Characteristics of global naturopathic education, regulation, and practice frameworks: results from an international survey.

BACKGROUND: This descriptive study provides the first examination of global naturopathic education, regulation and practice frameworks that have potential to constrain or assist professional formation and integration in global health systems. Despite increasing public use, a significant workforce, and World Health Organization calls for national policy development to support integration of services, existent frameworks as potential barriers to integration have not been examined. METHODS: This cross-sectional survey utilized purposive sampling of 65 naturopathic organisations (educational institutions, professional associations, and regulatory bodies) from 29 countries. Organizational representatives completed an on-line survey, conducted between Nov 2016 - Aug 2019. Frequencies and cross-tabulation statistics were analyzed using SPSSv.25. Qualitative responses were hand-coded and thematically analysed where appropriate. RESULTS: Sixty-five of 228 naturopathic organizations completed the survey (29% response rate) from 29 of 46 countries (63% country response rate). Most education programs (68%) were delivered via a national framework. Higher education qualifications (60%) predominated. Organizations influential in education were professional associations (75.4%), particularly where naturopathy was unregulated, and accreditation bodies (41.5%) and regulatory boards (33.8%) where regulated. Full access to controlled acts, and to health insurance rebates were more commonly reported where regulated. Attitude of decision-makers, opinions of other health professions and existing legislation were perceived to most impact regulation, which was globally heterogeneous. CONCLUSION: Education and regulation of the naturopathic profession has significant heterogeneity, even in the face of global calls for consistent regulation that recognizes naturopathy as a medical system. Standards are highest and consistency more apparent in countries with regulatory frameworks.

Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivation.

HLA-F represents one of the nonclassical MHC class I molecules in humans. Its main characteristics involve low levels of polymorphism in combination with a restricted tissue distribution. This signals that the gene product executes a specialised function, which, however, is still poorly understood. Relatively little is known about the evolutionary equivalents of this gene in nonhuman primates, especially with regard to population data. Here we report a comparative genetic analysis of the orthologous genes of HLA-F in various great ape, Old World monkey (OWM), and New World monkey (NWM) species. HLA-F-related transcripts were found in all subjects studied. Low levels of polymorphism were encountered, although the length of the predicted gene products may vary. In most species, one or two transcripts were discovered, indicating the presence of only one active F-like gene per chromosome. An exception was provided by a New World monkey species, namely, the common marmoset. In this species, the gene has been subject to duplication, giving rise to up to six F-like transcripts per animal. In humans, great apes, and OWM, and probably the majority of the NWM species, the evolutionary equivalents of the HLA-F gene experienced purifying selection. In the marmoset, however, the gene was initially duplicated, but the expansion was subjected afterwards to various mechanisms of genetic inactivation, as evidenced by the presence of pseudogenes and an array of genetic artefacts in a section of the transcripts.

Heterozygous loss of Rbm24 in the adult mouse heart increases sarcomere slack length but does not affect function.

RNA-binding proteins are key regulators of post-transcriptional processes such as alternative splicing and mRNA stabilization. Rbm24 acts as a regulator of alternative splicing in heart and skeletal muscle, and is essential for sarcomere assembly. Homozygous inactivation of Rbm24 in mice disrupts cardiac development and results in embryonic lethality around E12.5. In the present study, we generated somatic Rbm24 knockout (KO) mice and investigated the effects of reduced levels of Rbm24 in the adult heart. Due to the embryonic lethality of Rbm24 KO mice, we examined cardiac structure and function in adult Rbm24 heterozygotes (HETs). Rbm24 protein expression was 40% downregulated in HET hearts compared to WT hearts. Force measurements on isolated membrane-permeabilized myocytes showed increased sarcomere slack length and lower myofilament passive stiffness in adult Rbm24 HET compared to wildtype cardiomyocytes. As a result of the differences in sarcomere slack length, the relations between force development and sarcomere length differed between WT and Rbm24 HET hearts. No differences in sarcomere structure and titin isoform composition were observed. Likewise, in vivo cardiac function and myocardial structure was unaltered in Rbm24 HET mice compared to WT, at baseline and upon pressure overload after transverse aortic constriction. In conclusion, we generated a somatic Rbm24 KO model and recapitulated the previously reported embryonic phenotype. In adult Rbm24 HET cardiomyocytes we observed increased sarcomere slack length, but no difference in sarcomere structure and cardiac function.

The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update.

BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences.

MHC class I diversity of olive baboons (Papio anubis) unravelled by next-generation sequencing.

The olive baboon represents an important model system to study various aspects of human biology and health, including the origin and diversity of the major histocompatibility complex. After screening of a group of related animals for polymorphisms associated with a well-defined microsatellite marker, subsequent MHC class I typing of a selected population of 24 animals was performed on two distinct next-generation sequencing (NGS) platforms. A substantial number of 21 A and 80 B transcripts were discovered, about half of which had not been previously reported. Per animal, from one to four highly transcribed A alleles (majors) were observed, in addition to ones characterised by low transcripion levels (minors), such as members of the A*14 lineage. Furthermore, in one animal, up to 13 B alleles with differential transcription level profiles may be present. Based on segregation profiles, 16 Paan-AB haplotypes were defined. A haplotype encodes in general one or two major A and three to seven B transcripts, respectively. A further peculiarity is the presence of at least one copy of a B*02 lineage on nearly every haplotype, which indicates that B*02 represents a separate locus with probably a specialistic function. Haplotypes appear to be generated by recombination-like events, and the breakpoints map not only between the A and B regions but also within the B region itself. Therefore, the genetic makeup of the olive baboon MHC class I region appears to have been subject to a similar or even more complex expansion process than the one documented for macaque species.

No postcopulatory selection against MHC-homozygous offspring: Evidence from a pedigreed captive rhesus macaque colony.

The heterozygosity status of polymorphic elements of the immune system, such as the major histocompatibility complex (MHC), is known to increase the potential to cope with a wider variety of pathogens. Pre- and postcopulatory processes may regulate MHC heterozygosity. In a population where mating occurs among individuals that share identical MHC haplotypes, postcopulatory selection may disfavour homozygous offspring or ones with two MHC haplotypes identical to its mother. We tested these ideas by determining the incidence of MHC-heterozygous and MHC-homozygous individuals in a pedigreed, partially consanguineous captive rhesus monkey colony. Bayesian statistics showed that when parents share MHC haplotypes, the distribution of MHC-heterozygous and MHC-homozygous individuals significantly fitted the expected Mendelian distribution, both for the complete MHC haplotypes, and for MHC class I or II genes separately. Altogether, we found in this captive colony no evidence for postcopulatory selection against MHC-homozygous individuals. However, the distribution of paternally and maternally inherited MHC haplotypes tended to differ significantly from expected. Individuals with two MHC haplotypes identical to their mother were underrepresented and offspring with MHC haplotypes identical to their father tended to be overrepresented. This suggests that postcopulatory processes affect MHC haplotype combination in offspring, but do not prevent low MHC heterozygosity.

A quick and robust MHC typing method for free-ranging and captive primate species.

Gene products of the major histocompatibility complex (MHC) of human and non-human primates play a crucial role in adaptive immunity, and most of the relevant genes not only show a high degree of variability (polymorphism) but also copy number variation (CNV) is observed. Due to this diversity, MHC proteins influence the capability of individuals to cope with various pathogens. MHC and/or MHC-linked gene products such as odorant receptor genes are thought to influence mate choice and reproductive success. Therefore, MHC typing of wild and captive primate populations is considered to be useful in conservation biology, which is, however, often hampered by the need of invasive and time-consuming methods. All intact Mhc-DRB genes in primates appear to possess a complex and highly divergent microsatellite, DRB-STR. A panel of 154 pedigreed olive baboons (Papio anubis) was examined for their DRB content by DRB-STR analysis of genomic DNA. Using the same methodology on DNA of feces samples, DRB variability of a silvery gibbon population (Hylobates moloch) (N = 24), an endangered species, could successfully be studied. In both species, length determination of the DRB-STR resulted in the definition of unique genotyping patterns that appeared to be specific for a certain chromosome. Moreover, the different STR lengths were shown to segregate with the allelic variation of the respective gene. The results obtained expand data gained previously on DRB-STR typing in macaques, great apes, and humans and strengthen the conclusion that this protocol is applicable in molecular ecology, conservation biology, and colony management, especially of endangered primate species.

[Atrio-oesophageal fistula after thoracoscopic treatment of atrial fibrillation]. / Atrio-oesofageale fisteling na thoracoscopische behandeling van atriumfibrilleren.

BACKGROUND: An atrio-oesophageal fistula (AOF) is a rare but severe complication of radiofrequency ablation during video-assisted thoracoscopic pulmonary vein isolation (VATS-PVI). CASE DESCRIPTION: A 68-year-old man presented to the emergency department with reduced general well-being and a fever. Eight weeks prior he had undergone a VATS-PVI. Blood results revealed elevated inflammatory parameters, and blood cultures were positive for Streptococcus anginosus. A CT-scan demonstrated an air configuration in the left atrium. Shortly after this he developed a left-sided hemiparesis. As a cerebral air embolus due to an AOF was suspected, we decided to operate. The defects in the atrium and the oesophagus were closed primarily during open-heart surgery. CONCLUSION: An AOF is a rare complication following a VATS-PVI. Patients often present with non-specific symptoms like a fever. It is important to be alert of this complication after a VATS-PVI and to perform early diagnostic imaging.

Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations.

BACKGROUND: Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations. METHODS: Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller-Trumbore and Floyd-Warshall algorithms. IPM's were reconstructed from the BSP's. RESULTS: Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively. CONCLUSION: The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP's.

Tachyarrhythmia in patients with congenital heart disease: inevitable destiny?

The prevalence of patients with congenital heart disease (CHD) has increased over the last century. As a result, the number of CHD patients presenting with late, postoperative tachyarrhythmias has increased as well. The aim of this review is to discuss the present knowledge on the mechanisms underlying both atrial and ventricular tachyarrhythmia in patients with CHD and the advantages and disadvantages of the currently available invasive treatment modalities.

Endovascular catheter ablation of ventricular tachycardia in a patient with a surgically repaired congenital left ventricular aneurysm.

We present a patient with a congenital left ventricular aneurysm who visited our outpatient clinic for a routine check-up and, during this visit, lost consciousness due to sustained ventricular tachycardia. In our patient, endocardial mapping revealed extensive conduction abnormalities, and successful ablation was accomplished at the endocardial surface.

The future of atrial fibrillation therapy: intervention on heat shock proteins influencing electropathology is the next in line.

Atrial fibrillation (AF) is the most common age-related cardiac arrhythmia accounting for one-third of hospitalisations. Treatment of AF is difficult, which is rooted in the progressive nature of electrical and structural remodelling, called electropathology, which makes the atria more vulnerable for AF. Importantly, structural damage of the myocardium is already present when AF is diagnosed for the first time. Currently, no effective therapy is known that can resolve this damage.Previously, we observed that exhaustion of cardioprotective heat shock proteins (HSPs) contributes to structural damage in AF patients. Also, boosting of HSPs, by the heat shock factor-1 activator geranylgeranylacetone, halted AF initiation and progression in experimental cardiomyocyte and dog models for AF. However, it is still unclear whether induction of HSPs also prolongs the arrhythmia-free interval after, for example, cardioversion of AF.In this review, we discuss the role of HSPs in the pathophysiology of AF and give an outline of the HALT&REVERSE project, initiated by the HALT&REVERSE Consortium and the AF Innovation Platform. This project will elucidate whether HSPs (1) reverse cardiomyocyte electropathology and thereby halt AF initiation and progression and (2) represent novel biomarkers that predict the outcome of AF conversion and/or occurrence of post-surgery AF.