Phyllocoptes parviflori is a distinct species and a vector of the pervasive blackberry leaf mottle associated virus.

Several viruses are transmitted by eriophyid mites (Acariformes: Eriophyoidea) including blackberry leaf mottle-associated emaravirus (BLMaV) (Emaravirus rubi). BLMaV is transmitted by an unidentified eriophyid species and is involved in blackberry yellow vein, a devastating disease in the southeastern United States. In this study, we assessed the eriophyid mite Phylocoptes parviflori as a vector of BLMaV and clarified its taxonomic status as it was previously synonymized with Phyllocoptes gracilis. P. parviflori can efficiently transmit BLMaV. The virus was found to cause yellow vein disease symptoms on 'Ouachita' blackberry marking a paradigm shift as disease symptoms have always been associated with multiple virus infections. Therefore, we propose renaming the virus to blackberry leaf mottle virus. The occurrence of P. parviflori on wild and cultivated blackberries, as well as its ability to colonize other Rubus species, enhances its importance as a major contributor to the spread of yellow vein disease.

Información recibida sobre salud sexual y reproductiva asociada a conductas sexuales en universitarias. Medellín, Colombia 2021

Introducción: La juventud representa un periodo de vulnerabilidad acompañado de cambios físicos y psicológicos que predisponen a conductas sexuales de riesgo, en un contexto en el que la calidad de la educación en salud sexual y reproductiva no satisface las necesidades de la población. Objetivo: Identificar la asociación existente entre conductas sexuales de riesgo en mujeres universitarias y su satisfacción frente a la información que han recibido sobre salud sexual y reproductiva a lo largo de sus vidas. Métodos: Estudio descriptivo de tipo transversal aplicado a una muestra por conveniencia de 182 universitarias. Se analizaron variables relacionadas con características sociodemográficas, conductas sexuales de riesgo, fuentes de información y satisfacción frente a la información recibida sobre salud sexual y reproductiva. Se determinó la asociación entre las variables aplicando la prueba chi2 (p < 0,05) y la medida estadística OR. Resultados: Predominaron las mujeres sexualmente activas 70,3 % y mujeres que no deseaban quedar embarazadas al momento de ser encuestadas 98,9 %. Un 10,9 % de las mujeres encuestadas, son sexualmente activas y no planifican aunque no deseen quedar en embarazo. La fuente de educación que predominó fueron los profesionales de la salud (75,3 %). No se evidenció discrepancia significativa entre el porcentaje de mujeres satisfechas con la información que han recibido (51 %) y las no satisfechas (49 %). No se encontró asociación entre conductas sexuales de riesgo y la satisfacción con la información sobre salud sexual y reproductiva que han recibido a lo largo de su vida, teniendo en consideración que esta no representa en su totalidad una educación de calidad. Conclusión: Las estudiantes matriculadas en universidades ubicadas en la ciudad de Medellín muestran conductas sexuales de riesgo, que no se asocian a la satisfacción que poseen frente a la información en salud sexual y reproductiva que han obtenido a lo largo de su vida.

Introduction: Youth represents a period of vulnerability accompanied by physical and psychological changes that predispose individuals to risky sexual behaviors, from a context in which the quality of education in sexual and reproductive health does not meet the needs of the population. Objective: To identify the association between risky sexual behaviors in university women and their satisfaction with the information they have received on sexual and reproductive health throughout their lives. Methods: Descriptive cross-sectional study applied to a convenience sample of 182 university students. Variables related to sociodemographic characteristics, risky sexual behaviors, sources of information and satisfaction with the information received on sexual and reproductive health were analyzed. The association between the variables was determined by applying the chi2 test (p<0.05) and the OR statistical measure. Results: Sexually active women predominated (70.3%) and women who did not want to get pregnant at the time of being surveyed (98.9%);. 10.9% of the women surveyed, are sexually active, do not plan and do not want to get pregnant, the source of education that prevailed were the professionals of health (75.3%). There was no significant discrepancy between the percentage of women satisfied with the information they received (51%) and those who were not satisfied (49%). No association was found between risky sexual behaviors and satisfaction with the information on sexual and reproductive health received throughout their lives, considering that this does not fully represent quality education. Conclusión: The students enrolled in universities located in the city of Medellín show risky sexual behaviors that are not associated with the satisfaction they have with the information on sexual and reproductive health that they have obtained throughout their lives.

Ryanodine receptor type 1 content decrease-induced endoplasmic reticulum stress is a hallmark of myopathies.

BACKGROUND: Decreased ryanodine receptor type 1 (RyR1) protein levels are a well-described feature of recessive RYR1-related myopathies. The aim of the present study was twofold: (1) to determine whether RyR1 content is also decreased in other myopathies and (2) to investigate the mechanisms by which decreased RyR1 protein triggers muscular disorders. METHODS: We used publicly available datasets, muscles from human inflammatory and mitochondrial myopathies, an inducible muscle-specific RYR1 recessive mouse model and RyR1 knockdown in C2C12 muscle cells to measure RyR1 content and endoplasmic reticulum (ER) stress markers. Proteomics, lipidomics, molecular biology and transmission electron microscopy approaches were used to decipher the alterations associated with the reduction of RyR1 protein levels. RESULTS: RYR1 transcripts were reduced in muscle samples of patients suffering from necrotizing myopathy (P = 0.026), inclusion body myopathy (P = 0.003), polymyositis (P < 0.001) and juvenile dermatomyositis (P < 0.001) and in muscle samples of myotonic dystrophy type 2 (P < 0.001), presymptomatic (P < 0.001) and symptomatic (P < 0.001) Duchenne muscular dystrophy, Becker muscular dystrophy (P = 0.004) and limb-girdle muscular dystrophy type 2A (P = 0.004). RyR1 protein content was also significantly decreased in inflammatory myopathy (-75%, P < 0.001) and mitochondrial myopathy (-71%, P < 0.001) muscles. Proteomics data showed that depletion of RyR1 protein in C2C12 myoblasts leads to myotubes recapitulating the common molecular alterations observed in myopathies. Mechanistically, RyR1 protein depletion reduces ER-mitochondria contact length (-26%, P < 0.001), Ca2+ transfer to mitochondria (-48%, P = 0.002) and the mitophagy gene Parkinson protein 2 transcripts (P = 0.037) and induces mitochondrial accumulation (+99%, P = 0.005) and dysfunction (P < 0.001). This was associated to the accumulation of deleterious sphingolipid species. Our data showed increased levels of the ER stress marker chaperone-binding protein/glucose regulated protein 78, GRP78-Bip, in RyR1 knockdown myotubes (+45%, P = 0.046), in mouse RyR1 recessive muscles (+58%, P = 0.001) and in human inflammatory (+96%, P = 0.006) and mitochondrial (+64%, P = 0.049) myopathy muscles. This was accompanied by increased protein levels of the pro-apoptotic protein CCAAT-enhancer-binding protein homologous protein, CHOP-DDIT3, in RyR1 knockdown myotubes (+27%, P < 0.001), mouse RyR1 recessive muscles (+63%, P = 0.009), human inflammatory (+50%, P = 0.038) and mitochondrial (+51%, P = 0.035) myopathy muscles. In publicly available datasets, the decrease in RYR1 content in myopathies was also associated to increased ER stress markers and RYR1 transcript levels are inversely correlated with ER stress markers in the control population. CONCLUSIONS: Decreased RyR1 is commonly observed in myopathies and associated to ER stress in vitro, in mouse muscle and in human myopathy muscles, suggesting a potent role of RyR1 depletion-induced ER stress in the pathogenesis of myopathies.

Genomic analyses of a widespread blueberry virus in the United States.

Screening of blueberry accessions using high throughput sequencing revealed the presence of a new virus. Genomic structure and sequence are similar to that of nectarine stem pitting associated virus (NSPaV), a member of the genus Luteovirus, family Tombusviridae. The full genome of the new luteovirus, tentatively named blueberry virus L (BlVL), was characterized and analyzed. Similar to NSPaV, BlVL does not contain readily identifiable movement proteins in any of the seven isolates sequenced. More than 600 samples collected from five states were screened and 79% were found infected, making BlVL the most widespread blueberry virus in the United States.

Metabolic engineering of Rhodotorula toruloides IFO0880 improves C16 and C18 fatty alcohol production from synthetic media.

BACKGROUND: The oleaginous, carotenogenic yeast Rhodotorula toruloides has been increasingly explored as a platform organism for the production of terpenoids and fatty acid derivatives. Fatty alcohols, a fatty acid derivative widely used in the production of detergents and surfactants, can be produced microbially with the expression of a heterologous fatty acyl-CoA reductase. Due to its high lipid production, R. toruloides has high potential for fatty alcohol production, and in this study several metabolic engineering approaches were investigated to improve the titer of this product. RESULTS: Fatty acyl-CoA reductase from Marinobacter aqueolei was co-expressed with SpCas9 in R. toruloides IFO0880 and a panel of gene overexpressions and Cas9-mediated gene deletions were explored to increase the fatty alcohol production. Two overexpression targets (ACL1 and ACC1, improving cytosolic acetyl-CoA and malonyl-CoA production, respectively) and two deletion targets (the acyltransferases DGA1 and LRO1) resulted in significant (1.8 to 4.4-fold) increases to the fatty alcohol titer in culture tubes. Combinatorial exploration of these modifications in bioreactor fermentation culminated in a 3.7 g/L fatty alcohol titer in the LRO1Δ mutant. As LRO1 deletion was not found to be beneficial for fatty alcohol production in other yeasts, a lipidomic comparison of the DGA1 and LRO1 knockout mutants was performed, finding that DGA1 is the primary acyltransferase responsible for triacylglyceride production in R. toruloides, while LRO1 disruption simultaneously improved fatty alcohol production, increased diacylglyceride and triacylglyceride production, and increased glucose consumption. CONCLUSIONS: The fatty alcohol titer of fatty acyl-CoA reductase-expressing R. toruloides was significantly improved through the deletion of LRO1, or the deletion of DGA1 combined with overexpression of ACC1 and ACL1. Disruption of LRO1 surprisingly increased both lipid and fatty alcohol production, creating a possible avenue for future study of the lipid metabolism of this yeast.

CUT&RUN identifies centromeric DNA regions of Rhodotorula toruloides IFO0880.

Rhodotorula toruloides has been increasingly explored as a host for bioproduction of lipids, fatty acid derivatives and terpenoids. Various genetic tools have been developed, but neither a centromere nor an autonomously replicating sequence (ARS), both necessary elements for stable episomal plasmid maintenance, has yet been reported. In this study, cleavage under targets and release using nuclease (CUT&RUN), a method used for genome-wide mapping of DNA-protein interactions, was used to identify R. toruloides IFO0880 genomic regions associated with the centromeric histone H3 protein Cse4, a marker of centromeric DNA. Fifteen putative centromeres ranging from 8 to 19 kb in length were identified and analyzed, and four were tested for, but did not show, ARS activity. These centromeric sequences contained below average GC content, corresponded to transcriptional cold spots, were primarily nonrepetitive and shared some vestigial transposon-related sequences but otherwise did not show significant sequence conservation. Future efforts to identify an ARS in this yeast can utilize these centromeric DNA sequences to improve the stability of episomal plasmids derived from putative ARS elements.

Conocimientos y creencias sobre aspectos de salud sexual en adolescentes de una comunidad de Querétaro, México / Knowledge and believes about sexual health in teenagers from a rural area in Querétaro, Mexico

INTRODUCCIÓN. La adolescencia es una etapa en que la mayoría de este grupo etario inicia con su vida sexual, por ende, el problema en los adolescentes no es que sean sexualmente activos a temprana edad, sino que no cuentan con la preparación y orientación para una conducta sexual responsable, a consecuencia de ello se presentan conductas y factores de riesgo. OBJETIVO. Identificar los conocimientos y creencias sobre infecciones de transmisión sexual y embarazos no planificados en adolescentes de una comunidad rural de Querétaro. MATERIAL Y MÉTODOS. Investigación transversal descriptiva, realizada a 63 adolescentes. Se aplicó un cuestionario que consta de 86 preguntas divididas en cuatro secciones que abarcan: datos sociodemográficos, conocimientos sobre las infecciones de transmisión sexual, creencias y antecedentes de salud sexual. Se consideraron aspectos éticos en la investigación en humanos. RESULTADOS. 52,4% fueron del género femenino. Con respecto al nivel de conocimientos, 79,4% contestó erróneamente las preguntas planteadas. En relación a las creencias, llaman la atención afirmaciones como que la sexualidad fue creada para la reproducción, que todas las parejas deben tener hijos, efectos erróneos de los anticonceptivos, que el deber de la mujer es ser madre, entre otros aspectos. CONCLUSIONES. Es necesario reforzar el papel educativo del personal de enfermería en la educación sexual de los adolescentes en las zonas comunitarias.

INTRODUCTION. Adolescence it is a life period where these people start with sexual activity, and, with this situation, the problem is that they do not have proper preparation and information for an adequate sexual conduct and because of these, risk factors could be present. OBJECTIVE. To identify knowledge and believes about sexually transmitted diseases and unwanted pregnancies in adolescences from a rural community in Queretaro. MATERIAL AND METHODS. Cross sectional and descriptive research. 63 teenagers participated in the study. A questionary with 86 questions was applied, divided in four sections: sociodemographic data, knowledge about sexually transmitted diseases, believes and background about sexual health. Ethical aspects were considered. RESULTS. 52.4% female. Related with knowledge level, 79.4% answered in a wrong way. Regarded with believes, it was pointed out affirmations such: sexuality is just for reproduction, all couples must have children, fake effects of contraceptives, woman's duty must be being mother, and another. CONCLUSIONS. It is necessary to reinforce the educational paper of the nurse related with teenager's sexual life in rural areas.

Memory Support System training in mild cognitive impairment: Predictors of learning and adherence.

This study aimed to identify predictors of learning and adherence to a previously validated compensatory calendar and note-taking system (Memory Support System; MSS) in persons with amnestic mild cognitive impairment (aMCI). Age, education, global cognition, depression, and memory-related self-efficacy were studied as predictors of individuals' ability to learn the use of the MSS during the two-week training and of their adherence to the MSS 6, 12, and 18 months after training. How well an individual was able to learn the use of the MSS was itself examined as a predictor of adherence. Two-hundred-and-fifteen older adults with aMCI and their study partners (e.g., spouse, adult child) received MSS training one-hour daily for 10 days. Ordinal logistic regression analyses indicated that (1) global cognition predicted MSS learning at end of training, and (2) MSS learning at end of trainng predicted MSS adherence at 6, 12, and 18 months post-training. The current study suggests that offering compensatory strategies as early as possible for those with MCI might be of most benefit, and might have implications for long-term adherence.

Functional ability is associated with higher adherence to behavioral interventions in mild cognitive impairment.

Objective: Behavioral interventions during early memory decline hold promise in delaying the development of dementia. In the present study, participants in a multimodal behavioral intervention study were assessed for post-intervention adherence and predictors of adherence.Methods: Participants (N = 272, mean age = 75.04 ± 7.54) diagnosed with amnestic Mild Cognitive Impairment (aMCI) were assigned to intervention groups receiving four out of five behavioral intervention components, including yoga, memory compensation training, computerized cognitive training, support groups, and/or wellness education. Length of the intervention was 10 days, 4 h per day, with post-intervention follow-up at 6, 12, and 18 months.Results: Two-hundred and thirty-seven participants completed the 6-month post-intervention follow-up measures, 228 participants completed the 12-month measures, and 218 participants completed the 18-month measures. Participants fully adhered to a mean of 2 out of the 4 taught intervention components. Eighty-nine percent of participants were at least partially adherent to one or more taught intervention components at 6-, 12-, and 18-month post-intervention follow-up. Physical activity was the most adhered to intervention while group support was the least adhered to intervention across all three follow-up time-points. Higher educational level, higher baseline depressive symptoms, higher baseline global cognitive functioning, and better baseline and concurrent functional abilities were associated post-intervention adherence.Conclusion: Changes in functional abilities are associated with disease progression among persons with aMCI. In the present study, individuals with aMCI who have higher education, higher depressive symptoms, and better baseline functioning abilities are more likely to adhere to behavioral intervention components over time. Post-intervention adherence also associates with concurrent daily function.

COINFECCIÓN NATURAL DE VIRUS DE ARN EN CULTIVOS DE PAPA (Solanum tuberosum subsp. Andigena) EN ANTIOQUIA (COLOMBIA) / Natural coinfection of RNA viruses in potato (Solanum tuberosum subsp. Andigena) crops in Antioquia (Colombia)

RESUMEN Las enfermedades virales son uno de los principales problemas fitopatológicos de la papa. Con el fin de determinar los virus más prevalentes en cultivos de papa var. Diacol Capiro en el oriente Antioqueño (Colombia), se evaluó mediante RT-qPCR la presencia de diez virus de ARN (PVY, PVA, PVV, TaLMV, PVS, PLRV, PYVV, PVX, ToRSV y PMTV) en 36 muestras de tejido foliar. Los resultados indicaron la ocurrencia de cinco de los diez virus evaluados, con niveles de prevalencia de 88,9 %, 75 %, 75 %, 41,7 % y 25 % para PVY, PVX, PYVV, PLRV y PVS, respectivamente. Con fines comparativos, cuatro virus también se evaluaron mediante ELISA, siendo detectados PVS (80,5 %), PVY (55 %) y PLRV (5,5 %); mientras que PVX no fue encontrado con esta prueba. La comparación de estas técnicas mediante la razón de prevalencia (RP), indicó que la RT-qPCR ofrece niveles superiores de detección con valores de RP = 1,6 y RP = 7,5 para los virus PVY y PLRV; mientras que para PVS la ELISA detectó más muestras positivas que RT-qPCR (RP = 3,22), evidenciándose la necesidad de diseñar nuevos cebadores ajustados a la diversidad de este virus en Antioquia. La coinfección mixta más frecuente fue PVY-PYVV-PVX (22,2 %), mientras que los cinco virus se encontraron en el 11,1 % de las muestras. Finalmente, utilizando secuenciación Sanger de la cápside y NGS para los genomas completos, se confirmó la circulación de todos los virus detectados en los cultivos de papa del oriente Antioqueño. Estos resultados señalan la necesidad de fortalecer los programas de manejo integrado de enfermedades virales en Antioquia.

ABSTRACT Viral diseases are one of the main phytopathological problems affecting potato crops worldwide. To determine the most prevalent viruses in potato var. Diacol Capiro crops in Eastern Antioquia, 36 leaf samples were tested for the presence of PVY, PVA, PVV, TaLMV, PVS, PLRV, PYVV, PVX, ToRSV and PMTV using RT-qPCR. Detected viruses included PVY, PVX, PYVV, PLRV and PVS with prevalence levels of 88.9 %, 75.0 %, 75.0 %, 41.7 % and 25.0 %, respectively. PVS, PVY, PLRV and PVX were also tested by ELISA. PVS, PVY and PLRV tested positive in 80.5 %, 55.0 % and 5.5 % of samples; PVX was not detected. Prevalence Ratios (PR) suggests that detection is higher for PVY (PR = 1.6) and PLRV (PR = 7.5) using RT-qPCR. ELISA worked better for PVS with a PR of 3.2; this result suggests that the RT-qPCR primers used for PVS must be adjusted to reflect the genome diversity of virus in Antioquia. The most frequent coinfection was PVY-PYVV-PVX, which occurred in 22.2 % of samples; coinfection with PVY, PVX, PYVV, PLRV and PVS was present in 11.1 % of samples. The circulation of these viruses in Eastern Antioquia was further confirmed using Sanger and high-throughput sequence. This work highlights the need to strengthen integrated disease management programs of viruses in Antioquia.

Design of primers for specific detection of Potato Virus Y (PVY) by RT-PCR / Diseño de cebadores específicos para la detección por rt-pcr del potato virus y (pvy)

RESUMEN El Potato virus Y (PVY) es uno de los virus más limitantes para la producción de papa (Solanum tuberosum y S. phureja) en el mundo. Este virus es transmitido por tubérculo-semilla de papa y por diferentes especies de áfidos. Para su manejo es fundamental la siembra de tubérculos certificados por su sanidad viral, para lo que se requieren metodologías de detección altamente sensibles como ELISA y RT-PCR. Para éstas últimas pruebas, es necesario disponer de cebadores específicos que permitan el diagnóstico del virus en tejidos asintomáticos. En este estudio se reportan los cebadores PVY_Col para la detección del PVY en RT-PCR convencional y en tiempo real (RT-qPCR). Estos cebadores fueron diseñados con base en las secuencias de este virus que se han reportado en Colombia sobre diferentes hospedantes, así como de las diferentes variantes encontradas en el mundo. Una particularidad adicional de estos cebadores es que no presentan reacción cruzada con el genoma del Potato virus V (PVV), otro potyvirus que recientemente se ha encontrado afectando cultivos de papa en Colombia. Se espera que los cebadores PVY_Col sean utilizados para apoyar los programas de certificación de material de siembra de papa, así como para adelantar estudios epidemiológicos y de manejo fitosanitario de este virus.

ABSTRACT Potato virus Y (PVY) is one of the most limiting viruses in the production of potato (Solanum tuberosum and S. phureja) worldwide. This virus is transmitted by aphids and infected tuber-seeds, and for this reason, disease management of PVY requires, among others, using certified planting material through highly sensitive techniques such as ELISA and RT-PCR. However, RT-PCR-based methods require primers of high specificity to allow the unequivocal detection of viruses in asymptomatic tissues. In this work, we report a new set of primers (PVY_Col) for detection of PVY by RT-PCR and real-time RT-PCR (RT-qPCR). These primers were designed using sequences of PVY isolates from Colombia and the rest of the world. An essential feature of these primers is their specificity, since they don't amplify templates from Potato virus V (PVV), a close PVY relative that also infects potato crops in Colombia. It is expected that the PVY_Col primer set will be useful to support potato seed certification programs, epidemiological studies, and PVY disease management programs.

Shared decision making in mild cognitive impairment.

Shared decision making (SDM) occurs when patients and clinicians consider patients' values and preferences while discussing medical evidence to inform healthcare decisions. SDM enables patients with mild cognitive impairment (MCI) to express values and preferences when making current healthcare decisions and presents a unique opportunity to inform future decision making in the case of further cognitive decline. However, clinicians often fail to facilitate SDM with patients with MCI. This review describes research pertaining to value solicitation, weighing of the medical evidence, and medical decision making for individuals with MCI, explores the role of caregivers, identifies barriers to and facilitators of SDM in MCI, and suggests strategies to optimize SDM for persons with MCI in neurology clinical practice. Further research is needed to identify more strategies for decision support for individuals affected by cognitive impairment.

Self-Efficacy Mediates the Association Between Physical Function and Perceived Quality of Life in Individuals with Mild Cognitive Impairment.

BACKGROUND: Research has shown that individuals with mild cognitive impairment (MCI) value quality of life (QoL) above and beyond cognitive function or other potential outcomes in MCI. There is evidence supporting the negative impact of poor physical function on QoL ratings. OBJECTIVE: The study explored whether a modified measure of self-efficacy for managing MCI and education mediated and/or moderated the relationship between physical function and QoL in persons with MCI. METHODS: Baseline data from 200 participants with MCI were obtained from a larger study assessing the effectiveness of a behavioral intervention. Physical function was assessed by the Short Physical Performance Battery. QoL was assessed with the Quality of Life in Alzheimer's Disease scale. Memory-related self-efficacy was assessed using a modified 9-item version of the Chronic Disease Self-Efficacy Scales. Mediation and moderation analyses tested the hypotheses that self-efficacy and education alter the association between physical function and QoL in individuals with MCI. All analyses were adjusted for age, cognitive severity, and sex. RESULTS: Self-efficacy for managing MCI was a significant mediator of the association between physical function and perceived QoL. Individuals with better physical function reported higher self-efficacy which was associated with higher QoL ratings. CONCLUSIONS: Greater self-efficacy for managing MCI mediated the negative association between physical function and quality of life in this exploratory study. Interventions aimed at enhancing memory self-efficacy in MCI may improve perceived QoL, even in the presence of poor physical function. Future research is needed to investigate this further.

Progestogen safety and tolerance in hormonal replacement therapy.

INTRODUCTION: Today, it is a mandatory practice to prescribe a combination of estrogens and progestogens for menopausal women requiring hormone therapy and with a uterus. The WHI study and its reanalysis demonstrate a big difference in results between the conjugated equin estrogen (CEE) only vs.CEE plus medroxyprogesterone acetate (MPA) arms in relation with breast cancer and cardiovascular risk. The conclusion is that risk is clearly higher in the arm with MPA than in the CEE only arm. Although the only progestogen used in the WHI study was medroxyprogesterone acetate, side effects and intolerance have been extrapolated as a class effect to all progestogens. Areas covered: Progestogen tolerance and side effects in hormone therapy were reviewed. For that purpose, a limited literature search was conducted on key resources including Pubmed, the Cochrane Library, ECRI, and major international health technology agencies. Expert opinion: Many of the tolerance effects are based on limited data. There are no double-blind randomized trials comparing long-term safety for breast cancer and cardiovascular risk among different progestogens. Short-term clinical studies, observational, and in animal and in vitro studies indicate that both micronized progesterone and dydrogesterone are the safer progestogens with an acceptable metabolic profile.