Epidermal distribution of tetrodotoxin-rich cells in newly hatched larvae of Takifugu spp.

Pufferfish of the genus Takifugu possess tetrodotoxin (TTX), known as "pufferfish toxin" and it is believed that pufferfish eggs and newly hatched larvae utilize TTX as a defensive substance against predators. However, the mechanism for the placement of TTX to specific cells on the larval body surface during the developmental process remains unknown. In this study, we clarify the distribution and characteristics of TTX-rich cells. We performed whole-mount immunohistochemistry (IHC) using anti-TTX monoclonal antibody on larvae of two pufferfish species, Takifugu rubripes and Takifugu alboplumbeus, just after hatching. This allowed observation of the TTX location and compared it with those of wheat germ agglutinin (WGA)-positive (periodic acid-Schiff (PAS)-positive) cells for mucous cells and IHC using anti-Na+/K+-ATPase (NKA) monoclonal antibody for ionocytes. As a result, uniformly scattered localization of TTX-rich cells was commonly observed in the epidermis of the larvae of the two Takifugu species. TTX-rich cells were WGA-negative (PAS-negative) and structurally distinct from NKA-positive cells, suggesting that TTX-rich cells are unreported small cells unique to pufferfish skin, but not mucous cells nor ionocytes.

Bridging clinical informatics and implementation science to improve cancer symptom management in ambulatory oncology practices: experiences from the IMPACT consortium.

Objectives: To report lessons from integrating the methods and perspectives of clinical informatics (CI) and implementation science (IS) in the context of Improving the Management of symPtoms during and following Cancer Treatment (IMPACT) Consortium pragmatic trials. Materials and Methods: IMPACT informaticists, trialists, and implementation scientists met to identify challenges and solutions by examining robust case examples from 3 Research Centers that are deploying systematic symptom assessment and management interventions via electronic health records (EHRs). Investigators discussed data collection and CI challenges, implementation strategies, and lessons learned. Results: CI implementation strategies and EHRs systems were utilized to collect and act upon symptoms and impairments in functioning via electronic patient-reported outcomes (ePRO) captured in ambulatory oncology settings. Limited EHR functionality and data collection capabilities constrained the ability to address IS questions. Collecting ePRO data required significant planning and organizational champions adept at navigating ambiguity. Discussion: Bringing together CI and IS perspectives offers critical opportunities for monitoring and managing cancer symptoms via ePROs. Discussions between CI and IS researchers identified and addressed gaps between applied informatics implementation and theory-based IS trial and evaluation methods. The use of common terminology may foster shared mental models between CI and IS communities to enhance EHR design to more effectively facilitate ePRO implementation and clinical responses. Conclusion: Implementation of ePROs in ambulatory oncology clinics benefits from common understanding of the concepts, lexicon, and incentives between CI implementers and IS researchers to facilitate and measure the results of implementation efforts.

An evaluation of the effectiveness of platelet rich plasma epidural injections for low back pain suspected to be of disc origin - A pilot study with one-year follow-up.

Summary of background data: Low back pain of disc origin is common yet challenging to treat. Intradiscal platelet rich plasma (PRP) has been advocated, but is associated with risk of discitis. Epidural PRP is less invasive and avoids this risk. Few studies exist evaluating effectiveness and safety of epidural PRP for discogenic low back pain without radiculopathy and the follow-up of the studies tends to be short. Objective: Prospectively evaluate for 12 months the effectiveness of PRP epidural injections for patients with low back pain without radiculopathy, suspected to be of disc origin. Methods: 11 consecutive patients with refractory low back pain suspected to be of disc origin (compatible clinical assessment; negative lumbosacral medial branch blocks (MBBs) and/or magnetic resonance imaging (MRI) with high intensity zone (HIZ), Modic 1 or 2 changes) participated. Each underwent one (n = 5) or two (n = 6) epidural injections (caudal or interlaminar). The PRP was leukocyte/red cell depleted with an average platelet concentration of ∼2X whole blood. Numerical rating scale (NRS), Pain Disability Quality-Of-Life Questionnaire (PDQQ) score, Oswestry Disability Index (ODI) score, effect on analgesic intake, treatment satisfaction and endorsement were recorded prior to and at 3, 6 and 12-months post-treatment. Results: Significant improvements in pain and disability were documented post-treatment. Pre-, 3, 6, and 12-month post mean(sd) NRS scores were 7.8(1.8), 5.8(2.7), 5.1(2.5), 4.9(2.8) respectively (F = 7.2; p = 0.002). At 12 months post PRP epidural, the mean improvement in NRS was 36%, 36% had experienced ≥50% pain relief (95% confidence interval (CI): 2%, 70%), and 73% achieved minimal clinically important differences (MCID) (95% CI: 41%, 100%). Similar magnitude improvements in disability (PDQQ and ODI) were documented. At 1-year post, 50% of analgesic users had reduced intake, 91% were satisfied with the treatment and would recommend the procedure to family and friends. No complications were reported. Discussions/conclusion: This pilot project suggests that PRP epidural injections provide modest yet significant improvements in pain and disability that lasts at least 12 months in patients with low back pain suspected to be of disc origin. Additional research including larger sample size and robust study design is encouraged.

Navigating the Ethical Challenges of Clinical Decision-Making for Patients with Mental Illness Presenting with Self-Inflicted Burns.

Complex ethical considerations can arise when patients with severe, persistent mental illness (SPMI) present with critical illness resulting from self-injury. This article presents two clinical cases in which a patient with SPMI was admitted with severe injuries following self-inflicted burns, with substantial impact on their anticipated quality of life and challenges directing their medical care. In both cases, the medical teams held discussions with surrogate decision-makers in order to evaluate the patient's minimal acceptable quality of life and make medical decisions that best reflected the patient's voice and goals. These cases underscore the importance of advance care planning in SPMI, particularly the appointment of a surrogate decision-maker, and highlight the moral distress that can arise among surgical teams and trainees while caring for patients with illness resulting from self-harm. This article offers a framework for approaching decision-making in critical illness resulting from self-harm for patients with SPMI.

Increased behavioural inhibition and decreased behavioural activation in whiplash-associated disorders: Associations with health outcomes.

BACKGROUND: Motivation can be investigated with the BIS (Behavioural Inhibition System)/BAS (Behavioural Activation System) scale. BAS regulates the motivation to approach goal-oriented outcomes, particularly rewarding stimuli and situations, while BIS regulates escape and avoidance of unpleasant outcomes. Chronic whiplash-associated disorders (WAD) is a heterogenous pain condition with known alterations in motivated behaviour. The study aimed (1) to investigate the relationship between BIS/BAS, and pain and disability with quality of life and psychological measures in chronic WAD; (2) to determine if BIS and/or BAS mediate the relationships between pain, disability, and psychological symptoms and quality of life. METHODS: 254 chronic WAD patients participated in the study. Outcome measures were assessed using self-report questionnaires. BIS/BAS scores were compared to published normative data. Differences in health outcomes for participants within/outside normative 95% confidence intervals were compared and correlations with health measures tested. Mediation models explored bi-directional associations between stress, anxiety, depression, post-traumatic stress severity, pain catastrophizing, and quality of life with pain and disability. RESULTS: Participants who exceeded normative 95% confidence intervals for BIS demonstrated higher scores for pain interference, disability and all mental health measures. No mediating role of BIS/BAS on the relation between pain and disability with quality of life and health outcomes could be confirmed. CONCLUSIONS: A comparatively large proportion of the sample exceeded the 95% confidence interval for BIS and BAS scores with associations of these scores with health outcomes, but altered motivation to approach goal-oriented outcomes appears to play only a subordinate role in chronic WAD. SIGNIFICANCE STATEMENT: In line with current theories, we found a large proportion (30%-50%) of patients with whiplash-associated disorders (WAD) showing signs of altered function in the Behavioural Inhibition System (BIS) and Behavioural Activation System (BAS) suggesting altered reward processing and motivation in these patients. While such altered functions showed associations with pain interference, disability and all mental health measures, reward processing could no be demonstrated as a pathogenetically relevant factor in chronic WAD patients.

Cytologic findings in mandibular and superficial cervical lymph nodes of dogs with thyroid carcinoma.

Objective: To describe cytologic findings from mandibular and superficial cervical lymph nodes in dogs with thyroid carcinoma and to determine prognostic factors associated with lymph node metastasis. Animals: A total of 71 client-owned dogs with confirmed thyroid carcinoma that had cytologic results from at least 1 mandibular or superficial cervical lymph node between 2010 and 2020. Procedure: Medical records from 2 referral veterinary hospitals were retrospectively reviewed. Cytology of lymph nodes was reviewed for presence of metastasis by diplomates of the American College of Veterinary Pathologists. Thyroid tumor diameter and volume, tumor fixation, bilateral location, vascular invasion, and stage were recorded to determine effects on nodal metastasis. Results: A total of 154 lymph nodes (104 mandibular and 50 superficial cervical lymph nodes) from 71 dogs were cytologically evaluated, and 1/154 (0.6%) and 2/154 (1.3%) lymph nodes were noted to be definitively metastatic or probably metastatic, respectively. Given the infrequent rate of nodal metastasis (1.9% or less), statistical analysis of potential prognostic variables was not completed. Conclusion and clinical relevance: Routine lymph node cytology of mandibular and superficial cervical lymph nodes appeared to be of low yield when assessing for metastasis of canine thyroid carcinomas. The medial retropharyngeal and deep cervical lymph nodes should continue to be evaluated as they appeared to have higher metastatic rates, based on historic reports. Additional studies are needed to determine prognostic factors associated with lymph node metastasis and effects on patient survival.

Résultats cytologiques dans les ganglions lymphatiques cervicaux mandibulaires et superficiels de chiens atteints d'un carcinome thyroïdien. Objectif: Décrire les résultats cytologiques obtenus des ganglions lymphatiques mandibulaires et cervicaux superficiels chez des chiens atteints d'un carcinome thyroïdien et déterminer les facteurs pronostiques associés aux métastases ganglionnaires. Animaux: Un total de 71 chiens appartenant à des clients atteints d'un carcinome thyroïdien confirmé avec des résultats cytologiques d'au moins un ganglion lymphatique cervical mandibulaire ou superficiel entre 2010 et 2020. Procédure: Les dossiers médicaux de 2 hôpitaux vétérinaires de référence ont été examinés rétrospectivement. La cytologie des ganglions lymphatiques a été examinée pour détecter la présence de métastases par des diplomates de l'American College of Veterinary Pathologists. Le diamètre et le volume de la tumeur thyroïdienne, la fixation de la tumeur, la localisation bilatérale, l'invasion vasculaire et le stade ont été notés pour déterminer les effets sur les métastases ganglionnaires. Résultats: Au total, 154 ganglions lymphatiques (104 ganglions lymphatiques mandibulaires et 50 ganglions lymphatiques cervicaux superficiels) provenant de 71 chiens ont été évalués par cytologie, et 1/154 (0,6 %) et 2/154 (1,3 %) ganglions lymphatiques ont été notés comme définitivement métastatiques ou probablement métastatiques, respectivement. Compte tenu du taux peu fréquent de métastases ganglionnaires (1,9 % ou moins), l'analyse statistique des variables pronostiques potentielles n'a pas été complétée. Conclusion et pertinence clinique: La cytologie de routine des ganglions lymphatiques mandibulaires et cervicaux superficiels semblait être de faible rendement lors de l'évaluation des possibilités de métastases des carcinomes thyroïdiens canins. Les ganglions lymphatiques rétropharyngés médiaux et cervicaux profonds doivent continuer à être évalués car ils semblent présenter des taux métastatiques plus élevés, sur la base des rapports historiques. Des études supplémentaires sont nécessaires pour déterminer les facteurs pronostiques associés aux métastases ganglionnaires et les effets sur la survie des patients.(Traduit par Dr Serge Messier).

The Use of Remimazolam During Awake Craniotomy for Seizure Foci Resection in Adolescents: A Case Series.

Remimazolam is a novel benzodiazepine with sedative, anxiolytic, and amnestic properties similar to midazolam. Metabolism by tissue esterases results in a short clinical half-life of 5 - 10 min and a limited context sensitive half-life. We present initial retrospective clinical experience with the use of remimazolam as an intraoperative adjunct to sedation during awake craniotomy in a cohort of three adolescent patients. A remimazolam infusion was added to a combination of dexmedetomidine and remifentanil to deepen the level of sedation during surgical incision, craniotomy, duraplasty, and surgical dissection for exposure of the seizure foci. The remimazolam infusion was discontinued 30 min prior to the planned awake assessments and electrophysiology testing. The patients emerged calmly and were able to follow commands for intraoperative testing. Our anecdotal experience supports the efficacy of remimazolam for awake craniotomy and tumor resection using a standard asleep-awake-asleep technique. We noted adequate sedation, maintenance of spontaneous respiration, rapid awakening, and no limitations to intraoperative neuromonitoring or awake assessment in our three patients.

Tissue Localization of Tetrodotoxin in the Flatworm Planocera multitentaculata (Platyhelminthes: Polycladida).

Tetrodotoxin (TTX), a pufferfish toxin, is a highly potent neurotoxin that has been found in a wide variety of animals. The TTX-bearing flatworm Planocera multitentaculata possesses a large amount of TTX and is considered responsible for the toxification of TTX-bearing animals such as pufferfish (Takifugu and Chelonodon) and the toxic goby Yongeichthys criniger. However, the mechanism underlying TTX accumulation in flatworms remains unclear. Previous studies have been limited to identifying the distribution of TTX in multiple organs, such as the digestive organs, genital parts, and the remaining tissues of flatworms. Here, we performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis and immunohistochemical staining using a monoclonal anti-TTX antibody to elucidate the detailed localization of TTX in the tissues and organs of the flatworm P. multitentaculata. Immunohistochemical staining for P. multitentaculata showed that TTX-specific signals were detected not only in the ovaries and pharynx but also in many other tissues and organs, whereas no signal was detected in the brain, Lang's vesicle, and genitalia. In addition, combined with LC-MS/MS analysis, it was revealed for the first time that TTX accumulates in high concentrations in the basement membrane and epidermis. These findings robustly support the hypotheses of "TTX utilization protection from predators."

Can ultrasound-guided medial branch blocks be used to select patients for cervical facet joint radiofrequency neurotomy? - A matched retrospective cohort validation study.

BACKGROUND: Medial branch blocks are used to select patients for cervical facet joint radiofrequency neurotomy (CRFN). Blocks are typically performed under fluoroscopic guidance (FLB). The validity of ultrasound guided blocks (USB) is not well established. No prior research has compared cervical USB versus FLB validity using CRFN outcome as the criterion standard. OBJECTIVE: To evaluate cervical USB versus FLB validity using CRFN outcome as the criterion standard. METHODS: Demographic and outcome data were extracted from the EMRs of two affiliated MSK pain management clinics for all patients between 2015 and 2023 inclusive who had cervical USB leading to CRFN. CRFN outcomes of each USB patient were compared to a matched FLB patient from the RFN outcome database of the same clinics. Matching variables included patient age, sex, pain duration, diagnostics/prognostic block paradigm and CRFN number. Each patient completed a NRS pain score and Pain Disability Quality-of-Life Questionnaire (PDQQ) just before and 3-months post-CRFN. At repeat CRFN, patients provided a retrospective estimate of the duration and average magnitude (%) of relief following the CRFN. RESULTS: USB and FLB groups were comprised of 27 patients (58 RFNs) and 38 patients (58 RFNs) respectively. Post RFN NRS pain severity and PDQQ-S scores demonstrated comparable (p > 0.05) absolute improvements, proportion of patients achieving ≥50% improvement, and attainment of MCID. Retrospective estimates of pain relief magnitude and duration were also comparable. CONCLUSIONS: This study finds cervical USB and FLB to be comparably valid as defined by their ability to predict CRFN outcome. Within the limitations of operator competence, USB can be used to select patients for CRFN.

Hemoglobin scavenger receptor CD163 as a potential biomarker of hemolysis-induced hepatobiliary injury in sickle cell disease.

Sickle cell disease (SCD)-associated chronic hemolysis promotes oxidative stress, inflammation, and thrombosis leading to organ damage, including liver damage. Hemoglobin scavenger receptor CD163 plays a protective role in SCD by scavenging both hemoglobin-haptoglobin complexes and cell-free hemoglobin. A limited number of studies in the past have shown a positive correlation of CD163 expression with poor disease outcomes in patients with SCD. However, the role and regulation of CD163 in SCD-related hepatobiliary injury have not been fully elucidated yet. Here we show that chronic liver injury in SCD patients is associated with elevated levels of hepatic membrane-bound CD163. Hemolysis and increase in hepatic heme, hemoglobin, and iron levels elevate CD163 expression in the SCD mouse liver. Mechanistically we show that heme oxygenase-1 (HO-1) positively regulates membrane-bound CD163 expression independent of nuclear factor erythroid 2-related factor 2 (NRF2) signaling in SCD liver. We further demonstrate that the interaction between CD163 and HO-1 is not dependent on CD163-hemoglobin binding. These findings indicate that CD163 is a potential biomarker of SCD-associated hepatobiliary injury. Understanding the role of HO-1 in membrane-bound CD163 regulation may help identify novel therapeutic targets for hemolysis-induced chronic liver injury.

Social determinants of health in adults with whiplash associated disorders.

OBJECTIVES: Although it is well-known that chronic diseases need to be managed within the complex biopsychosocial framework, little is known about the role of sociodemographic features in adults with whiplash-associated disorders (WAD) and their association with health outcomes. The aim of this study was to investigate the association between various sociodemographic features (age, sex, ethnicity, education, working, marriage, caring for dependents, and use of alcohol and drugs) and health outcomes (pain, disability, and physical/mental health-related quality of life) in WAD, both through their individual relationships and also via cluster analysis. METHODS: Independent t-tests and Kruskal-Wallis tests (with Mann-Whitney tests where appropriate) were used to compare data for each health outcome. Variables demonstrating a significant relationship with health outcomes were then entered into two-step cluster analysis. RESULTS: N = 281 participated in study (184 females, mean (±SD) age 40.9 (±10.7) years). Individually, level of education (p = 0.044), consumption of non-prescribed controlled or illegal drugs (p = 0.015), and use of alcohol (p = 0.008) influenced level of disability. Age (p = 0.014), marriage status (p = 0.008), and caring for dependents (p = 0.036) influenced mental health quality of life. Collectively, two primary clusters emerged, with one cluster defined by marriage, care of dependents, working status, and age >40 years associated with improved mental health outcomes (F 1,265 = 10.1, p = 0.002). DISCUSSION: Consistent with the biopsychosocial framework of health, this study demonstrated that various sociodemographic features are associated with health outcomes in WAD, both individually and collectively. Recognizing factors that are associated with poor health outcomes may facilitate positive outcomes and allow resource utilization to be tailored appropriately.

Digital Navigator Training to Increase Access to Mental Health Care in Community-Based Organizations.

Providing human support for users of behavioral health technology can help facilitate the necessary engagement and clinical integration of digital tools in mental health care. A team conducted digital navigator training that taught participants how to promote patrons' digital literacy, evaluate and recommend health apps, and interpret smartphone data. The authors trained 80 participants from 21 organizations, demonstrating this training's feasibility, acceptability, and need. Case studies explore the implementation of this training curriculum. As technology's potential in mental health care expands, training can empower digital navigators to ensure that the use of digital tools is informed, equitable, and clinically relevant.

Extrapleural pneumonectomy for sarcoma: Outcomes of adult patients at a specialized center.

BACKGROUND: Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center. METHODS: Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications. RESULTS: Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy. CONCLUSIONS: In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.

Atrial fibrillation ablation during robotic mitral valve surgery: a systematic review and meta-analysis.

Background: Atrial fibrillation (AF) is the most common arrhythmia, and is also associated with mitral valve disease. Although the benefits of robotic mitral valve surgery are well documented, literature combining robotic mitral valve surgery with AF surgery remains sparse. The aim of this systematic review and meta-analysis is to evaluate the evidence assessing the efficacy and safety of AF ablation during robotic mitral valve surgery. Methods: Five electronic databases were searched from inception to April 2023. All studies reporting the primary outcome, freedom from AF, for patients with a history of AF undergoing robotic mitral valve surgery and AF ablation were identified. Studies which included mixed cohorts, or patients who did not undergo robotic mitral valve surgery were excluded. Relevant data were extracted and a meta-analysis of proportions was conducted using a random-effects model. Results: Five studies were included with a total of 241 patients. Cohort sizes ranged from 11 to 94 patients. The aggregate mean age was 58.5 years and patients had persistent AF (71.1%). All five studies utilised the da Vinci® Surgical System, and performed variable lesion sets. The freedom from AF was 88.1% at a weighted mean follow-up of 6.9 months. There were two mortalities (0.8%), two patients required conversion to sternotomy (1.4%) and eight required a permanent pacemaker (3.7%). Conclusions: AF ablation with robotic mitral valve surgery can be performed with adequate short-term efficacy and safety profile. Current evidence on AF ablation and robotic mitral valve surgery is limited to low-quality retrospective data with inherent selection bias. Further large-scale prospective data is required to verify these results.

The outcomes of concomitant catheter ablation in non-mitral valve cardiac surgery-a systematic review and meta-analysis of the literature.

Background: Atrial fibrillation (AF) is the most common form of cardiac arrythmia, with a key importance in the perioperative setting of cardiac surgery. In recent years, the question as to whether pre-existent AF should be treated concomitantly when undergoing cardiac surgery has been heatedly debated. This systematic review and meta-analysis sought to delineate the outcomes of patients undergoing concomitant AF ablation procedures alongside cardiac surgery. Methods: The methods for this systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Four databases were searched, ultimately yielding 22 papers for inclusion, using appropriate search terminology. Meta-analysis using proportions or means, as appropriate, were applied. Kaplan-Meier curves were digitized and aggregated using previously reported and validated techniques. Results: A total of 9,428 patients (67% male) were identified across the study period as having received non-mitral cardiac surgery and concomitant AF ablation procedures. On actuarial assessment, freedom from AF was found to be 93%, 88%, 85%, 82%, and 79% at 1 through to 5 years, respectively. Freedom from mortality was found to be 94%, 93%, 91%, 90%, and 87% at 1 through to 5 years, respectively. Conclusions: This review demonstrated excellent freedom from AF out to a long-term follow-up of 5 years. Freedom from mortality was also encouraging. Emerging data are increasingly illustrating that in this patient cohort, concurrent treatment of pre-existent AF with cardiac and/or valvular disease at the point of operation should be the standard of care. Robust data in the form of randomized control trials will hopefully solidify this assertion.

Surgical ablation of atrial fibrillation during mitral valve surgery: a systematic review and meta-analysis.

Background: Atrial fibrillation (AF) is a common tachyarrhythmia, affecting approximately 33 million people worldwide, and is frequently associated with mitral valve disease. Surgical ablation during mitral valve surgery provides an opportune circumstance for arrhythmia correction. The results of recent randomized trial data are promising, demonstrating both safety and efficacy. The aim of this systematic review is to report the efficacy and morbidity of concomitant surgical ablation for AF during mitral valve surgery. Methods: Five electronic databases were searched from inception to March 2023. All studies reporting the primary outcome, freedom from AF (FFAF), for patients with a history of AF undergoing concomitant mitral valve surgery were identified. Studies with patient cohorts less than 100 were excluded. Relevant data were extracted and a meta-analysis of proportions was conducted using a random-effects model. Survival data were pooled from original Kaplan-Meier curves and reconstructed, reporting aggregate FFAF and survival. Results: Thirty-six studies with a total of 8,340 patients were included in the systematic review. All 36 papers reported postoperative FFAF with a pooled result of 76.9% [95% confidence interval (CI): 73.8-79.9%] at a weighted mean follow-up of 40.2 months, however this result was associated with significant heterogeneity (I2=89%). A total of 31 studies reported postoperative short-term mortality, with a pooled result of 1.68% (95% CI: 1.15-2.29%). Aggregate survival at 1 to 5 years was 93.7%, 92.5%, 91.3%, 89.4%, and 87%, respectively, and aggregate FFAF for 1 to 5 years was 90.2%, 83.5%, 79.5%, 76.4% and 73.2%, respectively. Conclusions: Evaluation of the evidence suggests that concomitant ablation for AF during mitral valve surgery is both safe and efficacious. The results were associated with significant heterogeneity, reflective of variable institutional protocols, patient characteristics, and lesion sets. Randomized data with longer term follow-up would help validate these results.

Mid-to-long-term recurrence of atrial fibrillation in surgical treatment vs. catheter ablation: a meta-analysis using aggregated survival data.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and leading cardiac cause of stroke. Catheter and surgical ablation are two techniques used currently to resolve prolonged disease by limiting the excitatory potential of specific areas of myocardium in the atria of the heart. The aim of this systematic review and meta-analysis was to provide a graphical amalgamation of mid-to-long-term rhythm outcomes following transcatheter and surgical intervention, whether primary or concomitant ablation. Methods: Three electronic databases were selected to complete the initial literature search from inception of records until April 2023. Primary outcomes were freedom from AF at 12 months, as well as long term time-to-event recurrence data. These data were calculated using aggregated Kaplan-Meier curves according to established methods. The secondary outcome was procedural time for each ablation method. Results: Following independent screening, 36 studies were included for analysis. A total of 6,700 patients were followed, of whom 4,863 (72.6%) were male. Freedom from AF recurrence at 1, 3 and 5 years for the surgical cohort was 71.7%, 57.6% and 47.6%, respectively. Comparatively, the recurrence rates of the catheter ablation cohort at 1, 3 and 5 years were 71.5%, 56.5% and 50.3%, respectively. Conclusions: Despite potentially more complex diseases, surgical ablation patients have non-inferior long-term AF recurrence when compared to those undergoing catheter ablation. Recurrence at 12 months as well as procedural time are also similar between these groups. Ultimately, both ablation methods were able to prevent recurrence of AF in approximately 50% of patients at five years following the procedure.

The structural repertoire of Fusarium oxysporum f. sp. lycopersici effectors revealed by experimental and computational studies.

Plant pathogens secrete proteins, known as effectors, that function in the apoplast or inside plant cells to promote virulence. Effector recognition by cell-surface or cytosolic receptors results in the activation of defence pathways and plant immunity. Despite their importance, our general understanding of fungal effector function and recognition by immunity receptors remains poor. One complication often associated with effectors is their high sequence diversity and lack of identifiable sequence motifs precluding prediction of structure or function. In recent years, several studies have demonstrated that fungal effectors can be grouped into structural classes, despite significant sequence variation and existence across taxonomic groups. Using protein X-ray crystallography, we identify a new structural class of effectors hidden within the secreted in xylem (SIX) effectors from Fusarium oxysporum f. sp. lycopersici (Fol). The recognised effectors Avr1 (SIX4) and Avr3 (SIX1) represent the founding members of the Fol dual-domain (FOLD) effector class, with members containing two distinct domains. Using AlphaFold2, we predicted the full SIX effector repertoire of Fol and show that SIX6 and SIX13 are also FOLD effectors, which we validated experimentally for SIX6. Based on structural prediction and comparisons, we show that FOLD effectors are present within three divisions of fungi and are expanded in pathogens and symbionts. Further structural comparisons demonstrate that Fol secretes effectors that adopt a limited number of structural folds during infection of tomato. This analysis also revealed a structural relationship between transcriptionally co-regulated effector pairs. We make use of the Avr1 structure to understand its recognition by the I receptor, which leads to disease resistance in tomato. This study represents an important advance in our understanding of Fol-tomato, and by extension plant-fungal interactions, which will assist in the development of novel control and engineering strategies to combat plant pathogens.

Patient Satisfaction With a Coach-Guided, Technology-Based Mental Health Treatment: Qualitative Interview Study and Theme Analysis.

BACKGROUND: Technology-based mental health interventions address barriers rural veterans face in accessing care, including provider scarcity and distance from the hospital or clinic. webSTAIR is a 10-module, web-based treatment based on Skills Training in Affective and Interpersonal Regulation, designed to treat posttraumatic stress disorder and depression in individuals exposed to trauma. Previous work has demonstrated that webSTAIR is acceptable to participants and effective at reducing symptoms of posttraumatic stress disorder and depression when delivered synchronously or asynchronously (over 5 or 10 sessions). OBJECTIVE: This study explored factors that lead to greater patient satisfaction with webSTAIR, a web-based, coach-guided intervention. METHODS: We analyzed qualitative interview data to identify themes related to patient satisfaction with webSTAIR delivered with synchronous video-based coaching. RESULTS: Four themes emerged from the data: (1) coaching provides accountability and support, (2) self-pacing offers value that meets individual needs, (3) participants like the comfort and convenience of the web-based format, and (4) technical issues were common but not insurmountable. CONCLUSIONS: We conclude that participants valued the accountability, flexibility, and convenience of tech-based interventions with video-delivered coaching.