The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-γ locus.

Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler's [cleanup Salmonella not Theiler's]) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ (IFN-γ) abundance in activated CD8(+) T cells, increased Theiler's virus persistence, and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN-γ locus. Thus, this lncRNA regulates epigenetic marking of IFN-γ-encoding chromatin, expression of IFN-γ, and susceptibility to a viral and a bacterial pathogen.

Revealing the short-range structure of the mirror nuclei 3H and 3He.

When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon-nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure1-3, and mapping out the strength and the isospin structure (neutron-proton (np) versus proton-proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements3-5. Two-nucleon knockout or 'triple coincidence' reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements6-8 have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon-nucleon interaction.

Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

Integration of CTCF loops, methylome, and transcriptome in differentiating LUHMES as a model for imprinting dynamics of the 15q11-q13 locus in human neurons.

Human cell line models, including the neuronal precursor line LUHMES, are important for investigating developmental transcriptional dynamics within imprinted regions, particularly the 15q11-q13 Angelman (AS) and Prader-Willi (PWS) syndrome locus. AS results from loss of maternal UBE3A in neurons, where the paternal allele is silenced by a convergent antisense transcript UBE3A-ATS, a lncRNA that terminates at PWAR1 in non-neurons. qRT-PCR analysis confirmed the exclusive and progressive increase in UBE3A-ATS in differentiating LUHMES neurons, validating their use for studying UBE3A silencing. Genome-wide transcriptome analyses revealed changes to 11 834 genes during neuronal differentiation, including the upregulation of most genes within the 15q11-q13 locus. To identify dynamic changes in chromatin loops linked to transcriptional activity, we performed a HiChIP validated by 4C, which identified two neuron-specific CTCF loops between MAGEL2-SNRPN and PWAR1-UBE3A. To determine if allele-specific differentially methylated regions (DMR) may be associated with CTCF loop anchors, whole genome long-read nanopore sequencing was performed. We identified a paternally hypomethylated DMR near the SNRPN upstream loop anchor exclusive to neurons and a paternally hypermethylated DMR near the PWAR1 CTCF anchor exclusive to undifferentiated cells, consistent with increases in neuronal transcription. Additionally, DMRs near CTCF loop anchors were observed in both cell types, indicative of allele-specific differences in chromatin loops regulating imprinted transcription. These results provide an integrated view of the 15q11-q13 epigenetic landscape during LUHMES neuronal differentiation, underscoring the complex interplay of transcription, chromatin looping, and DNA methylation. They also provide insights for future therapeutic approaches for AS and PWS.

Integrated photon pair source based on a silicon nitride micro-ring resonator for quantum memories.

We report the design of an integrated photon pair source based on spontaneous four-wave mixing (SFWM), implemented in an integrated micro-ring resonator in the silicon nitride platform (Si3N4). The signal photon is generated with emission at 606 nm and bandwidth of 3.98 MHz, matching the spectral properties of praseodymium ions (Pr), while the idler photon is generated at 1430.5 nm matching the wavelength of a CWDM channel in the E-band. This novel, to the best of our knowledge, device is designed to interact with a quantum memory based on a Y2SiO5 crystal doped with Pr3+ ions, in which we used cavity-enhanced SFWM along with dispersion engineering to reach the required wavelength and the few megahertz signal photon spectral bandwidth.

Novel Measurement of the Neutron Magnetic Form Factor from A=3 Mirror Nuclei.

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6

Development of robust chiroptical systems through spirobifluorenes.

Chiroptical responses are valuable for the structural determination of dissymmetric molecules. However, the development of everyday applications based on chiroptical systems is yet to come. We have been earlier using axially chiral allenes for the construction of linear, cyclic, and cage-shaped molecules that present remarkable chiroptical responses. Additionally, we have developed chiral surfaces through upstanding chiral architectures. Since the goal is to obtain robust chiroptical materials, more recently we have been studying spirobifluorenes (SBFs), a well-established building block in optoelectronic applications. After theoretical and experimental demonstration, the suitability of chiral SBFs for the development of robust chiroptical systems was certified by the construction all-carbon double helices, flexible shape-persistent macrocycles, chiral frameworks for surface functionalization, and structures featuring helical or spiroconjugated molecular orbitals. Here, we give an overview of our contribution to these matters.

Modified Rosi-Cahill technique after left extended colectomy for splenic flexure advanced tumors.

Advanced splenic flexure tumors are uncommon and have a higher risk of relapse. To ensure that the resection includes the entire area of lymphatic drainage with a complete mesocolic excision (CME), a left extended colectomy is needed. In peritoneal carcinomatosis, there is often extensive involvement of the sigma and splenic flexure of the colon. In many instances, total colectomies are chosen for these patients, even when a significant portion of the colon could be preserved. The potential impact on quality of life after splenic flexure colon resection is discussed, as well as the importance of anatomical knowledge and expertise in performing this type of surgery. Overall, this work presents a modified technique that aims to improve the outcomes and quality of life for patients with splenic flexure colon cancer. Creating a tension-free anastomosis after extended left-sided colorectal resection is challenging. There is a negative impact on quality of life when an ileorectal anastomosis is created. The colorectal anastomosis performed after modified Rosi-Cahill or Deloyers' technique allows reduced small bowel bacterial overgrowth, achieves better water and sodium absorption, and altogether permits improved stool consistency. There are potential advantages of the Rosi-Cahill technique over other popular options such as Deloyers' procedure as there is no torsion of the ileocolic vessels and no mesenteric windows. A video was recorded showing a potential pitfall during Deloyers' technique resulting in the creation of a mesenteric window. The proper rotation of the colon during the modified Rosi-Cahill procedure was also filmed. Overall, this work presents a modified technique for reconstruction after left extended colectomy that aims to improve the outcomes and quality of life for patients with splenic flexure colon cancer.

Clinical and Sociodemographic Features of Alopecia Areata in Five Colombian Cities: An Analysis of the RENAAC Registry.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by non-scaring hair loss and preservation of hair follicles. The information available on disease course, and clinical features of AA is scarce worldwide, and almost nonexistent in Colombia. OBJECTIVE: To determine the clinical and sociodemographic characteristics of patients diagnosed with AA who presented to a dermatology consultation in five Colombian cities. MATERIAL AND METHODS: This was a retrospective and multicenter study on data from an ongoing National Registry of Alopecia Areata in Colombia (RENAAC) collected in Bogota, Cali, Cartagena, Barranquilla, and Medellin, Colombia from March 2022 through April 2023. Data was recorded in a standardized form by trained physicians. The variables were expressed as measures of central tendency and dispersion, and absolute and relative frequencies. RESULTS: A total of 562 patients were included, 59.4% of whom were women, aged between 15 and 49 years (63.9%) with a mean disease course of 1.7 years. The most common finding was multiple plaque (53.2%), the predominant AA subtype was patchy (71.4%), and 29.5% of the patients had a past dermatological history, 18.3% had a past endocrinological history, and 8.9% had a past psychiatric history. The treatments most widely used were steroid injections (76.4%), 5% topical minoxidil (46.4%), followed by high-potency corticosteroids (42.5%). STUDY LIMITATIONS AND CONCLUSIONS: AA was slightly predominant in women. As seen in other populations, this disease had an earlier onset in men vs women. Presentation in pediatric age was uncommon. The previous history of other dermatological diseases was checked in almost one third of the patients. Analysis of the co-presentation of AA with other autoimmune diseases is biased due to excluding patients with systemic erythematous lupus from the study.

Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Shaping the spectral correlation of bi-photon quantum frequency combs by multi-frequency excitation of an SOI integrated nonlinear resonator.

We reveal the generation of a broadband (> 1.9 THz) bi-photon quantum frequency comb (QFC) in a silicon-on-insulator (SOI) Fabry-Pérot micro-cavity and the control of its spectral correlation properties. Correlated photon pairs are generated through three spontaneous four-wave mixing (SFWM) processes by using a co-polarized bi-chromatic coherent input with power P1 and P2 on adjacent resonances of the nonlinear cavity. Adjusting the spectral power ratio r = P1/(P1 + P2) allows control over the influence of each process leading to an enhancement of the overall photon pair generation rate (PGR) µ(r) by a maximal factor of µ(r = 0.5)/µ(r = 0) ≈ 1.5, compared to the overall PGR provided by a single-pump configuration with the same power budget. We demonstrate that the efficiency aND of the non-degenerate excitation SFWM process (NDP) doubles the efficiency a1 ≈ a2 of the degenerate excitation SFWM processes (DP), showing a good agreement with the provided model.

Blazar spectral variability as explained by a twisted inhomogeneous jet.

Blazars are active galactic nuclei, which are powerful sources of radiation whose central engine is located in the core of the host galaxy. Blazar emission is dominated by non-thermal radiation from a jet that moves relativistically towards us, and therefore undergoes Doppler beaming. This beaming causes flux enhancement and contraction of the variability timescales, so that most blazars appear as luminous sources characterized by noticeable and fast changes in brightness at all frequencies. The mechanism that produces this unpredictable variability is under debate, but proposed mechanisms include injection, acceleration and cooling of particles, with possible intervention of shock waves or turbulence. Changes in the viewing angle of the observed emitting knots or jet regions have also been suggested as an explanation of flaring events and can also explain specific properties of blazar emission, such as intra-day variability, quasi-periodicity and the delay of radio flux variations relative to optical changes. Such a geometric interpretation, however, is not universally accepted because alternative explanations based on changes in physical conditions-such as the size and speed of the emitting zone, the magnetic field, the number of emitting particles and their energy distribution-can explain snapshots of the spectral behaviour of blazars in many cases. Here we report the results of optical-to-radio-wavelength monitoring of the blazar CTA 102 and show that the observed long-term trends of the flux and spectral variability are best explained by an inhomogeneous, curved jet that undergoes changes in orientation over time. We propose that magnetohydrodynamic instabilities or rotation of the twisted jet cause different jet regions to change their orientation and hence their relative Doppler factors. In particular, the extreme optical outburst of 2016-2017 (brightness increase of six magnitudes) occurred when the corresponding emitting region had a small viewing angle. The agreement between observations and theoretical predictions can be seen as further validation of the relativistic beaming theory.

Design and fabrication of Mach-Zehnder interferometers in soda-lime glass for temperature sensing applications.

High sensitivity represents one of the main goals that sensing devices need to satisfy for their applications. This work presents to the best of our knowledge the first integrated Mach-Zehnder interferometer (MZI) embedded in soda-lime glass with comparable sensitivity to silicon-on-insulator (SOI) devices. We manufactured the MZIs by the femtosecond direct laser writing (FDLW) technique and characterized them with temperature. Four buried MZIs were manufactured by slightly increasing the optical path due to separation between the arms of the interferometer (Δ s). We achieved a fringe shift of ∼8n m for an increase of 0.18 µm. We have characterized one of these devices with temperature from 30°C to 70°C obtaining a sensitivity of ∼28p m/ ∘ C. We improved the sensitivity of the device to ∼54p m/ ∘ C due to the advantage of the unique three-dimensional (3D) capabilities that FDLW provides, overcoming the characteristically low thermo-optic coefficient of soda-lime glass just by rotating the MZI structure 11°.

Sport fishing and vessel pressure on the endangered cetacean Delphinus delphis. Towards an international agreement of micro-sanctuary for its conservation.

Delphinus delphis Linnaeus 1758 is considered an endangered species in the Mediterranean. The species is resident in the Bay of Algeciras - Gibraltar (southern Spain; waters partially shared with Gibraltar, UK). This area is subject to strong anthropogenic pressure, but with an input of renewed waters in its central area. During three consecutive years (March 2017-March 2020), sightings were observed concentrated along the submarine canyon that runs north to south across the bay, forming a "specular S″ with a maximum depth of 460 m. The pods of Dd showed a continuous or semi-continuous spatial distribution along the vertical axis of the submarine canyon, where they feed, mate, breed and rear calves in a well-defined area that constitutes a critical habitat. This area has been cartographically delimited, choosing the area of maximum dolphin frequency as highly vulnerable due to the possibility of collisions with small vessels (<15 m) and interactions with sport fishing activities (popping, ballooning, trolling) which constitute the main threat counting the derived impacts from noise pollution. Spatio-temporal mapping has been developed to visualize the overlapping between the dolphin groups and small vessels. Mapping analysis has shown that an international Spanish-British micro-sanctuary urgently needs to be established in order to create a protected area specifically for the common dolphins, and for other species which inhabit/use the waters between Spain and Gibraltar. Coordinates and a delimited surface area have been proposed in this paper.

Live-Animal Epigenome Editing: Convergence of Novel Techniques.

Epigenome editing refers to the generation of precise chromatin alterations and their effects on gene expression and cell biology. Until recently, much of the efforts in epigenome editing were limited to tissue culture models of disease. However, the convergence of techniques from different fields including mammalian genetics, virology, and CRISPR engineering is advancing epigenome editing into a new era. Researchers are increasingly embracing the use of multicellular model organisms to test the role of specific chromatin alterations in development and disease. The challenge of successful live-animal epigenomic editing will depend on a well-informed foundation of the current methodologies for cell-specific delivery and editing accuracy. Here we review the opportunities for basic research and therapeutic applications.

Measurement of the Nucleon F_{2}

The ratio of the nucleon F_{2} structure functions, F_{2}^{n}/F_{2}^{p}, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from ^{3}H and ^{3}He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19

Estimating personal solar ultraviolet radiation exposure through time spent outdoors, ambient levels and modelling approaches.

BACKGROUND: Evidence on validation of surrogates applied to evaluate the personal exposure levels of solar ultraviolet radiation (UVR) in epidemiological studies is scarce. OBJECTIVES: To determine and compare the validity of three approaches, including (i) ambient UVR levels, (ii) time spent outdoors and (iii) a modelling approach integrating the aforementioned parameters, to estimate personal UVR exposure over a period of 6 months among indoor and outdoor workers and in different seasons (summer/winter). METHODS: This validation study was part of the European Commission-funded ICEPURE project and was performed between July 2010 and January 2011 in a convenience sample of indoor and outdoor workers in Catalunya, Spain. We developed linear regression models to quantify the variation in the objectively measured personal UVR exposure that could be explained, separately, by the ambient UVR, time spent outdoors and modelled UVR levels. RESULTS: Our 39 participants - mostly male and with a median age of 35 years - presented a median daily objectively measured UVR of 0·37 standard erythemal doses. The UVR dose was statistically significantly higher in summer and for outdoor workers. The modelled personal UVR exposure and self-reported time spent outdoors could reasonably predict the variation in the objectively measured personal UVR levels (R2 range 0·75-0·79), whereas ambient UVR was a poor predictor (R2 = 0·21). No notable differences were found between seasons or occupation. CONCLUSIONS: Time outdoors and our modelling approach were reliable predictors and of value to be applied in epidemiological studies of the health effects of current exposure to UVR.

Use of a vaginal CO2 laser for the management of genitourinary syndrome of menopause in gynecological cancer survivors: a systematic review.

Genitourinary syndrome of menopause (GSM) may arise from the hypoestrogenism caused by ovarian function destruction following gynecological cancer treatments. GSM may also be present in menopausal women and its symptoms might be exacerbated by cancer treatments. Historically, patients with hormone-dependent gynecological cancer and physicians have been less comfortable using vaginal estrogen due to fear of recurrence. CO2 vaginal laser therapies have demonstrated efficacy as a non-hormonal alternative for GSM treatment in healthy menopausal patients. The objective of this study was to evaluate the data on the effect of a CO2 vaginal laser for the management of GSM in gynecological cancer patients. Databases searched included MEDLINE, Embase, PubMed, Cochrane and Google Scholar. Selected studies assessed use of a CO2 vaginal laser in gynecological cancer patients with GSM. A total of 269 studies were retrieved. Four studies met the inclusion criteria. Each study followed a different type of CO2 vaginal laser protocol for the management of GSM in gynecological cancer patients. There are no randomized controlled trials that assess the use of a CO2 vaginal laser in gynecologic cancer patients. The number of published gynecological cancer patients treated with a CO2 laser for the management of GSM is extremely limited (N < 100). There is a lack of literature on the impact and safety of vaginal CO2 laser use to manage GSM in gynecologic cancer patients.

Biosorption of nickel, cobalt, zinc and copper ions by Serratia marcescens strain 16 in mono and multimetallic systems.

The metallurgical industry is one of the main sources of heavy metal pollution, which represents a severe threat to life. Metals can be removed from aqueous solutions by using microbial biomasses. This paper analyses the heavy metal biosorption capacity of Serratia marcescens strain 16 in single and multimetallic systems. The results obtained show that Co(II), Ni(II) and Zn(II) biosorption in monometallic systems is two to three times higher than in the presence of bi-metallic and multimetallic solutions. Fourier transform infrared spectroscopy confirmed that carbonyl, carboxyl and hydroxyl were the main functional groups, as well as the amide bands I and II involved in metal uptake, which are present in external structures of the bacterial cell. The results obtained demonstrated the viability of S. marcescens strain 16 as a biosorbent for the design of eco-friendly technologies for the treatment of waste liquor.

Pre-induction cervical ripening with different initial doses of intravaginal misoprostol: time to delivery and peri-natal outcomes.

From 2016 to 2018, a total of 300 pregnant women underwent induction of labour. Those women were allocated in two groups according to the initial dose of misoprostol. Group I (150 women) received intravaginally 50 µg misoprostol followed by 25 µg every four hours, up to a maximum of four doses whereas in group II (150 women) the initial dose was 25 µg intravaginal followed by the same dose every four hours up to a maximum of four doses. Women with previous uterine scar, abnormal foetal heart rate, severe foetal malformation, foetal growth restriction or multiple pregnancy were excluded. The aim of study was to compare the effectiveness (hours until delivery) and perinatal outcomes of both schemes of cervical ripening. Initial doses of 50 µg of misoprostol reduced the time until delivery (17.65 ± 8.2 hours vs. 20.85 ± 9.3 hours; p=.007) and the need of oxytocin (34.6% vs. 46.67%; p=.046), compared to the use of 25 µg misoprostol in all doses. No differences were observed regarding perinatal outcomes.In conclusion, starting with 50 µg of misoprostol in the first dose reduced time to vaginal delivery and decreased the use of oxytocin without worse perinatal outcomes.Impact StatementWhat is already known on this subject? The rate of labour induction is increasing. Mechanical and medical methods try to establish the active phase of labour as quickly and safely as possible. For this reason, there are numerous studies assessing different protocols, dosages and indications.What do the results of this study add? Despite the numerous studies, due to ethical restrictions, it is difficult to carry out prospective studies. For this reason, studies like this help to establish the most appropriate dose of misoprostol in two of the most common indications for induction of labour. We demonstrated that increasing initial doses up to 50 mg of misoprostol are safer and more effective.What are the implications of these findings for clinical practice and/or further research? This study could be useful for future prospective and randomised studies as well for including these data in a meta-analysis. In addition, these results may update the clinical protocols and reduce hospital stay without worse perinatal outcomes.