Internal podalic version of second twin: Improving feet identification using a simulation model.

Podalic version and breech extraction require high obstetrical expertise. Identifying fetal extremities is the first crucial step for trainees. When this skill is not polished enough, it increases the inter-twin delivery interval and can even jeopardize the whole manoeuver. We present a model for simulating and training this specific skill, with obstetrical mannequin, and 3D printed hands and feet. Five feet and five hands (five rights and five lefts of each one) were printed in 3D after initial ultrasound acquisition of a near term fetus. Each foot and hand, was individually set in a condom filled with 100 cc of water and closed with a knot. A Sophie's Mum Birth Simulator Version 4.0 de MODEL-med was placed on the edge of the table. Each hand and foot was inserted into the pelvic mannequin. An evaluation of the students' skills using this model was performed. A significant reduction of the global mean to extract the first foot and all the feet was noticed at three month of interval. This model is an option to train and assess a crucial skill for version and breech extraction

Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.

Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification

Ensilaje de forraje de vegas naturales en Tierra del Fuego, Argentina

722-728Livestock activity in the Argentinian «Tierra del Fuego» island is based on highly variable natural grasslands (NG). The conservation of fodder, despite the unfavorable environment, is restricted to hay; conservation as silage could be constrained by fodder quality and low temperatures. The objective was to assess the quality of NG silages fermented under contrasting storing conditions. Typical meadow forage was ensiled in minisilos and stored under shelter (Shelter) or in the field (Field) in a complete block design with repeated measures in time (t). Forage was chopped and inoculated with lactic acid bacteria plus enzymes, and harvested with 420 g dry matter (DM) kg-1 fresh matter, 111 g crude protein kg-1 DM, 665 g ash-free neutral detergent fibre kg-1 DM, and 64 g water soluble carbohydrates kg-1 DM. Shelter minisilos had higher metabolizable energy concentration at 236 d (PTrat×t = 0.03; Shelter = 10.2 ; Field = 9.6 MJ kg-1 DM, P = 0.01), and lower DM losses (Shelter = -0.2; Campo = 22 percent, P = 0.02) and values of pH and N-NH3/total N (Field: 5.6 and 12 percent and Shelter: 4.4 and 6.8 percent, P = 0.01). Fermentation acids concentration was similar for both treatments with preponderance of lactic acid, but acetic acid concentration increased over time (Pt = 0.01). It was concluded that in «Tierra del Fuego», natural meadow forage quality is compatible with ensiling, but environmental conditions can limit the fermentation process. Additional key words: forage conservation, natural grasslands, Patagonia, silage

Ensilaje de forraje de vegas naturales en Tierra del Fuego, Argentina

722-728Livestock activity in the Argentinian «Tierra del Fuego» island is based on highly variable natural grasslands (NG). The conservation of fodder, despite the unfavorable environment, is restricted to hay; conservation as silage could be constrained by fodder quality and low temperatures. The objective was to assess the quality of NG silages fermented under contrasting storing conditions. Typical meadow forage was ensiled in minisilos and stored under shelter (Shelter) or in the field (Field) in a complete block design with repeated measures in time (t). Forage was chopped and inoculated with lactic acid bacteria plus enzymes, and harvested with 420 g dry matter (DM) kg-1 fresh matter, 111 g crude protein kg-1 DM, 665 g ash-free neutral detergent fibre kg-1 DM, and 64 g water soluble carbohydrates kg-1 DM. Shelter minisilos had higher metabolizable energy concentration at 236 d (PTrat×t = 0.03; Shelter = 10.2 ; Field = 9.6 MJ kg-1 DM, P = 0.01), and lower DM losses (Shelter = -0.2; Campo = 22 percent, P = 0.02) and values of pH and N-NH3/total N (Field: 5.6 and 12 percent and Shelter: 4.4 and 6.8 percent, P = 0.01). Fermentation acids concentration was similar for both treatments with preponderance of lactic acid, but acetic acid concentration increased over time (Pt = 0.01). It was concluded that in «Tierra del Fuego», natural meadow forage quality is compatible with ensiling, but environmental conditions can limit the fermentation process. Additional key words: forage conservation, natural grasslands, Patagonia, silage

AI in obstetrics: Evaluating residents' capabilities and interaction strategies with ChatGPT.

In line with the digital transformation trend in medical training, students may resort to artificial intelligence (AI) for learning. This study assessed the interaction between obstetrics residents and ChatGPT during clinically oriented summative evaluations related to acute hepatic steatosis of pregnancy, and their self-reported competencies in information technology (IT) and AI. The participants in this semi-qualitative observational study were 14 obstetrics residents from two university hospitals. Students' queries were categorized into three distinct types: third-party enquiries; search-engine-style queries; and GPT-centric prompts. Responses were compared against a standardized answer produced by ChatGPT with a Delphi-developed expert prompt. Data analysis employed descriptive statistics and correlation analysis to explore the relationship between AI/IT skills and response accuracy. The study participants showed moderate IT proficiency but low AI proficiency. Interaction with ChatGPT regarding clinical signs of acute hepatic steatosis gravidarum revealed a preference for third-party questioning, resulting in only 21% accurate responses due to misinterpretation of medical acronyms. No correlation was found between AI response accuracy and the residents' self-assessed IT or AI skills, with most expressing dissatisfaction with their AI training. This study underlines the discrepancy between perceived and actual AI proficiency, highlighted by clinically inaccurate yet plausible AI responses - a manifestation of the 'stochastic parrot' phenomenon. These findings advocate for the inclusion of structured AI literacy programmes in medical education, focusing on prompt engineering. These academic skills are essential to exploit AI's potential in obstetrics and gynaecology. The ultimate aim is to optimize patient care in AI-augmented health care, and prevent misleading and unsafe knowledge acquisition

Mouse SLX4 Is a Tumor Suppressor that Stimulates the Activity of the Nuclease XPF-ERCC1 in DNA Crosslink Repair

SLX4 binds to three nucleases (XPF-ERCC1, MUS81-EME1, and SLX1), and its deficiency leads to genomic instability, sensitivity to DNA crosslinking agents, and Fanconi anemia. However, it is not understood how SLX4 and its associated nucleases act in DNA crosslink repair. Here, we uncover consequences of mouse Slx4 deficiency and reveal its function in DNA crosslink repair. Slx4-deficient mice develop epithelial cancers and have a contracted hematopoietic stem cell pool. The N-terminal domain of SLX4 (mini-SLX4) that only binds to XPF-ERCC1 is sufficient to confer resistance to DNA crosslinking agents. Recombinant mini-SLX4 enhances XPF-ERCC1 nuclease activity up to 100-fold, directing specificity toward DNA forks. Mini-SLX4-XPF-ERCC1 also vigorously stimulates dual incisions around a DNA crosslink embedded in a synthetic replication fork, an essential step in the repair of this lesion. These observations define vertebrate SLX4 as a tumor suppressor, which activates XPF-ERCC1 nuclease specificity in DNA crosslink repairope

The EarthCARE satellite: the next step forward in global measurements of clouds, aerosols, precipitation, and radiation

The collective representation within global models of aerosol, cloud, precipitation, and their radiative properties remains unsatisfactory. They constitute the largest source of uncertainty in predictions of climatic change and hamper the ability of numerical weather prediction models to forecast high-impact weather events. The joint European Space Agency (ESA)–Japan Aerospace Exploration Agency (JAXA) Earth Clouds, Aerosol and Radiation Explorer (EarthCARE) satellite mission, scheduled for launch in 2018, will help to resolve these weaknesses by providing global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by its collocated active and passive sensors. EarthCARE will improve our understanding of cloud and aerosol processes by extending the invaluable dataset acquired by the A-Train satellites CloudSat, Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), and Aqua. Specifically, EarthCARE’s cloud profiling radar, with 7 dB more sensitivity than CloudSat, will detect more thin clouds and its Doppler capability will provide novel information on convection, precipitating ice particle, and raindrop fall speeds. EarthCARE’s 355-nm high-spectral-resolution lidar will measure directly and accurately cloud and aerosol extinction and optical depth. Combining this with backscatter and polarization information should lead to an unprecedented ability to identify aerosol type. The multispectral imager will provide a context for, and the ability to construct, the cloud and aerosol distribution in 3D domains around the narrow 2D retrieved cross section. The consistency of the retrievals will be assessed to within a target of ±10 W m–2 on the (10 km)2 scale by comparing the multiview broadband radiometer observations to the top-of-atmosphere fluxes estimated by 3D radiative transfer models acting on retrieved 3D domains

NANOSPRESSO: toward personalized, locally produced nucleic acid nanomedicines

The NANOSPRESSO project is a pioneering response to the complex challenge of treating orphan diseases, which, despite affecting millions of people globally, have only scant therapeutic options. This initiative represents a paradigm shift by decentralizing the production of personalized nucleic acid nanomedicines. Integrating advanced microfluidic technology with lipid nanoparticle engineering platforms—validated by their efficacy in COVID-19 messenger (m)RNA vaccines—the NANOSPRESSO model enables hospital pharmacists to seamlessly assemble tailored therapeutic cartridges for gene/RNA therapy administration at the patient’s bedside. This innovative model subverts the traditional constraints of high-cost, intricate manufacturing and the instability of nucleic acid-based treatments, offering a streamlined. localized, flexible, and patient-centric alternative. Inspired by the traditional art of compounding in pharmacy, NANOSPRESSO strives to democratize access to innovative treatments for rare diseases, challenging the conventional, monolithic medical approach. Alongside its technological breakthroughs, the project also engages in proactive dialogue with regulatory authorities to ensure compliance with stringent quality, safety, and efficacy standards, applying an array of analytical techniques recently developed for nucleic acid nanomedicines. Orchestrated by an extensive European consortium of multidisciplinary experts, NANOSPRESSO embodies the collaborative spirit driving the next wave of healthcare innovation, placing patients at the center of a precision medicine revolution. This article conveys the core mission of NANOSPRESSO: to redefine the reach and impact of nanomedicine, heralding a future in which personalized therapy for rare and orphan diseases—and potentially other conditions—is a reality, available to patients and affordable by public health systems. We outline the scientific and technological basis for this model, explore various regulatory, legal, economic, and societal implications and challenges, and advocate for interdisciplinary solutions across the research and innovation ecosystem