Reprogenetics

The online version contains supplementary material available at 10.1007/s11032-025-01615-8.

Introdução: As queixas de disfunção sexual são comuns entre mulheres no climatério e na pós-menopausa. Devido a relação entre essas queixas e as alterações hormonais presentes nessa fase da vida da mulher, o tratamento hormonal com utilização de estrogênios, progestagênios e androgênios é a principal indicação terapêutica, desde que aplicado dentro da janela de oportunidade. Objetivo: Definir sexualidade e desejo sexual hipoativo na mulher no climatério e pós-menopausa e atualizar sobre o melhor tratamento hormonal empregado, especificando quais hormônios utilizar e suas doses. Metodologia: Revisão bibliográfica integrativa dos artigos nos últimos dez anos (2012 a 2022), somente na língua inglesa e que utilizaram dentro da metodologia, estudos duplo-cego placebo controlados e randomizados. Os estudos e análises foram buscados na biblioteca PUBMED. Resultados: Foram encontrados seis trabalhos duplo cego placebo controlado randomizados dos últimos dez anos, que estudaram trezentos e vinte e sete pacientes com queixas de disfunção sexual durante o período do climatério e pós-menopausa que foram tratadas através de reposição hormonal com estrogênios, progestagênios e testosterona em quantidades fisiológica. O estradiol tem sido marcado como hormônio importante para a modulação do desejo sexual feminino e habitualmente é utilizado junto com os progestagênios para proteção endometrial. Já a prescrição da testosterona, ainda se apresenta no contexto “off label”, visto que apesar de obtidos resultados satisfatórios e aparentemente seguros, ainda existem poucos estudoss duplo-cego placebo randomizados sobre o assunto. Conclusão: Ao analisar os resultados das pesquisas pode-se concluir que a reposição de estrógenos e progestagenios e/ou testosterona em doses fisiológicas, alcançou sucesso no tratamento do Transtorno do desejo sexual hipoativo na mulher pós menopausa.

Sperm DNA fragmentation (SDF) is implicated in male infertility and adverse reproductive outcomes. With the publication of many studies regarding the etiologies and contributors to SDF, as well as the effects of SDF, guidelines are necessary to aid clinicians in the application of SDF for male fertility evaluation. Two recent clinical practice guidelines were published by Agarwal et al and Esteves et al. In this article, we have evaluated and compared both guidelines. We have found fairly similar recommendations between the two guidelines and have also highlighted the differences between them. Finally, we have summarized and combined the best practice recommendations from both guidelines.

Most aggressive thyroid cancers are commonly associated with a BRAF V600E mutation. Preclinical and clinical data in BRAF V600E cancers suggest that combined BRAF and MEK inhibitor treatment results in a response, but resistance is common. One mechanism of acquired resistance is through persistent activation of tyrosine kinase (TK) signaling by alternate pathways. We hypothesized that combination therapy with BRAF and multitargeting TK inhibitors (MTKI) might be more effective in BRAF V600E thyroid cancer than in single-agent or BRAF and MEK inhibitors. The combined drug activity was analyzed to predict any synergistic effect using high-throughput screening (HTS) of active drugs. We performed follow-up in vitro and in vivo studies to validate and determine the mechanism of action of synergistic drugs. The MTKI ponatinib and the BRAF inhibitor PLX4720 showed synergistic activity by HTS. This combination significantly inhibited proliferation, colony formation, invasion, and migration in BRAF V600E thyroid cancer cell lines and downregulated pERK/MEK and c-JUN signaling pathways, and increased apoptosis. PLX4720-resistant BRAF V600E cells became sensitized to the combination treatment, with decreased proliferation at lower PLX4720 concentrations. In an orthotopic thyroid cancer mouse model, combination therapy significantly reduced tumor growth (P < 0.05), decreased the number of metastases (P < 0.05), and increased survival (P < 0.05) compared with monotherapy and vehicle control. Combination treatment with ponatinib and PLX4720 exhibited significant synergistic anticancer activity in preclinical models of BRAF V600E thyroid cancer, in addition to overcoming PLX4720 resistance. Our results suggest this combination should be tested in clinical trials.

Interprofessional collaboration (IPC) is an essential component of care delivery needed to achieve optimal patient- and system-level outcomes. The purpose of this project was to measure the impact of a structured IPC model, RAMPED-UP, on hospital length of stay (LOS) in a surgical trauma population. The study design was a prospective cohort with a historical comparison group. The project was conducted at a Level 1 trauma center. The RAMPED-UP group constituted trauma patients admitted from October to December 2017 (n = 96). Trauma patients admitted from October to December 2016 constituted the pre-RAMPED-UP group (n = 98). The 2 groups were similar in demographics. Hospital LOS was not statistically significant between groups. Median RAMPED-UP LOS, defined as the number of days the patient received RAMPED-UP rounds, was 3 days. Patients in the RAMPED-UP group were more likely to be discharged home, with higher discharge-by-noon (DBN) rates of 18.2% (p = .005). A statistically significant correlation was found between incentive spirometry (I/S) values and hospital LOS and RAMPED-UP LOS in the RAMPED-UP group (95% CI: rs -0.301, p = .008; 95% CI: rs -0.270, p = .018, respectively). Although the RAMPED-UP model did not decrease hospital LOS, the model did significantly improve DBN and RAMPED-UP LOS. Further exploration of I/S values as a predictor of LOS is warranted. The use of a structured IPC model that includes essential members of the IPC team can aid in improving patient outcomes such as DBN.

Producción de Hidrógeno a partir de energía solar en el campus de la UNI Johnny Nahui Ortiz, Caroline Camarena Gamarra, Alejandro Mendoza Rojas Universidad Nacional de Ingeniería, Av. Túpac Amaru 2010 - Rímac, Lima, Perú Recibido 16 de junio del 2019, Revisado el 21 de julio de 2019 Aceptado el 22 de julio de 2019 DOI: https://doi.org/10.33017/RevECIPeru2019.0007/ Resumen El presente proyecto se desarrolló en la Universidad Nacional de Ingeniería (UNI), en la cual existe interés en investigar acerca de la energía del hidrógeno como posible combustible del futuro, en el contexto del aprovechamiento de las energías renovables que es uno de los pilares de la Ingeniería Ambiental constituyendo un aspecto clave en el proceso formativo de los estudiantes. El objetivo general es evaluar experimentalmente la eficiencia energética de la producción de hidrógeno a partir de energía solar fotovoltaica. Se hicieron mediciones de irradiación solar, temperatura y humedad relativa en las instalaciones de la Facultad de Ingeniería Ambiental (FIA-UNI). Se registraron valores máximos de temperatura cercanos a los 30°C en un día del mes de noviembre, valores mínimos de humedad relativa de 50% en un día del mes de noviembre y valores máximos de irradiación solar cercanos a los 900 W/m2, en un día del mes de marzo. Se implementó un sistema de producción de electricidad a partir del recurso solar, constituido por dos módulos fotovoltaicos, dos baterías, un controlador y un inversor. Este sistema se ha implementado como módulo demostrativo para ser usado como parte del proceso formativo de los estudiantes de la FIA-UNI. Se hicieron pruebas de producción de hidrógeno mediante electrólisis, utilizando un sistema integrado equipado con una celda de combustible tipo PEM. En promedio, se obtuvo un ratio de 50.13 kW.h/kg de producción de hidrógeno a partir de energía solar fotovoltaica utilizando una celda de combustible tipo PEM en el campus de la UNI. Se anticipa un próximo trabajo de investigación utilizando un sistema híbrido integrado al sistema solar fotovoltaico. Descriptores: Recurso Solar, Sistema Fotovoltaico, Energía Eléctrica / Electrólisis / Producción de Hidrógeno. Abstract The present study was carried out at the National University of Engineering (UNI) that is very interested in research work about hydrogen energy as a potential fuel for the future, within the framework of utilization of renewable energies which is a core competency for Environmental Engineering in the academic work of students. The main objective is to evaluate energy efficiency associated with hydrogen production based on solar photovoltaic energy. Measurements for solar irradiation, temperature, and relative humidity were conducted in the facilities of the Environmental Engineering Department (FIA-UNI). Maximum values for temperatures around 30°C were registered in November, minimum values for relative humidity around 50% were registered in November, and maximum values for solar irradiation around 900 W/m2 were registered in March. An electricity production system based on solar resource was implemented and has two photovoltaic modules, two storage batteries, a controller and an inverter. The system has been implemented as a demonstrative module in order to be used as part of the academic work of the students at FIA-UNI. Test of hydrogen production through electrolysis were carried out using a systems integrated with a PEM-type fuel cell. An average ratio of 50.13 kW.h/kg of hydrogen production based on solar energy was obtained using a PEM-type fuel cell on campus at UNI. Further research is expected to be conducted using a hybrid system with integration to the solar energy system. Keywords: Solar Resource, Photovoltaic System, Electric Power, Electrolysis, Hydrogen Production.

STUDY QUESTION Can quantification of mitochondrial DNA (mtDNA) in trophectoderm (TE) biopsy samples provide information concerning the viability of a blastocyst, potentially enhancing embryo selection and improving IVF treatment outcomes? SUMMARY ANSWER This study demonstrated that euploid blastocysts of good morphology, but with high mtDNA levels had a greatly reduced implantation potential. WHAT IS KNOWN ALREADY Better methods of embryo selection leading to IVF outcome improvement are necessary, as the transfer of chromosomally normal embryos of high morphological grade cannot guarantee the establishment of an ongoing pregnancy. The quantity of mtDNA in embryonic cells has been proposed as a new biomarker of viability-higher levels of mtDNA associated with reduced implantation potential. STUDY DESIGN, SIZE, DURATION mtDNA was quantified in 199 blastocysts, previously biopsied and shown to be chromosomally normal using preimplantation genetic testing for aneuploidy (PGT-A). These were generated by 174 couples (average female age 37.06 years). All patients underwent IVF in a single clinic. The study took place in a blinded, non-selection manner-i.e. mtDNA quantity was not known at the time of single embryo transfer. The fate of the embryos transferred was subsequently compared to the mtDNA levels measured. PARTICIPANTS/MATERIALS, SETTING, METHODS Embryos were biopsied at the blastocyst stage. The TE samples obtained were subjected to whole genome amplification followed by comprehensive chromosome analysis via next generation sequencing. The same biopsy specimens were also tested using quantitative PCR, allowing highly accurate mtDNA quantification. After blastocyst transfer, the code used for blinding was broken and analysis undertaken to reveal whether the amount of mtDNA had any association with embryo implantation. MAIN RESULTS AND THE ROLE OF CHANCE mtDNA analysis of the 199 blastocysts revealed that 9 (5%) contained unusually high levels of mtDNA. All embryo transfers involved a single chromosomally normal blastocyst of good morphology. Of these, 121 (60%) led to ongoing pregnancies, 11(6%) led to biochemical pregnancies, and 10 (5%) spontaneously miscarried. All (100%) of these blastocysts had mtDNA levels considered to be normal/low. The remaining 57 (29%) blastocysts failed to implant. Among these non-viable embryos there were 9 (16%) with unusually high levels of mtDNA. This meant that the ongoing pregnancy rate for morphologically good, euploid blastocysts, with normal/low levels of mtDNA was 64% (121/190). In contrast, the ongoing pregnancy rate for the same type of embryos, but with elevated mtDNA levels, was 0/9 (0%). This difference was highly statistically significant (P < 0.0001). LIMITATIONS REASONS FOR CAUTION To determine the true extent of any clinical benefits a randomized clinical trial will be necessary. Research is needed to improve understanding of the biology of mtDNA expansion. WIDER IMPLICATIONS OF THE FINDINGS This is the first investigation to evaluate the clinical impact of increased mtDNA in a prospective blinded manner. Results confirm that embryos with elevated mtDNA rarely implant, supporting its use as a viability biomarker. A total of 64% of euploid blastocysts with normal/low mtDNA implanted versus 60% for the cohort as a whole. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by institutional funding (Reprogenetics UK and Reprogenetics). DW is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme. None of the authors have any competing interests.

Molecular testing is a promising approach to differential diagnostics and especially to prognostication of uveal melanoma (UM). We have tested a complex biomarker panel that included pathology and a number of cytogenetic and molecular markers on a series of 58 UM samples as a part of a prospective clinical study. Testing of all biomarkers has proved feasible on both FFPE and FNA samples. Molecular verification of UM diagnosis via mutation analysis demonstrated very high sensitivity. Cytogenetic and molecular genetic classifications gave discordant results in most samples from our series; prognostic significance of this discrepancy is yet to be elucidated through final data analysis of this and other prospective studies.