown of LsERK promoted virus infection in SBPHs. A phosphomimetic mutant of the N Ser290 (S290D) completely abolished virus infection because of impaired self-interaction of BYSMV N and formation of unstable N–RNA complexes. Altogether, our results demonstrate that the conserved MAPK and ERK directly phosphorylate the viral nucleoprotein to trigger immunity against cross-kingdom infection of BYSMV in host plants and its insect vectors.
Long-term use of glucocorticoids for polymyalgia rheumatica: follow-up of the PMR Cohort Study
Authors: Muller Sara , Hider Samantha L , Singh Sokhal Balamrit , Lawton Sarah A , Helliwell Toby , Mallen Christian D
Published: May 2022

Objectives

PMR is a common inflammatory condition in older adults, characterized by bilateral hip and shoulder pain and stiffness. Reducing oral glucocorticoids, classically used for ≤2 years, are the mainstay of treatment. This study considers the factors early in the disease course that might be associated with prolonged treatment.

Methods

Six hundred and fifty-two people with incident PMR were recruited from English general practices (2012–2014). Participants completed seven questionnaires over 2 years (used to allocate people to pain–stiffness trajectories) and a further long-term follow-up (LTFU) questionnaire a median of 5.16 years after diagnosis. Characteristics of those still taking and having ceased glucocorticoids were described and compared using Kruskal–Wallis and χ2 and Student’s 2-sample t-tests as appropriate.

Results

Of the 197 people completing the LTFUQ questionnaire, 179 people reported ever having taken glucocorticoids. Of these, 40.1% were still on treatment, with a median (quartile 1, quartile 3) daily dose of 5 (1.5, 9)  mg. People still taking glucocorticoids were more likely to be older (72.5 vs 70.2 years, P = 0.035), live alone (31.8 vs 15.0%, P = 0.01) and have self-managed their glucocorticoid dose (39.1 vs 11.0%, P < 0.0001). They were also more likely to belong to a pain–stiffness trajectory class with sustained symptoms.

Conclusions

PMR is not always a time-limited condition. Few patient characteristics are associated with prolonged treatment early in the disease course, but those who are older and who have sustained symptoms might be at greater risk. Although accurate prediction is not yet possible, clinicians should monitor people with PMR carefully to manage symptoms and reduce the cumulative glucocorticoid dose.
High-fat diet and alcohol induced-mice could cause colonic injury through molecular mechanisms of endogenous toxins
Authors: Zhu Shumin , Huang Haiyang , Xu Shuoxi , Liu Ying , Wu Yayun , Xu Shijie , Huang Song , Gao Jie , He Lian
Published: May 2022

Due to the complexity and diverse causes, the pathological mechanism of diet-induced colonic injury and colitis remains unclear. In this study, we studied the effects of the combination of a high-fat diet (HFD) plus alcohol on colonic injury in mice. We found HFD plus alcohol treatment induced disturbance of the gut microbiota; increased the production of intestinal toxins lipopolysaccharide (LPS), indole, and skatole; destroyed the stability of the intestinal mucosa; and caused the colonic epithelial cells damage through the activation of nuclear factor (NF)-κB and aromatic hydrocarbon receptors (AhR) signaling pathways.

To mimic the effect of HFD plus alcohol in vivo, NCM460 cells were stimulated with alcohol and oleic acid with/without intestinal toxins (LPS, indole, and skatole) in vitro. Combinative treatment of alcohol and oleic acid caused moderate damage on NCM460 cells, while combination with intestinal toxins induced serious cell apoptosis. Western blot data indicated that the activation of NF-κB and AhR pathways further augmented after intestinal toxins treatment in alcohol- and oleic acid-treated colonic cells.

This study provided new evidence for the relationship between diet pattern and colonic inflammation, which might partly reveal the pathological development of diet-induced colon disease and the involvement of intestinal toxins.
Chromatographic profile, in silico and in vivo study of the pharmacokinetic and toxicological properties of major constituent present in kefir, the kefiran
Authors: Barros Susy Érika de Lima , de Lima Henrique Barros , Gonçalves Leandra Karoline Alves , Correia Lenir Cabral , Brito Maiara de Fátima de Brito , Barcelos Mariana Pegrucci , Silva Guilherme Martins , da Silva Carlos Henrique Tomich de Paula , da Costa Rafael Garrett , Cruz Rodrigo Alves Soares , Carvalho José Carlos Tavares , da Silva Hage-Melim Lorane Izabel
Published: May 2022

Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software. In silico toxicity assessment was performed using the DEREK (deductive estimate of risk from existing knowledge) software. In the chromatographic, kefiran was identified as the major component. Results showed that the kefiran had low human oral absorption and intestinal absorption its due poor solubility profile; low logP value, indicating its lipophilicity and the low MDCK and Caco-2 cells permability, and unable to cross the blood–brain barrier. Kefiran did not present any structural warning for in silico toxicity. In zebrafish, the dose of 2,000 mg/kg of kefiran produced nonsignificant alterations in the analyzed organs. It can be said then that kefiran has an acceptable degree of safety for use in the development of drugs or functional foods. Further research such as in vivo testing to confirm its pharmacological potential is currently underway.
Do Smaller Local Governments Bring Citizens More? Evidence from Direct Elections in Indonesia
Authors: Singhania Deepak
Published: May 2022

Do smaller local governments provide more for their citizens, especially when they are also held accountable to their citizens? This paper extends the empirical literature on the size of local governments by explicitly exploring one of the key influencing factors – direct local elections, a proxy for local accountability. Using an Indonesian panel of village-level outcomes data, the paper shows that a reduction in local government size (due to district splitting) increases public good provision but that this effect is restricted to districts that had direct local elections. It also provides suggestive evidence to show that increased revenue was channeled into developmental expenditures only in those split districts that faced direct elections. The identification strategy relies on a surprise local election announced while the number of local governments in Indonesia was increasing, which also abruptly imposed a moratorium on the process of splitting.
Recognizing vestibular migraine
Authors: Kovalchick Jessica
Published: May 2022

Vestibular migraine is a recently defined disorder that is underrecognized by clinicians across specialties. Acute attacks cause symptoms of migraine headaches as well as vestibular symptoms such as dizziness or vertigo. Further research is needed to determine the pathophysiology of vestibular migraine. No consensus treatment guidelines exist for this condition, and treatment is based on other migraine guidelines. Clinicians who are aware of vestibular migraine can speed diagnosis and treatment for patients and improve their quality of life.
Retrospective comparison of rates of aseptic loosening in fixed-bearing unicompartmental knee arthroplasty (UKA) implants
Authors: Boucher Henry R. , Hawken Jessica , Lee Ji Won , Mistretta Katherine , Gallagher Brian , Passano Brandon , Desale Sameer
Published: May 2022

Background:

A prominent cause for failure and revision in unicompartmental knee arthroplasty (UKA) is aseptic implant loosening. This study compared the revision rates for aseptic loosening of a new UKA implant, Aesculap Univation X (B. Braun, Tuttlingen, Germany), versus a well-established standard design, Miller Galante (Zimmer, Warsaw, Indiana).

Methods:

Patient charts were retrospectively reviewed of medial UKAs performed using two different fixed-bearing UKA implants from different manufacturers between January 1, 2002, and November 6, 2020. Of 308 patients included in the study, 44 had the new implant (AUK) and 264 patients had a standard implant (ZUK). The revision rates for all-cause and aseptic loosening were compared. The Kaplan Meier curve for 5-year survival rate was calculated based on aseptic loosening as the cause of failure. Hazard ratios for failure were calculated with multivariable Cox regression analysis.

Results:

All-cause revision and revision from aseptic loosening were significantly higher for AUK versus ZUK (20% versus 5.30% and 18.18% versus 3.41%, respectively). The log-rank test showed significantly longer survival for ZUK versus AUK group (P<0.001). Multivariable Cox regression analysis found a hazard ratio of 21.62 (95% CI: 4.07, 114.72; P<0.001) for revision for the AUK versus ZUK group, controlling for sex, age, and body mass index.

Conclusions:

Among these patients, AUK had lower survivorship than the established implant, ZUK, due to significantly higher hazard of all-cause revision and revision from aseptic loosening. These findings suggest a need for caution with use of this new implant.

Level of Evidence:

Level III.
Clinically Detected Leg Length Discrepancy in Patients With Idiopathic Clubfoot Deformity: Prevalence and Outcomes
Authors: Addar Abdullah , Bouchard Maryse
Published: May 2022

Background:

This study evaluates the prevalence and outcomes of patients with idiopathic clubfoot and clinically detected limb length discrepancy (LLD).

Methods:

This is a retrospective cohort study of idiopathic clubfoot patients in a Research Ethics Board–approved clubfoot registry. Patients with LLD ≥0.5 cm (LLD+) were compared with those with no or <0.5 cm LLD (LLD−). LLD was determined by documented clinical examination. Exclusion criteria included nonidiopathic clubfoot deformity, <2-year follow-up, and incomplete records.

Results:

Of the 300 patients included, 27 (9.0%) had an LLD, of whom 23 patients had a unilateral clubfoot deformity. The prevalence of LLD was 15.3% and 2.67% in unilateral and bilateral clubfoot patients, respectively. The mean LLD was 1.21 cm (0.5 to 3.5 cm, SD: 0.78 cm) in LLD+ patients, with a mean of 1.27 cm (SD: 0.79 cm) in unilateral clubfoot patients and 0.88 cm (SD: 0.75 cm) in bilateral patients. The total number of casts applied in LLD+ unilateral clubfoot patients was significantly higher than in LLD− unilateral patients (9.5 vs. 6.8 casts; P=0.015). The overall relapse rate in all patients was 30.3% and was significantly higher in the unilateral only LLD+ group [relative risk (RR)=2.89] and the total LLD+ patient cohort (RR=1.68). The risk of repeat casting for relapse was also higher in the unilateral LLD+ group (RR=2.45) and the total LLD+ group (RR=1.87). The risk of surgery for relapse was significantly higher in the unilateral LLD+ group for any surgery (P=0.046), and most specifically for open tendo-Achilles tenotomy (P=0.008) and tibialis anterior tendon transfer (P=0.019). There was no correlation between the severity of LLD and Pirani score at presentation.

Conclusions:

LLD was present in 9% of idiopathic clubfoot patients, and most were <2 cm. There is a significantly higher risk of relapse in patients with unilateral clubfoot and LLD. The risk of surgery overall was higher in all patients with a unilateral LLD. Assessment of LLD should be routinely performed in clubfoot patients.

Level of Evidence:

Level III.
Pitching Behaviors in Youth Fast-Pitched Softball: High Pitching Volumes With Unequal Pitch Counts Among Pitchers are Common
Authors: Greiner Justin J. , Trotter Cameron A. , McGuine Tim A. , Walczak Brian E. , Baer Geoffrey S.
Published: May 2022

Background:

Softball is a popular sport among youth female athletes. While youth baseball has well-established, evidence-based pitching guidelines, youth softball pitching guidelines lack both evidence and enforcement. Adherence to pitch count limits in youth softball is infrequent and results in pitchers with exceedingly high pitching volumes.

Methods:

Pitch counts for youth fast-pitch softball teams competing for 1 consecutive year between January 2018 to December 2019 in age groups 8 and under (8U) to 14 and under (14U) were collected. Pitching volume was assessed based on individual games, single calendar days, and tournaments in which games are played on 2 or more consecutive days. Pitchers on teams were subdivided based on pitch count volumes and compared using a logarithmic transformation and geometric mean.

Results:

Data was collected for 10 teams from each age division resulting in analysis of 538 pitchers on 70 teams. The average pitcher threw 813 pitches per year and appeared in 20.0% of games while the average highest volume pitcher threw 2500 pitches per year and appeared in 54.5% of games. On average, the highest volume pitcher on each team threw 40% of all team pitches, while the 3 highest volume pitchers combined threw 82% of all team pitches. The average and high-volume pitcher threw pitches in 2 or more games on the same day in 37.5% and 48.6% of possible games while pitching 2 or more consecutive days in 64.0% and 79.6% of possible games, respectively.

Conclusions:

Softball pitchers throw high volumes of pitches while also pitching multiple days consecutively. A disparity among pitchers on softball teams exists as 40% of team pitches are thrown by 1 player and over 80% of team pitches are thrown by the top 3 pitchers. These high-volume pitchers may be engaging in unsustainable pitching practices that could predispose to injury.

Level of Evidence:

Level IV—cross-sectional.
Post-Intensive Care COVID Survivorship Clinic: A Single-Center Experience
Authors: Gilmartin Michael , Collins Jack , Mason Sabina , Horgan Anna , Cuadrado Elena , Ryberg Melanie , McDermott Garret , Baily-Scanlan Maria , Hevey David , Donnelly Maria , O’Doherty Veronica , Kelly Yvelynne P.
Published: May 2022

OBJECTIVES:

Patients discharged from the ICU post-COVID-19 pneumonitis may experience long-term morbidity related to their critical illness, the treatment for this and the ICU environment. The aim of this study was to characterize the cognitive, psychologic, and physical consequences of COVID-19 in patients admitted to the ICU and discharged alive.

DESIGN:

Prospective cohort study.

SETTING:

Post-intensive care syndrome (PICS) follow-up clinic at Tallaght University Hospital, a tertiary referral center with a 16-bed mixed medical-surgical ICU, including critical care physicians, a psychologist, a physiotherapist, and a research nurse.

PATIENTS:

Patients who had been admitted to the ICU in our tertiary referral center with COVID-19 pneumonitis 6 months earlier.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 22 patients attended the 6-month PICS follow-up clinic following admission to ICU with COVID-19 pneumonitis. Mean grip strength was low at the 6-month follow-up at 24.1 pounds (sd 9.8) with a minimally active median metabolic equivalent (MET) of 970 METs/wk (interquartile range, 0–7,794 METs/wk). Only 59% of patients were independent with regard to their activities of daily living. Eight of 14 patients (57%) had returned to work by 6 months post-ICU discharge. Their mean Intensive Care Psychological Assessment Tool (IPAT) score was 6.6 (sd 4.6) with a Post-Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5th Edition (PCL-5) score of 21.1 (sd 17.5) and a mean Montreal Cognitive Assessment (MoCA) score of 24 (sd 8.4); suggestive of mild cognitive impairment. In a multivariable regression model, only Acute Physiology and Chronic Health Evaluation II score was significantly independently associated with MoCA score as a cognitive PICS outcome (beta-coefficient, –1.6; se, 0.6; p = 0.04). None of the predictor variables were significantly independently associated with IPAT and PCL-5 as psychologic outcomes, nor with International Physical Activity Questionnaire-Short Form as a physical PICS outcome.

CONCLUSIONS:

In this single-center prospective cohort study, we found that patients have a high burden of physical and psychologic impairment at 6 months following ICU discharge post-COVID-19 pneumonitis; in many cases requiring specialist referrals for long-term input. We advocate for increased resources for this much needed follow-up multidisciplinary intervention for an ever-growing population of patients.
Does temporomandibular disorder correlate with menopausal symptoms?
Authors: Galhardo Alessandra Pucci Mantelli , Mukai Marcia Katsuyoshi , Baracat Maria Cândida P. , da Fonseca Angela Maggio , Roa Cristiane Lima , Sorpreso Isabel Cristina Espósito , Baracat Edmund Chada , Soares Jose Maria
Published: May 2022

Objective:

To assess the correlation between menopausal symptoms and pain caused by temporomandibular disorder (TMD) and the impact of sociodemographic factors on the association.

Methods:

In this cross-sectional study, a total of 74 women with TMD symptoms were enrolled and divided into three groups according to the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria: G1 (n = 25, late menopausal transition), G2 (n = 30, early postmenopause), and G3 (n = 19, late postmenopause). Sociodemographic data were collected, along with data on menopausal symptoms (Blatt-Kupperman menopausal index) and TMD-induced pain (craniomandibular index). Statistical analysis was performed using a chi-squared test and linear correlation tests (Spearman and Pearson).

Results:

Analysis of the three groups showed that TMD-induced pain was more intense in G1 than in G3 (P = 0.0426, r 
= 0.2364, r
2 = 0.05589), and menopausal symptoms correlated with the intensity of TMD-induced pain (P = 0.0004, r 
= 0.4020). This correlation was more significant during the late menopausal transition (G1: P 
= 0.0267, r 
= 0.4427, r
2 = 0.1960). In G2, women with fewer than 4 years of schooling had a higher total Blatt- Kupperman menopausal index score (17.0 ± 85.0) and craniomandibular index (0.29 ± 0.23) than women with more than 4 years of schooling (P 
= 0.02 for both indices).

Conclusions:

Our results suggest that TMD-induced pain and menopausal symptoms are correlated, and more strongly so in the late menopausal transition. Additionally, sociodemographic factors, such as schooling, have a major influence on symptoms in early postmenopause. Performing the TMD evaluation during the climacteric period may be important.
Standardized Perioperative Protocol and Routine Ketorolac Use for Head and Neck Free Flap Reconstruction
Authors: Luthringer Margaret M. , Kim Kevin G. , Mukherjee Thayer J. , Van Kouwenberg Emily A. , Agag Richard L. , Sinkin Jeremy C.
Published: May 2022

Background:

No consensus exists on ideal perioperative management or anticoagulation regimen for free flap reconstruction of the head and neck. Perceived benefits from antiplatelet therapy need to be balanced against potential complications. Ketorolac, a platelet aggregation inhibitor and a parenteral analgesic, was introduced as part of a standardized perioperative protocol at our institution. In this study, we aimed to examine the impact of implementation of this protocol as well as complications associated with the routine use of perioperative ketorolac in a diverse group of patients who underwent head and neck free flap reconstruction.

Methods:

A single institution retrospective review was performed, including all patients who underwent head and neck free flap reconstruction between October 2016 and November 2019. Patients were divided into two cohorts: those who received ketorolac as part of a standardized protocol, and those who did not.

Results:

Twenty-four consecutive patients with 24 head and neck free flaps were evaluated. Eighteen patients were in the standard protocol, and six were not. There were no microvascular thromboses, flap failures, or hematomas in either group. Intensive care unit length of stay and opiate use were significantly reduced in the standardized protocol group.

Conclusions:

A standardized perioperative protocol for head and neck free flap reconstruction can reduce hospital and intensive care unit length of stay. No statistically significant differences in complication rates were identified when comparing ketorolac use and perioperative regimens among patients undergoing a diverse set of microsurgical head and neck free flap reconstructions.