bluuebunny/crossref_metadata_2025 huggingface dataset:
Shortcomings of human-in-the-loop optimization for an ankle-foot prosthesis: a case series
Authors: Welker Cara G. , Voloshina Alexandra S. , Chiu Vincent L. , Collins Steven H.
Published: October 2020

Human-in-the-loop optimization allows for individualized device control based on measured human performance. This technique has been used to produce large reductions in energy expenditure during walking with exoskeletons but has not yet been applied to prosthetic devices. In this series of case studies, we applied human-in-the-loop optimization to the control of an active ankle-foot prosthesis used by participants with unilateral transtibial amputation. We optimized the parameters of five control architectures that captured aspects of successful exoskeletons and commercial prostheses, but none resulted in significantly lower metabolic rate than generic control. In one control architecture, we increased the exposure time per condition by a factor of five, but the optimized controller still resulted in higher metabolic rate. Finally, we optimized for self-reported comfort instead of metabolic rate, but the resulting controller was not preferred. There are several reasons why human-in-the-loop optimization may have failed for people with amputation. Control architecture is an unlikely cause given the variety of controllers tested. The lack of effect likely relates to adaptation protocol or differences in the learning mechanisms or objectives of people with amputation. Future work should investigate these causes to determine whether human-in-the-loop optimization for prostheses could be successful.
Fine tuning cyclic-di-GMP signaling inPseudomonas aeruginosausing the type 4 pili alignment complex
Authors: Webster Shanice S. , Lee Calvin K. , Schmidt William C. , Wong Gerard C. L. , O’Toole George A.
Published: October 2020

To initiate biofilm formation it is critical for bacteria to sense a surface and respond precisely. Type 4 pili (T4P) have been shown to be important in surface sensing, however, mechanism(s) driving downstream changes important for the switch to biofilm growth have not been clearly defined. Here, using macroscopic bulk assays and single cell tracking analyses ofPseudomonas aeruginosa, we uncover a new role of the T4P alignment complex protein, PilO, in modulating the activity of the diguanylate cyclase (DGC) SadC. Two hybrid and bimolecular fluorescence complementation assays show that PilO physically interacts with SadC and that the PilO-SadC interaction inhibits SadC’s activity resulting in decreased biofilm formation and increased motility. We show that disrupting the PilO-SadC interaction contributes to greater variation of cyclic-di-GMP levels among cells, thereby increasing cell-to-cell heterogeneity in the levels of this signal. Thus, this work shows thatP. aeruginosauses a component of the T4P scaffold to fine-tune the levels of this nucleotide signal during surface commitment. Finally, given our previous findings linking SadC to the flagellar machinery, we propose that this DGC acts as a bridge to integrate T4P and flagellar-derived input signals during initial surface engagement.

Significance Statement

T4P ofP. aeruginosaare important for surface sensing and regulating intracellular cyclic-di-GMP levels. This work identifies a new role for the T4P alignment complex, previously known for its role in supporting pili biogenesis, in surface-dependent signaling. Furthermore, our findings indicate thatP. aeruginosauses a single DGC, via a complex web of protein-protein interactions, to integrate signaling through the T4P and the flagellar motor to fine-tune cyclic-di-GMP levels. A key implication of this work is that more than just regulating signal levels, cells must modulate the dynamic range of cyclic-di-GMP to precisely control the transition to a biofilm lifestyle.
Progenesis as an intrinsic factor of ecological opportunity in a polyphenic amphibian
Authors: Lejeune Benjamin , Bissey Lucie , Didaskalou Emilie Alexia , Sturaro Nicolas , Lepoint Gilles , Denoël Mathieu
Published: October 2020

Paedomorphosis, a developmental heterochrony involving the retention of larval traits at the adult stage, is considered a major evolutionary process because it can generate phenotypic variation without requiring genetic modifications. Two main processes underlie paedomorphosis: neoteny, a slowdown of somatic development, and progenesis, a precocious maturation associated with body size reduction. Being essentially a truncation of ontogeny, progenesis has often been deemed an evolutionary dead end with advantages attributed to precocious reproduction or small body size required in specific environmental contexts (e.g. parasitism, interstitial life), but there is a lack of studies on the immediate ecological consequences of progenesis.

Because body size is a key factor determining trophic ecology in animals, we hypothesized that progenesis might intrinsically promote ecological opportunity via body size reduction (i.e. ‘the trophic advantage of progenesis’ hypothesis). We tested this hypothesis in facultatively progenetic palmate newts Lissotriton helveticus using stable isotope niche modelling and diet reconstruction in conjunction with traditional stomach content analyses and body condition (BC) assessment.

We show that not only did progenetic individuals occupy a different trophic niche than metamorphic individuals in all populations, but the smaller they were compared to metamorphs due to progenesis, the more different they were in terms of trophic ecology, with no negative effect on their BC.

Altogether, the results suggest that via body size reduction, progenesis may generally act as an intrinsic factor of ecological opportunity, allowing the use of existing but previously unavailable resources, even in habitats where seemingly little opportunity exists. We argue that beyond the classically recognized fitness advantages of progenetic development, this process may also generally bring an immediate trophic advantage via body size reduction, which would have important implications to understand the evolution and adaptiveness of this process in many different taxa, from marine meiofauna to primates.

A free Plain Language Summary can be found within the Supporting Information of this article.
Physician trajectories of abandoning long‐course breast radiotherapy and their cost impact
Authors: Xu Xiao , Soulos Pamela R. , Herrin Jeph , Wang Shi‐Yi , Pollack Craig Evan , Evans Suzanne B. , Yu James B. , Gross Cary P.
Published: October 2020

Objective

To examine variation in trajectories of abandoning conventionally fractionated whole‐breast irradiation (CF‐WBI) for adjuvant breast radiotherapy among physician peer groups and the associated cost implications.

Data Sources

Medicare claims data were obtained from the Chronic Conditions Data Warehouse for fee‐for‐service beneficiaries with breast cancer in 2011‐2014.

Study Design

We used social network methods to identify peer groups of physicians that shared patients. For each physician peer group in each time period (T1 = 2011‐2012 and T2 = 2013‐2014), we calculated a risk‐adjusted rate of CF‐WBI use among eligible women, after adjusting for patient clinical characteristics. We applied a latent class growth analysis to these risk‐adjusted rates to identify distinct trajectories of CF‐WBI use among physician peer groups. We further estimated potential savings to the Medicare program by accelerating abandonment of CF‐WBI in T2 using a simulation model.

Data Collection/Extraction Methods

Use of conventionally fractionated whole‐breast irradiation was determined from Medicare claims among women ≥ 66 years of age who underwent adjuvant radiotherapy after breast conserving surgery.

Principal Findings

Among 215 physician peer groups caring for 16 988 patients, there were four distinct trajectories of abandoning CF‐WBI: (a) persistent high use (mean risk‐adjusted utilization rate: T1 = 94.3%, T2 = 90.6%); (b) decreased high use (T1 = 81.3%, T2 = 65.3%); (c) decreased medium use (T1 = 60.1%, T2 = 44.0%); and (d) decreased low use (T1 = 31.6%, T2 = 23.6%). Peer groups with a smaller proportion of patients treated at free‐standing radiation facilities and a larger proportion of physicians that were surgeons tended to follow trajectories with lower use of CF‐WBI. If all physician peer groups had practice patterns in T2 similar to those in the “decreased low use” trajectory, the Medicare program could save $83.3 million (95% confidence interval: $58.5 million‐$112.2 million).

Conclusions

Physician peer groups had distinct trajectories of abandoning CF‐WBI. Physician composition and setting of radiotherapy were associated with the different trajectories. Distinct practice patterns across the trajectories had important cost implications.
Comparing propofol with placebo for early resolution of acute migraine in adult emergency department patients: A double‐blind randomised controlled trial
Authors: Meek Robert , Graudins Andis , McDonald Micah , McGannon Daniel , Limm Ezra
Published: October 2020

Objective

To compare propofol with placebo in adult ED patients with acute migraine. Primary outcome was headache resolution by 1 h. Secondary outcome was reduction in headache severity by two or more points on a numerical rating scale.

Methods

Double‐blind randomised controlled clinical trial comparing propofol (10 mg/mL) with placebo (20% intralipid). Adults with acute migraine without aura were included. The study drug was administered as an initial dose of 4 mL followed by up to five doses of 2 mL, delivered 5 min apart. Pain scores were taken prior to each dose and further administration was ceased when either the pain score was zero or the maximum dosage reached (140 mg of propofol or 14 mL of 20% intralipid).

Results

Of 40 recruited patients, 21 received propofol and 19 placebo. Headache resolution occurred for 5 (24%, 95% CI 13–57) and 6 (32%, 95% CI 13–57) patients, respectively, difference 8% (95% CI −20 to 36). Headache severity reduction by two or more numerical rating scale points was reported by 17 (81%, 95% CI 58–95) and 7 (37%, 95% CI 16–62) patients, respectively, difference 44% (95% CI 17–71).

Conclusions

Propofol was not superior to placebo for the primary outcome of early headache resolution. Superiority of propofol for the secondary outcome of headache severity reduction suggests that further research may be warranted.
Impact of national lockdown towards emergency department visits and admission rates during the COVID‐19 pandemic in Thailand: A hospital‐based study
Authors: Wongtanasarasin Wachira , Srisawang Thanchanok , Yothiya Wanwisa , Phinyo Phichayut
Published: October 2020

Objective

To evaluate the impact of the national lockdown because of the 2019 coronavirus (COVID‐19) pandemic towards the ED visits and admission rates in Thailand.

Methods

We retrospectively reviewed the electronic medical database of patients presenting to the ED during the national lockdown period (from 26 March to 30 June 2020). We used the same time interval in the year 2019 as the control period in our analysis. We collected baseline characteristics and outcomes of each patient in the ED. The primary outcome was the incidence rate ratio (IRR) with a 95% confidence interval (CI) of the average daily ED visits. Secondary outcomes included the IRR with 95% CI of total admissions and intensive care unit (ICU) admissions.

Results

The average number of daily ED visits decreased significantly from 89.1 to 57.0 (−36.0%, IRR 0.69, 95% CI 0.67–0.70). However, the proportions of ‘Resuscitation’ and ‘Emergency’ triage level were increased (29.1% vs 19.2%, P < 0.001). Total ED admission rate and ICU admission rate were also increased (33.5% vs 28.3%, P < 0.001 and 10.2% vs 7.5%, P < 0.001, respectively). The IRR for the admission rate was 1.18 (95% CI 1.11–1.26), and the IRR for the ICU admission rate was 1.35 (95% CI 1.21–1.52).

Conclusion

The national lockdown in Thailand was associated with a significant reduction in average daily ED visits across traumatic and non‐traumatic patients. Communication from healthcare professionals and public health officers is necessary to reinforce the importance of timely ED visits for acute health conditions.
TOA: A software package for automated functional annotation in non‐model plant species
Authors: Mora‐Márquez Fernando , Chano Víctor , Vázquez‐Poletti José Luis , López de Heredia Unai
Published: October 2020

The increase of sequencing capacity provided by high‐throughput platforms has made it possible to routinely obtain large sets of genomic and transcriptomic sequences from model and non‐model organisms. Subsequent genomic analysis and gene discovery in next‐generation sequencing experiments are, however, bottlenecked by functional annotation. One common way to perform functional annotation of sets of sequences obtained from next‐generation sequencing experiments, is by searching for homologous sequences and accessing the related functional information deposited in genomic databases. Functional annotation is especially challenging for non‐model organisms, like many plant species. In such cases, existing free and commercial general‐purpose applications may not offer complete and accurate results. We present TOA (Taxonomy‐oriented annotation), a Python‐based user‐friendly open source application designed to establish functional annotation pipelines geared towards non‐model plant species that can run in Linux/Mac computers, HPCs and cloud servers. TOA performs homology searches against proteins stored in the PLAZA databases, NCBI RefSeq Plant, Nucleotide Database and Non‐Redundant Protein Sequence Database, and outputs functional information from several ontology systems: Gene Ontology, InterPro, EC, KEGG, Mapman and MetaCyc. The software performance was validated by comparing the runtimes, total number of annotated sequences and accuracy of the functional information obtained for several plant benchmark data sets with TOA and other functional annotation solutions. TOA outperformed the other software in terms of number of annotated sequences and accuracy of the annotation and constitutes a good alternative to improve functional annotation in plants. TOA is especially recommended for gymnosperms or for low quality sequence data sets of non‐model plants.
Is there any association between psoriasis, psoriatic arthritis and thyroid autoimmunity?
Authors: Vastarella Maria , Megna Matteo , Lupoli Gelsy Arianna , Napolitano Maddalena , Gallo Lucia , Balato Anna , Tasso Marco , Costa Luisa , Fabbrocini Gabriella , Peluso Rosario
Published: October 2020

Background

Autoimmune diseases share a significant part of their genetic background and tend to coexist in the same patient. Some studies have investigated the possible association between autoimmune thyroiditis and psoriasis or psoriatic arthritis (PsA), with conflicting results. This study aimed to investigate the prevalence of autoimmune thyroiditis in psoriatic patients with (PsA) or without (PsC) joint involvement.

Methods

208 patients with psoriasis and/or PsA were recruited. These patients were divided into two groups: psoriasis patients (without PsA) (PsC group: 100 patients; mean age of 50.1 ± 11.7 years) and subjects with psoriasis and psoriatic arthritis (PsA group: 108 subjects: mean age of 39.8 ± 10.8 years). Assessment of psoriasis severity was conducted using the Psoriasis Area and Severity Index (PASI) score. The diagnosis of psoriatic arthritis was made according to CASPAR criteria. All patients had thyroid evaluation through evaluation of thyroid function, thyroperoxidase antibodies and thyroid ultrasound examination.

Results

A statistically significant difference was found between the prevalence of autoimmune thyroiditis in the PsA group than the PsC group (25.9 vs 9.0 %; P = 0.018) with higher trends to hypothyroidism in the PsA group compared to the PsC group (13.9% vs 2.0%, P = 0.0018).

Conclusions

The higher prevalence of autoimmune thyroiditis in the PsA group may be due to an immune dysfunction pathway in patients with psoriatic arthritis with a higher risk to develop other autoimmune diseases. This evidence confirms that psoriatic arthritis is an autoimmune disease with an overactive immune system that can involve multiple organs. Thyroid function evaluation should be part of the clinical and laboratory examination of patients with psoriatic arthritis.
Effectiveness of water as the neutralising agent for glycolic acid peels in skin phototypes IV‐V
Authors: Sitohang Irma Bernadette S. , Rahmayunita Githa , Hosfiar Vashty Amanda , Ninditya Shafira , Augustin Maureen
Published: October 2020

The aim of the study is to evaluate the effectiveness of water as a substitute for sodium bicarbonate plus solution in the neutralisation process of chemical peeling using a 35% glycolic acid solution. This randomised, double‐blind, split‐face, controlled trial was conducted in an outpatient setting. A total of 126 healthy patients with skin phototypes IV–V aged between 18 and 60 years old were recruited. Chemical peeling was performed with 35% glycolic acid solution. One side of the face was neutralised with water, and the other side of the face was neutralised with a sodium bicarbonate plus solution. The main outcome of this study was measured by the degree of erythema, pruritus and pain scores. Significant difference in the pain score immediately after the neutralisation process of the chemical peeling with glycolic acid was seen. However, there were no significant differences in the degree of erythema or the pruritus score. These results indicate that water can be used as a substitute for sodium bicarbonate plus solution in the neutralisation process of chemical peeling with 35% glycolic acid in patients with skin phototypes IV–V.
Alteration of systemic and uterine endometrial immune populations in patients with endometriosis
Authors: Le Nhung X. H. , Loret de Mola Julio R. , Bremer Pamela , Groesch Kathleen , Wilson Teresa , Diaz‐Sylvester Paula , Braundmeier‐Fleming Andrea G.
Published: October 2020

Problem

Endometriosis is defined as growth of endometrial tissue in ectopic locations; it is associated with infertility and chronic pain and affects ~12% of reproductive‐aged women. Although inflammation is known to play a key role in endometriosis, knowledge related to immune phenotypes associated with this disease is lacking. This study aimed to characterize immune profiles in patients with endometriosis, to assess inflammatory mediators, to and determine if surgical and/or hormonal therapies restore immune homeostasis.

Methods of study

Samples from nine controls and 20 histologically confirmed endometriosis patients were collected upon surgery and ~1‐3 weeks post‐surgical intervention. Subjects were either not utilizing hormonal suppression or were currently on monophasic hormonal therapy. Tolerant regulatory T cells (Tregs = natural [nTregs] +inducible [iTregs]) and inflammatory T helper 17 (Th17) cells were identified in peripheral blood via flow cytometry and within the eutopic/ectopic endometrial tissues via immunohistochemistry and real‐time‐qPCR. Cytokines were assessed via 10‐plex‐ELISA.

Results

Patients with endometriosis not utilizing hormonal therapy exhibited lower iTregs (tolerant), greater Th17 (inflammatory), and a reduction in Treg/Th17 ratio (P < .05), indicative of systemic inflammation. Treg and Th17 localizations were enhanced within the ectopic endometrial implant, which promotes lesion development. Hormonal therapy decreased systemic and local inflammation (eutopic/ectopic endometrium) via decreased iTregs and Th17 cells in patients with endometriosis (P < .05). Thus, imbalance within immune populations correlated with increased inflammation in patients with endometriosis, which was mitigated by hormonal therapy.

Conclusions

Patients with endometriosis exhibited systemic and localized inflammation within ectopic and endometrial tissues. Hormonal therapy dampened inflammation caused by disease.
QT correction using Bazett’s formula remains preferable in long QT syndrome type 1 and 2
Authors: Dahlberg Pia , Diamant Ulla‐Britt , Gilljam Thomas , Rydberg Annika , Bergfeldt Lennart
Published: October 2020

Background

The heart rate (HR) corrected QT interval (QTc) is crucial for diagnosis and risk stratification in the long QT syndrome (LQTS). Although its use has been questioned in some contexts, Bazett's formula has been applied in most diagnostic and prognostic studies in LQTS patients. However, studies on which formula eliminates the inverse relation between QT and HR are lacking in LQTS patients.

We therefore determined which QT correction formula is most appropriate in LQTS patients including the effect of beta blocker therapy and an evaluation of the agreement of the formulae when applying specific QTc limits for diagnostic and prognostic purposes.

Methods

Automated measurements from routine 12‐lead ECGs from 200 genetically confirmed LQTS patients from two Swedish regions were included (167 LQT1, 33 LQT2). QT correction was performed using the Bazett, Framingham, Fridericia, and Hodges formulae. Linear regression was used to compare the formulae in all patients, and before and after the initiation of beta blocking therapy in a subgroup (n = 44). Concordance analysis was performed for QTc ≥ 480 ms (diagnosis) and ≥500 ms (prognosis).

Results

The median age was 32 years (range 0.1–78), 123 (62%) were female and 52 (26%) were children ≤16 years. Bazett's formula was the only method resulting in a QTc without relation with HR. Initiation of beta blocking therapy did not alter the result. Concordance analyses showed clinically significant differences (Cohen's kappa 0.629–0.469) for diagnosis and prognosis in individual patients.

Conclusion

Bazett's formula remains preferable for diagnosis and prognosis in LQT1 and 2 patients.
Successful trans‐septal ablation of a left concealed accessory pathway in a patient receiving surgical mitral valve repair and mechanical aortic valve replacement
Authors: Huang Ting‐Chun , Tsai Jing‐Hsiung , Chen Ju‐Yi
Published: October 2020

We presented a case of severe aortic regurgitation and moderate mitral regurgitation s/p aortic valve replacement and mitral valve repair. Deterioration of tachyarrhythmia attacks was noted. In EP study, left lateral accessory pathway with orthodromic atrioventricular reentrant tachycardia was identified. We successfully ablated the accessory pathway by trans‐septal approach. Even though trans‐septal approach currently is a daily routine of invasive interventional electrophysiologists, in this case, we want to emphasize and illustrate the distance between true mitral annulus and coronary sinus. Unrecognizing this concept could result in efficacy and safety of catheter‐based therapy.
Torsade de pointes induced by intravenous amiodarone therapy accompanied by marked augmentation of the transmural dispersion of repolarization in a patient with tachycardia‐induced‐cardiomyopathy
Authors: Yonai Ryo , Kawabata Mihoko , Maeda Shingo , Kawashima Tomoyuki , Tsuda Yasuhide , Nakasone Takashi , Nakane Hiroki , Hirao Kenzo
Published: October 2020

We report a 77‐year‐old human on renal dialysis for end‐stage renal disease with heart failure and atrial fibrillation (AF) complicated by a high ventricular frequency. The underlying disease was thought as tachycardia‐induced‐cardiomyopathy. Intravenous infusion of amiodarone was initiated, and direct current cardioversion succeeded in converting AF to sinus rhythm. Then, excessive increases in the QT and Tpeak‐Tend (Tp‐e) intervals were seen and hypokalemia induced by hemodialysis led to the development of numerous episodes of torsades de pointes (TdP). Magnesium repletion was effective in preventing TdP, while Tp‐e intervals returned to the previous values 2 days after the discontinuation of amiodarone.
Percutaneous balloon mitral valvotomy during pregnancy: A systematic review and meta‐analysis
Authors: Sreerama Damini , Surana Mahak , Moolchandani Kailash , Chaturvedula Latha , Keepanasseril Arun , Keepanasseril Anish , Pillai Ajith A. , Nair Narayanapillai Sreekumaran
Published: October 2020

Introduction

The objective of this study was to systematically review the maternal and fetal outcomes in pregnant women who underwent percutaneous balloon mitral valvuloplasty (PBMV) during pregnancy.

Material and methods

A search was conducted on MEDLINE and Embase databases to identify studies published between 2000 and 2018 that reported on maternal and fetal outcomes following PBMV performed in pregnancy. Randomized controlled trials, cohort studies, case‐control studies, cross‐sectional studies and case series with four or more pregnancies in which PBMV was performed during pregnancy were included. Reference lists from relevant articles were also hand‐searched for relevant citations. A successful procedure was defined as one where there was a reported improvement in the valve area or reduction in the mitral valve gradient. A random effects model was used to derive pooled estimates of various outcomes and the final estimates were reported as percentages with a 95% confidence interval (95% CI).

Results

Twenty‐one observational studies reporting 745 pregnancies were included in the review, all of them having reported outcomes without a comparison group. Most of the studies fell into the low‐risk category as determined using the Joanna Briggs Institute (JBI) critical appraisal checklist for case series. Most of the studies (86%) were reported from low‐ to middle‐income countries and PBMV was mostly performed during the second trimester of pregnancy. Forty‐three procedures (5.7%) were unsuccessful, nearly half (n = 19) of them reported among women with the severe subvalve disease (Wilkins subvalve score 3 or more). There were 11 maternal deaths among those with suboptimal valve anatomy (severe subvalve disease or Wilkin score >8). Mitral regurgitation was the most common cardiac complication (12.7%; 95% CI 7.3%‐19.1%), followed by restenosis (2.4%; 95% CI 0.02%‐7.2%). Pooled incidence of cesarean section was 12.1% (95% CI 3.6%‐23.8%), preterm delivery 3.9% (95% CI 0.6%‐9.0%), stillbirth 0.9% (95%CI 0.2%‐2.2%) and low birthweight 5.4% (95% CI 0.2%‐14.7%).

Conclusions

PBMV may be an effective and safe procedure for optimizing outcomes in pregnant women with mitral stenosis in the absence of severe subvalve disease.
PTBP1‐targeting microRNAs regulate cancer‐specific energy metabolism through the modulation of PKM1/M2 splicing
Authors: Taniguchi Kohei , Uchiyama Kazuhisa , Akao Yukihiro
Published: October 2020

Understanding of the microRNAs (miRNAs) regulatory system has become indispensable for physiological/oncological research. Tissue and organ specificities are key features of miRNAs that should be accounted for in cancer research. Further, cancer‐specific energy metabolism, referred to as the Warburg effect, has been positioned as a key cancer feature. Enhancement of the glycolysis pathway in cancer cells is what primarily characterizes the Warburg effect. Pyruvate kinase M1/2 (PKM1/2) are key molecules of the complex glycolytic system; their distribution is organ‐specific. In fact, PKM2 overexpression has been detected in various cancer cells. PKM isoforms are generated by alternative splicing by heterogeneous nuclear ribonucleoproteins. In addition, polypyrimidine tract‐binding protein 1 (PTBP1) is essential for the production of PKM2 in cancer cells. Recently, several studies focusing on non‐coding RNA elucidated PTBP1 or PKM2 regulatory mechanisms, including control by miRNAs, and their association with cancer. In this review, we discuss the strong relationship between the organ‐specific distribution of miRNAs and the expression of PKM in the context of PTBP1 gene regulation. Moreover, we focus on the impact of PTBP1‐targeting miRNA dysregulation on the Warburg effect.
Allergenicity at component level of sub‐pollen particles from different sources obtained by osmolar shock: A molecular approach to thunderstorm‐related asthma outbreaks
Authors: Cecchi Lorenzo , Scala Enrico , Caronni Sarah , Citterio Sandra , Asero Riccardo
Published: October 2020

Background

The so‐called “thunderstorm asthma” (TA) is an uncommon but dramatic outbreak of asthma attacks occurring during a thunderstorm in the pollen and moulds season. Mechanisms which make the pollen able to enter the deeper airways and provoke severe asthma symptoms are still unclear.

Objective

To test the hypothesis that sub‐pollen particles (SPPs) originated from the rupture by an osmotic shock of pollen associated with TA contain allergens.

Methods

After hydration, SPPs released from pollen grains of grass, pellitory, olive, cypress, ragweed and birch were isolated and determined by microscopy. Allergens were determined by in vitro ELISA inhibition tests indirectly using the sera from 10 polyreactive patients. An inhibition <50% was considered as negative, 50%‐75% moderate and > 75% complete.

Results

The inhibition experiments showed that the SPPs from birch and cypress were unable to inhibit serum IgE reactivity to Bet v 1 and Cup a 1, respectively. Ragweed SPPs inhibited ragweed pollen extract and Amb a 1 by 75.8 ± 0.11% and 81.2 ± 0.15%, respectively. Olive and pellitory SPPs retained almost the whole IgE‐binding capability in all cases tested. Grass SPPs inhibited 32 ± 0.06% of Lolium perenne Lol p 1 and 65% of Phleum pratense extracts, but results were highly variable for individual allergens (97.5%‐0.03% for Phl p 2, 45.3 ± 0.12% for Phl p 5, 24.7 ± 0.22% for Phl p 6, and 38.3 ± 0.2% for Phl p 1).

Conclusions

Inhibition experiments confirm the hypothesis that SSPs obtained after the osmotic shock of pollen involved in TA, namely grass, pellitory and olive tree pollen, contain allergens and therefore they can induce severe asthma attacks during thunderstorms.
Randomized trial of 3 maintenance regimens (TAC/SRL vs. TAC/MMF vs. CSA/SRL) with low‐dose corticosteroids in primary kidney transplantation: 18‐year results
Authors: Ciancio Gaetano , Gaynor Jeffrey J. , Guerra Giselle , Roth David , Chen Linda , Kupin Warren , Mattiazzi Adela , Ortigosa‐Goggins Mariella , Moni Lissett , Burke George W.
Published: October 2020

A randomized trial of 150 primary kidney transplant recipients, initiated in May 2000, compared tacrolimus (TAC)/sirolimus (SRL) vs. TAC/mycophenolate mofetil (MMF) vs. cyclosporine microemulsion (CSA)/SRL (N = 50/group). All patients received daclizumab induction and maintenance corticosteroids. With current median follow‐up of 18 years post‐transplant, biopsy‐proven acute rejection (BPAR) occurred less often in TAC/MMF (26% (13/50)), vs. the TAC/SRL (36% (18/50)) and CSA/SRL (34% (17/50)) arms combined (p = .23), with statistical significance favoring TAC/MMF (p = .05) after controlling for the multivariable (Cox model) effects of recipient age, recipient race/ethnicity, and donor age. First BPAR rate was clearly more favorable for TAC/MMF after stratifying patients by having 0–1 (N = 72) vs. 2–3 (N = 78) unfavorable baseline characteristics (recipient age <50 years, African American or Hispanic recipient, and donor age ≥50 years) (p = .02). Mean estimated glomerular filtration rate (eGFR), using the CKD‐EPI formula, was consistently higher for TAC/MMF, particularly after controlling for the multivariable effect of donor age, throughout the first 96 months post‐transplant (p ≤ .008). These differences were translated into an observed more favorable graft failure due to immunologic cause (CAI/TG) rate for TAC/MMF (p = .06), although no significant differences in overall death‐uncensored graft loss were observed. Previously reported significantly higher study drug discontinuation and requirement for antilipid therapy rates in the SRL‐assigned arms were maintained over time. Overall, these results at 18 years post‐transplant more definitively show that TAC/MMF should be the gold standard for achieving optimal, long‐term maintenance immunosuppression in kidney transplantation.
Climate overrides the effects of land use on the functional composition and diversity of Mediterranean reptile assemblages
Authors: Barnagaud Jean‐Yves , Geniez Philippe , Cheylan Marc , Crochet Pierre‐André
Published: October 2020

Aim

To test the hypothesis that spatial variations in climate and land use explain the distribution and diversity of reptiles’ ecological traits in a biodiversity hotspot of the Mediterranean basin.

Location

French Mediterranean region.

Taxon

Reptiles (25 species).

Methods

We defined 288 species assemblages from 27,858 opportunistic occurrence records within 10 × 10 km square grid cells. Using a RLQ analysis, we investigated the distribution of nine ecological traits describing reptiles’ reproductive, dietary and behavioural strategies along environmental gradients formed by 10 climatic, topographic and land‐use descriptors. After homogenizing survey effort through rarefaction, we used generalized additive models to assess variations in species richness and several measures of functional diversity and composition along these gradients.

Results

Although ecological traits were not structured by environmental gradients at a species level, species richness and all measures of functional diversity varied nonlinearly with climate, elevation and secondarily land use. Species richness and body size peaked at intermediate altitudes, indicating a climatic transition zone between Mediterranean and medio‐European herpetofaunas. Conversely, functional diversity increased from Mediterranean plains, dominated by urbanization and agriculture, to higher elevations. These changes were associated with shifts towards less productive, more diurnal and more forest‐related species.

Main conclusions

Species‐scale patterns are insufficient to assess regional variations in ecological traits in space. Our results support the hypothesis that climatic limitations in species’ distributions, rather than environmental filtering, explain the taxonomic and ecological diversity of reptiles at a regional scale. Although secondary to climate, land abandonment has a strong structuring effect which may contribute to homogenize the composition of reptile assemblages.
The proof is in the appendage: A case report of a fenestrated membrane overlying the left atrial appendage
Authors: Holbert Jaime , Shepple Ben , Rogers Bret , Hirsh Jeffrey
Published: October 2020

A 35‐year‐old man with history of recurrent arrhythmias presented for pulmonary vein isolation. He underwent pre‐procedural screening for thromboembolism risk with transesophageal echocardiogram. He had an incidental finding of a rare fenestrated membrane overlying his left atrial appendage. Additional workup throughout his clinical course revealed genetic mutations in the LMNA and SNTA1 genes. There have been no previous reported genetic mutations reported in cases with LAA membranes.
The beneficial effect of low‐intensity exercise on cardiac performance assessed by two‐dimensional speckle tracking echocardiography
Authors: Yaman Belma , Akpınar Onur , Kemal Hatice S. , Cerit Levent , Sezenöz Burak , Açıkgöz Eser , Duygu Hamza
Published: October 2020

Background

Regular physical activity is associated with cardiovascular health; however, intensive exercise can have harmful effects on the heart. Two‐dimensional (2D) speckle tracking echocardiography (STE) is a well‐established diagnostic tool to evaluate subclinical myocardial dysfunction and has been widely used in athletes in recent years. This study is designed to evaluate whether low‐intensity exercise has beneficial effects on myocardial performance. We aimed to evaluate systolic and diastolic functions of myocardium derived from STE in sports practitioners in a low‐intensity exercise training program.

Method

Eighty‐four sports practitioners and eighty‐two sedentary healthy controls were prospectively included in our study. In addition to standard 2D echocardiographic measurements, left ventricular (LV) global longitudinal strain (GLS), right ventricular (RV) GLS, RV‐free wall strain (FWS), left atrium (LA) strain, and strain rate were analyzed.

Results

Mean LV GLS was significantly higher in sports practitioners compared with sedentary population (−19.21 ± 2.61% vs −18.37 ± 2.75%, P = .044). RV GLS was significantly higher in sports practitioners than sedentary population (−21.82 ± 4.86% vs −20.04 ± 4.62%, P = .016). Longitudinal strain and strain rate of LA conduit phase were significantly higher in sports practitioners than sedentary participants (−23.60 ± 6.83% vs −20.20 ± 6.64%, P = .001; −2.45 ± 0.81 L/s vs −2.10 ± 0.89 L/s, P = .010; respectively). Also, LA conduit phase strain/contraction phase strain and conduit phase strain rate/contraction phase strain rate ratios were higher in sports practitioners (1.88 ± 0.93 vs 1.48 ± 0.63, P = .001; 1.42 ± 0.65 vs 1.16 ± 0.53, P = .005; respectively).

Conclusion

The findings in the current study suggest that regular low‐intensity exercise may have a beneficial effect on both systolic and diastolic functions of the myocardium.
Myocardial performance index is associated with cardiac computed tomography findings in patients with suspected coronary artery disease
Authors: Olsen Flemming Javier , Lassen Mats Christian Højbjerg , Brainin Philip , Bech Jan , Alhakak Alia Saed , Pedersen Sune , Claggett Brian , Fritz‐Hansen Thomas , Folke Fredrik , Gislason Gunnar H. , Biering‐Sørensen Tor
Published: October 2020

Background

Studies suggest cardiac time intervals to be associated with cardiac ischemia. A novel method to assess cardiac time intervals by tissue Doppler echocardiography has been proposed. Cardiac time intervals can assess the myocardial performance index (MPI), which quantifies the proportion of time spent contributing effective myocardial work. We hypothesized that MPI associates with coronary artery lesions detected by cardiac computed tomography (CT) in patients suspected of coronary artery disease (CAD).

Methods

We investigated patients referred for cardiac CT under suspicion of CAD who had an echocardiogram performed. Curved m‐mode tissue Doppler imaging was used to measure cardiac time intervals and MPI. The outcome was coronary artery lesions, defined as a calcium score > 400 and/or coronary artery stenosis (>70% luminal narrowing). Logistic regression was applied with multivariable models including: (a) SCORE chart risk factors and (b) SCORE chart risk factors, body mass index, dyslipidemia, familial history of CAD, diabetes mellitus, LVEF, and left ventricular mass index.

Results

Of 404 patients, 41 (10%) had a coronary artery lesion. Overall, 42% were male, mean age was 58 years, and LVEF was 58%. Patients with coronary artery lesions exhibited higher MPI than those without (0.52 vs. 0.44, P < .001).

MPI associated with coronary artery lesions in unadjusted analyses (OR = 1.69 [1.30–2.19], per 0.1 increase), and this association persisted when adjusted for SCORE chart risk factors (OR = 1.55 [1.16–2.07], P = .003, per 0.1 increase), and additional risk factors (OR = 1.64 [1.11–2.41], P = .013, per 0.1 increase).

Conclusion

Curved m‐mode‐derived MPI is associated with coronary artery lesions detected by cardiac CT in suspected CAD patients.
Molecular signature of extracellular matrix pathology in schizophrenia
Authors: Pantazopoulos Harry , Katsel Pavel , Haroutunian Vahram , Chelini Gabriele , Klengel Torsten , Berretta Sabina
Published: October 2020

Growing evidence points to a critical involvement of the extracellular matrix (ECM) in the pathophysiology of schizophrenia (SZ). Decreases of perineuronal nets (PNNs) and altered expression of chondroitin sulphate proteoglycans (CSPGs) in glial cells have been identified in several brain regions. GWAS data have identified several SZ vulnerability variants of genes encoding for ECM molecules. Given the potential relevance of ECM functions to the pathophysiology of this disorder, it is necessary to understand the extent of ECM changes across brain regions, their region‐ and sex‐specificity and which ECM components contribute to these changes. We tested the hypothesis that the expression of genes encoding for ECM molecules may be broadly disrupted in SZ across several cortical and subcortical brain regions and include key ECM components as well as factors such as ECM posttranslational modifications and regulator factors. Gene expression profiling of 14 neocortical brain regions, caudate, putamen and hippocampus from control subjects (n = 14/region) and subjects with SZ (n = 16/region) was conducted using Affymetrix microarray analysis. Analysis across brain regions revealed widespread dysregulation of ECM gene expression in cortical and subcortical brain regions in SZ, impacting several ECM functional key components. SRGN, CD44, ADAMTS1, ADAM10, BCAN, NCAN and SEMA4G showed some of the most robust changes. Region‐, sex‐ and age‐specific gene expression patterns and correlation with cognitive scores were also detected. Taken together, these findings contribute to emerging evidence for large‐scale ECM dysregulation in SZ and point to molecular pathways involved in PNN decreases, glial cell dysfunction and cognitive impairment in SZ.
Genetic profile and clinical characteristics of Chinese patients with spinocerebellar ataxia type 2: A multicenter experience over 10 years
Authors: Yang Lu , Dong Yi , Ma Yin , Ni Wang , Wu Zhi‐Ying
Published: October 2020

Background and purpose

Spinocerebellar ataxia type 2 (SCA2) is the second most common type of spinocerebellar ataxia in China. However, data on the clinical and genetic features of Chinese SCA2 patients are scarce. This study aims to provide a comprehensive description of in the Chinese SCA2 cohort.

Methods

A total of 135 patients with SCA2 from 92 families and 104 unrelated normal controls were recruited from three medical centers between 2008 and 2020. Sanger sequencing and TA cloning were used to determine the CAG repeat length and intrinsic structure. The clinical data of patients with SCA2, including electromyography, magnetic resonance imaging, positron‐emission tomography, and clinical scale scores, were recorded.

Results

The mean ± SD age at onset of SCA2 patients was 32.6 ± 11.9 years and the corresponding CAG repeat length was 42.1 ± 3.6. CAG repeat length accounted for 64% of the age‐at‐onset variance. We observed that patients had a significantly lower proportion of (CAG)8CAA(CAG)4CAA(CAG)8 within normal alleles than normal controls (48.8% vs. 64.9%; p = 0.003), while the distribution of the proportion of (CAG)13CAA (CAG)8 was the opposite. Peripheral neuropathy was frequent, occurring in 75.9% of the patients. Parkinsonism was relatively common, with a frequency of 11.8%. Two patients with parkinsonism had a significantly more severe reduction in dopamine transporter levels in the bilateral striatum than the one patient with pure ataxia. An infant‐onset case of SCA2 with more than 180 CAG repeats was characterized by global development delay, hypotonia and hearing impairment.

Conclusions

This study describes the genetic profile and clinical characteristics of the largest SCA2 cohort to date in the Chinese population and analyzes inter‐population differences. Many aspects of this study population were different from other populations with SCA2.
High concordance between hippocampal transcriptome of the mouse intra‐amygdala kainic acid model and human temporal lobe epilepsy
Authors: Conte Giorgia , Parras Alberto , Alves Mariana , Ollà Ivana , De Diego‐Garcia Laura , Beamer Edward , Alalqam Razi , Ocampo Alejandro , Mendez Raúl , Henshall David C. , Lucas José J. , Engel Tobias
Published: October 2020

Objective

Pharmacoresistance and the lack of disease‐modifying actions of current antiseizure drugs persist as major challenges in the treatment of epilepsy. Experimental models of chemoconvulsant‐induced status epilepticus remain the models of choice to discover potential antiepileptogenic drugs, but doubts remain as to the extent to which they model human pathophysiology. The aim of the present study was to compare the molecular landscape of the intra‐amygdala kainic acid model of status epilepticus in mice with findings in resected brain tissue from patients with drug‐resistant temporal lobe epilepsy (TLE).

Methods

Status epilepticus was induced via intra‐amygdala microinjection of kainic acid in C57BL/6 mice, and gene expression was analyzed via microarrays in hippocampal tissue at acute and chronic time‐points. Results were compared to reference datasets in the intraperitoneal pilocarpine and intrahippocampal kainic acid model and to human resected brain tissue (hippocampus and cortex) from patients with drug‐resistant TLE.

Results

Intra‐amygdala kainic acid injection in mice triggered extensive dysregulation of gene expression that was ~3‐fold greater shortly after status epilepticus (2729 genes) when compared to epilepsy (412). Comparison to samples from patients with TLE revealed a particularly high correlation of gene dysregulation during established epilepsy. Pathway analysis found suppression of calcium signaling to be highly conserved across different models of epilepsy and patients. cAMP response element‐binding protein (CREB) was predicted as one of the main upstream transcription factors regulating gene expression during acute and chronic phases, and inhibition of CREB reduced seizure severity in the intra‐amygdala kainic acid model.

Significance

Our findings suggest the intra‐amygdala kainic acid model faithfully replicates key molecular features of human drug‐resistant TLE and provides potential rational target approaches for disease‐modification through new insights into the unique and shared gene expression landscape in experimental epilepsy.
Medical management of a large intra‐abdominal mass caused by Rhodococcus equi in a foal
Authors: Shaw S. D. , Arroyo L. G. , zur Linden A. , Allen C. , Giraldo A. , Cohen N. D.
Published: October 2020

A 4‐month‐old Thoroughbred filly presented with pyrexia, inappetence and diarrhoea. Abdominal ultrasonography revealed a multilobulated abdominal mass that was determined to be associated with the caecum using computed tomography. Computed tomography also identified mesenteric lymphadenopathy and a pulmonary mass in the left caudal lung lobe. Percutaneous aspiration of the abdominal mass yielded pure growth of Rhodococcus equi. The filly responded in a positive fashion to the administration of clarithromycin, rifampin and gallium maltolate. Follow‐up computed tomography revealed complete resolution of the abdominal mass and lymphadenopathy. Extrapulmonary disorders associated with R. equi should be considered even when thoracic ultrasonography reveals no evidence of pulmonary pathology. Although intra‐abdominal abscesses have a grave prognosis, successful treatment is possible. Gallium maltolate can be safely administered to foals and may improve patient outcomes.