We present the rare case of a 71 year old man with intracranial primary dural Hodgkin lymphoma (PDHL). He underwent subtotal resection of the mass, followed by adjuvant chemotherapy and consolidative radiotherapy, with no recurrence at 5 years follow up.

Insects often harbor heritable symbionts that provide defense against specialized natural enemies, yet little is known about symbiont protection when hosts face simultaneous threats. In pea aphids (Acyrthosiphon pisum), the facultative endosymbiont Hamiltonella defensa confers protection against the parasitoid, Aphidius ervi, and Regiella insecticola protects against aphid-specific fungal pathogens, including Pandora neoaphidis. Here we investigated whether these two common aphid symbionts protect against a specialized virus A. pisum virus (APV), and whether their anti-fungal and anti-parasitoid services are impacted by APV infection. We found that APV imposed large fitness costs on symbiont-free aphids and these costs were elevated in aphids housing H. defensa. In contrast, APV titers were significantly reduced and costs to APV infection were largely eliminated in aphids with R. insecticola. To our knowledge, R. insecticola is the first aphid symbiont shown to protect against a viral pathogen, and only the second arthropod symbiont reported to do so. In contrast, APV infection did not impact the protective services either R. insecticola or H. defensa. To better understand APV biology, we produced five genomes and examined transmission routes. We found that moderate rates of vertical transmission, combined with horizontal transfer through food plants, were the major route of APV spread, although lateral transfer by parasitoids also occurred. Transmission was unaffected by facultative symbionts. In summary, the presence and species identity of facultative symbionts resulted in highly divergent outcomes for aphids infected with APV, while not impacting defensive services that target other enemies. These findings add to the diverse phenotypes conferred by aphid symbionts, and to the growing body of work highlighting extensive variation in symbiont-mediated interactions.

Urethral duplication is uncommon with few cases reported in the literature. We report a case in which a patient presented with discharge from proximal part of penis since childhood and recent history of infection. The diagnosis of pre-pubic sinus was made and complete excision of the sinus tract was done.

A set of new rasagiline derivatives is presented. They were designed to be antioxidant compounds with the potential to be used for treating neurodegenerative disorders. They are expected to be multifunctional molecules that can help reduce oxidative stress, which is thought to contribute to neurodegenerative disorders. The CADMA-Chem computational protocol was used to produce rasagiline derivatives and to evaluate their likeliness as oral drugs and antioxidants. Three of them were identified as the most promising ones. They are proposed to be better free radical scavengers than rasagiline. In addition, they are expected to keep the parent's molecule neuroprotective capability. Hopefully, the results presented here would promote further experimental and theoretical investigations on these compounds.

Our understanding of the hydrological processes in cocoa agroforests is extremely limited. Most work has focused on characterising throughfall and transpiration processes under various management approaches and climate change scenarios. However, little is currently understood about the soil hydrological processes which serve as a link to throughfall and transpiration. We monitored the soil properties, soil water repellency and hydraulic conductivity in a 5, 12 and >30 year old cocoa plantation in the wet and dry seasons. During the wet season repellent conditions were absent in all stands while the hydraulic conductivity showed no significant differences among them. This suggests that stand age has little effect on water movement during the wet period. During the dry season, the soil at the 5 and 12 year old stands became extremely repellent and was twice as severe as that of the >30 year old plantation. It was expected that the extreme repellency in the younger stands would reduce infiltration rates; however, higher rates were recorded in the 5 and 12 year old stands. This was likely due to the combination of a repellent soil matrix and the presence of large, deep soil cracks which enhanced preferential flow. As the repellency was not significantly correlated with soil properties, we hypothesised that the high grass/sedge cover and temperatures in the 5 and 12 year old stands enhanced it. While further research is needed to investigate the role that grass and sedges play in developing repellent conditions, managing their cover may prove beneficial for the growth and survival of young cocoa trees.

The two cases we present are the first to demonstrate novel manifestations of COVID-19- related interaction between the liver and the immune system in pediatric patients. Written informed consent was obtained from the parent/guardian to publish this report in accordance with the journal’s patient consent policy.

Introduction: Case definitions are used to guide clinical practice, surveillance, and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the CDC, ECDC, WHO, and UKHSA case definitions by age, region, and time. Case fatality ratios (CFR) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test-result were excluded. Results: 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC), and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients that met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread.

This editorial discusses the report titled “Cardiac Resynchronization Therapy Response in Cardiac Sarcoidosis” by Shabtaie et al.

Smooth-coated otters (Lutrogale perspicillata) and Malayan water monitor lizards (Varanus salvator) occupy similar habitats and and interact regularly in Singapore’s waterways. These interactions have a range of potential outcomes and are sometimes lethal. Few formal behavioral studies exist for either species. We analyzed interactions between otters and monitor lizards by gleaning data from publicly available videos from citizen scientists to examine what factors influence aggressive and defensive behaviors, and what influences vigilance in otters. Behavioral sequence analysis revealed no obvious monitor lizard behavior that predicted otter aggression towards monitors. We found that the presence and number of otter pups is positively associated with otter aggression. Otters also tended to be more vigilant in groups with more pups, and more vigilant on land than water. Monitor lizards displayed aggressive and defensive behaviors more frequently than did otters, regardless of whether the otters were aggressive towards lizards. These observations suggests that otters vary their aggression and vigilance levels depending on the context of each interaction.

This paper settles event-triggered synchronization and H∞ synchronization matters for two types of coupled delayed reaction-diffusion memristive neural networks (CDRDMNNs). First of all, several synchronization and H∞ synchronization conditions are acquired for CDRDMNNs with state coupling in virtue of exploiting Lyapunov stability theory in combination with proper controllers of the triggering event. Then, for CDRDMNNs with spatial diffusion coupling, event-triggered synchronization and H∞ synchronization are investigated as well. Finally, the correctness of the deduced synchronization and H∞synchronization results is verified by two given numerical examples.

Background. Oral immunotherapy (OIT) is an emerging method for treating food allergy in children. However, data regarding adults undergoing this process is lacking. Methods. We retrospectively analyzed the medical records of patients with food allergy aged ≥17 years who completed OIT treatment between April 2010 to December 2020 at Shamir medical Center. Data was compared to that of children aged 4 to <11 years and adolescents aged ≥11 to 17 treated during the same time period. Results. A total of 96 adults at a median age of 22.3 years who underwent OIT for milk (n=53), peanut (n=18), sesame (n=7), egg (n=5) and tree nuts (n=13) were analyzed and compared to 1299 children and 309 adolescents. Adults experienced more adverse reactions requiring injectable epinephrine, both during in-clinic up-dosing (49% vs. 15.9% and 26.5% for children and adolescents respectively, p<0.0001) and during home treatment (22.9% vs. 10.5%, p=0.001 for children, and 14.2%, p=0.06 for adolescents). Most adults (61.5%) were fully desensitized, but rates of full desensitization were significantly lower compared to children (73.4%, p=0.013). Significantly more adults (28.3%) undergoing milk OIT failed treatment compared to children (14.3%, p=0.015) and adolescents (14.1%, p=0.022), while failure rates in adults undergoing OIT for other foods were low (9.3%) and comparable to children and adolescents. Conclusions. OIT is successful in desensitizing most adults with IgE-mediated food allergy. Adults undergoing milk OIT are at increased risk for severe reactions and for OIT failure while failure rates in adults undergoing OIT for other foods are low.

Employing New Criteria for Confirmation of Conduction Pacing – Achieving True Left Bundle Branch Pacing May Be Harder Than Meets the EyeJoshua Sink, MD1, Nishant Verma, MD, MPH2Northwestern University, Feinberg School of Medicine, Department of Internal MedicineNorthwestern University, Feinberg School of Medicine, Division of CardiologyCorresponding Author:Nishant Verma, MD, MPH251 East Huron Street, Feinberg 8-503Chicago, IL [email protected]: NoneDisclosures: Dr. Sink has nothing to disclose. Dr. Verma receives speaker honoraria from Medtronic, Biotronik and Baylis Medical and consulting fees from Boston Scientific, Biosense Webster, AltaThera Pharmaceuticals and Knowledge 2 Practice.Word Count: 1200In recent years, conduction system pacing (CSP) has garnered significant attention from the electrophysiology (EP) community. This movement has been driven by the hypothesis that using the natural conduction system activation is desirable and clinically beneficial in patients with advanced conduction disease and ventricular desynchrony. Permanent His-bundle pacing (PHBP) is generally seen as the purest form of conduction system activation. (Figure 1) PHBP was first described over 20 years ago but the idea has attracted substantial investigative effort in recent years. When successfully achieved, His bundle pacing has been associated with reduction in mortality, reduction in heart failure (HF) admissions, and improvement in left ventricular (LV) function compared to right ventricular (RV) pacing.1 Despite this, consistent achievability in real-world practice remains limited due to a variety of factors including narrow anatomic targetability, lead stability, high pacing thresholds, low ventricular sensing, and inability to correct the QRS in bundle branch block.2Thus, while waiting for the next iteration of improved delivery techniques, pacing leads and programming algorithms,, alternative methods of conductive system pacing have emerged, with the potential to surmount the challenges described.Left bundle branch pacing (LBBP) has recently emerged as an alternative method of CSP. The technique was first described by Huang et al. in 2017 and has seen a momentous rise in interest since.3 In 2019, Huang et al. produced a user manual for a successful LBBP procedure, and in it they attempted to develop the first iteration of criteria for the confirmation of LBBP.4 Utilizing these criteria, or close variations of them, a number of studies were published afterwards that demonstrated preliminary safety, feasibility, and efficacy of LBBP.5,6,7 LBBP became an attractive alternative to His bundle pacing because of the lower thresholds, improved lead stability, and higher procedural success rates. When compared against RV pacing in patients requiring a high burden of pacing, LBBP has demonstrated reduced mortality, HF admissions, and need for upgrade to a BiV device.8 In a small, non-randomized patient sample, LBBP showed greater improvement in LV ejection fraction (EF) compared to BiV pacing.9 Most notably, perhaps, is the astonishing rate of lead placement success, with achievement rates reported as high as 98% in sizable studies.6Differences between the two forms of CSP were apparent from the beginning, including in the appropriate QRS morphology after a successful case. Unlike PHBP, LBBP did not reproduce the native QRS and the QRS duration was often greater than at baseline (Figure 2). The arena of LBBP underwent a notable shift in the Fall of 2021 when Wu et al. proposed new criteria to prove LBBP.10 In this study, they presented an exquisite display of fundamental electrophysiologic principles by using mapping catheters positioned on the His and LV septum during LBB lead placement. Through this painstaking work, they clarified the difference between true LBBP and left bundle branch area pacing (LBBAP), which can incorporate both LBBP and left ventricular septal pacing (LVSP). In their proposed framework, without the presence of a His or LV septum mapping catheter, output dependent QRS transition from non-selective (NS-LBBP) to selective-LBBP (S-LBBP) or LVSP is necessary to prove LBBP and had a sensitivity and specificity of 100%.The present study by Shimeno et al, published in the current issue of the Journal of Cardiovascular Electrophysiology , is the first known effort to document achievement rates of LBBP by utilizing the modified criteria proposed by Wu et al.11 The primary finding of the study is that achieving true LBBP with an acceptable pacing threshold is likely harder than previously realized. As expected, there was improvement after a learning curve, but even in the last third of patients enrolled, the achievement rate of LBBP was only 50%. This is dramatically lower than previously reported achievement rates using the original Huang et al. criteria, and it suggests that not all patients in the previously described studies were actually achieving true LBBP. An unknown subset of patients in these studies was likely only achieving LVSP. This is probably due to a prior reliance on indicators such as a paced right bundle branch block (RBBB) pattern, identification of an intrinsic LBB potential, and/or use of V6 R-wave peak time cutoffs (RWPT) without clear output-dependent QRS transition. It is also worth noting that a variety of RWPT cutoffs have been used seemingly arbitrarily as ‘evidence of LBBP’. This presents a major dilemma and highlights the need for a clear set of LBBP criteria to be defined by the collective EP community. Despite these caveats, many of these previous studies did not fully confirm LBBP in their patients, yet the outcomes from these studies were still clinically promising. This raises the obvious question, does obtaining true LBBP matter? Future studies will need to explore the differences in clinical outcomes between true LBBP and LVSP.Secondarily, Shimeno et al. have provided a useful tool in identifying that LBB potential to QRS-onset ≥ 22ms had a specificity of 98% in predicting LBBP.11 This target measure can help future operators ensure proximal enough engagement of the LBB conduction system. Additionally, the group took a close look at validating a RWPT cutoff time for the prediction of LBBP. Unfortunately, a RWPT cutoff of 68 ms (in non-LBBB patients), determined by the ROC curve, was not highly predictive. This runs contrary to previous reports by Wu et al. and Jastrzebski et al., which reported higher predictive value of RWPT cutoffs10,12 Looking at the data surrounding RWPT cutoffs as a collective, it likely should not be used as a primary metric for confirming LBBP due to imperfect sensitivity and specificity, but it may be an alternative if output dependent QRS transition or change in RWPT of ≥10 ms is not observed. Additionally, in the event that capture thresholds are similar between the LBB and the adjacent myocardium, programmed stimulation is an option to try to reveal a QRS transition by exploiting differences in refractory periods.This study also highlighted one of the unique complications of LBBP by demonstrating a high rate of septal perforation. Paradoxically, more perforations were seen with increased experience, likely highlighting that deeper penetration into the septum is often sought as operators become more familiar with the procedure. The long-term clinical implications of this complication are, thus far, unknown.Looking forward, clear guidelines for confirmation of LBBP need to be defined. This is necessary to ensure quality before undertaking multi-center randomized controlled trials to assess LBBP in comparison to current pacing methods. To date, Wu et al. seem to have provided the best framework to achieve this.10 That said, there are concerns given that this has only been validated in 30 patients (and only 9 with LBBB). In an ideal world, these criteria would be validated in a larger population, though the work to accomplish this would be meticulous given the current gold standard of using an LV septal mapping catheter to prove conduction system capture. Shimeno et al. should be congratulated for their effort in putting this framework to practice. In their work, they have demonstrated that achieving true LBBP as defined by Wu et al. may be harder than meets the eye, and this is very important in assessing the practicality of using LBBP as a widespread alternative to other pacing methods.References:Abdelrahman M, Subzposh FA, Beer D, et al. Clinical Outcomes of His Bundle Pacing Compared to Right Ventricular Pacing. J Am Coll Cardiol . 2018;71(20):2319-2330. doi:10.1016/j.jacc.2018.02.048Zanon F, Abdelrahman M, Marcantoni L, et al. Long term performance and safety of His bundle pacing: A multicenter experience. J Cardiovasc Electrophysiol . 2019;30(9):1594-1601. doi:10.1111/jce.14063Huang W, Su L, Wu S, et al. A Novel Pacing Strategy With Low and Stable Output: Pacing the Left Bundle Branch Immediately Beyond the Conduction Block. Can J Cardiol . 2017;33(12):1736.e1-1736.e3. doi:10.1016/j.cjca.2017.09.013Huang W, Chen X, Su L, Wu S, Xia X, Vijayaraman P. A beginner’s guide to permanent left bundle branch pacing. Heart Rhythm . 2019;16(12):1791-1796. doi:10.1016/j.hrthm.2019.06.016Padala SK, Master VM, Terricabras M, et al. Initial Experience, Safety, and Feasibility of Left Bundle Branch Area Pacing: A Multicenter Prospective Study. JACC Clin Electrophysiol . 2020;6(14):1773-1782. doi:10.1016/j.jacep.2020.07.004Su L, Wang S, Wu S, et al. Long-Term Safety and Feasibility of Left Bundle Branch Pacing in a Large Single-Center Study. Circ Arrhythm Electrophysiol . 2021;14(2):e009261. doi:10.1161/CIRCEP.120.009261Huang W, Wu S, Vijayaraman P, et al. Cardiac Resynchronization Therapy in Patients With Nonischemic Cardiomyopathy Using Left Bundle Branch Pacing. JACC Clin Electrophysiol . 2020;6(7):849-858. doi:10.1016/j.jacep.2020.04.011Sharma PS, Patel NR, Ravi V, et al. Clinical outcomes of left bundle branch area pacing compared to right ventricular pacing: Results from the Geisinger-Rush Conduction System Pacing Registry. Heart Rhythm . 2022;19(1):3-11. doi:10.1016/j.hrthm.2021.08.033Wu S, Su L, Vijayaraman P, et al. Left Bundle Branch Pacing for Cardiac Resynchronization Therapy: Nonrandomized On-Treatment Comparison With His Bundle Pacing and Biventricular Pacing. Can J Cardiol . 2021;37(2):319-328. doi:10.1016/j.cjca.2020.04.037Wu S, Chen X, Wang S, et al. Evaluation of the Criteria to Distinguish Left Bundle Branch Pacing From Left Ventricular Septal Pacing. JACC Clin Electrophysiol . 2021;7(9):1166-1177. doi:10.1016/j.jacep.2021.02.018Shimeno K, Tamura S, Hayashi Y, et al. Achievement Rate and Learning Curve of Left Bundle Branch Capture in Left Bundle Branch Area Pacing Procedure Performed to Demonstrate Output-Dependent QRS Transition.J Cardiovasc Electrophysiol . 2022Jastrzębski M, Kiełbasa G, Curila K, et al. Physiology-based electrocardiographic criteria for left bundle branch capture. Heart Rhythm . 2021;18(6):935-943. doi:10.1016/j.hrthm.2021.02.021Figure LegendsFigure 1: Permanent His Bundle PacingPanel A: A 12-lead electrocardiogram (EKG) shows baseline conduction in a patient with exertional intolerance. The PR interval is markedly prolonged and, with exercise, this patient developed AV block. A permanent His-bundle pacemaker was implantedPanel B: An EKG demonstrating permanent His-bundle pacing in the same patient as panel A. Selective His-bundle capture results in reproduction of the intrinsic QRS complex.Figure 2: Non-Selective Left Bundle Branch PacingA 12-Lead electrocardiogram showing non-selective left bundle branch pacing. The paced QRS morphology is not a direct match for native conduction and the QRS duration is longer than at baseline. However, conduction system capture was confirmed with an output dependent QRS morphology change.FiguresFigure 1: Permanent His-Bundle Pacing

Background: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y12 receptor (P2Y12R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients which in emergency situations requires platelet transfusion although there is ongoing debate on its effectiveness following ticagrelor therapy. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y12R. Methods: Studies were performed in human platelets with both P2Y12R-stimulated GTPase activity and platelet aggregation assessed. Cell-based bioluminescence resonance energy transfer (BRET) assays were also undertaken to assess G protein subunit activation downstream of P2Y12R activation. Results: Initial studies revealed a range of P2Y12R ligands including ticagrelor displayed inverse agonist activity at the P2Y12R. Of these only ticagrelor was resistant to wash-out. In both human platelets and cell-based assays, washing failed to reverse ticagrelor-dependent inhibition of ADP-stimulated P2Y12R function in contrast to other P2Y12R antagonists. The P2Y12R agonist 2MeSADP, which was also resistant to wash-out, was able to effectively compete with ticagrelor. In silico docking revealed that ticagrelor and 2MeSADP penetrated more deeply into the orthosteric binding pocket of the P2Y12R than other P2Y12R ligands. Conclusion: Ticagrelor binding to the P2Y12R is prolonged and more akin to that of an irreversible antagonist especially versus the endogenous P2Y12R agonist ADP. This study highlights the potential clinical need for novel ticagrelor reversal strategies in patients with spontaneous major bleeding and bleeding associated with urgent invasive procedures.

Introduction: Assessment of and intervention for sleep-disordered breathing and malnutrition are related to respiratory management for preventing recurrent respiratory tract infections (RRTIs) and acute respiratory failure (ARF) in children with spinal muscular atrophy (SMA). However, the specific standard has not been clarified. Purpose: The study aimed to obtain the risk factors and the predictive index for RRTIs and/or ARF in children with SMA. Methods: In this retrospective study, the differences in clinical characteristics in patients with or without RRTIs and ARF were compared, and binary logistic regression analysis was carried out. The best cutoff points of the positive predictive index were obtained. Results: Type 1 (OR = 4.12, 95% CI 1.30-13.07, P =.016) and apnea hypopnea index (AHI) (OR = 1.14, 95% CI 1.05-1.24, P =.001) were risk factors, while body mass index z score (BMIz) (OR = 0.68, 95% CI 0.49-0.94, P =.018) and mean pulse oxygen saturation (MSpO 2) (OR = 0.67, 95% CI 0.50-0.91, P =.010) were protective factors. The sensitivity and specificity of the standard of MSpO 2 < 96% and AHI > 10 events/h or BMIz < -1 with the occurrence of RRTIs and/or ARF were 0.513 and 0.957, respectively. Conclusion: SMA Type 1, BMIz, AHI and MSpO 2 should be used to estimate the risk for RRTI or ARF in children with SMA. MSpO 2 < 96%, and AHI > 10 events/h or BMIz < -1 should be used as the intervention standard.

Chylous ascites following trauma in children is very rare, and to the best of our knowledge, there are very few reports in this regard. Here, we report a 7-year-old girl who was referred to our center with CA after a car accident.

Protein structures are stabilized by several types of chemical interactions between amino acids, which can compete with each other. This is the case of chalcogen and hydrogen bonds formed by the thiol group of cysteine, which can form three hydrogen bonds with one hydrogen acceptor and two hydrogen donors and a chalcogen bond with a nucleophile along the extension of the C-S bond. A survey of the Protein Data Bank shows that hydrogen bonds are about 40-50 more common than chalcogen bonds, suggesting that they are stronger and, consequently, prevail, though not always. It is also observed that frequently a thiol group that forms a chalcogen bond is also involved, as a hydrogen donor, in a hydrogen bond.

The author's intent is to bring one such case to focus wherein just mere lack of knowledge and casual approach towards one's own health having undiagnosed underlying blood coagulation disorder led to catastrophic sequence of events, leaving behind a cautionary learning tale from a loss of life.

A healthy 48-years-old male patient was referred to our department to take radiographs of a displaced implant. Upon radiographic evaluation, it was unveiled that the implant has migrated to the nasal cavity and is trapped under the middle concha. The implant was removed under endoscopy through the right nostril.