Montane species are generally predicted to respond to climate change via upslope movement. In birds, these potential elevational range shifts have primarily been examined in tropical regions. Although desert bird species may be at the edge of their aridity tolerances, elevational range shifts of desert bird species rarely have been studied. Here, we examine shifts in the elevational distributions of breeding birds from two regions of the Great Basin, a desert in the western United States, over 10 to 20 years. We collected data annually from 2001-2020, a relatively long time series that is uncommon in research on distributional shifts. We used single-species occupancy models of 32 bird species to examine elevational shifts at three extents: the full elevational gradient (1650-3200 m) and the lowest and highest edges (25%) of the gradient. We then conducted simulations to test whether population stochasticity could confound inferences about shifts. We examined whether temperature, precipitation, and primary productivity (normalized difference vegetation index) were associated with occupancy and shifts. The elevational distributions of 19 species shifted, and simulations indicated that shifts in the distributions of 12 species were unlikely to be stochastic. The three shifts along the full elevational gradient were downslope, and the majority of distributional shifts occurred at the elevational range edges. Occupancy of 10 species with elevational distributions that shifted was associated significantly with precipitation, and 8 of those associations were negative. Although we found that climate changed considerably even over the short temporal extent of our study, our results suggested that this community of desert birds is relatively resilient to the direct effects of climate change.

The genomics revolution continues to change how ecologists and evolutionary biologists study the evolution and maintenance of biodiversity. It is now easier than ever to generate large molecular data sets consisting of hundreds to thousands of independently evolving nuclear loci to estimate a suite of evolutionary and demographic parameters. However, any inferences will be incomplete or inaccurate if incorrect taxonomic identities and perpetuated throughout the analytical pipeline. Due to decades of research and comprehensive online databases, sequencing of mitochondrial DNA (mtDNA), chloroplast DNA (cpDNA) and select nuclear genes can provide researchers with a cost effective and simple means to verify the species identity of samples prior to subsequent phylogeographic and population genomic analysis. The addition of these sequences to genomic studies can also shed light on other important evolutionary questions such as explanations for gene tree-species tree discordance, species limits, sex-biased dispersal patterns, and mtDNA introgression. Although the mtDNA and cpDNA genomes often should not be used exclusively to make historical inferences given their well-known limitations, the addition of these data to modern genomic studies adds little cost and effort while simultaneously providing a wealth of useful data that can have significant implications for both basic and applied research.

Objective: This study aimed to investigate the effect of magnesium sulfate treatment on fetal cardiac function during seizure prophylaxis of pregnant women diagnosed with severe preeclampsia and eclampsia. Fetal cardiac function was evaluated with the modified myocardial performance index (mod-MPI) before and after prophylaxis. Methods: A total of 50 pregnant women diagnosed with severe preeclampsia or eclampsia were involved. The characteristics of the participants, medical and obstetric history, ultrasound and laboratory findings were recorded. Fetal mod-MPI was obtained before and after magnesium treatment. Data were analyzed with appropriate statistical tests and p < 0.05 was considered to indicate statistical significance . Results: The mean maternal and gestational ages of pregnant women were 31.7 ± 5.9 and 32.4 ± 4.5. Mean mod-MPI before and after prophylaxis were 0.41 ± 0.18 and 0.49 ± 0.09, respectively (p<0.05). Conclusion: There was a significant increase in fetal mod-MPI after magnesium prophylaxis was given to severe preeclampctic/eclamptic women. The higher the mod-MPI, the worse the fetal cardiac function. This might have been the result of magnesium leading to an increased isovolumetric relaxation time. Key words: Preeclampsia, magnesium sulfate, myocardial performance index, eclampsia, fetus

Sucrose synthase (SuSy, EC 2.4.1.13) is a unique glycosyltransferase (GT) for developing cost-effective glycosylation processes. Up to now, some SuSys derived from plants and bacteria have been used to recycle uridine 5’-diphosphate glucose in the reactions catalyzed by Leloir GTs. In this study, after sequence mining and experimental verification, a SuSy from Micractinium conductrix (McSuSy), a single-cell green alga, was identified. In the direction of sucrose cleavage, the optimum temperature and pH of the recombinant McSuSy were 60 °C and pH 7.0. The mutations of the predicted N-terminal phosphorylation site (S31D) and the QN motif (K684T and N685D) significantly stimulated the activity of McSuSy. When the mutant S31D/684T/685D of McSuSy, with the highest activity, was applied by coupling the engineered yeast glycosyltransferase UGT51 in a one-pot two-enzyme reaction, 8 mM protopanaxadiol was transformed into 6.02 mM (3.75 g/L) ginsenoside Rh2 within 3 h at 37 °C. The yield was comparable to the control reaction of AtSuSy1 from Arabidopsis thaliana. This work reveals the lower eukaryotes as a promising resource for SuSys of industrial interest.

Spinal bulbar muscular atrophy (SBMA) is a neurodegenerative genetic disorder, which results because of a mutation in the start codon of the Androgen Receptor (AR) gene. The mutant Androgen Receptor gene features the polyglutamine expansion (CAG) repeats, undergoing inappropriate post-translational modifications, which leads to development of toxin production functionality. In order to inhibit the production of mutant AR gene, CRISPR-Cas9 based model to cure the trinucleotide repeat disorder is proposed in this research. CRISPR cas9 constructed guided RNAs are expected to showed max treatment accuracy an effective silencing method in the functional genetic disorder of SBMA. It demonstrates the on-target and off-target scores that hold GC content within 40 - 60%. Further validation comes from the minimum free energy that is correlated with the gRNA’s structural accuracy. Although, currently, there is no effective and complete cure of SBMA is available except symptomatic treatments, CRISPR-Cas9 provides a better approach to target this disease at the molecular level, which gives a hope to develop an effective treatment against this currently non-curable disease. Possible results are constructed using in-silico and computational therapeutic approach for SBMA. The CRISPR-Cas9 protein shows promising results in an artificial environment. Thus, this study presents for the first time a specific possible future candidate in the treatment of SBMA that holds potential as a therapeutic approach for a genetic disorder. Imbued by the CRISPR mechanism and the suitability of gRNA, this strategy can be utilized as a novel therapeutic approach.

Background: Subcutaneous implantable cardioverter defibrillators (S-ICD) are widely accepted therapy in congenital heart disease (CHD) patients at risk of life-threatening ventricular arrhythmias or sudden cardiac death (SCD) when pacing is not required. Occasionally, pacemaker (PM) dependent CHD patients will subsequently develop an indication for a cardioverter defibrillator. The use of S-ICD in complex CHD who have had already PM devices implanted implies some specific considerations, as the safety for these patients in unknown and recommendations among physicians may vary widely. Methods: We review the data and studied the indications for S-ICD in complex CHD with previous PM and discuss its usefulness in clinical practice. Results: From a large cohort of 345 patients enrolled in the S-ICD “Monaldi care” registry, that encompass all the patients implanted in the Monaldi Hospital of Naples, we considered 11 consecutive complex CHD patients (10M/1F aged 40.4±18.4 years) who underwent S-ICD implant after a previous PM implant, from February 2015 to October 2022. Mean follow-up was 23.7±22.5 months. All the patients showed a good compliance to the device system with no complications (infections or skin erosions). Conclusions: In complex CHD with already implanted PM devices, S-ICD implant appears to be a safe alternative to PM upgrading to transvenous ICD system, avoiding abandoned leads or life-threatening lead extraction. However, there are important issues with regards to testing and programming that need to be addressed at the time of implantation.

Introduction: Asthma and Allergic Rhinitis (AR) are among the most prevalent diseases worldwide and they frequently persist throughout life. These have significant effect on physical, financial and mental wellbeing of patients and caregivers. There have been few attempts previously, assessing quality of life in affected families suffering from these diseases. However, data from developing countries are scarce. Quality of life (QOL) assessment in children and caregivers of patients suffering can help in symptomatic management and provide inputs for better utilization of resources to achieve optimal treatment. Methods: Patient and caregiver QOLs were ascertained using mPAQLQ and PACQLQ respectively in the study and correlated with disease severity and chronicity using parametric and non-parametric statistical tools. Results: There were 246 pairs of children diagnosed with Asthma and/or AR and their caregivers attending the Pediatric Allergy and Asthma clinic. Symptom score, emotional domain and activity limitation in children did not validate a statistically significant difference in QOL in various grades of AR/Asthma (p=0.632)(p=0.772), (p=0.496) (p=0.918) and (p=0.384), (p=0.561) respectively. Additionally there was no significant correlation between the severity of asthma and caregiver emotional disturbance (p=0.594) or caregiver activity limitation (p=0.446). Conclusions: Quality of life in children and caregivers where children are suffering from either AR or Asthma, or both has not shown any significant difference as per the disease severity or chronicity in various domains. There was no significant difference in quality of life noted as per change in age group, gender of patients or education status of caregivers.

Seed dispersal is one of the most important ecosystem services globally. It shapes plant populations, encourages forest succession, and has multiple, indirect benefits for humans, yet it is one of the most threatened processes in plant regeneration, worldwide. The restricted movement of local frugivores, through habitat fragmentation, is one of the main threats to seed dispersal. These restrictions alter the behaviour associated with movements before, during and after interacting with fruits and seeds. Consequently, there have been recent calls for animal movement and behaviour to be better integrated with seed dispersal studies to enable researchers to fully understand the processes that determine seed rain. To assess the current use of animal tracking in frugivory studies and to provide a baseline for future studies, we provide a comprehensive review and synthesis on the existing primary literature of global tracking studies that monitor movement of frugivorous animals. Specifically, we identify studies that estimate dispersal distances and how they vary with morphological and environmental traits. We show that over the last two decades there has been a large increase in frugivore tracking studies that determine seed dispersal distances. However, gaps across taxa and geographic distribution still exist. Furthermore, we found that certain morphological and environmental traits can be used to predict seed dispersal distances. We demonstrate that an increase in body mass significantly increases the estimated seed dispersal mean and maximum distances, as does species flight ability. Our results also suggest that protected areas have a positive effect on mean seed dispersal distances when compared to unprotected areas. We anticipate that this review act as a reference for future frugivore tracking studies to build upon, specifically to understand the drivers of movement, and to interpret how seed dispersal and other ecosystem services will be impacted by human disturbance and land use changes.

Introduction: Delayed enhancement - magnetic resonance imaging (DE-MRI) has demonstrated that nonischemic cardiomyopathy is mainly characterized by intramural or epicardial fibrosis whereas global endomyocardial fibrosis suggests cardiac involvement in autoimmune rheumatic diseases or amyloidosis. Conduction disorders and sudden cardiac death are important manifestations of autoimmune rheumatic diseases with cardiac involvement but the substrates of ventricular arrhythmias in autoimmune rheumatic diseases have not been fully elucidated. Methods and Results: 20 patients with autoimmune rheumatic diseases presenting with ventricular tachycardia (VT) (n=11) or frequent ventricular extrasystoles (n=9) underwent DE-MRI and / or endocardial electroanatomical mapping of the left ventricle (LV). 10 patients with autoimmune rheumatic diseases underwent VT ablation. Global endomyocardial fibrosis without myocardial thickening and unrelated to coronary territories was detected by DE-MRI or electroanatomical voltage mapping in 9 of 20 patients with autoimmune rheumatic diseases. In the other patients with autoimmune rheumatic diseases, limited regions of predominantly epicardial (n = 4) and intramyocardial (n = 5) fibrosis or only minimal fibrosis (n = 2) were found using DE-MRI. Endocardial low-amplitude diastolic potentials and pre-systolic Purkinje or fascicular potentials, mostly within fibrotic areas, were identified as the targets of successful VT ablation in 7 of 10 patients with autoimmune rheumatic diseases. Conclusion: Global endomyocardial fibrosis can be a tool to diagnose severe cardiac involvement in autoimmune rheumatic diseases and may serve as the substrate of ventricular arrhythmias in a substantial part of patients.

Introduction: Antitachycardia pacing (ATP) is used to terminate ventricular tachycardia (VT) by delivering rapid, low energy pacing to the right ventricle (RV). Unfortunately, ATP is not effective against all VT episodes and can result in adverse outcomes, such as VT acceleration and degeneration into ventricular fibrillation (VF). Improving ATP is therefore desirable. Our objective was to compare the efficacy and safety of ATP delivered at the His bundle to traditional ATP. Methods: Six dogs were anesthetized and pacing leads were implanted in the RV and His bundle. The lateral anterior descending artery (LAD) was occluded for 2 hours to create an ischemic injury. In a study 4-7 days later, a 128-electrode sock was placed snugly around the ventricles and VT was induced using rapid pacing. ATP was delivered from either the His bundle or RV lead, then attempted at the other location if unsuccessful. Success rates and instances of VT acceleration and degeneration into VF were calculated. Results: We induced 83 runs of VT and attempted ATP 128 times. RV ATP was successful in 36% of attempts; His ATP was successful in 38% of attempts. RV ATP resulted in significantly more adverse outcomes. RV and His ATP induced VT acceleration in 9% and 3% of trains respectively, and induced degeneration into VF in 5% and 1% of trains, respectively. Conclusion: His bundle ATP is safer, but not significantly more effective, than RV ATP.

Background: eHealth CF-CBT is the first digital mental health intervention for depression/anxiety in adults with cystic fibrosis (awCF); an 8-session therapist-guided internet-delivered program that was developed in English and Dutch with stakeholder input and evaluation indicating high acceptability and usability. Methods: Dutch eHealth CF-CBT was piloted in awCF with mild-moderate symptoms of depression and/or anxiety. Feasibility, usability, acceptability, and preliminary efficacy were assessed, measuring pre-post changes in depression (PHQ-9), anxiety (GAD-7), perceived stress (PSS) and health-related quality of life (CFQ-R). Results: All participants (n=10, 7 female, mean age 29 (range 21-43), mean FEV1 71%pred (range 31-115)) completed all sessions. Patient-rated feasibility, usability and acceptability of eHealth CF-CBT was positive on validated scales, as were qualitative assessments of content and format. GAD-7 improved in 90% of participants; in 50% by ≥ the minimally important difference (MID) of 4 points. PHQ-9 improved in 90%; 40% by ≥ the MID of 5. PSS improved in 80%. CFQ-R improved in the domain Health Perceptions (70%). Conclusions: eHealth CF-CBT demonstrated feasibility, usability, acceptability and promising preliminary efficacy in this pilot trial with Dutch awCF with mild to moderate symptoms of depression and anxiety.

Background: To explore the long-term safety and dynamics of the immune response induced by the second and third doses of the BNT162b2 mRNA COVID-19 vaccine in adolescents with juvenile-onset autoimmune inflammatory rheumatic diseases (AIIRD) compared with healthy controls. Methods: This international prospective study included adolescents with AIIRD and controls vaccinated with two (AIIRD n=124; controls n=80) or three (AIIRD n=64; controls n=30) doses of the BNT162b2 vaccine, evaluated for vaccine side-effects, disease activity, COVID-19 breakthrough infection rates and severity, and anti-spike S1/S2 IgG antibody titres in a sample from both groups. Results: The vaccination safety profile was favourable, with most patients reporting mild or no side-effects. The rheumatic disease remained stable among 98% and 100% after the second and third doses, respectively. The two-dose vaccine induced comparable seropositivity rates among patients (91%) and controls (100%), (p=0.55), which declined within 6 months to 87% and 100%, respectively (p=0.3), and increased to 100% in both groups, after the third vaccine dose. The overall post-vaccination COVID-19 infection rate was comparable between patients and controls, 47.6% (n=59) and 35% (n=28), respectively; p=0.5278, with most infections occurring during the Omicron surge. In relation to the last vaccination, time-to-COVID-19 infection was similar between patients and controls, at a median of 5.5 vs. 5.2 months, respectively (log-rank p=0.1555). Conclusion: The safety profile of three doses of the BNT162b2 mRNA vaccine was excellent, with an adequate humoral response and similar efficacy among patients and controls. These results support the recommendation for vaccinating adolescents with juvenile-onset AIIRD against COVID-19.

Pulmonary Vein Isolation-induced Vagal Nerve Injury and Gastric Motility DisordersBachir Lakkiss, MD; Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: PVI-induced vagal nerve injury and gastric motility disordersWords: 665 (excluding the title page and references)Keywords: Heart Diseases, Cardiovascular Diseases, Cardiac Arrhythmias, Atrial Fibrillation, Catheter Ablation, Pulmonary Vein IsolationFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FRCPTenured Professor of MedicineTenured Professor of Biochemistry and Molecular GeneticsVan Dyck Medical Educator and Director of the Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: mr48@aub.edu.lbAtrial fibrillation (AF) is the most prevalent heart rhythm abnormality worldwide. An estimated three to six million people in the United States have AF. It is expected that this number is likely to double by 2050, making AF a significant public health burden. (1) AF is a leading cause of stroke and thromboembolism and is associated with a reduced quality of life. (2) Furthermore, it is linked to an increased mortality in both men and women, with an OR for death of 1.5 in men and 1.9 in women. (3) Medical expenditures for AF are significant, ranging from an annual cost of $1,632 to $21,099, with acute care accounting for the largest cost component in addition to anticoagulation therapy, which accounted for almost one-third of these costs. (4) The four pillars of AF management include rhythm control, rate control, stroke prevention and risk factor management. (5, 6) While antiarrhythmic drugs are used in some patients for AF rhythm control, AF ablation using pulmonary vein isolation (PVI) is regarded as the major modality for rhythm control. (6)The vagal nerve provides most of the parasympathetic innervation to the abdominal organs, including the stomach, esophagus, and a significant portion of the intestines. It serves a major role in the regulation of gastric and esophageal motility, in addition to maintaining lower esophageal sphincter tone. (7-9) Due to the relatively close vicinity of the vagal nerve plexus located on the anterior surface of the esophagus and the left atrial posterior wall, the thermal energy utilized during ablation can result in uncommon but potentially fatal complications such as esophageal perforation and atrial-esophageal fistula formation. (10-12) In addition, radiofrequency ablation for AF is associated with non-fatal complications such as an increased risk of gastric motility disorders and acid reflux. (13, 14)In the current issue of the Journal of Cardiovascular Electrophysiology, Meininghaus et al. recruited 85 patients to assess the incidence of ablation-induced vagal nerve injury (VNI) using both cryoballoon and radiofrequency ablation. Although many cases of VNI induced by PVI have been documented previously, this is one of the first studies to utilize electrophysiologic measurements of gastric motility (EGG) using cutaneous electrodes to record the electrical activity of the stomach two days prior to and two days after the procedure. (15-17) Moreover, the authors have used endoscopy to detect lesions such as erosions, ulcers, and perforations in the esophagus one week prior to and within two days of the procedure.The findings from this study add to our understanding of one of the complications of PVI in patients with AF (13, 14). One of the key outcomes the researchers observed was the perceived direct link between VNI and preexisting esophageal vulnerability. The authors have found that patients who had preexisting esophagitis had an elevated risk of developing VNI. In addition, the authors identified that in patients in whom EGG showed VNI, the elevated risk of ablation-induced endoscopic pathology was present in the post-procedure endoscopy. Furthermore, another significant finding was the detection of VNI on EGG in approximately one-third of PVI patients, irrespective of energy source, whether high power short duration, or moderate power moderate duration. These findings did not corroborate other studies, which showed that titration of the duration of the ablation energy could prevent VNI in patients undergoing AF ablation. (18)Overall, the authors should be commended for their tremendous efforts in attempting to understand the intricate pathophysiology and the association of esophageal lesions, atrial-esophageal fistula formation, and vagal nerve injury following PVI using EGG. Certainly, the results of this study have tremendous clinical implications. EGG could have a very important role in the prevention of atrial-esophageal fistula formation in the future. The article had a few limitations, mainly that the results were from a single-center study. Further studies incorporating additional patients from different medical centers should be conducted to better understand the complex pathophysiology of vagal nerve injury and gastric motility disorders following PVI. Advances in esophageal protection technologies will help in decreasing esophageal lesions during PVI. (19-20)References1. Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, et al. Secular Trends in Incidence of Atrial Fibrillation in Olmsted County, Minnesota, 1980 to 2000, and Implications on the Projections for Future Prevalence. Circulation. 2006;114(2):119-25. doi: doi:10.1161/CIRCULATIONAHA.105.595140.2. Jalloul Y, Refaat MM. IL-6 Rapidly Induces Reversible Atrial Electrical Remodeling by Downregulation of Cardiac Connexins. J Am Heart Assoc. 2019;8(16):e013638. Epub 2019/08/20. doi: 10.1161/jaha.119.013638. PubMed PMID: 31423871; PubMed Central PMCID: PMCPMC6759896.3. Benjamin EJ, Wolf PA, D’Agostino RB, Silbershatz H, Kannel WB, Levy D. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation. 1998;98(10):946-52. Epub 1998/09/16. doi: 10.1161/01.cir.98.10.946. PubMed PMID: 9737513.4. Wodchis WP, Bhatia RS, Leblanc K, Meshkat N, Morra D. A review of the cost of atrial fibrillation. Value Health. 2012;15(2):240-8. Epub 2012/03/22. doi: 10.1016/j.jval.2011.09.009. PubMed PMID: 22433754.5. Lakkis B, Refaat MM. Is esophageal temperature management needed during cryoballoon ablation for atrial fibrillation? Journal of Cardiovascular Electrophysiology. 2022;33(12):2567-8. doi: https://doi.org/10.1111/jce.15725.6. Chung MK, Refaat M, Shen W-K, Kutyifa V, Cha Y-M, Di Biase L, et al. Atrial Fibrillation: JACC Council Perspectives. Journal of the American College of Cardiology. 2020;75(14):1689-713. doi: https://doi.org/10.1016/j.jacc.2020.02.025.7. Richards WG, Sugarbaker DJ. Neuronal control of esophageal function. Chest Surg Clin N Am. 1995;5(1):157-71. Epub 1995/02/01. PubMed PMID: 7743145.8. Hsu M, Safadi AO, Lui F. Physiology, Stomach. StatPearls. Treasure Island (FL): StatPearls PublishingCopyright © 2022, StatPearls Publishing LLC.; 2022.9. Goyal RK, Chaudhury A. Physiology of normal esophageal motility. J Clin Gastroenterol. 2008;42(5):610-9. Epub 2008/03/28. doi: 10.1097/MCG.0b013e31816b444d. PubMed PMID: 18364578; PubMed Central PMCID: PMCPMC2728598.10. Kapur S, Barbhaiya C, Deneke T, Michaud GF. Esophageal Injury and Atrioesophageal Fistula Caused by Ablation for Atrial Fibrillation. Circulation. 2017;136(13):1247-55. doi: doi:10.1161/CIRCULATIONAHA.117.025827.11. D’Avila A, Ptaszek LM, Yu PB, Walker JD, Wright C, Noseworthy PA, et al. Images in cardiovascular medicine. Left atrial-esophageal fistula after pulmonary vein isolation: a cautionary tale. Circulation. 2007;115(17):e432-3. Epub 2007/05/02. doi: 10.1161/circulationaha.106.680181. PubMed PMID: 17470703.12. Sánchez-Quintana D, Cabrera JA, Climent V, Farré J, Mendonça MCd, Ho SY. Anatomic Relations Between the Esophagus and Left Atrium and Relevance for Ablation of Atrial Fibrillation. Circulation. 2005;112(10):1400-5. doi: doi:10.1161/CIRCULATIONAHA.105.551291.13. Shah D, Dumonceau J-M, Burri H, Sunthorn H, Schroft A, Gentil-Baron P, et al. Acute Pyloric Spasm and Gastric Hypomotility: An Extracardiac Adverse Effect of Percutaneous Radiofrequency Ablation for Atrial Fibrillation. Journal of the American College of Cardiology. 2005;46(2):327-30. doi: https://doi.org/10.1016/j.jacc.2005.04.030.14. Park S-Y, Camilleri M, Packer D, Monahan K. Upper gastrointestinal complications following ablation therapy for atrial fibrillation. Neurogastroenterology & Motility. 2017;29(11):e13109. doi: https://doi.org/10.1111/nmo.13109.15. Choi SW, Kang SH, Kwon OS, Park HW, Lee S, Koo BS, et al. A case of severe gastroparesis: indigestion and weight loss after catheter ablation of atrial fibrillation. Pacing Clin Electrophysiol. 2012;35(3):e59-61. Epub 2010/10/05. doi: 10.1111/j.1540-8159.2010.02912.x. PubMed PMID: 20883511.16. Lakkireddy D, Reddy YM, Atkins D, Rajasingh J, Kanmanthareddy A, Olyaee M, et al. Effect of atrial fibrillation ablation on gastric motility: the atrial fibrillation gut study. Circ Arrhythm Electrophysiol. 2015;8(3):531-6. Epub 2015/03/17. doi: 10.1161/circep.114.002508. PubMed PMID: 25772541.17. Kuwahara T, Takahashi A, Takahashi Y, Kobori A, Miyazaki S, Takei A, et al. Clinical characteristics and management of periesophageal vagal nerve injury complicating left atrial ablation of atrial fibrillation: lessons from eleven cases. J Cardiovasc Electrophysiol. 2013;24(8):847-51. Epub 2013/04/05. doi: 10.1111/jce.12130. PubMed PMID: 23551640.18. KUWAHARA T, TAKAHASHI A, KOBORI A, MIYAZAKI S, TAKAHASHI Y, TAKEI A, et al. Safe and Effective Ablation of Atrial Fibrillation: Importance of Esophageal Temperature Monitoring to Avoid Periesophageal Nerve Injury as a Complication of Pulmonary Vein Isolation. Journal of Cardiovascular Electrophysiology. 2009;20(1):1-6. doi: https://doi.org/10.1111/j.1540-8167.2008.01280.x.19. D’Avila A, Ptaszek LM, Yu PB, Walker JD, Wright C, Noseworthy PA, Myers A, Refaat M, Ruskin JN: Left Atrial-Esophageal Fistula After Pulmonary Vein Isolation. Circulation May 2007; 115(17): e432-3.20. El Moheb MN, Refaat MM. Protecting the Esophagus During Catheter Ablation: Evaluation of a Novel Vacuum Suction-Based Retractor. J Cardiovasc Electrophysiol Jul 2020; 31 (7): 1670-1671.

Quality control of herbal medicines is an important and necessary issue, especially the role of herbal drug identification to avoid misuse of herb that affect efficacy, or cause toxicity. Scleromitrion diffusum (SD) is one of the most common herbs but often confused with Oldenlandia corymbosa (OC). 10 samples of SD and 10 samples of OC were collected on the Taiwan markets. This study conducted the analysis of morphology, microscopy, TLC, HPLC using two markers Asperuloside (ASP) and Scandoside methyl ester (SME) to distinguish SD and OC. Through quantification of total polyphenols and total flavanoids, investigating antioxidant activity through DPPH free radical scavenging effect, ABTS •+ scavenging effect and reducing power to further clarify the biological effects of two herbs. Study results show the differences in microscopy and suggests a TLC method for distinguishing two herbs on the markets. In HPLC, the ratio of two markers ASP and SME in two herbs was also different when SD contained higher content of ASP and conversely OC higher SME. With more total polyphenols and total flavonoids in SD than that in OC, the antioxidant activity of SD is superior to that of OC. This study provides a more comprehensive perspective for identification and quality evaluation of SD on the markets.

Oral mucosal lesions may persist years before diagnosis of inflammatory bowel disease (IBD) and subsequent primary sclerosing cholangitis (PSC). It may be that a dental practitioner may be the first clinician to suspect IBD. Suspect IBD; early referral and close collaboration with a gastroenterologist are recommended.

Error Augmentation training using a robotic interface is thought to promote motor recovery by enhancing proprioceptive feedback, which motivates and challenges patients to optimize their performance during training. Here, we investigated the effectiveness of robotic Error Augmentation training on motor recovery after a stroke, compared to standard robotic training in a null field. Post-stroke patients were randomly assigned to one of two groups: a study group (n=9) that was trained on a 3D robotic system applying Error Augmentation forces, and a control group (n=7) that carried out the same protocol in null field conditions. The robotic rehabilitation intervention was applied in addition to the standard rehabilitation protocol of the rehabilitation center. Error Augmentation training increased clinical scores compared to standard robotic training by 266% on the Motor Assessment Scale, and 88% on the Fugl-Meyer scale. The Motor Assessment Scale scores were significantly correlated with the Fugl-Meyer scores (p=0.03, r=0.541). There were more movement errors on the initial trials of the game sequence using the DeXtreme robotic device with Error Augmentation compared to trials with no force field. This difference vanished however after 10 trials. Error Augmentation training decreased the number of movement units and jerkiness compared to the control treatment. These findings suggest that Error Augmentation training may enhance motor performance possibly through motor adaptation.

The differential proteolytic susceptibilities of different types of linkers joining the same two protein domains were investigated, to identify linkers displaying the highest resistance to degradation by proteases in the environment. Five linkers, namely Rigid [3 repeats of EAAAK], Flexible [two repeats of SGGGG], Nat-Full, Nat-Half and Nat-Quarter [3 linkers of 42, 21, and 9 residues, respectively, derived from a naturally-occurring Coh2-adjacent sequence] were used to fuse two thermostable, and proteolytically-resistant, domains, namely Coh2 (from C. thermocellum CipA), and BSX (from Bacillus sp. NG-27). The produced fusions were examined for linker degradation, using electrophoretic (SDS-PAGE) and chromatographic (size exclusion) experiments, following different periods of storage at 4 ⁰C. Rigid, Nat-Full, Nat-Half and Nat-Quarter were degraded, and released free Coh2 and BSX. However, Flexible displayed a remarkable resistance to both environmental proteases and Subtilisin A (a non-specific protease). Our data suggests that Flexible imparts freedom of movement to Coh2 and BSX, and then reciprocally receives protection against proteolysis from Coh2 and BSX, through their dynamic steric inhibition (or ‘batting away’) of protease approach.

Aim: The present study aimed to evaluate time to onset, incidence rates, and outcomes for pembrolizumab-induced cardiac adverse events (AEs) in patients with cancer using the Japanese Adverse Drug Event Report database. Methods: We analysed data for the period from April 2004 to March 2022. Data on cardiac AEs were extracted and relative risks of AEs were estimated using the reporting odds ratio. Results: We analysed 2,021,907 reports and identified 15,306 reports of AEs caused by pembrolizumab. Of these, 399 cardiac AEs were associated with pembrolizumab. Signals were detected for six cardiac AEs: myocarditis, immune-mediated myocarditis, pericardial effusion, cardiac tamponade, pericarditis, and pericarditis malignant. A histogram of median times to onset showed occurrence from 33 to 138 days, but some cases occurred even more than 1 year after the start of administration. Among these, myocarditis was the most frequently reported (27.1%), with fatal cases also reported. Conclusion: This study focused on cardiac AEs caused by pembrolizumab as post-marketing AEs. Some cases could potentially involve serious outcomes, so patients should be monitored for signs of onset of these AEs not only at the start of administration, but also over an extended period, especially for myocarditis.

Aims: This study aimed to evaluate the effect of remifentanil pretreatment on sufentanil-induced cough (SIC) during general anesthesia induction. Methods: A total of 120 patients who were scheduled for elective surgery were equally randomized into two groups (n=60 each). Patients in R group received 0.5 μg/kg remifentanil and N group received same volume of normal saline 1 minute before sufentanil (0.5 μg/kg) intravenous injection. Remifentanil and sufentanil were diluted to 5ml and then administered to patients in both R and N groups within 5 seconds. Then midazolam, etomidate and rocuronium bromide were given to facilitate tracheal intubation. The incidence and severity of cough in both groups were recorded within 2 minutes after sufentanil administration during general anesthesia induction. The mean arterial pressure (MAP), heart rate (HR), and pulse oxygen saturation (SpO2) were recorded at T1 (before the injection of remifentanil or normal saline), T2 (1 minute after remifentanil administration), T3 (before intubation) and T4 (1 minute after intubation). Additionally, the incidences of adverse events, including dizziness, nausea, apnea, truncal rigidity, bradycardia or other adverse effects were also recorded. Results: The incidence of SIC in R group was significantly decreased when compared with N group (3.33% vs 35.00%, respectively; P < 0.001). No statistical differences were found in MAP, HR, SpO2, and the incidences of other side effects between two groups at T1, T2, T3, and T4 (P > 0.05). Conclusion: Pretreatment with remifentanil 0.5 μg/kg can effectively and safely suppress the incidence and severity of sufentanil-induced cough.

A document by Carmen H. Li. Click on the document to view its contents.

Purpose — To evaluate hypoglycemia incidence rate during treatment with a fixed-dose combination of glimepiride and metformin in patients non-responders to metformin monotherapy. Data were collected during customary specialized practice in Peru where access to effective and safe, but low-cost medications, is needed. Methods— This was an observational, prospective, active pharmacovigilance, cohort study with in-person medical assessments. Medical assessments were conducted every 3-months, with monthly follow-up through phone calls. Data regarding use and administration of treatment were recorded by patients. Adverse events (AE) reported by patients and/or ascertained by attending physicians during the period of 18 months along with treatment-related events were identified. Cumulative incidence and hypoglycemia incidence rate were estimated. Poisson and logistic regression models were applied to study their relationship with risk factors and patterns of use. Results— 206 patients were enrolled in the study from 10 centers and were followed for a median duration of 12 months (range, 2-18 months). Forty treatment-related AEs were reported (cumulative incidence = 19.4%). No severe hypoglycemic events were observed. Most common AE found was non-severe hypoglycemia (cumulative incidence = 2.4%; incidence rate = 2.6/100 person/years). Self-administration of a higher dose than prescribed was associated with a higher probability of an AE (p=0.03). Conclusions— Administration of a fixed-dose combination of glimepiride plus metformin was associated with low incidence of non-severe hypoglycemia, and no incidence of severe hypoglycemia. These results advocate the use of fixed-dose combination of glimepiride plus metformin in low- and middle-income countries with limited resources, even more so in wake of COVID-19 pandemic.

It is not known whether patients with schizophrenia can improve their ability to learn new information through tests. We conducted two experiments—to explore the forward testing effects in schizophrenic patients in learning a new route—with 124 schizophrenic patients and a control group of 124 randomly selected healthy. All participants were tasked with learning a two-dimensional planar route map consisting of four lists (Experiment 1) and three-dimensional video spatial route information (Experiment 2). Results from Experiment 1 demonstrated that in a two-dimensional planar route map, both schizophrenic and healthy participants recalled the spatial route information under the test condition versus the repetitive learning condition. In Experiment 2, we used three-dimensional video spatial route information and obtained the same results found in Experiment 1. This study suggests that by using preposed tests, patients with schizophrenia could suppress proactive interference and gain general benefits, including forward-backward effects of retrieval practice. Therefore, tests may be a powerful tool for improving learning and memory in patients with schizophrenia.

In neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli. However, such studies often lack calibration procedure implementation, have a vague protocol description, do not provide data quality quantification, and omit required control for gender pain differences. All this hampers study repetition and interexperimental comparisons. Moreover, typical calibration procedures require a high number of stimulations which may cause participants’ discomfort and stimuli habituation. To overcome those shortcomings, we present an automatic staircase pain calibration method for A-delta-specific stimulation adjusted to the magnetoencephalography environment. We provide an in-depth data analysis of the collected self-reports from seventy healthy volunteers (37 males) and propose a method based on a dynamic truncated linear regression model (tLRM). We compare its estimates for the sensation (t), and pain (T) thresholds, as well as for the mid-pain stimulation (MP), with those calculated using a traditional threshold method and standard linear regression models. Compared to the other threshold methods, tLRM exhibits higher R2 and requires 36% fewer stimuli application and has significantly higher t and lower T and MP intensities. Regarding sex differences, both lower t and T were found for females compared to males, regardless of the calibration method. The proposed tLRM method quantifies the quality of the calibration procedure, minimizes its duration and invasiveness, as well as provides validation of linearity between stimuli intensity and subjective scores, making it an enabling technique for further studies. Moreover, our results highlight the importance of control for gender in pain studies.

The drifting fish eggs are more likely to collide with ships, rocks etc. as they hatch while migrating through the river. For fish resources protection and waterway management, it’s important to clarify the upper threshold of hitting velocity and the effect of the hitting shock on their hatching. Thus, natural spawned and domesticated fish eggs were studied and compared. The effects of hitting objects, hitting velocity and the developmental level of the fish eggs on their hatching was also studied. The developmental stage was the most sensitive factor to hitting shock. Almost 70% of natural spawned semi-buoyant fish eggs can’t hatch successfully when the hitting velocity was 4.4 m s-1 and collided with rock, and this hatching rate was about 10%-30% higher than that of farmed ones at the same conditions. The results are of great significance for the protection of fish resources in the high-velocity rivers.