Identification of Secondary Metabolites from the Mangrove-Endophyte Lasiodiplodia iranensis F0619 by UPLC-ESI-MS/MS.

Lasiodiplodia is a widely distributed fungal genus, frequently found in tropical and subtropical regions where it can cause disease in important crops. It represents a promising source of active secondary metabolites with uses in chemical, pharmaceutical, and agrochemical processes. In this study, the strain Lasiodiplodia iranensis F0619 was isolated from the mangrove Avicennia ger-minans, collected from Sarigua National Park in the Republic of Panama. Fractions of crude extract were analyzed by UPLC-ESI-MS/MS, and five compounds, previously reported from Lasiodiplodia genus were identified, including 11,12-didehydro-7-iso-jasmonic acid (1), 4,5-didehydro-7-iso-jasmonic acid (2), cyclo-(L-Leu-L-Pro) (3), jasmonate-threonine (4), and abscisic acid (5). We describe and analyze their MS/MS fragmentation patterns to confirm the compounds 'chemical structures.

Patient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization.

BACKGROUND: Polygenic risk scores (PRS), which offer information about genomic risk for common diseases, have been proposed for clinical implementation. The ways in which PRS information may influence a patient's health trajectory depend on how both the patient and their primary care provider (PCP) interpret and act on PRS information. We aimed to probe patient and PCP responses to PRS clinical reporting choices METHODS: Qualitative semi-structured interviews of both patients (N=25) and PCPs (N=21) exploring responses to mock PRS clinical reports of two different designs: binary and continuous representations of PRS. RESULTS: Many patients did not understand the numbers representing risk, with high numeracy patients being the exception. However, all the patients still understood a key takeaway that they should ask their PCP about actions to lower their disease risk. PCPs described a diverse range of heuristics they would use to interpret and act on PRS information. Three separate use cases for PRS emerged: to aid in gray-area clinical decision-making, to encourage patients to do what PCPs think patients should be doing anyway (such as exercising regularly), and to identify previously unrecognized high-risk patients. PCPs indicated that receiving "below average risk" information could be both beneficial and potentially harmful, depending on the use case. For "increased risk" patients, PCPs were favorable towards integrating PRS information into their practice, though some would only act in the presence of evidence-based guidelines. PCPs describe the report as more than a way to convey information, viewing it as something to structure the whole interaction with the patient. Both patients and PCPs preferred the continuous over the binary representation of PRS (23/25 and 17/21, respectively). We offer recommendations for the developers of PRS to consider for PRS clinical report design in the light of these patient and PCP viewpoints. CONCLUSIONS: PCPs saw PRS information as a natural extension of their current practice. The most pressing gap for PRS implementation is evidence for clinical utility. Careful clinical report design can help ensure that benefits are realized and harms are minimized.

Blood DNA Methylation and Incident Coronary Heart Disease: Evidence From the Strong Heart Study.

Importance: American Indian communities experience a high burden of coronary heart disease (CHD). Strategies are needed to identify individuals at risk and implement preventive interventions. Objective: To investigate the association of blood DNA methylation (DNAm) with incident CHD using a large number of methylation sites (cytosine-phosphate-guanine [CpG]) in a single model. Design, Setting, and Participants: This prospective study, including a discovery cohort (the Strong Heart Study [SHS]) and 4 additional cohorts (the Women's Health Initiative [WHI], the Framingham Heart Study [FHS], the Atherosclerosis Risk in Communities Study ([ARIC]-Black, and ARIC-White), evaluated 12 American Indian communities in 4 US states; African American women, Hispanic women, and White women throughout the US; White men and White women from Massachusetts; and Black men and women and White men and women from 4 US communities. A total of 2321 men and women (mean [SD] follow-up, 19.1 [9.2] years) were included in the SHS, 1874 women (mean [SD] follow-up, 15.8 [5.9] years) in the WHI, 2128 men and women (mean [SD] follow-up, 7.7 [1.8] years) in the FHS, 2114 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-Black, and 931 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-White. Data were collected from May 1989 to December 2018 and analyzed from February 2019 to May 2021. Exposure: Blood DNA methylation. Main Outcome and Measure: Using a high-dimensional time-to-event elastic-net model for the association of 407 224 CpG sites with incident CHD in the SHS (749 events), this study selected the differentially methylated CpG positions (DMPs) selected in the SHS and evaluated them in the WHI (531 events), FHS (143 events), ARIC-Black (350 events), and ARIC-White (121 events) cohorts. Results: The median (IQR) age of participants in SHS was 55 (49-62) years, and 1359 participants (58.6%) were women. Elastic-net models selected 505 DMPs associated with incident CHD in the SHS beyond established risk factors, center, blood cell counts, and genetic principal components. Among those DMPs, 33 were commonly selected in 3 or 4 of the other cohorts and the pooled hazard ratios from the standard Cox models were significant at P < .05 for 10 of the DMPs. For example, the hazard ratio (95% CI) for CHD comparing the 90th and 10th percentiles of differentially methylated CpGs was 0.86 (0.78-0.95) for cg16604233 (tagged to COL11A2) and 1.23 (1.08-1.39) for cg09926486 (tagged to FRMD5). Some of the DMPs were consistent in the direction of the association; others showed associations in opposite directions across cohorts. Untargeted independent elastic-net models of CHD showed distinct DMPs, genes, and network of genes in the 5 cohorts. Conclusions and Relevance: In this multi-cohort study, blood-based DNAm findings supported an association between a complex blood epigenomic signature and CHD that was largely different across populations.

Algunos factores que condicionan la intoxicación por plomo en trabajadores que reconstruyen baterias, distrito - Miraflores 1995

El presente estudio titulado "Agunos factores condicionantes de la intoxicación por plomo, en trabajadores que reconstruyen bacterias. Miraflores 1995"; lo realizamos motivadas por la no existencia de estudios sobre la problemática de salud de este sector trabajador. El trabajo se efectuó en los meses de marzo y abril de 1995, en 15 talleres del distrito de Miraflores con un total de 40 trabajadores. El objetivo general fue: Determinar si los factores físicos, sociales y culturales condicionan la intoxicación por plomo en los trabajadores que reconstruyen baterías. El estudio fue de tipo Epidemiológico con un diseño Observacional Analítico. Para la recolección de la información se utilizó como técnicas la entrevista y la observación, utilizando como instrumento una guía de entrevista y una guía de observación. Para el análisis de los resultados encontrados en la investigación, se utilizó la prueba estadística del Ji cuadrado, la que comprueba la hipótesis general y la relación entre variables.