Dipetalonema viteae: in vitro blastogenesis of hamster spleen and lymph node cells to phytohemagglutinin and filarial antigens

Hamsters of the randomly bred LAKZ and inbred LSH strains were infected with Dipetalonema viteae, and the in vitro responses of lymph node and spleen lymphocytes to male and female worm antigens and phytohemagglutinin (PHA) were measured by a [³H]-thymidine-uptake assay at various times after infection. The PHA response remained unchanged at the level of controls in infected LAKZ hamsters while LSH hamsters showed a depressed response to the mitogen during late infection. Stimulation of lymph node cells by filarial antigens was maximal in both strains of hamsters at Week 4 postinfection, almost reaching values obtained in PHA stimulated cultures. A similar high lymphocyte transformation reaction was measured after the injection of dead third stage larvae. During transient microfilaremia, when antibody titers reached a maximal level, the lymphocyte reactivity to filarial antigens decreased drastically and only occasionally was demonstrated in hamsters 20 and 30 weeks after infection. No correlation between lymphocyte reactivity and parasitological findings (worm load or intensity and duration of microfilaremia) could be demonstrated. The cellular unresponsiveness to filarial antigens was further analyzed in chronically infected LAKZ hamsters. No suppressor cells could be found in lymphocyte suspensions of nonresponding hamsters. A challenge infection did not restore lymphocyte reactivity. Serum of chronically infected hamsters caused marked inhibition when added to filarial antigen-sensitive lymphocytes. Lymphocytes from hamsters with a mixed D. viteae and Schistosoma mansoni infection responded as well to soluble schistosomal egg antigens at Week 30 of a D. viteae infection as lymphocytes from hamsters infected with S. mansoni alone. The humoral immune response to schistosomal antigens, however, was significantly lower in animals with a mixed infection.     

Zika virus spreads through infection of lymph node-resident macrophages

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2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.     

Choosing Optimal Microcarcinoma Patients for Active Surveillance Study (Compass): Effectiveness Evaluation of a Preoperative Clinical Framework

ObjectiveActive surveillance (AS) is a management alternative for patients with low-risk papillary thyroid microcarcinoma (PTMC). To decide the best candidates for AS, clinicians can use a framework to classify PTMC patients as ideal, appropriate, or inappropriate. This study aimed to explore the correlation between the framework categories and surgical pathology.MethodsThis multicenter retrospective study was conducted between 2014 and 2016. We included 1997 patients who underwent thyroid surgery for the first time due to suspected PTMC and were confirmed as PTMC by postoperative pathology. The consistency of modified preoperative risk stratification and the pathologic condition were evaluated using a consistency ratio and the Kappa coefficient. Stratified analysis was also performed to test consistency in different age groups.ResultsBased on the decision-making framework, 558 (27.9%) patients could receive AS while 810 (40.6%) patients did not require immediate surgery according to the actual postoperative pathology. The sensitivity, false-positive rate, specificity, false-negative rate, and consistency rate were 82.39%, 56.91%, 43.09%, 17.61%, and 66.45%, respectively. The Kappa value was 0.268. Stratified analysis showed that the sensitivity was 87.7% among patients aged 18 to 59 years. In the group aged ≥60 years, the specificity was up to 87.5%, but the sensitivity was low.ConclusionThe results of the modified risk-stratified clinical decision-making framework did not have a high consistency with the postoperative results. However, the framework showed a good effect in selecting patients for immediate surgery in the younger group and patients for AS in the older group.     

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer

ObjectiveTo compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC.MethodsA total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups.ResultsOf the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037).ConclusionAlthough preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.     

The role of para-aortic nodal irradiation in cervical cancer

The current standard of care for locally advanced cervical cancer is whole pelvis and para-aortic radiation when indicated, delivered concomitantly with chemotherapy and brachytherapy. Para-aortic node involvement is a predictor of survival in locally advanced disease but presence of metastases is difficult to determine because the currently available imaging methods lack enough sensitivity to be able to detect accurately para-aortic metastases when surgical staging is not feasible. The objective of this review is to describe the current status of para-aortic lymph node irradiation in locally advanced cervical cancer. It includes analysis of the diagnostic imaging and surgical approaches for assessment of para-aortic lymph node dissemination, together with indications for radiotherapy and radiotherapeutic techniques.     

Recalcitrant Grain Legume Vigna radiata, Mung Bean, Made to Regenerate on Change of Hormonal and Cultural Conditions

Induction of shoots is possible from cotyledonary node of Vigna radiata seedlings by culturing them on a low concentration of thidiazuron (TDZ 1.0 μM). Interestingly, flooding the seedlings with the same concentration of TDZ considerably enhanced this effect and also led to the induction of shoots from the epicotyl – an unexpected and significant finding. Even plain mineral medium evoked this response on flooding. But seedlings raised on TDZ and flooding with mineral medium was not so effective. Instead seedlings raised on TDZ (1.0 μM) medium as well as flooding with it had synergistic effect. In a comparative study TDZ (1.0 μM) was found to be more effective than BAP (10 μM). Marked repression of root formation and expansion of shoot–apex were noted in seedlings raised on TDZ or BAP, particularly in cultures that were flooded.     

Assessing the sensitivity of divergence time estimates to locus sampling,calibration points,and model priors in a RAD-seq phylogeny of Carex section Schoenoxiphium

Restriction site-associated DNA sequencing (RAD-seq) and related methods have become relatively common approaches to resolve species-level phylogeny. It is not clear, however, whether RAD-seq data matrices are well suited to relaxed clock inference of divergence times, given the size of the matrices and the abundance of missing data. We investigated the sensitivity of Bayesian relaxed clock estimates of divergence times to alternative analytical decisions on an empirical RAD-seq phylogenetic matrix. We explored the relative contribution of secondary calibration strategies, amount of missing data, and the data partition analyzed to overall variance in divergence times inferred using BEAST MCMC analyses of Carex section Schoenoxiphium (Cyperaceae)—a recent radiation for which we have nearly complete species sampling of RAD-seq data. The crown node for Schoenoxiphium was estimated to be 15.22 (9.56–21.18) Ma using a single calibration point and low missing data, 11.93 (8.07–16.03) Ma using multiple calibration points and low missing data, and 8.34 (5.41–11.22) using multiple calibrations but high missing data. We found that using matrices with more than half of the individuals with missing data inferred younger mean ages for all nodes. Moreover, we have found that our molecular clock estimates are sensitive to the positions of the calibration(s) in our phylogenetic tree (using matrices with low missing data), especially when only a single calibration was applied to estimate divergence times. These results argue for sensitivity analyses and caution in interpreting divergence time estimates from RAD-seq data.     

Generation of cardiomyocytes by atrioventricular node cells in long-term cultures

Turnover of cardiac pacemaker cells may occur during the lifetime of the body, and we recently raised the hypothesis that specialized cardiac cells have in common the potential to generate cardiomyocytes from fibroblasts. To examine this hypothesis, we analyzed the ability of atrioventricular node cells (AVNCs) to generate functional cardiomyocytes in long-term culture. AVNCs were isolated from adult guinea pig hearts and cultured for up to three weeks. Under phase-contrast microscopic observation over time, it was found that within a week, a number of fibroblasts gathered around the AVNCs and formed cell clusters, and thereafter the cell clusters started to beat spontaneously. The nascent cell clusters expanded their area gradually by three weeks in culture and expressed specific cardiac genes and proteins. Maturation of newly formed cardiomyocytes seems to be slow in cultures of AVNCs compared with those of sinoatrial node cells. Stimulation of muscarinic receptors with acetylcholine induced a beating rate decrease which was blocked by atropine, and activation of adenylate cyclase activity with forskolin increased the beat rate, while stimulation of beta adrenoceptors by isoproterenol had no effect. These results indicate that AVNCs form a cluster of cells with properties of functional cardiomyocytes and provide evidence to support the hypothesis.     

Developmental processes and the evolution of plant clonality

A common type of clonal plant grows limited ramets that are connected by modified stems. Three major developmental processes are required for this clonality: the differentiation of specialized plagiotropic stems which act as spacers, the localized formation of adventitious roots, and a limitation of vertical development which is coupled with repeated rejuvenation. Intermediate forms, in which one of these processes occurs without the others, are readily found. Studies of apical initiation and differentiation in a-clonal plants suggest mechanisms for these processes, based on modified hormonal correlations and maturation processes within apices. The consideration of developmental processes, which has been relatively neglected, can therefore be a key to understanding the possibilities and limitations of clonal evolution. For example, comparative developmental studies point to convergent or parallel evolution, in which a similar outcome has been based on different developmental mechanisms. A consideration of developmental processes also throws new light on clonal organization and raises concrete questions that are amenable to experimental work.