In this study, we aimed to investigate the anticancer activity of the extract, fractions, and isolated compounds of the flowers of Fridericia platyphylla, and to characterize the bioactive compounds. The chemical diversity of the extracts and fractions was investigated using liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS). We were able to annotate 26 compounds from the classes of flavones, flavonols, flavanones, isoflavones, and cinnamic acid and its derivatives. The dichloromethane fraction showed greater cytotoxicity at a concentration of 100 µg mL−1. In addition, the inhibitory concentrations of the dichloromethane fraction were 22.14 and 30.9 µg mL−1 for MCF-7 and MDA-MB-231 cell lines, respectively, and were capable of inhibiting tumor cell migration. Brachydins A and C were isolated from the dichloromethane fraction and showed the greatest cytotoxicity. The results obtained from this study show the potential biological effect of F. platyphylla flowers as a possible antitumor pharmacological agent. extract LCHRMS. LCHRMS LC HRMS . (LC-HRMS) 2 flavones flavonols flavanones isoflavones derivatives 10 mL1 mL 1 addition 2214 22 14 22.1 309 30 9 30. mL− MCF7 MCF 7 MCF- MDAMB231 MDAMB MDA MB 231 MDA-MB-23 lines respectively migration F agent (LC-HRMS 221 22. 3 MDAMB23 23 MDA-MB-2 MDAMB2 MDA-MB- MDA-MB

Resumen Introducción: Las malformaciones del desarrollo cortical se deben a alteraciones en la migración del neuroblasto durante la formación de la corteza cerebral. Se desconoce su frecuencia en embarazos monocoriales. Objetivo: Reportar el caso de un embarazo monocorial con diagnóstico de malformación del desarrollo cortical en uno de los fetos y revisar la literatura referente a su diagnóstico y pronóstico. Método: Mujer de 19 años, embarazo monocorial biamniótico de 26 semanas, que acudió con estudio ecográfico y resonancia fetal que evidenció en uno de los fetos asimetría de los hemisferios cerebrales, hipoplasia de la cisura de Silvio izquierda con simplificación del patrón giral por focos de paquigiria y polimicrogiria, con confirmación posnatal de alteración en la migración neuronal asociada a hipoplasia vermiana. Resultados: Se encontraron en la literatura tres casos de embarazo múltiple monocorial con trastorno de la migración neuronal con recién nacidos vivos. Los hallazgos más comunes fueron microcefalia, lisencefalia e hipoplasia cerebelosa. Conclusiones: El diagnóstico prenatal del trastorno de la migración neuronal se realiza con ecografía y resonancia fetal. La más frecuente es la alteración de la migración neuronal tipo II. El pronóstico depende del tipo de alteración; sin embargo, la mayoría de los casos presentan trastornos epileptiformes con alteraciones del neurodesarrollo.

Abstract Introduction: Malformations of cortical development are the result from alterations in the neuroblast migration during the cerebral cortex formation. It’s frequency in monochorial multiple pregnancies remains unknown. Objective: To report a case of monochorial multiple pregnancy with diagnosis of malformation of the cortical development in one of the fetuses. In addition, to review the literature regarding the diagnosis and prognosis of this entity. Method: A 19-year-old female with a monochorial diamniotic pregnancy of 26 weeks’ gestation, arrived with an ultrasound anatomy scan visit, and fetal magnetic resonance imaging, we detected asymmetry in the cerebral hemispheres one of the fetuses, hypoplasia of the left sulcus of Sylvius with simplification of the gyrus pattern due to clusters of pachygyria and polymicrogyria. Those findings were confirmed afterbirth, with a definite diagnosis of neuronal migration disorder associated with vermian hypoplasia. Results: Three cases of monochorial pregnancy with neuronal migration disorder with live newborn, common findings like microcephaly, lissencephaly and vermian hypoplasia. Conclusions: Prenatal diagnosis with neuronal migration disorder is done via ultrasound and magnetic resonance imaging. Neuronal migration disorders type II are the most common of them. Prognosis depends on the type of disorder; however, most patients have epileptiform activity and neurodevelopment impairment.

ABSTRACT The aim of this study was to update the epidemiological information of brucellosis in the province of Formosa, Argentina, based on records from the Research and Transfer Centre during the 2018-2021 period. In total, 151 218 samples of bovine sera from 1953 establishments in the province of Formosa were serologically analysed. Data analysis was done using logistic regression. The presence of spatial association clusters for populations with heterogeneous distribution was evaluated by scanning a data group less than 50% of the population at risk. The distribution of herds positive for brucellosis was assumed as a Bernoulli distribution. The prevalence of bovine brucellosis was 0.88%, while that of herds positive for brucellosis was 17.1%. The intra-herd prevalence was 5.73% (95% CI 0.34-24.18%). In 2018, a prevalence of 0.44% was observed with increases in 2019 (1.77%) and 2021 (0.52%). The spatial analysis identified four significant clusters, two of them with a higher risk of developing the disease and two with a lower risk, presenting Relative Risk (RR) values of 3.92, 30.13, 0.02 and 0.014, respectively. The disease continues to be present in the province with high prevalence, concentrating in the central and eastern areas of the province of Formosa.

RESUMEN El objetivo del trabajo fue actualizar la información epidemiológica de la brucelosis en la provincia de Formosa, Argentina, con base de registros provenientes del Centro de Investigaciones y Transferencia durante el periodo 2018-2021. Se analizaron serológicamente 151 218 muestras de sueros bovinos provenientes de 1953 establecimientos de provincia de Formosa. El análisis de los datos se hizo mediante una regresión logística. Se evaluó la presencia de clústeres de asociación espacial para poblaciones con distribución heterogénea escaneando un grupo de datos menor al 50% de la población bajo riesgo. La distribución de rodeos positivos a brucelosis fue asumida como una distribución Bernoulli. La prevalencia de brucelosis bovina fue de 0.88%, mientras que la de rodeos positivos a brucelosis fue de 17.1%. La prevalencia intra-rodeo fue de 5.73% (IC95% 0.34-24.18%). En 2018 se observó una prevalencia de 0.44% con incrementos en 2019 (1.77%) y 2021 (0.52%). El análisis espacial identificó cuatro clústeres significativos, dos de ellos de mayor riesgo de presentar la enfermedad y dos de menor riesgo, presentando valores de Riesgo Relativo (RR) de 3.92, 30.13, 0.02 y 0.014, respectivamente. La enfermedad continua presente en la provincia con prevalencias elevadas, concentrándose en las zonas centro y este de la provincia de Formosa.

Abstract Objective To determine the frequency of radiographic changes in the temporomandibular joint, in a representative population of patients with Juvenile Idiopathic Arthritis (JIA) and to compare with findings in healthy controls matched by sex and age. Patients and Methods One hundred and thirty-seven panoramic radiographies (PR) from JIA patients of a pediatric rheumatology outpatient clinic were prospectively evaluated and compared to 137 PR from healthy individuals. Results 102 (74.5%) JIA patients and 47 (34.3%) controls showed at least one radiological alteration (p < 0.001). The following radiographic alterations were more frequently observed in JIA patients than in controls: erosion (p < 0.001), altered condylar morphology (p < 0.001), disproportion between condylar process and the coronoid process (p < 0.001) and accentuated curve in the antegonial notch (p = 0.002). Twenty patients (14.6%) presented the four radiographic alterations simultaneously compared to only two controls (1.5%) (p < 0.001). Conclusion Due to the difference in the frequency of findings in the PR of patients and controls, we concluded that PR has value as a screening tool. In the presence of major changes in the mandible head in the PR of patients with a confirmed diagnosis of JIA, MRI should be considered to detect an active inflammatory process in this joint. joint (JIA age thirtyseven thirty seven (PR 13 individuals 10 74.5% 745 74 5 (74.5% 4 34.3% 343 34 3 (34.3% p 0.001. 0001 0.001 . 0 001 0.001, , 0.002. 0002 0.002 002 0.002) 14.6% 146 14 6 (14.6% 1.5% 15 1 (1.5% tool 74.5 7 (74.5 34.3 (34.3 000 0.00 00 14.6 (14.6 1.5 (1.5 74. (74. 34. (34. 0.0 14. (14. 1. (1. (74 (34 0. (14 (1 (7 (3 (

Abstract Staphylus evemerus Godman & Salvin, 1896 is a species with a unique set of morphological characters within Carcharodini. Also, mitochondrial cytochrome oxidase subunit 1 (COI) sequences analysis demonstrated a large genetic distance with other related genera of the tribe. Therefore, this paper aims to describe a new genus for this species, which is named as Uniphylus gen. nov. Besides the morphological redescription of the male of Uniphylus evemerus (Godman & Salvin, 1896) new comb., the description of the female is provided for the first time, as well as an updated distributional map with all records known so far for this species. Salvin 189 Carcharodini Also COI (COI tribe Therefore gen nov comb comb. time 18

Abstract UVB-irradiation increases the risk of various skin disorders, therefore leading to inflammation and oxidative stress. In this sense, antioxidant-rich herbs such as Rosmarinus officinalis may be useful in minimizing the damage promoted by reactive oxygen species. In this work, we report the efficacy of a R. officinalis hydroethanolic extract (ROe)-loaded emulgel in preventing UVB-related skin damage. Total phenols were determined using Folin-Ciocalteu assay, and the main phytocomponents in the extract were identified by UHPLC-HRMS. Moreover, in vitro sun protection factor (SPF) value of ROe was also assessed, and we investigated the in vivo protective effect of an emulgel containing ROe against UVB-induced damage in an animal model. The ROe exhibited commercially viable SPF activity (7.56 ± 0.16) and remarkable polyphenolic content (24.15 ± 0.11 mg (Eq.GA)/g). HPLC-MS and UHPLC-HRMS results showcased that the main compounds in ROe were: rosmarinic acid, carnosic acid and carnosol. The evaluation of the in vitro antioxidant activity demonstrated a dose-dependent effect of ROe against several radicals and the capacity to reduce iron. Therefore, we demonstrated that topical application of the formulation containing ROe inhibited edema formation, myeloperoxidase activity, GSH depletion and maintained ferric reducing (FRAP) and ABTS scavenging abilities of the skin after UVB exposure. UVBirradiation irradiation disorders stress sense antioxidantrich rich species work R ROeloaded loaded UVBrelated related FolinCiocalteu Folin Ciocalteu assay UHPLCHRMS. UHPLCHRMS UHPLC HRMS. HRMS Moreover (SPF assessed UVBinduced induced model 7.56 756 7 56 (7.5 0.16 016 0 16 24.15 2415 24 15 (24.1 011 11 0.1 Eq.GA/g. EqGAg Eq.GA /g . Eq GA g (Eq.GA)/g) HPLCMS HPLC MS carnosol dosedependent dose dependent iron Therefore formation FRAP (FRAP exposure 7.5 75 5 (7. 01 1 24.1 241 2 (24. 0. Eq.GA/g EqGA (Eq.GA)/g 7. (7 24. (24 ( (2

Resumen Objetivo: El objetivo primario fue conocer la actual aplicación de instrumentos de evaluación de competencias quirúrgicas en las residencias acreditadas por la AAOT. Como objetivos secundarios, se describieron los tipos de herramientas utilizadas, el conocimiento de los diferentes instrumentos de evaluación y qué tipo de evaluación se utiliza para la promoción de año. Se analizó si existen diferencias en las características entre las residencias que evalúan las competencias quirúrgicas y las que no. Materiales y Métodos: Se realizó un estudio descriptivo, para lo cual se diseñó una encuesta enfocada en mostrar cuántas residencias evalúan las competencias quirúrgicas con una herramienta formal. Además, a través de ella, se logró responder a los objetivos secundarios. La encuesta se envió a los responsables docentes de las 123 residencias acreditadas por la AAOT. Resultados: Se obtuvieron 105 (85,4%) respuestas, el 59% utiliza algún tipo de herramienta para evaluar las competencias quirúrgicas. Solo el 12,9% de las herramientas utilizadas evalúan las competencias quirúrgicas en forma específica y el resto lo hace con un puntaje general. Un 61% conoce las herramientas disponibles. Para la promoción de año, la mayoría utiliza evaluaciones periódicas múltiples para competencias clínicas y quirúrgicas (63,8% y 67,6%, respectivamente). No hubo diferencias significativas en las características de las residencias que evalúan las competencias quirúrgicas y las que no. Conclusión: El 59% de las residencias implementa algún puntaje o formulario para evaluar las competencias quirúrgicas, solo el 12,9% las evalúa en forma específica, y el resto lo hace con un puntaje subjetivo global.

Abstract Objective: The primary objective was to evaluate the current application of surgical competency (SC) assessment tools in residences accredited by the AAOT. There was also interest in knowing the types of assessment tools used, the knowledge of the different evaluation instruments and what type of evaluation they use for the promotion of the year. We analyzed whether there were differences in the characteristics between the residences that evaluate the SCs and those that do not. Materials and Methods: A descriptive study was carried out, for which a survey was developed focused on assessing how many residences evaluate the SCs with a formal tool. In addition, through the survey it was possible to answer the secondary objectives. It was sent to the chief of residency of the 123 accredited residencies. Results: 105 (85.4%) responses were obtained, 59% (62) used some type of tool for the evaluation of the SC. Only 12.9% (8/62) of the tools used evaluate the SC in a specific way but the majority assed them with a general score. 61% (64/105) know the tools available. For the promotion of the year, the majority use multiple periodic evaluations for clinical and surgical competencies (63.8% and 67.6% respectively). No significant differences were found in the characteristics of the residences that evaluate SC and those that do not. Conclusions: 59% of the residences implement some score or tool for the evaluation of SC, the majority perform the evaluation with a subjective global score. Only the 12.9% evaluate the SC specifically.

ABSTRACT In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults “Detected” positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, “not Detected”, using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

Platonia insignis fruit, popularly known as bacuri, is traditionally used in folk medicine for its anti-inflammatory and antioxidant properties. Therefore, this study determined the chemical composition and biological activities of the bacuri’s shell and seeds extracts, considered residues from its consumption and industrial uses. Four biflavonoids (GB-2a, GB-1a, morelloflavone, and volkensiflavone) were identified in the extracts by high-performance liquid chromatography-diode array detection (HPLC-DAD), liquid chromatography tandem mass spectrometry (LC-MS/MS), and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) techniques. Morelloflavone was identified as the main compound in the shell ethyl acetate extract, being responsible for the high in vitro antioxidant (50% effective concentration (EC50) ranging from 8.0-10.5 µg mL−1 in different protocols), anti-glycant (80%), and moderate inhibition of nitric oxide (1.56 µg mL−1 for > 90% cell viability) activities. This extract showed promising in vivo anti-inflammatory activity evaluated through the paw edema protocol after its incorporation into a liquid-crystalline drug carrier system, reducing the edema by up to 31%. The results demonstrated the potential of the fruit for the development of drugs of natural origin and corroborated to add economic value to these discarded residues.

Abstract This study analysed the mycobiota on exoskeleton debris of the crab Neohelice granulata collected from an alkaline salt marsh and assessed the in vitro enzyme ability of selected isolates at different temperatures and pH. Exoskeleton fragments were incubated in moist chambers on paper and on agar medium. Growth and enzyme ability of selected fungi were also evaluated in agar media with 0.5 % casein, 1% Tween®20, and Chitin-Azure® by the production of a halo/growth ratio. We identified 22 fungal species using both methods. Since the two isolation methods added information to one another, both ones are necessary to recover the cultivable mycobiota associated with the exoskeleton debris. All fungi showed greater levels of enzyme activity in alkaline than acid medium with Tween®20. The halo diameter on casein and chitin varied according to the fungal isolate and pH. Most fungi had a larger halo at 4°C than at the other temperatures tested. Clonostachys rosea showed the greatest activity in all media at 4ºC. We conclude that exoskeletons of the N. granulata are a source of fungi able to produce enzyme activities that show differences upon incubation conditions to which they are cultivated such as ones including specific temperatures and pH values.

Resumen Introducción: Los hongos entomopatógenos se han utilizado como agentes de control biológico de plagas de insectos y han demostrado una capacidad prometedora para colonizar una amplia gama de especies de plantas como endófitos. Objetivo: Los objetivos de este estudio fueron: evaluar las técnicas de inoculación más efectivas para B. bassiana en plantas de pimiento; evaluar la presencia de endófitos naturales y su interacción con B. bassiana y evaluar el efecto de B. bassiana sobre la preferencia de alimentación de la hoja de pimiento y el crecimiento de la plaga de áfidos M. persicae. Métodos: Se evaluaron tres técnicas de inoculación: aspersión foliar, inmersión de semillas e inmersión de raíces. Las plantas de pimiento se inocularon con una suspensión de conidias ajustada a 1x108 conidias/ml. La presencia de B. bassiana en las plántulas se evaluó a los 7, 15 y 28 días después de la inoculación. Resultados: Se encontraron diferencias significativas entre las técnicas de inoculación. La aspersión foliar mostró la frecuencia más alta. Los endófitos naturales presentaron frecuencias más altas en los tratamientos en los que B. bassiana tuvo una frecuencia baja, esto podría indicar la presencia de actividad antifúngica que interfiere con el establecimiento del entomopatógeno en los tejidos de pimiento. No se encontraron diferencias significativas en la mortalidad, reproducción y preferencia alimentaria de M. persicae. Conclusiones: Se demostró que la cepa B. bassiana LPSC 1067 se estableció efectivamente como endófito en los tejidos de pimiento. La técnica de inoculación más efectiva fue la aspersión foliar. No se encontraron diferencias significativas con respecto a la mortalidad, reproducción y preferencia alimentaria de M. persicae. Sin embargo, la inoculación con B. bassiana mostró una tendencia a aumentar la mortalidad de los adultos y a disminuir la descendencia (ninfas). Se necesitan estudios futuros que evalúen los efectos indirectos de los entomopatógenos endofíticos tanto en plantas como en insectos herbívoros para explorar más a fondo su posible uso en el manejo de insectos plaga.

Abstract Introduction: Entomopathogenic fungi have been used as biological control agents of insect pests and have demonstrated a promising ability to colonize as endophytes a wide range of plant species. Objective: The aims of this study were to evaluate, in pepper plants, the most effective Beauveria bassiana inoculation techniques. In order to evaluate the presence of natural endophytes and its interaction with B. bassiana. Also to assess the effect of B. bassiana on the aphid Myzus persicae pepper leaf feeding preference and growth. Methods: Three inoculation techniques were evaluated: leaf spraying, seed immersion and root dipping. The pepper plants were inoculated with a conidia suspension adjusted to 1×108 conidia/ml. The presence of B. bassiana in the seedlings was evaluated at 7, 15 and 28 days after inoculation. Results: We found significant statistical differences between inoculation techniques. Foliar spraying showed the highest B. bassiana colonizationfrequency. The natural endophytes presented higher presence in the treatments in which B. bassiana had a low presence. This might indicate the occurrence of antifungal activity that interferes with the establishment of the entomopathogen in pepper tissues. We did not find statistical differences between inoculated and control pepper leaves with regard to the mortality and reproduction of the aphid pest M. persicae. However, the inoculation with B. bassiana showed a tendency to increase the mortality of adults and to decrease the offspring (nymphs). We did not find significant differences in the feeding preference between inoculated and control leaves, although there was a higher number of individuals on control leaves compared to those inoculated. Conclusions: The strain B. bassiana LPSC 1067 was established effectively as an endophyte in the pepper tissues. The most effective inoculation technique was leaf spraying. We did not find differences of statistical significance with regard to the mortality and reproduction of the aphid pest M. persicae. However, the inoculation with B. bassiana showed a tendency to increase the mortality of adults and to decrease the offspring (nymphs). Future studies evaluating the indirect effects of endophytic entomopathogens on both plants and herbivorous insects are needed to further explore their potential use in the management of insect pests.

Wiskott-Aldrich syndrome is a rare X chromosome-linked primary immunodeficiency syndrome associated with an increased incidence of infections, autoimmune disorders and neoplasms. We present the case of a 41-year-old man with a diagnosis of Wiskott-Aldrich syndrome with ileitis as a form of presentation of a lymphoproliferative syndrome. The ileitis, in the context of the patient, represents a clinical challenge given the large number of differential diagnoses (inflammatory bowel disease, infections, neoplasms and lymphoproliferative diseases), so it usually requires anatomopathological diagnosis and particular considerations regarding the subsequent specific treatment.

El síndrome de Wiskott-Aldrich (SWA) es un raro síndrome de inmunodeficiencia primaria ligado al cromosoma X que se asocia con aumento de incidencia de infecciones, trastornos autoinmunes y neoplasias. Se presenta el caso de un varón de 41 años con diagnóstico de síndrome de Wiskott-Aldrich y cuadro de ileítis como forma de presentación de un síndrome linfoproliferativo. La ileítis, en el contexto del paciente, representa un problema clínico dado el gran número de diagnósticos diferenciales (enfermedad inflamatoria intestinal, infecciones, neoplasias y enfermedades linfoproliferativas) por lo que suele requerir diagnóstico anatomopatológico y consideraciones particulares respecto al posterior tratamiento específico.

Gitelman syndrome is one of the salt losing tubulopathies. Hypokalemia and hypomagnesemia appear in the setting of the partial blockade of salt absorption in the distal tubule. We conducted a descriptive study of a case series of five patients with Gitelman syndrome (4 women, from 28 to 85 years) in our institution, between the years 2004 and 2015. The most frequent form of diagnosis in our series was by laboratory finding. The only acknowledged clinical symptom was malaise. Regarding laboratory findings, the mean potassemia was of 2.5 ± 0.5 mmol/l, with a minimum value of 2.1 mmol/l. Additionally, the serum magnesium value was of 1.3 ± 0.3 mg/dl. In conclusion, we observed that the forms of presentation consist of biochemical alterations with or without nonspecific manifestations, which currently represents the greatest diagnostic difficulty and reinforces the importance to achieve a timely diagnosis, especially in young patients with critical serum potassium values.

El síndrome de Gitelman forma parte de las denominadas tubulopatías perdedoras de sal. El bloqueo parcial de la reabsorción de sodio en el túbulo contorneado distal determina la aparición de hipokalemia e hipomagnesemia. Se realizó un estudio descriptivo de una serie de cinco casos de síndrome de Gitelman (4 mujeres, de 28 a 85 años de edad) atendidos en nuestra institución entre los años 2004 y 2015. La forma de diagnóstico más frecuente en nuestra serie fue por hallazgo de laboratorio. El único síntoma clínico manifestado en forma espontánea fue astenia. En cuanto a los valores de laboratorio, la potasemia fue 2.5 ± 0.5 mmol/l, con un valor mínimo de 2.1. Adicionalmente, el valor de magnesio en sangre fue 1.3 ± 0.3 mg/dl. Como conclusión, observamos que las formas de presentación consisten en alteraciones bioquímicas con o sin manifestaciones inespecíficas, lo que representa actualmente la mayor dificultad diagnóstica y refuerza la importancia de lograr un diagnóstico oportuno, en especial en pacientes jóvenes y con valores críticos de potasio sérico.

Abstract: In the current context of scarce financial resources, technology transfer offices are pressured to find ways to increase revenues through technology transfers or reduce expenses with their portfolio of technologies, especially patents. The Patent assessment seeks to detect the market potential of patents for transfer through licensing, abandonment, or maintenance. In this context, the objective of this study is to validate the leading indicators used in the patent evaluation to develop a framework for evaluating academic patent portfolio in the Brazilian context. For this, we used mapping and analysis methods of the current models besides focus group consultations, exploratory factorial analysis, and Analytical Hierarchy Process (AHP) to validate the indicators. The results show that seven factors are determinant in the evaluation of academic patents, having positive implications for the management of Intellectual Property since technology transfer decision-makers can use the factors and their identified weights as value indicators to evaluate patents with the most significant market potential.

ABSTRACT In the last decade, the risk benefits ratio of MHT has been evaluated mainly in terms of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these Recommendations is to provide a simple and updated reference on postmenopausal MHT. The term MHT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential (Seq) when progestogen is added to ERT for 10-14 days a month, or continuous combined (CC) when progestogen is administered continuously every day along with a fixed amount of estrogen. MHT also includes Tibolone and the Tissue Selective Estrogen Complex (TSEC).