[Cloning and functional analysis of 3ß-hydroxysteroid dehydrogenase gene involved in biosynthesis of digitoxin].

Digitoxin, an important secondary metabolite of Digitalis purpurea, is a commonly used cardiotonic in clinical practice. 3ß-Hydroxysteroid dehydrogenase(3ßHSD) is a key enzyme involved in the biosynthesis of digitoxin. It belongs to the short-chain dehydrogenase/reductase(SDR) family, playing a role in the biosynthesis of cardiac glycosides by oxidizing and isomerizing the precursor sterol. In this study, two 3ßHSD genes were cloned from D. purpurea. The results showed that the open reading frame(ORF) of Dp3ßHSD1 was 780 bp, encoding 259 amino acid residues. The ORF of Dp3ßHSD2 was 774 bp and encoded 257 residues. Dp3ßHSD1/2 had the cofactor binding site TGxxxA/GxG and the catalytic site YxxxK. In vitro experiments confirmed that Dp3ßHSD1/2 catalyzed the generation of progesterone from pregnenolone, and Dp3ßHSD1 had stronger catalytic capacity than Dp3ßHSD2. The expression level of Dp3ßHSD1 was much higher than that of Dp3ßHSD2 in leaves, and digitoxin was only accumulated in leaves. The results implied that Dp3ßHSD1 played a role in the dehydrogenation of pregnenolone to produce progesterone in the biosynthesis of digitoxin. This study provides a reference for further exploring the biosynthetic pathway of cardiac glycosides in D. purpurea.

Progesterone Metabolism In Digitalis And Other Plants - 60 Years Research And Recent Results.

5ß-Cardenolides are pharmaceutically important metabolites of the specialized metabolism of Digitalis lanata. They were used over decades to treat cardiac insufficiency and supraventricular tachycardia. Since the 1960s, plant scientists have known that progesterone is an essential precursor of cardenolide formation. Therefore, plant progesterone biosynthesis was mainly analyzed in species of the cardenolide-containing genus Digitalis during the following decades. Today, Digitalis enzymes catalyzing the main steps of progesterone biosynthesis are known. Most of them were found in a broad range of organisms. This review will summarize the findings of 60 years of research on plant progesterone metabolism with a particular focus on the recent results in Digitalis lanata and other plants.

Selection of a Digitalis purpurea Cell Line with Improved Bioconversion Capacity of Hydroquinone into Arbutin.

This study aimed to investigate the biotransformation capabilities of a hydroquinone-tolerant Digitalis purpurea cell line (DpHQ) for bioconverting hydroquinone (HQ) into arbutin, a compound with significant therapeutic and cosmetic applications. The research evaluated the influence of various HQ concentrations, feeding protocols, and carbon sources on arbutin bioconversion yield. By using HPLC-MS for the quantification of arbutin in biomass and medium, the study revealed that higher precursor (HQ) concentration led to a more pronounced growth inhibition under single dosing than sequential dosing. At lower sugar (3%) and precursor (4 mM HQ) levels, arbutin predominantly remained within the cells, whereas higher sugar (6%) and HQ (5-6 mM) levels promoted its release into the medium. Arbutin production ranged from 591 mg/L under single dosing to 3049 mg/L with sequential dosing, with the highest yield being achieved with 5 mM HQ in divided doses and 6% glucose. This study holds novelty for being the first to demonstrate the DpHQ's tolerance to high concentrations of HQ and its efficient capabilities to bioconvert HQ to arbutin, indicating that D. purpurea is equipped with the enzymes required for this process. These aspects highlight its potential as a biotechnological source for arbutin synthesis.

The Association Between Digoxin Use and Long-Term Mortality After Acute Coronary Syndrome.

Digoxin is used to treat atrial fibrillation and heart failure. Previous studies have reported an association between digoxin and higher mortality, but the results have been conflicting. This study assessed the association between digoxin use and all-cause mortality using comprehensive health data of patients treated for acute coronary syndrome (ACS). This was a retrospective analysis of 8,388 consecutive ACS patients treated in Tays Heart Hospital between 2007 and 2017, with a follow-up until the end of 2018. The adjusted Cox regression model was used to analyze the association between digoxin treatment and all-cause mortality with and without the inverse probability of treatment weighting (IPTW) method. IPTW was applied to estimate the residual confounding by the treatment selection. Clinical phenotype data were collected from various sources, including a prospectively updated online database maintained by physicians. The median follow-up time was 6.0 years (interquartile range 3.5 to 9.0 years). During the follow-up, 30.8% (n = 2,580) of the patients died. Altogether, 4.0% (n = 333) of the patients were treated with digoxin during hospitalization. In the Cox regression model, digoxin associated with increased mortality (age- and sex-adjusted hazard ratio [HR] 1.76 [1.51 to 2.05], p <0.001 and in the full risk factor-adjusted HR 1.23 [1.04 to 1.45], p = 0.016). The IPTW Cox analysis average treatment effect HR was 1.71 (1.12 to 2.62, p = 0.013), standardized average treatment effect HR was 1.35 (0.96 to 1.90, p = 0.082), and treatment effect among the treated HR was 1.32 (1.09 to 1.59, p = 0.004). In conclusion, digoxin treatment during ACS associates with increased mortality, despite adjusting for other risk factors and after accounting for factors explaining the residual confounding by selection bias.

Endogenous Digitalis-like Factors as a Key Molecule in the Pathophysiology of Pregnancy-Induced Hypertension and a Potential Therapeutic Target in Preeclampsia.

Preeclampsia (PE), the most severe presentation of hypertensive disorders of pregnancy, is the major cause of morbidity and mortality linked to pregnancy, affecting both mother and fetus. Despite advances in prophylaxis and managing PE, delivery of the fetus remains the only causative treatment available. Focus on complex pathophysiology brought the potential for new treatment options, and more conservative options allowing reduction of feto-maternal complications and sequelae are being investigated. Endogenous digitalis-like factors, which have been linked to the pathogenesis of preeclampsia since the mid-1980s, have been shown to play a role in the pathogenesis of various cardiovascular diseases, including congestive heart failure and chronic renal disease. Elevated levels of EDLF have been described in pregnancy complicated by hypertensive disorders and are currently being investigated as a therapeutic target in the context of a possible breakthrough in managing preeclampsia. This review summarizes mechanisms implicating EDLFs in the pathogenesis of preeclampsia and evidence for their potential role in treating this doubly life-threatening disease.

[Health goals amongst patients with Crohn's disease.] / Egészséggel kapcsolatos célok Crohn-betegek körében.

INTRODUCTION: Inflammatory bowel diseases, including Crohn's disease, have a significant impact on patients' lifestyle, requiring lifelong attention to health behavior. OBJECTIVE: The aim of our study was to investigate health-related goals, emotions related to health goals, the use of infocommunication tools and their associations. METHOD: 79 patients with Crohn's disease (59.5% female, mean age 40.7 years, SD = 11.89) participated in the study. They answered demographic and health behaviour questions and completed the Personal Health Plans Questionnaire, which assessed their personal health goals, positive and negative emotions about health goal(s), support for personal health goals from their physician, negative and positive effects (barriers/support) of achieving health goals, and digital technology and internet use. RESULTS: 70% of patients had at least 1 health goal. The health goals were classified into four categories: physical activity (43.6%), stress management (25.4%), nutrition (18%) and smoking cessation (7%). 71% of participants experienced at least average levels of positive emotions related to the health goal, but about 50% also experienced negative emotions. 51% of those with a health goal regularly use the internet and apps on smartphones. Infocommunication device use showed a medium-strength correlation with perceived health goal-related barrier/support (ρ = 0.55, p<0.01), support from the person's doctor (ρ = 0.45, p<0.05) and physical activity (ρ = 0.40, p<0.01). DISCUSSION: More than two-thirds of patients had a health goal; most of the goals were related to health behaviours that are also relevant to Crohn's disease, but few had healthy eating and smoking cessation as health goals. Half of those with a health goal regularly use the internet and apps on smartphones. Among health behaviours, physical activity was associated with infocommunication device use. CONCLUSION: It is recommended to investigate patients' health goals and infocommunication device use in the care of patients with Crohn's disease. This would allow the development of specific interventions to improve their health behaviour, which could increase the quality of life and disease prognosis. Orv Hetil. 2023; 164(28): 1102-1110.

Of mixed vegetables and cardiac arrhythmias - Digitalis purpurea confused with Borago officinalis: A case series of accidental digitoxin intoxications.

We present the case series of two women aged 35 and 60 years who presented to our emergency department with severe vomiting, nausea, and malaise. Their symptoms started approximately 2 h after the ingestion of home-made mixed vegetables with freshly picked vegetables and leaves from the patients' garden, of which one was supposed to be borage. An electrocardiogram revealed diffuse ST-segment depression with down-up sloping in both patients. We supposed an accidental confusion of wild borage (Borago officinalis) with foxglove (Digitalis purpurea). Both patients were subsequently admitted to the intermediate-care-unit for close monitoring and continuous activated charcoal administration. Digitoxin serum concentrations were elevated in both patients (40.9 and >50 ng/ml, respectively - reference therapeutic range 8-18 ng/ml). The younger woman, despite the relatively lower serum digitoxin concentrations, presented a single episode of advanced atrioventricular block and long-lasting sinus bradycardia. Both showed a complete recovery. Although not uncommon, our case series reiterates the fact that such plant misclassifications are potentially life-threating and warrant the treating physicians' full attention. Learning objective: Plant poisoning is a frequent reason for consultation of poison information centers and may result in life-threatening cardiac arrhythmias. Confusion of foxglove leaves (Digitalis purpurea) with borage leaves (Borago officinalis L.), which is a popular food ingredient for mixed salads, is not uncommon. Without a dedicated medical history, such cases are difficult to diagnose and warrant the treating physicians' full attention and the involvement of a local poison information center.

Variation in the chemical profiles of three foxglove species in the central Balkans.

The aim of this study was to determine intra- and interspecies variation in the qualitative and quantitative composition of methanol-soluble metabolites in the leaves of three Digitalis species (D. lanata, D. ferruginea, and D. grandiflora) from the central Balkans. Despite the steady use of foxglove constituents for human health as valuable medicinal products, populations of the genus Digitalis (Plantaginaceae) have been poorly investigated to describe their genetic and phenetic variation. Following untargeted profiling using UHPLC-LTQ Orbitrap MS, by which we identified a total of 115 compounds, 16 compounds were quantified using the UHPLC(-)HESI-QqQ-MS/MS approach. In total, 55 steroid compounds, 15 phenylethanoid glycosides, 27 flavonoids, and 14 phenolic acid derivatives were identified across the samples with D. lanata and D. ferruginea showing a great similarity, while 15 compounds were characteristic only for D. grandiflora. The phytochemical composition of methanol extracts, considered here as complex phenotypes, are further examined along multiple levels of biological organization (intra- and interpopulation) and subsequently subjected to chemometric data analysis. The quantitative composition of the selected set of 16 chemomarkers belonging to the classes of cardenolides (3 compounds) and phenolics (13 compounds) pointed to considerable differences between the taxa studied. D. grandiflora and D. ferruginea were found to be richer in phenolics as compared to cardenolides, which otherwise predominate in D. lanata over other compounds. PCA revealed lanatoside C, deslanoside, hispidulin, and p-coumaric acid to be the main compounds contributing to the differences between D. lanata on one side and D. grandiflora and D. ferruginea on the other, while p-coumaric acid, hispidulin, and digoxin contribute to the diversification between D. grandiflora and D. ferruginea. However, quantitative variation in the metabolite content within species was faint with mild population diversification visible in D. grandiflora and particularly in D. ferruginea. This pointed to the highly conserved content and ratio of targeted compounds within the analyzed species, which was not severely influenced by the geographic origin or environmental conditions. The presented metabolomics approach might have, along with morphometrics and molecular genetics studies, a high information value for further elucidation of the relationships among taxa within the genus Digitalis.

Effect of Digitalis on ICD or CRT-D Recipients: A Systematic Review and Meta-Analysis.

BACKGROUND: Digitalis has been widely utilized for heart failure therapy and several studies have demonstrated an association of digitalis and adverse outcome events in patients receiving implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). Hence, we conducted this meta-analysis to assess the effect of digitalis on ICD or CRT-D recipients. METHODS: We systematically retrieved relevant studies using the Cochrane Library, PubMed, and Embase database. A random effect model was used to pool the effect estimates (hazard ratios (HRs) and 95% confidence intervals (CIs)) when the studies were of high heterogeneity, otherwise a fixed effect model was used. RESULTS: Twenty-one articles containing 44,761 ICD or CRT-D recipients were included. Digitalis was associated with an increased rate of appropriate shocks (HR = 1.65, 95% CI: 1.46-1.86, p < 0.001) and a shortened time to first appropriate shock (HR = 1.76, 95% CI: 1.17-2.65, p = 0.007) in ICD or CRT-D recipients. Furthermore, the all-cause mortality increased in ICD recipients with digitalis therapy (HR = 1.70, 95% CI: 1.34-2.16, p < 0.01), but the all-cause mortality was unchanged in CRT-D recipients (HR = 1.55, 95% CI: 0.92-2.60, p = 0.10) or patients who received ICD or CRT-D therapy (HR = 1.09, 95% CI: 0.80-1.48, p = 0.20). The sensitivity analyses confirmed the robustness of the results. CONCLUSION: ICD recipients with digitalis therapy may tend to have higher mortality rates, but digitalis may not be associated with the mortality rate of CRT-D recipients. Further studies are required to confirm the effects of digitalis on ICD or CRT-D recipients.

Evaluation Of The Effectiveness of Dantrolene Sodium against Digoxin-Induced Cardiotoxicity In Adult Rats.

BACKGROUND: Digoxin poisoning commonly occurs in people treated with digoxin. It has been suggested that treatment with dantrolene may be a suitable strategy for digoxin-induced cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the protective effect of dantrolene on digoxin-induced cardiotoxicity in male rats. METHODS: This study was approved by the ethics committee of Birjand University of Medical Sciences (Ethical number: IR.BUMS.REC.1400.067). Forty-two Wistar rats weighing between 300- 350 gr were randomly allocated to 7 groups (n=6) as follows:Normal Saline (NS) group, Normal Saline + Ethanol (NS + ETOH) group), Normal Saline + dantrolene 10 mg/kg (NS + Dan 10) group, Digoxin (Dig) group), Digoxin + dantrolene 5 mg/kg (Dig + Dan 5) group),Digoxin + dantrolene 10 mg/kg (Dig + Dan 10) group), Digoxin + dantrolene 20 mg/kg (Dig + Dan 20) group), Dig was injected intravenously at 12 mL / h (0.25 mg / mL). Dan (5, 10 and 20 mg/kg) was injected intravenously at 5-8 min/mL. After 1 hour, blood samples were obtained from the animals&#039; cavernous sinus and each animal&#039;s heartremoved. The blood sample was rapidly centrifuged at 2,500 rpm for 10 minutes and the serum was separated for measurement of creatine phosphokinase (CPK), potassium (K), sodium (Na), calcium (Ca), and magnesium (Mg). The samples were stored at -20 oC. The heart samples were fixed in formalin 10% for histopathological evaluation. RESULTS: K levels slightly increased in the dig group versus the NS group. A significant increase in the K levels was observed in the Dig + Dan 20 group versus the NS group (p < 0.001). dig slightly decreased Ca levels in the treated group versus the NS group. The levels of Ca significantly increased in the Dig + Dan 10 group versus the Dig group (p < 0.05). Histological examination of the heart tissue in the dig group showed cardiomyocyte degeneration, increased edematous intramuscular space associated with hemorrhage, and congestion. Focal inflammatory cell accumulation in the heart tissue was also seen. Cardiomyocytes were clear and arranged in good order in the Dig + Dan 10 group. CONCLUSION: dantrolene (10 mg/kg) was cardioprotective in a model of digoxin-induced cardiotoxicity, secondary to cardiac remodeling and hyperkalemia. However, further research is necessary to determine dantrolene&#039;s cardioprotective and cardiotoxic doses in animal models.

[E-physicians in Hungary: Experiences and opinions related to digital health among Hungarian physicians]. / E-orvosok Magyarországon: Digitális egészséggel kapcsolatos tapasztalatok és vélemények a hazai orvosok körében.

INTRODUCTION: The digitalization of healthcare is one of the most topical issues in terms of the present and future of healthcare. The coronavirus pandemic has shed light on the potential inherent in these technologies, and at the same time brought to the surface countless tasks and problems that need to be solved. OBJECTIVE: In our national survey, our aim is to find out how medical doctors are adapting to digital healthcare solutions. METHOD: Between July 2021 and May 2022, we conducted an online questionnaire survey among doctors working in Hungary. 1774 people answered our questions, including 1576 general practitioners and 198 dentists. In this paper, the 1576 general practitioners' responses are presented. RESULTS: 78.8% of the respondent doctors recommend websites to their patients on a more or less regular basis, 52.8% have recommended apps and 46.0% have recommended social media resources. The respondent doctors perceive a high demand from patients for communication by e-mail (83.7% indicated). 86.4% of doctors are aware of telemedicine solutions and 47.5% of respondents would like to use them intensively in the next 3 years. A significant proportion of respondents would like to use apps (56.2%), sensors, portable diagnostic devices (49.0%) and artificial intelligence (28.3%) in the next 3 years. Websites, apps and social media resources are significantly more frequently recommended by general practitioners and they are the ones who are most in favour of the use of the internet for patient health and telemedicine. CONCLUSION: Our respondents manifest fundamentally positive feelings towards the digitalization of healthcare and are characterized by a cautious openness regarding the implementation and adaptation of technologies. Orv Hetil. 2023; 164(4): 132-139.

Cardenolide Increase in Foxglove after 2,1,3-Benzothiadiazole Treatment Reveals a Potential Link between Cardenolide and Phytosterol Biosynthesis.

Cardenolides are steroidal metabolites in Digitalis lanata with potent cardioactive effects on animals. In plants, cardenolides are likely involved in various stress responses. However, the molecular mechanism of cardenolide increase during stresses is mostly unknown. Additionally, cardenolides are proposed to arise from cholesterol, but indirect results show that phytosterols may also be substrates for cardenolide biosynthesis. Here, we show that cardenolides increased after methyl jasmonate (MJ), sorbitol, potassium chloride (KCl) and salicylic acid analog [2,1,3-benzothiadiazole (BTH)] treatments. However, the expression of three known genes for cardenolide biosynthesis did not correlate well with these increases. Specifically, the expression of progesterone-5ß-reductases (P5ßR and P5ßR2) did not correlate with the cardenolide increase. The expression of 3ß-hydroxysteroid dehydrogenase (3ßHSD) correlated with changes in cardenolide levels only during the BTH treatment. Mining the D. lanata transcriptome identified genes involved in cholesterol and phytosterol biosynthesis: C24 sterol sidechain reductase 1 (SSR1), C4 sterol methyl oxidase 1, and 3 (SMO1 and SMO3). Surprisingly, the expression of all three genes correlated well with the cardenolide increase after the BTH treatment. Phylogenetic analysis showed that SSR1 is likely involved in both cholesterol and phytosterol biosynthesis. In addition, SMO1 is likely specific to phytosterol biosynthesis, and SMO3 is specific to cholesterol biosynthesis. These results suggest that stress-induced increase of cardenolides in foxglove may correlate with cholesterol and phytosterol biosynthesis. In summary, this work shows that cardenolides are important for stress responses in D. lanata and reveals a potential link between phytosterol and cardenolide biosynthesis.

[New opportunities offered by digital technology in melanoma malignum screening.] / A digitális technológia kínálta új lehetoségek a melanoma malignum szurésében.

INTRODUCTION: In Eastern and Central Europe, Hungary has the third highest incidence of melanoma after the Czech Republic and Slovakia. In order to improve the efficiency of melanoma diagnostics and screening, several technological developments have been made in recent years, one is the integrated automated total body mapping and digital dermatoscopy. OBJECTIVE: The aim of this targeted literature review is to demonstrate the potential of new digital technologies developed for total body mapping in relation to melanoma screening. METHOD: Targeted literature review was performed to collect information. We searched in publicly available databases for guidelines and recommendations as well as scientific publications on screening and early detection of melanoma. RESULTS: We identified 15 international guidelines and recommendations summarizing screening and early detection of melanoma. We did not find any Hungarian guidelines on melanoma screening. We analyzed 2 clinical, 5 observational studies and 8 systematic reviews on the effectiveness of digital dermatoscopy and automated total body mapping. We found 10 studies that investigated the complementary role of machine learning algorithms in the early diagnosis of melanoma. DISCUSSION: Digital dermatoscopy and total body mapping can help identify skin malignancies or new melanoma at high-risk individuals. Due to the lack of reliable data of melanoma screening programmes on cancer mortality, population-based melanoma screening is not recommended by international guidelines. CONCLUSION: International guidelines highlight the role of automated total body mapping and sequential digital dermatoscopic imaging in screening of individuals at increased risk of melanoma. Orv Hetil. 2022; 163(49): 1943-1951.

Diagnostic performance of non-contrast magnetic resonance angiography in patients with lower extremity arterial disease / A kontrasztanyag nélküli mágnesesrezonancia-angiográfia diagnosztikus teljesítménye alsó végtagi veroérbetegekben

Hungary. Knowing the consequences of burnout syndrome, it is important to prevent and recognize symptoms as early as possible.

Epineural methylene blue nerve staining on cadaver hand / Perifériás ideg epineuralis metilénkékfestése kadáverkézen

Introduction: Limited fasciectomy is the gold-standard treatment in Dupuytren's surgery. The anatomical position of digital nerves can be altered by Dupuytren's tissue resulting in a difficult dissection and localization, with a relatively high risk of iatrogenic nerve injury. This risk could be decreased by using intraoperative neural marking to facilitate locating the potentially displaced nerves. We recently demonstrated in an animal model that in vivo nerve staining with methylene blue is a suitable method to mark nerves without damaging them. Objective: We aimed to test the efficacy of our methylene blue nerve staining technique developed in a rat sciatic nerve model on human cadaveric digital nerves. Method: First, we performed epineural staining using 40 µl 1 : 80 diluted methylene blue solution on four human cadaver digital nerves fixed with formalin. In the second experiment, we stained six cadaver digital nerves without previous fixation. To increase the length of the stained segments, we used 200 µl solution on two nerves. Results: The epineural nerve labeling was not successful on formalin-fixed tissues. However, nerves without fixation were successfully stained with methylene blue. Forty µl methylene blue solution marked a 13 mm long segment, while 200 µl stained a 18 mm long segment. Conclusion: The epineural methylene blue nerve staining is limited on formalin-fixed digital nerves due tissue shrink-age. Non-fixed nerves with preserved histological structure can be stained in an 18 mm long segment. Further studies are necessary to determine the technique's value in hand surgery by testing digital nerves surrounded by Dupuytren's and scar tissues.

Modern treatment of massive hemothorax / A masszív haemothorax modern kezelése

Introduction and objective: Hemothorax is an umbrella term for pathologies with an extremely wide range of etiology and severity. Most commonly it is of tramuatic origin, frequently iatrogenic (intervention, blood coagulation altering therapy) and rarely unknown. Depending on the cause, volume, and dynamics, it requires a patient-adapted treatment determined by access to certain therapeutical methods. We aim to provide a practical overview of these. Methods: Retrospective analysis of patients treated for haemothorax at the Thoracic Surgery Department of Borsod-Abaúj-Zemplén County Teaching Hospital in the period 1 January 2017­31 December 2021 has been performed. We used the hospital's database to collect data. In this paper, we analyze the cause of hemothorax, method of treatment, the efficacy of chosen therapeutic modality, duration of hospital stay, complication rate, 30-day survival. Results: 77 patients were treated with hemothorax, 57 male, 20 female patients. Average age was 53,4 (23­90, SD:14,9) years. Surgery was performed in 31 cases, with 10 cases needing reintervention. In 7 cases, multimodal approach was chosen, with chest wall stabilization. Average hospital stay: 14 (2­79) days. 30-day survival: 95%. Discussion: Thoracic drainage is our first therapeutic choice. The methods used in the treatment of hemothorax in our practice have been extended with the use of digital subtraction angiography (DSA), which yields immediate and effective bleeding control. We performed video-assisted thoracoscopic surgery (VATS) in increasing numbers. Conclusions: As long as the intensity of bleeding and patient's general status allows it, after drainage, the first therapeutic option ­ when accessible ­ should be DSA bleeding control. In cases which do not resolve after drainage, VATS evacuation of hematoma is a safe method used in the treatment of hemothorax. In the past 5 years, we used thoracoscopy in increasing numbers while treating this entity. Based on our results and the literature, we can safely state that the use of thoracoscopy in the treatment of hemothorax is a safe and reliable option in eligible patients, and the results are comparable with those treated by thoracotomy.

Continuous inbreeding affects genetic variation, phenology, and reproductive strategy in ex situ cultivated Digitalis lutea.

PREMISE: Ex situ cultivation is important for plant conservation, but cultivation in small populations may result in genetic changes by drift, inbreeding, or unconscious selection. Repeated inbreeding potentially influences not only plant fitness, but also floral traits and interactions with pollinators, which has not yet been studied in an ex situ context. METHODS: We studied the molecular genetic variation of Digitalis lutea from a botanic garden population cultivated for 30 years, a frozen seed bank conserving the original genetic structure, and two current wild populations including the source population. In a common garden, we studied the effects of experimental inbreeding and between-population crosses on performance, reproductive traits, and flower visitation of plants from the garden and a wild population. RESULTS: Significant genetic differentiation was found between the garden population and the wild population from which the seeds had originally been gathered. After experimental selfing, inbreeding depression was only found for germination and leaf size of plants from the wild population, indicating a history of inbreeding in the smaller garden population. Moreover, garden plants flowered earlier and had floral traits related to selfing, whereas wild plants had traits related to attracting pollinators. Bumblebees visited more flowers of outbred than inbred plants and of wild than garden plants. CONCLUSIONS: Our case study suggests that high levels of inbreeding during ex situ cultivation can influence reproductive traits and thus interactions with pollinators. Together with the effects of genetic erosion and unconscious selection, these changes may affect the success of reintroductions into natural habitats.

Clinical outcomes in patients with atrial fibrillation treated with digoxin, according to the presence of heart failure: Insights from the MISOAC-AF trial.

BACKGROUND: Digoxin is widely used in atrial fibrillation (AF) and heart failure (HF). However, current evidence regarding its association with clinical outcomes is conflicting. AIM: To investigate the relationship between digoxin therapy and adverse outcomes in patients with AF, with or without HF, in a contemporary AF cohort. METHODS: We performed a retrospective analysis of data from 698 patients, who were followed over a median of 2.5 years. The primary outcome was all-cause mortality and the secondary outcome was all-cause hospitalization, in a time-to-event analysis. Propensity scores were used to derive matched populations, balanced on key baseline covariates. To limit potential confounding, inverse probability of treatment weighting (IPTW) analysis was performed. RESULTS: Among patients with HF, 39 (10.5%) were administered digoxin at baseline, whereas 331 (89.5%) were not. Digoxin administration was not associated with an increased risk of death (hazard ratio (HR) in the digoxin group, 1.21; 95% Confidence Interval (CI), 0.69 to 2.13, p = 0.50) or hospitalization of any cause (HR 1.15; 95% CI, 0.67 to 1.96; p = 0.60). Among patients without HF, 11 (3.5%) were administered digoxin, with neutral effects on all-cause mortality (HR: 3.25; 95% CI, 0.98 to 10.70), p = 0.06) and all-cause hospitalization (HR, 1.15; 95% CI, 0.67 to 1.96, p = 0.60). Qualitatively, consistent results were observed using IPTW. CONCLUSIONS: Among patients with AF, digoxin administration was not associated with an increased risk of death and hospitalization for any cause, irrespective of HF status.

Self-care behavior and associated factors among patients with heart failure in public hospitals of Southeast Ethiopia.

OBJECTIVE: This study was performed to assess self-care behavior and associated factors among patients with heart failure attending public hospitals in Southeast Ethiopia in 2021. METHODS: An institutional-based cross-sectional study was conducted among 420 patients with heart failure from 15 May to 30 June 2021 using a simple random sampling technique. A multivariable binary logistic model was used to identify factors associated with self-care behavior. Statistical significance was declared at p < 0.05. RESULTS: The magnitude of good self-care behavior among patients with heart failure was 53.6% [95% confidence interval (CI), 48.9-58.3]. Factors associated with self-care behavior were treatment with a beta blocker [adjusted odds ratio (AOR), 0.49; 95% CI, 0.27-0.89], treatment with digitalis (AOR, 0.11; 95% CI, 0.05-0.24), the level of social support (AOR, 0.07; 95% CI, 0.03-0.15), and the presence of depressive symptoms (AOR, 0.21; 95% CI, 2.70-8.33). CONCLUSION: Slightly more than half of the respondents had good self-care behavior. Attention should be given to enhancing good self-care practice through integration of health education as routine care.

Digitalis therapy in patients with ventricular tachyarrhythmias.

Objective. The study sought to assess the prognostic value of treatment with digitalis on long-term prognosis in patients with ventricular tachyarrhythmias and atrial fibrillation (AF) and/or heart failure (HF). Background. Data regarding the outcome of digitalis therapy following ventricular tachyarrhythmias is limited. Methods. A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with digitalis were compared to patients without. The primary prognostic endpoint was all-cause mortality at 3 years, secondary endpoints comprised a composite arrhythmic endpoint (i.e. recurrences of ventricular tachyarrhythmias, appropriate implantable cardioverter defibrillator (ICD) therapies, sudden cardiac death) and cardiac rehospitalization. Kaplan Mayer survival curves, multivariable cox regression, and time trend analyses were applied for statistics. Results. Eight hundred and thirty-one patients were included (20% treated with digitalis and 80% without). At 3 years, digitalis treatment was not associated with all-cause mortality following ventricular tachyarrhythmias (24 vs. 21%, log-rank p = .736; HR = 1.063; 95% CI 0.746-1.515; p = .736). However, digitalis therapy was associated with an increased risk of the composite arrhythmic endpoint (38 vs. 23%; log-rank p = .001; HR = 1.719; 95% CI 1.279-2.311; p = .001) and cardiac rehospitalization (31 vs. 18%; log-rank p = .001; HR = 1.829; 95% CI 1.318-2.538; p = .001), which was still evident within multivariable Cox regression analyses. Finally, digitoxin may be associated with a worse prognosis than digoxin. Conclusion. Digitalis therapy was not associated with mortality in patients with ventricular tachyarrhythmias, but with increased risk of the composite arrhythmic endpoint and cardiac rehospitalization at 3 years.