Non-valvular atrial fibrillation in patients on peritoneal dialysis, prevalence, treatment and professionals involved.

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1,403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% or in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scores used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.

Fibrilación auricular no valvular en pacientes en diálisis peritoneal: prevalencia, tratamiento y profesionales implicados / Non-valvular atrial fibrillation in patients on peritoneal dialysis: prevalence, treatment and professionals involved

La fibrilación auricular (FA) es la arritmia crónica más frecuente en pacientes con enfermedad renal crónica (ERC). La anticoagulación oral con antagonistas de la vitamina K (AVK) y actualmente los anticoagulantes orales de acción directa (ACOD) han sido el pilar fundamental para la prevención de eventos tromboembólicos. Sin embargo, no existen ensayos clínicos aleatorizados de su perfil riesgo-beneficio en pacientes con ERC estadio 5 en diálisis peritoneal (DP) y son pocas las evidencias en la literatura sobre esta población. El objetivo del estudio fue conocer la prevalencia, tratamiento y profesionales implicados en el manejo de la FA en DP en nuestro entorno mediante el análisis descriptivo de una encuesta enviada a diferentes unidades de DP de España. Se incluyeron en el estudio 1.403 pacientes en programa de DP, de los cuales 186 (13,2%) presentaban FA no valvular (FANV). Además, observamos que la valoración de los scores para el inicio del tratamiento anticoagulante la realizaba mayoritariamente el cardiólogo (60% de los centros), así como la prescripción de anticoagulación (cardiólogo 47% o en conjunto con el nefrólogo 43%). En conclusión, los pacientes en DP presentan una notable prevalencia de FANV. Reciben frecuentemente anticoagulación oral (ACO) con AVK, así como con ACOD. Los datos obtenidos respecto a las escalas utilizadas para la valoración de riesgo tromboembólico y de sangrado, tratamiento e implicación por parte de Nefrología indican que existe una necesidad de formación e involucramiento del nefrólogo en esta patología.(AU)

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillar for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scales used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.(AU)

Hyperbolic graph embedding of MEG brain networks to study brain alterations in individuals with subjective cognitive decline.

An expansive area of research focuses on discerning patterns of alterations in functional brain networks from the early stages of Alzheimer's disease, even at the subjective cognitive decline (SCD) stage. Here, we developed a novel hyperbolic MEG brain network embedding framework for transforming high-dimensional complex MEG brain networks into lower-dimensional hyperbolic representations. Using this model, we computed hyperbolic embeddings of the MEG brain networks of two distinct participant groups: individuals with SCD and healthy controls. We demonstrated that these embeddings preserve both local and global geometric information, presenting reduced distortion compared to rival models, even when brain networks are mapped into low-dimensional spaces. In addition, our findings showed that the hyperbolic embeddings encompass unique SCD-related information that improves the discriminatory power above and beyond that of connectivity features alone. Notably, we introduced a unique metric-the radius of the node embeddings-which effectively proxies the hierarchical organization of the brain. Using this metric, we identified subtle hierarchy organizational differences between the two participant groups, suggesting increased hierarchy in the dorsal attention, frontoparietal, and ventral attention subnetworks among the SCD group. Last, we assessed the correlation between these hierarchical variations and cognitive assessment scores, revealing associations with diminished performance across multiple cognitive evaluations in the SCD group. Overall, this study presents the first evaluation of hyperbolic embeddings of MEG brain networks, offering novel insights into brain organization, cognitive decline, and potential diagnostic avenues of Alzheimer's disease.

Prevalence of diagnosed depression, anxiety, and ADHD among youth with type 1 or type 2 diabetes mellitus.

We examined the prevalence of diagnosed depression, anxiety, and ADHD among youth by diabetes type, insurance type, and race/ethnicity. These mental disorders were more prevalent among youth with diabetes, particularly those with type 2 diabetes, with non-Hispanic White youth with Medicaid and diabetes having a higher prevalence than other races/ethnicities.

Immunomodulatory role of decidual prolactin on the human fetal membranes and placenta.

The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.

Melanin Induction Restores the Pathogenicity of Gaeumannomyces graminis var. tritici in Wheat Plants.

One of the most challenging aspects of long-term research based on microorganisms is the maintenance of isolates under ex situ conditions, particularly the conservation of phytopathological characteristics. Our research group has worked for more than 10 years with Gaumannomyces graminis var. tritici (Ggt), the main biotic factor affecting wheat. In this sense we preserved the microorganisms in oil overlaid. However, several strains preserved for a long time lost their pathogenicity. These strains show white and non-infective mycelia. In this sense, we hypothesized that this is attributable to low melanin content. Melanin is a natural pigment mainly involved in UV protection, desiccation, salinity, oxidation, and fungal pathogenicity. Therefore, understanding the melanin role on Ggt pathogenicity is fundamental to developing melanin activation strategies under laboratory studies. In this study, we induce melanin activation by UV-A light chamber, 320 to 400 nm (T1) and temperature changes of 30 °C, 15 °C, and 20 °C (T2). Fungal pathogenicity was evaluated by determination of blackening roots and Ggt was quantified by real-time PCR in inoculated wheat plants. Results revealed that Ggt grown under UV-A (T1) conditions showed around 40% higher melanin level with a concomitant effect on root infection (98% of blackened roots) and 4-fold more Ggt genome copy number compared with the control (non-infective mycelia) being T1, a more inductor factor compared with T2. These findings would support the role of melanin in pathogenicity in darkly pigmented fungi such as Ggt and could serve as a basis for activating pathogenicity under laboratory conditions.

Prevalence of Mental, Behavioral, and Developmental Disorders Among Children and Adolescents with Diabetes, United States (2016-2019).

OBJECTIVE: To assess the association of diabetes and mental, behavioral, and developmental disorders in youth, we examined the magnitude of overlap between these disorders in children and adolescents. STUDY DESIGN: In this cross-sectional study, we calculated prevalence estimates using the 2016-2019 National Survey of Children's Health. Parents reported whether their child was currently diagnosed with diabetes or with any of the following mental, behavioral, or developmental disorders: attention-deficit/hyperactivity disorder, autism spectrum disorder, learning disability, intellectual disability, developmental delay, anxiety, depression, behavioral problems, Tourette syndrome, or speech/language disorder. We present crude prevalence estimates weighted to be representative of the US child population and adjusted prevalence ratios (aPRs) adjusted for age, sex, and race/ethnicity. RESULTS: Among children and adolescents (aged 2-17 years; n = 121 312), prevalence of mental, behavioral, and developmental disorders varied by diabetes status (diabetes: 39.9% [30.2-50.4]; no diabetes: 20.3% [19.8-20.8]). Compared with children and adolescents without diabetes, those with diabetes had a nearly 2-fold higher prevalence of mental, behavioral, and developmental disorders (aPR: 1.72 [1.31-2.27]); mental, emotional, and behavioral disorders (aPR: 1.90 [1.38-2.61]) and developmental, learning, and language disorders (aPR: 1.89 [1.35-2.66]). CONCLUSIONS: These results suggest that approximately 2 in 5 children and adolescents with diabetes have a mental, behavioral, or developmental disorder. Understanding potential causal pathways may ultimately lead to future preventative strategies for mental, behavioral, and developmental disorders and diabetes in children and adolescents.

Glutamatergic system components as potential biomarkers and therapeutic targets in cancer in non-neural organs.

Glutamate is one of the most abundant amino acids in the blood. Besides its role as a neurotransmitter in the brain, it is a key substrate in several metabolic pathways and a primary messenger that acts through its receptors outside the central nervous system (CNS). The two main types of glutamate receptors, ionotropic and metabotropic, are well characterized in CNS and have been recently analyzed for their roles in non-neural organs. Glutamate receptor expression may be particularly important for tumor growth in organs with high concentrations of glutamate and might also influence the propensity of such tumors to set metastases in glutamate-rich organs, such as the liver. The study of glutamate transporters has also acquired relevance in the physiology and pathologies outside the CNS, especially in the field of cancer research. In this review, we address the recent findings about the expression of glutamatergic system components, such as receptors and transporters, their role in the physiology and pathology of cancer in non-neural organs, and their possible use as biomarkers and therapeutic targets.

Health Care Access and Use Among Adults With and Without Vision Impairment: Behavioral Risk Factor Surveillance System, 2018.

INTRODUCTION: Adults with vision impairment may have unique needs when accessing health care to maintain good health. Our study examined the relationship between vision status and access to and use of health care. METHODS: We analyzed data on adults aged 18 years or older who participated in the 2018 Behavioral Risk Factor Surveillance System. Vision impairment was identified by a yes response to the question "Are you blind or do you have serious difficulty seeing, even when wearing glasses?" Survey questions assessed health care access over the past year (having health insurance coverage, a usual health care provider, or unmet health care needs because of cost) and use of health care during that period (routine checkup and dental visit). We estimated age-adjusted prevalence of our outcomes of interest and used bivariate analyses to compare estimates of the outcomes by vision impairment status. RESULTS: The prevalence of self-reported vision impairment was 5.3%. Compared with adults without impaired vision, adults with vision impairment had a lower prevalence of having health insurance coverage (80.6% vs 87.6%), a usual health care provider (71.9% vs 75.7%), or a dental visit in the past year (52.9% vs 67.2%) and a higher prevalence of having an unmet health care need in the past year because of cost (29.2% vs 12.6%). CONCLUSION: Adults with vision impairment reported lower access to and use of health care than those without. Further research can better identify and understand barriers to care to improve access to and use of health care among this population.

Cardiovascular Disease Risk Factors in US Adults With Vision Impairment.

INTRODUCTION: Adults with vision impairment (VI) have a higher prevalence of cardiovascular disease (CVD) compared with those without VI. We estimated the prevalence of CVD and CVD risk factors by VI status in US adults. METHODS: We used nationally representative data from the 2018 National Health Interview Survey (N = 22,890 adults aged ≥18 years). We estimated the prevalence of self-reported diagnosis of CVD (coronary heart disease [including angina and myocardial infarction], stroke, or other heart disease) by VI status. We used separate logistic regression models to generate adjusted prevalence ratios (aPRs), controlling for sociodemographic covariates, for those with VI (reference group, no VI) for CVD and CVD risk factors: current smoking, physical inactivity, excessive alcohol intake, obesity, hypertension, high cholesterol, and diabetes. RESULTS: Overall, 12.9% (95% CI, 12.3-13.5) of the sample had VI. The prevalence of CVD was 26.6% (95% CI, 24.7-28.6) in people with VI versus 12.2% (95% CI, 11.7-12.8) in those without VI (aPR = 1.65 [95% CI, 1.51-1.80]). Compared with adults without VI, those with VI had a higher prevalence of all risk factors examined: current smoking (aPR = 1.40 [95% CI, 1.27-1.53]), physical inactivity (aPR = 1.14 [95% CI, 1.06-1.22]), excessive alcohol intake (aPR = 1.29 [95% CI, 1.08-1.53]), obesity (aPR = 1.28 [95% CI, 1.21-1.36]), hypertension (aPR = 1.29 [95% CI, 1.22-1.36]), high cholesterol (aPR = 1.21 [95% CI, 1.14-1.29]), and diabetes (aPR = 1.54 [95% CI, 1.38-1.72]). CONCLUSION: Adults with VI had a higher prevalence of CVD and CVD risk factors compared with those without VI. Effective clinical and lifestyle interventions, adapted to accommodate VI-related challenges, may help reduce CVD risk in adults with VI.

Multi-organ involvement and intratubular calcium phosphate deposition in the kidney biopsy: what should we investigate?

BACKGROUND: Anorexia nervosa is frequently associated with alcohol use disorder. Both of them may adversely affect almost every body system, leading to worse clinical outcomes and high mortality risk. Nonetheless, there is little evidence interrelating anorexia nervosa, alcohol use disorder, and kidney failure. CASE: We report a case of a 30-year-old male with multi-organ involvement at admission, including pancytopenia, electrolyte alterations, impaired liver function, and renal failure. The kidney biopsy revealed calcium phosphate crystalline nephropathy and IgA nephropathy. The bone marrow biopsy and aspiration showed a hypocellular bone marrow and a focal spindle cell infiltrate with atypical vascular proliferation. Nonspecific liver disease was revealed by ultrasound. Further investigation was performed, uncovering a possible masked diagnosis of anorexia nervosa and alcohol use disorder. With the restoration of adequate nutrition and the withdrawal of possible external triggers, a partial recovery was achieved. CONCLUSIONS: Anorexia nervosa and alcohol use disorder may promote tissue injury, including kidney failure, specifically calcium phosphate crystalline nephropathy and IgA nephropathy. This multi-organ involvement may lose its reversibility if anorexia nervosa and alcohol use disorder remain persistent. An early diagnosis and a successful multidisciplinary approach may prevent life-threatening complications. LEVEL OF EVIDENCE: Level V, case report.

Cognitive Training Modulates Brain Hypersynchrony in a Population at Risk for Alzheimer's Disease.

BACKGROUND: Recent studies demonstrated that brain hypersynchrony is an early sign of dysfunction in Alzheimer's disease (AD) that can represent a proxy for clinical progression. Conversely, non-pharmacological interventions, such as cognitive training (COGTR), are associated with cognitive gains that may be underpinned by a neuroprotective effect on brain synchrony. OBJECTIVE: To study the potential of COGTR to modulate brain synchrony and to eventually revert the hypersynchrony phenomenon that characterizes preclinical AD. METHODS: The effect of COGTR was examined in a sample of healthy controls (HC, n = 41, 22 trained) and individuals with subjective cognitive decline (SCD, n = 49, 24 trained). Magnetoencephalographic activity and neuropsychological scores were acquired before and after a ten-week COGTR intervention aimed at improving cognitive function and daily living performance. Functional connectivity (FC) was analyzed using the phase-locking value. A mixed-effects ANOVA model with factors time (pre-intervention/post-intervention), training (trained/non-trained), and diagnosis (HC/SCD) was used to investigate significant changes in FC. RESULTS: We found an average increase in alpha-band FC over time, but the effect was different in each group (trained and non-trained). In the trained group (HC and SCD), we report a reduction in the increase in FC within temporo-parietal and temporo-occipital connections. In the trained SCD group, this reduction was stronger and showed a tentative correlation with improved performance in different cognitive tests. CONCLUSION: COGTR interventions could mitigate aberrant increases in FC in preclinical AD, promoting brain synchrony normalization in groups at a higher risk of developing dementia.

Diabetes Self-Management Education and Association With Diabetes Self-Care and Clinical Preventive Care Practices.

PURPOSE: The purpose of the study is to assess self-reported receipt of diabetes education among people with diabetes and its association with following recommended self-care and clinical preventive care practices. METHODS: We analyzed data from the 2017 and 2018 Behavioral Risk Factor Surveillance System for 61 424 adults (≥18 years) with self-reported diabetes in 43 states and Washington, DC. Diabetes education was defined as ever taking a diabetes self-management class. The association of diabetes education with self-care practices (daily glucose testing, daily foot checks, smoking abstention, and engaging in leisure-time physical activity) and clinical practices (pneumococcal vaccination, biannual A1C test, and an annual dilated eye exam, influenza vaccination, health care visit for diabetes, and foot exam by a medical professional) was assessed. Multivariable logistic regression with predicted margins was used to predict the probability of following these practices, by diabetes education, controlling for sociodemographic factors. RESULTS: Of adults with diabetes, only half reported receiving diabetes education. Results indicate that receipt of diabetes education is associated with following self-care and clinical preventive care practices. Those who did receive diabetes education had a higher predicted probability for following all 4 self-care practices (smoking abstention, daily glucose testing, daily foot check, and engaging in leisure-time physical activity) and all 6 clinical practices (pneumonia vaccination, biannual A1C test, and an annual eye exam, flu vaccination, health care visit, and medical foot exam). CONCLUSIONS: The prevalence of adults with diabetes receiving diabetes education remains low. Increasing receipt of diabetes education may improve diabetes-related preventive care.

Developing an International Occupational Therapy Service: Perspectives and Implications.

Mali is one of the poorest countries in sub-Saharan Africa. Limited infrastructure renders access to health care difficult. There is a need to establish functional ways to improve Malian people's health and treat disability. From this point of view, our project aims to implement a remote occupational therapy service for the beneficiaries of the Kalana clinic in Mali through international cooperation. Using a spiral iterative model, a proposal for a remote occupational therapy service was developed and refined for a multidisciplinary context. The International Classification of Functioning, Disability, and Health (ICF) was used as a means to work from a multidisciplinary approach to treat all needs. The results are exemplified with a case report and qualitative impressions of the services.

Ongoing Oscillatory Electrophysiological Alterations in Frail Older Adults: A MEG Study.

Objective: The role of the central nervous system in the pathophysiology of frailty is controversial. We used magnetoencephalography (MEG) to search for abnormalities in the ongoing oscillatory neural activity of frail individuals without global cognitive impairment. Methods: Fifty four older (≥70 years) and cognitively healthy (Mini-Mental State Examination ≥24) participants were classified as robust (0 criterion, n = 34) or frail (≥ 3 criteria, n = 20) following Fried's phenotype. Memory, language, attention, and executive function were assessed through well-validated neuropsychological tests. Every participant underwent a resting-state MEG and a T1-weighted magnetic resonance imaging scan. We performed MEG power spectral analyses to compare the electrophysiological profiles of frail and robust individuals. We used an ensemble learner to investigate the ability of MEG spectral power to discriminate frail from robust participants. Results: We identified increased relative power in the frail group in the mu (p < 0.05) and sensorimotor (p < 0.05) frequencies across right sensorimotor, posterior parietal, and frontal regions. The ensemble learner discriminated frail from robust participants [area under the curve = 0.73 (95% CI = 0.49-0.98)]. Frail individuals performed significantly worse in the Trail Making Test, Digit Span Test (forward), Rey-Osterrieth Complex Figure, and Semantic Fluency Test. Interpretation: Frail individuals without global cognitive impairment showed ongoing oscillatory alterations within brain regions associated with aspects of motor control, jointly to failures in executive function. Our results suggest that some physical manifestations of frailty might partly arise from failures in central structures relevant to sensorimotor and executive processing.

The impact of volume overload on technique failure in incident peritoneal dialysis patients.

BACKGROUND: Technique failure in peritoneal dialysis (PD) can be due to patient- and procedure-related factors. With this analysis, we investigated the association of volume overload at the start and during the early phase of PD and technique failure. METHODS: In this observational, international cohort study with longitudinal follow-up of incident PD patients, technique failure was defined as either transfer to haemodialysis or death, and transplantation was considered as a competing risk. We explored parameters at baseline or within the first 6 months and the association with technique failure between 6 and 18 months, using a competing risk model. RESULTS: Out of 1092 patients of the complete cohort, 719 met specific inclusion and exclusion criteria for this analysis. Being volume overloaded, either at baseline or Month 6, or at both time points, was associated with an increased risk of technique failure compared with the patient group that was euvolaemic at both time points. Undergoing treatment at a centre with a high proportion of PD patients was associated with a lower risk of technique failure. CONCLUSIONS: Volume overload at start of PD and/or at 6 months was associated with a higher risk of technique failure in the subsequent year. The risk was modified by centre characteristics, which varied among regions.

Acute tubulointerstitial nephritis induced by the tyrosine kinase inhibitor vandetanib.

Few cases of immunoallergic tubulointerstitial nephritis associated with tyrosine kinase inhibitors have been described. We describe the first report case associated with vandetanib, a tyrosine kinase inhibitor indicated for the treatment of aggressive and symptomatic medullary thyroid cancer (CMT) in patients with locally advanced or metastatic non-resectable disease.

Abnormal organization of inhibitory control functional networks in future binge drinkers.

BACKGROUND AND AIMS: Adolescent Binge drinking has become an increasing health and social concern, which cause several detrimental consequences for brain integrity. However, research on neurophysiological traits of vulnerability for binge drinking predisposition is limited at this time. In this work, we conducted a two-year longitudinal study with magnetoencephalography (MEG) over a cohort of initially alcohol-naive adolescents with the purpose of characterize inhibitory cortical networks' anomalies prior to alcohol consumption onset in those youths who will transit into binge drinkers years later. METHODS: Sixty-seven participant's inhibitory functional networks, and dysexecutive/impulsivity traits were measured by means of inhibitory task (go/no-go) and questionnaires battery. After a follow-up period of two years, we evaluated their alcohol consumption habits, sub-dividing them in two groups according to their alcohol intake patterns: future binge drinkers (fBD): n = 22; future Light/non-drinkers (fLD): n = 17. We evaluated whole-brain and seed-based functional connectivity profiles, as well as its correlation with impulsive and dysexecutive behaviours, searching for early abnormalities before consumption onset. RESULTS: For the first time, abnormalities in MEG functional networks and higher dysexecutive and impulsivity profiles were detected in alcohol-naïve adolescents who two years later became binge drinkers. Concretely, fBD exhibit a distinctive pattern of beta band hyperconnectivity among crucial regions of inhibitory control networks, positively correlated with behavioral traits and future alcohol intake rate. CONCLUSIONS: These findings strongly support the idea of early neurobiological vulnerabilities for substances consumption initiation, with inhibitory functional networks' abnormalities as a relevant neurophysiological marker of subjects at risk- we hypothesize this profile is due to neurodevelopmental and neurobiological differences involving cognitive control networks and neurotransmission pathways.

Catalytic Enantioselective Alkylation of Indoles with trans-4-Methylthio-ß-Nitrostyrene.

The reaction of the rhodium aqua-complex (S Rh,R C)-[Cp*Rh{(R)-Prophos} (OH2)][SbF6]2 [Cp* = C5Me5, Prophos = propane-1,2-diyl-bis(diphenylphosphane)] (1) with trans-4-methylthio-ß-nitrostyrene (MTNS) gives two linkage isomers (S Rh,R C)-[Cp*Rh{(R)-Prophos}(κ1 O-MTNS)]2+ (3-O) and (S Rh,R C)-[Cp*Rh{(R)-Prophos}(κ1 S-MTNS)]2+ (3-S) in which the nitrostyrene binds the metal through one of the oxygen atoms of the nitro group or through the sulfur atom, respectively. Both isomers are in equilibrium in dichloromethane solution, the equilibrium constant being affected by the temperature in such a way that when the temperature increases, the relative concentration of the oxygen-bonded isomer 3-O increases. The homologue aqua-complex of iridium, (S Ir,R C)-[Cp*Ir{(R)-Prophos}(OH2)][SbF6]2 (2), also reacts with MTNS; but only the sulfur-coordinated isomer (S Ir,R C)-[Cp*Ir{(R)-Prophos}(κ1 S-MTNS)]2+ (4-S) is detected in the solution by NMR spectroscopy. The crystal structures of 3-S and 4-S have been elucidated by X-ray diffractometric methods. Complexes 1 and 2 catalyze the Friedel-Crafts reaction of indole, N-methylindole, 2-methylindole, or N-methyl-2-methylindole with MTNS. Up to 93% ee has been achieved for N-methyl-2-methylindole. With this indole, the ee increases as conversion increases, ee at 263 K is lower than that obtained at 298 K, and the sign of the chirality of the major enantiomer changes at temperatures below 263 K. Detection and characterization of the catalytic intermediates metal-aci-nitro and the free aci-nitro compound as well as detection of the Friedel-Crafts (FC)-adduct complex involved in the catalysis allowed us to propose a plausible double cycle that accounts for the catalytic observations.

Antifungal Effects of Drimane Sesquiterpenoids Isolated from Drimys winteri against Gaeumannomyces graminis var. tritici.

Gaeumannomyces graminis var. tritici is a soilborne pathogen that causes "take-all" disease, affecting cereal roots. In wheat, G. graminis var. tritici is the most important biotic factor, causing around 30 to 50% losses of yield. Chemical control of this fungal disease is difficult because G. graminis var. tritici is able to reside for a long time in soils. Therefore, the development of environmentally friendly biotechnological strategies to diminish the incidence of soilborne diseases is highly desirable. Natural products are a promising strategy for biocontrol of plant pathogens. A special emphasis is on medicinal plants due to their reported fungitoxic effects. Drimys winteri (canelo) is a medicinal plant that is widely used by the Mapuche ethnic group from Chile due to its anti-inflammatory activity. In addition, inhibitory effects of canelo against phytopathogenic fungi and pest insects have been reported. In this study, we isolated, purified, and identified six drimane sesquiterpenoid compounds from canelo (drimenin, drimenol, polygodial, isodrimeninol, valdiviolide, and drimendiol). Then, we evaluated their antimicrobial effects against G. graminis var. tritici. Compounds were identified by comparing Fourier-transform infrared spectroscopy (FTIR) data and the retention time in thin-layer chromatography (TLC) with those of pure standards. The putative antagonistic effects were confirmed by assessing hyphal cell wall damage using confocal microscopy and lipid peroxidation. Here, we reported the high potential of drimane sesquiterpenoids as natural antifungals against G. graminis var. tritici. Polygodial and isodrimeninol were the most effective, with 50% lethal concentrations (LC50s) between 7 and 10 µg ml-1 and higher levels of fungal lipid peroxidation seen. Accordingly, natural sesquiterpenoids purified from canelo are biologically active against G. graminis var. tritici and could be used as natural biofungicides for sustainable agriculture.IMPORTANCE More than two billion tons of pesticides are used every year worldwide. An interesting sustainable alternative to control plant pathogens is the use of natural products obtained from plants, mainly medicinal plants that offer secondary metabolites important to human/animal health. In this study, we isolated and identified six pure drimane sesquiterpenoids obtained from the bark of Drimys winteri Additionally, we evaluated their antifungal activities against Gaeumannomyces graminis (the main biotic factor affecting cereal production, especially wheat) by assessing fungal cell wall damage and lipid peroxidation. The compounds obtained showed important antifungal properties against G. graminis var. tritici, mainly isodrimenol, which was the second-most-active compound after polygodial, with an LC50 against G. graminis var. tritici of around 9.5 µg ml-1 This information could be useful for the development of new natural or hemisynthetic antifungal agents against soilborne phytopathogens that could be used in green agriculture.