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BackgroundAn estimated 6.7 million persons are living with dementia in the United States, a number expected to double by 2060. Persons experiencing moderate to severe dementia are 4 to 5 times more likely to fall than those without dementia, due to agitation and unsteady gait. Socially assistive robots fail to address the changing emotional states associated with agitation, and it is unclear how emotional states change, how they impact agitation and gait over time, and how social robots can best respond by showing empathy. ObjectiveThis study aims to design and validate a foundational model of emotional intelligence for empathetic patient-robot interaction that mitigates agitation among those at the highest risk: persons experiencing moderate to severe dementia. MethodsA design science approach will be adopted to (1) collect and store granular, personal, and chronological data using Personicle (an open-source software platform developed to automatically collect data from phones and other devices), incorporating real-time visual, audio, and physiological sensing technologies in a simulation laboratory and at board and care facilities; (2) develop statistical models to understand and forecast the emotional state, agitation level, and gait pattern of persons experiencing moderate to severe dementia in real time using machine learning and artificial intelligence and Personicle; (3) design and test an empathy-focused conversation model, focused on storytelling; and (4) test and evaluate this model for a care companion robot (CCR) in the community. ResultsThe study was funded in October 2023. For aim 1, architecture development for Personicle data collection began with a search for existing open-source data in January 2024. A community advisory board was formed and met in December 2023 to provide feedback on the use of CCRs and provide personal stories. Full institutional review board approval was received in March 2024 to place cameras and CCRs at the sites. In March 2024, atomic marker development was begun. For aim 2, after a review of open-source data on patients with dementia, the development of an emotional classifier was begun. Data labeling was started in April 2024 and completed in June 2024 with ongoing validation. Moreover, the team established a baseline multimodal model trained and validated on healthy-person data sets, using transformer architecture in a semisupervised manner, and later retrained on the labeled data set of patients experiencing moderate to severe dementia. In April 2024, empathy alignment of large language models was initiated using prompt engineering and reinforcement learning. ConclusionsThis innovative caregiving approach is designed to recognize the signs of agitation and, upon recognition, intervene with empathetic verbal communication. This proposal has the potential to have a significant impact on an emerging field of computational dementia science by reducing unnecessary agitation and falls of persons experiencing moderate to severe dementia, while reducing caregiver burden. International Registered Report Identifier (IRRID)PRR1-10.2196/55761

Glyoxalase I (GLO1) is the primary enzyme for detoxification of the reactive dicarbonyl methylglyoxal (MG). Loss of GLO1 promotes accumulation of MG resulting in a recapitulation of diabetic phenotypes. We previously demonstrated attenuated GLO1 protein in skeletal muscle from individuals with type 2 diabetes (T2D). However, whether GLO1 attenuation occurs prior to T2D and the mechanisms regulating GLO1 abundance in skeletal muscle are unknown. GLO1 expression and activity were determined in skeletal muscle tissue biopsies from 15 lean healthy individuals (LH, BMI: 22.4 ± 0.7) and 5 individuals with obesity (OB, BMI: 32.4 ± 1.3). GLO1 protein was attenuated by 26 ± 0.3 % in OB compared to LH skeletal muscle (p = 0.019). Similar reductions for GLO1 activity were observed (p = 0.102). NRF2 and Keap1 expression were equivocal between groups despite a 2-fold elevation in GLO1 transcripts in OB skeletal muscle (p = 0.008). GLO1 knock-down (KD) in human immortalized myotubes promoted downregulation of muscle contraction and organization proteins indicating the importance of GLO1 expression for skeletal muscle function. SIRT1 KD had no effect on GLO1 protein or activity whereas, SIRT2 KD attenuated GLO1 protein by 28 ± 0.29 % (p

Introduction The quality and safety of care within residential aged care facilities (RACFs) have been linked to their organisational culture. However, evidence for understanding and improving culture in this setting is limited. This research programme aims to validate a survey to measure organisational culture and determine the relationship of culture with safety and quality of care, then to evaluate an organisational culture change programme in Australian RACFs.Methods and analysis This is a longitudinal mixed methods programme of research conducted across four studies in collaboration with a national aged care provider that cares for more than 5000 residents:Study 1: Cross-sectional staff survey of organisational culture in >50 RACFs with concurrent collection of data on quality and safety of care, and staff outcomes, to explore their associations with culture.Study 2: Ethnographic fieldwork in eight RACFs sampled to achieve maximum variation. Data from interviews, observations and documents will be analysed to identify the underlying assumptions and how cultural assumptions influence the enactment of safety and quality.Study 3: Evaluation of the implementation of the Speak Up for Safety culture change programme, focusing on its contextualisation for RACFs, implementation determinants and outcomes. Data will be collected through semistructured interviews, complimented with secondary data from program training and feedback system usage.Study 4: Evaluation of the effectiveness of the culture change programme using baseline data from study 1 and a follow-up survey of organisational culture postimplementation to assess changes in organisational culture and staff behaviour.Ethics and dissemination The study has received approval from the Macquarie University Human Research Ethics Committee. Informed consent will be sought from all participants. Findings will be disseminated through journal articles, conference presentations and reports to the collaborating provider and RACFs. Survey data will be deposited into a data repository for use by others working on related research.

Abstract Background Tumor cells have the ability to invade and form small clusters that protrude into adjacent tissues, a phenomenon that is frequently observed at the periphery of a tumor as it expands into healthy tissues. The presence of these clusters is linked to poor prognosis and has proven challenging to treat using conventional therapies. We previously reported that p60AmotL2 expression is localized to invasive colon and breast cancer cells. In vitro, p60AmotL2 promotes epithelial cell invasion by negatively impacting E-cadherin/AmotL2-related mechanotransduction. Methods Using epithelial cells transfected with inducible p60AmotL2, we employed a phenotypic drug screening approach to find compounds that specifically target invasive cells. The phenotypic screen was performed by treating cells for 72 h with a library of compounds with known antitumor activities in a dose-dependent manner. After assessing cell viability using CellTiter-Glo, drug sensitivity scores for each compound were calculated. Candidate hit compounds with a higher drug sensitivity score for p60AmotL2-expressing cells were then validated on lung and colon cell models, both in 2D and in 3D, and on colon cancer patient-derived organoids. Nascent RNA sequencing was performed after BET inhibition to analyse BET-dependent pathways in p60AmotL2-expressing cells. Results We identified 60 compounds that selectively targeted p60AmotL2-expressing cells. Intriguingly, these compounds were classified into two major categories: Epidermal Growth Factor Receptor (EGFR) inhibitors and Bromodomain and Extra-Terminal motif (BET) inhibitors. The latter consistently demonstrated antitumor activity in human cancer cell models, as well as in organoids derived from colon cancer patients. BET inhibition led to a shift towards the upregulation of pro-apoptotic pathways specifically in p60AmotL2-expressing cells. Conclusions BET inhibitors specifically target p60AmotL2-expressing invasive cancer cells, likely by exploiting differences in chromatin accessibility, leading to cell death. Additionally, our findings support the use of this phenotypic strategy to discover novel compounds that can exploit vulnerabilities and specifically target invasive cancer cells.

High‐throughput drug screening enables the discovery of new anticancer drugs. Although monolayer cell cultures are commonly used for screening, their limited complexity and translational efficiency require alternative models. Three‐dimensional cell cultures, such as multicellular tumor spheroids (MCTS), mimic tumor architecture and offer promising opportunities for drug discovery. In this study, we developed a neuroblastoma MCTS model for high‐content drug screening. We also aimed to decipher the mechanisms underlying synergistic drug combinations in this disease model. Several agents from different therapeutic categories and with different mechanisms of action were tested alone or in combination with selective inhibition of prostaglandin E2 by pharmacological inhibition of microsomal prostaglandin E synthase‐1 (mPGES‐1). After a systematic investigation of the sensitivity of individual agents and the effects of pairwise combinations, GFP‐transfected MCTS were used in a confirmatory screen to validate the hits. Finally, inhibitory effects on multidrug resistance proteins were examined. In summary, we demonstrate how MCTS‐based high‐throughput drug screening has the potential to uncover effective drug combinations and provide insights into the mechanism of synergy between an mPGES‐1 inhibitor and chemotherapeutic agents.

Abstract Consistent handling of samples is crucial for achieving reproducible molecular and functional testing results in translational research. Here, we used 229 acute myeloid leukemia (AML) patient samples to assess the impact of sample handling on high-throughput functional drug testing, mass spectrometry-based proteomics, and flow cytometry. Our data revealed novel and previously described changes in cell phenotype and drug response dependent on sample biobanking. Specifically, myeloid cells with a CD117 (c-KIT) positive phenotype decreased after biobanking, potentially distorting cell population representations and affecting drugs targeting these cells. Additionally, highly granular AML cell numbers decreased after freezing. Secondly, protein expression levels, as well as sensitivity to drugs targeting cell proliferation, metabolism, tyrosine kinases (e.g., JAK, KIT, FLT3), and BH3 mimetics were notably affected by biobanking. Moreover, drug response profiles of paired fresh and frozen samples showed that freezing samples can lead to systematic errors in drug sensitivity scores. While a high correlation between fresh and frozen for the entire drug library was observed, freezing cells had a considerable impact at an individual level, which could influence outcomes in translational studies. Our study highlights conditions where standardization is needed to improve reproducibility, and where validation of data generated from biobanked cohorts may be particularly important.

Abstract Autophagy is activated in response to a variety of stress conditions including anti-cancer therapies, and tumors cells often depend on autophagy for survival. In this study, we have evaluated inhibition of autophagy as therapeutic strategy in acute lymphoblastic leukemia (ALL) in children, both as a single treatment and in combination with glucocorticoid (GC) Dexamethasone (Dexa). Analysis of proteomics and RNA-seq of ALL cell lines and primary samples identified an upregulation of Vps34 and ATG14 proteins and autophagy and lysosomal pathway enrichment in a genetic subgroup with a recurrent t(12;21) translocation. Cells from this sugbroup were also significantly more sensitive to the selective autophagy or lysosomal inhibitors than cells with other genetic rearrangements. Further, combination of Dexa with either lysosomal or autophagy inhibitors was either synergistic or additive in killing leukemic cells across various genetic and lineage backgrounds, for both cell lines and primary samples, as assessed using viability assays and SynergyFinder as well as apoptotic caspase 3/7-based live-cell assays. Our data demonstrate that targeting autophagy represents a promising strategy for the treatment of pediatric ALL, both as a selective modality for the t(12;21) pre-B-ALL subgroup, and in combination treatments to sensitize to GC-induced cytotoxicity.

Abstract Background An informed understanding of older adults’ perceptions of the impact (positive or negative) of recurrent COVID-19 long lockdowns is important for the development of targeted interventions and resources for future restrictions. This study aimed to understand self-reported impacts of COVID-19 recurrent restrictions on older adults and how technology has been used to mitigate these. Methods A cross-sectional national study of 257 community-dwelling older Australians based in Victoria (mean age = 67.6 years [SD = 7.2]; 20.6% male) completed an online or postal survey as part of a larger study examining the physical and mental health impacts of a second extended COVID-19 lockdown period. This secondary analysis reports on the findings from free-text responses to two open-ended questions included in that survey that asked participants to comment on the greatest impacts of the COVID-19 lockdowns (positive or negative) and the role of technology in supporting their wellbeing during this time. Responses were collected between July and September 2020. Data were analysed using content (COVID-19 impacts) and thematic (role of technology) analysis. Results Respondents gave more negative responses (75.5%) than mixed (15.2%) and positive responses (6.2%) in reporting on the biggest impact of COVID-19 lockdowns. Inductive content analysis revealed two first-order main categories (Positive impacts and Negative impacts). Axial coding of main categories showed five second-order categories (Environmental, Physical Health, Social, Mental Health, and Personal) for both negative and positive main categories (totalling 10 second-order categories). Overall, respondents highlighted social loss as the key negative experience (70%), with acute feelings of social isolation contributing to negative impacts on mental wellbeing. The most commonly reported positive impact reported (11%) was having more time for relationships, relaxation, and new hobbies. Technology was primarily used to sustain socialisation and provide access to essential resources, services, and goods, which respondents perceived to contribute to maintaining their wellbeing. Conclusions Findings suggest a critical need for interventions that address the social loss experienced by older adults during COVID-19 recurrent lockdowns, particularly to alleviate the associated negative impact on mental wellbeing. Recognising the positive aspect of increased time for relationships and leisure activities indicates potential areas for resilience-building strategies. The pivotal role of technology in mitigating adverse effects highlights its significance in building social connections and supporting overall wellbeing during challenging times. These implications can guide future efforts to enhance older adults’ resilience, mental health, and holistic wellbeing in future public health crises.

Purpose in life is a key construct in the development of young adults, particularly college students. There are many instruments measuring sense of purpose in life, but few studies have examined their measurement properties among college students. The current study compares the measurement invariance properties of the Purpose in Life (PIL) scale and the Claremont Purpose Scale (CPS) across college year and undergraduate school. Using both a unidimensional and a two-dimensional model, we found that the PIL's interpretability is limited among college students. Using a three-dimensional model, the CPS was invariant with respect to both grouping variables. The study suggests that the CPS can be used to make meaningful comparisons among college students categorized by school year and undergraduate school. The study also has some implications about the construct of purpose in life; namely, scale structures that work well statistically and theoretically among adults might not generalize to young adults.

IntroductionChrononutrition studies the relation between diet, circadian rhythms and metabolism, which may alter the metabolic intrauterine environment, influencing infant fat-mass (FM) development and possibly increasing obesity risk.AimTo evaluate the association of chrononutrition in pregnancy and infant FM at 6 months.MethodsHealthy pregnant women and term-babies (n = 100pairs) from the OBESO cohort (2017–2023) were studied. Maternal registries included pregestational body-mass-index (BMI), gestational complications/medications, weight gain. Diet (three 24 h-recalls, 1 each trimester) and sleep-schedule (first and third trimesters) were evaluated computing fasting (hours from last–first meal), breakfast and dinner latencies (minutes between wake up-breakfast and dinner-sleep, respectively), number of main meals/day, meal skipping (≥1 main meal/d on three recalls) and nighttime eating (from 9:00 pm–5:59 am on three recalls). Neonatal weight, length, BMI/age were assessed. At 6 months, infant FM (kg, %; air-displacement plethysmography) was measured, and FM index (FMI—kgFM/length2) computed. Exclusive breastfeeding (EBF) was recorded. Multiple linear regression models evaluated the association between chrononutrition and 6 month infant FM.ResultsMean fasting was 11.7 ± 1.3 h; breakfast, dinner latency were 87.3 ± 75.2, 99.6 ± 65.6 min, respectively. Average meals/day were 3.0 ± 0.5. Meal skipping was reported in 3% (n = 3) of women and nighttime eating in 35% (n = 35). Most neonates had normal BMI/age (88%, n = 88). Compared to those who did not, mothers engaged in nighttime-eating had infants with higher %FM (p = 0.019). Regression models (R2 ≥ 0.308, p ≤ 0.001) showed that nighttime eating was positively associated with %FM (B: 2.7, 95%CI: 0.32–5.16). When analyzing women without complications/medications (n = 80), nighttime eating was associated with higher FM [%FM, B: 3.24 (95%CI: 0.59–5.88); kgFM, B: 0.20 (95%CI: 0.003–0.40); FMI, B: 0.54 (95%CI: 0.03–1.05)]. Infant sex and weight (6 months) were significant, while maternal obesity, pregnancy complications/medications, parity, energy intake, birth-BMI/age, and EBF were not.ConclusionMaternal nighttime eating is associated with higher adiposity in 6 month infants.

Introduction Digital mental health interventions (DMHIs) can offer affordable, accessible and anonymous delivery of mental health treatment as an alternative or complement to face-to-face services. To enhance acceptability of, and treatment engagement with, youth DMHIs, they should be co-designed with young people and their caregivers. This study focuses on co-design with caregivers. Objective To explore caregivers’ perspectives, preferences, and ideas to inform the co-design of a digital youth mental health platform for anxiety and depression: ‘Momentum’. Methods and Measures Six group discussions were conducted with 16 caregivers of young people aged 7–17 years. In relation to Momentum, and DMHIs more broadly, participants’ views were sought on purpose and acceptability, access, assessments and feedback, information sharing, caregiver involvement and engagement. Data were thematically analysed using an inductive codebook approach, guided by template analysis. Results Seven themes were identified: (1) providing therapeutic and educational resources; (2) promoting shared and positive communication about mental health; (3) enhancing user experience and understanding; (4) facilitating personalisation and offering customisation of platform features; (5) encouraging end-user engagement through interactivity, incentives, relatability and attracting and maintaining attention; (6) enabling caregivers to provide support while promoting young people's independence; and (7) reducing concerns about, and enhancing trust in, DMHIs. Conclusions Participants expressed favourable views towards DMHIs and Momentum. They shared design ideas for a user-friendly, engaging, interactive, trustworthy, personalised and transparent platform that offered educational resources and mental health treatment. Two sets of recommendations were derived from the study findings: (1) recommendations for co-designing DMHIs with caregivers and (2) recommendations for the design of youth DMHIs.

Whilst attendance in mainstream school helps encourage inclusivity, these environments are recognised as being particularly challenging for young people with an autism spectrum disorder (ASD). The COVID-19 pandemic brought a novel transition as young people moved from school to home-learning. This study compared the experiences of parents of children with ASD and co-occurring health difficulties of school-learning environments with their home-learning environments during COVID-19 lockdown. An interpretative phenomenological analysis was conducted on semi-structured interviews from six parents of children (aged 8-15 years old) with ASD. Four superordinate themes were generated: Interactions between Health, ASD and Learning Environments; School Support and Managing Health Needs; Seeking Solutions; and Learning from COVID-19 Lockdown. The study highlighted the impact of ASD and co-occurring health difficulties on learning where parents found ways to provide positive home-learning environments which could be used and/or transferred back into school environments. These results hold real-world implications where educators could treat sensory and ASD friendly environments as standard and include genuine adjustments for children with ASD and additional needs. A flexible home-learning approach using parental knowledge around environmental adjustments that support learning, wellbeing and a sense of inclusion should be prioritised for children's overall development and wellbeing in these unprecedented times, and beyond.

Abstract The mosquito species Aedes aegypti (L.) is known to act as a vector in the transmission of various diseases, including dengue fever and yellow fever. The use of insect repellents is one of precautionary measures used to mitigate the risk of these diseases in humans by reducing mosquito biting. Nepetalactone, a potent natural insect repellent primarily found in catnip (Nepeta cataria) essential oil, has emerged as a promising candidate for mosquito repellence. Here, we evaluated the potential of catnip essential oil (> 95% nepetalactone) for use as a mosquito repellent. Using a Y-tube olfactometer and human hands as an attractant, we analysed the effectiveness of catnip oil at repelling the mosquito species Aedes aegypti. We tested a range of dilutions of catnip essential oil and found that concentrations as low as 2% were effective at repelling > 70% of mosquitoes for between one and four hours after repellent application. These findings suggest that nepetalactone could potentially be used as a natural, effective alternative to synthetic mosquito repellents, thereby offering protection against vector-borne diseases.

Abstract Objective To identify barriers and facilitators associated with the sustainability of implemented and evaluated improvement programs in healthcare delivery systems. Data sources and study setting Six academic databases were searched to identify relevant peer-reviewed journal articles published in English between July 2011 and June 2022. Studies were included if they reported on healthcare program sustainability and explicitly identified barriers to, and facilitators of, sustainability. Study design A systematic integrative review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Study quality was appraised using Hawker’s Quality Assessment Tool. Data collection/extraction methods A team of reviewers screened eligible studies against the inclusion criteria and extracted the data independently using a purpose-designed Excel spreadsheet. Barriers and facilitators were extracted and mapped to the Integrated Sustainability Framework (ISF). Frequency counts of reported barriers/facilitators were performed across the included studies. Results Of the 124 studies included in this review, almost half utilised qualitative designs (n = 52; 41.9%) and roughly one third were conducted in the USA (n = 43; 34.7%). Few studies (n = 29; 23.4%) reported on program sustainability beyond 5 years of program implementation and only 16 of them (55.2%) defined sustainability. Factors related to the ISF categories of inner setting (n = 99; 79.8%), process (n = 99; 79.8%) and intervention characteristics (n = 72; 58.1%) were most frequently reported. Leadership/support (n = 61; 49.2%), training/support/supervision (n = 54; 43.5%) and staffing/turnover (n = 50; 40.3%) were commonly identified barriers or facilitators of sustainability across included studies. Forty-six (37.1%) studies reported on the outer setting category: funding (n = 26; 56.5%), external leadership by stakeholders (n = 16; 34.8%), and socio-political context (n = 14; 30.4%). Eight studies (6.5%) reported on discontinued programs, with factors including funding and resourcing, poor fit, limited planning, and intervention complexity contributing to discontinuation. Conclusions This review highlights the importance of taking into consideration the inner setting, processes, intervention characteristics and outer setting factors when sustaining healthcare programs, and the need for long-term program evaluations. There is a need to apply consistent definitions and implementation frameworks across studies to strengthen evidence in this area. Trial registration https://bmjopen.bmj.com/content/7/11/e018568 .

Apple cultivars ‘Annurca’ and ‘Limoncella’ are grown locally in the Campania region of Italy and are valued for their distinctive flavour and characteristics, including a high content of nutritionally important bioactive compounds. However, apples are typically stored chilled for several months before consumption, so it is important to assess if the valuable characteristics are still present after postharvest storage. Here, we compare the quality, nutritional parameters, and aroma of these two cultivars with two widely grown international cultivars, ‘Golden Delicious’ and ‘Fuji’, after 60 days of storage. The aroma profiles of all four apples were analysed using thermal desorption and gas chromatography–time-of-flight mass spectrometry. We show that the local cultivars are distinct from the international cultivars in their bioactive compound content and their antioxidant activity. ‘Limoncella’ shows high sugar content, which may be acting as a cryoprotectant during storage, and high total phenolics in the flesh, which is of nutritional interest. We identified 104 volatile organic compounds (VOCs) and showed that the overall aroma profile is distinct for each cultivar, containing 11 published odorant compounds. The ‘Annurca’ profile is uniquely low in esters. Seven VOCs retain good discrimination across the four cultivars and, together with the quality and nutritional data, separate the two local cultivars from the international cultivars by hierarchical clustering. Overall, the data emphasize the unique characteristics of the two local cultivars and their value.

Mainstream primary and secondary schools are increasingly committed to the inclusion of students with Tourette Syndrome (TS). This qualitative study explores teachers' perceptions of factors that have contributed to, or hindered, their success in creating an inclusive environment for children with Tourette Syndrome (TS). Eight teachers (two males, six females) from mainstream primary and secondary schools in the United Kingdom (UK) took part in semi-structured interviews to ascertain their knowledge, training and experience of TS during their professional careers in the UK. Thematic analysis of the transcripts revealed three main themes: teachers' lack of real knowledge and awareness of TS; training provision and marginalisation of TS; and finding solutions and building alliances. Although many of the teachers described their mainstream school as an inclusive environment, many still believed they lacked the professional training to adequately understand the disorder. By enhancing teacher training related to TS, improvements may be seen in the communications between the teachers and parents, and opportunities to educate children and the wider community will also result in a more inclusive environment, reducing specific and generic stressors for children with TS.

Abstract Most patients with advanced ovarian cancer (OC) relapse and progress despite systemic therapy, pointing to the need for improved and tailored therapy options. Functional precision medicine can help to identify effective therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional precision medicine platform: DET3Ct (Drug Efficacy Testing in 3D Cultures), where the response of patient cells to drugs and drug combinations are quantified with live-cell imaging. We demonstrate the delivery of individual drug sensitivity profiles in 20 samples from 16 patients with ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing results six days after operation. In this cohort all patients received carboplatin. The carboplatin sensitivity scores were significantly different for patients with a progression free interval (PFI) less than or equal to 12 months and those with more than 12 months (p

Abstract The urban community faces a significant obstacle in effectively utilising Earth Observation (EO) intelligence, particularly the Copernicus EO program of the European Union, to address the multifaceted aspects of urban sustainability and bolster urban resilience in the face of climate change challenges. In this context, here we present the efforts of the CURE project, which received funding under the European Union’s Horizon 2020 Research and Innovation Framework Programme, to leverage the Copernicus Core Services (CCS) in supporting urban resilience. CURE provides spatially disaggregated environmental intelligence at a local scale, demonstrating that CCS can facilitate urban planning and management strategies to improve the resilience of cities. With a strong emphasis on stakeholder engagement, CURE has identified eleven cross-cutting applications between CCS that correspond to the major dimensions of urban sustainability and align with user needs. These applications have been integrated into a cloud-based platform known as DIAS (Data and Information Access Services), which is capable of delivering reliable, usable and relevant intelligence to support the development of downstream services towards enhancing resilience planning of cities throughout Europe.

Pregnancy complicated by obesity represents an increased risk of unfavorable perinatal outcomes such as gestational diabetes mellitus (GDM), hypertensive disorders in pregnancy, preterm birth, and impaired fetal growth, among others. Obesity is associated with deficiencies of micronutrients, and pregnant women with obesity may have higher needs. The intrauterine environment in pregnancies complicated with obesity is characterized by inflammation and oxidative stress, where maternal nutrition and metabolic status have significant influence and are critical in maternal health and in fetal programming of health in the offspring later in life. Comprehensive lifestyle interventions, including intensive nutrition care, are associated with a lower risk of adverse perinatal outcomes. Routine supplementation during pregnancy includes folic acid and iron; other nutrient supplementation is recommended for high-risk women or women in low-middle income countries. This study is an open label randomized clinical trial of parallel groups (UMIN Clinical Trials Registry: UMIN000052753, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000060194) to evaluate the effect of an intensive nutrition therapy and nutrient supplementation intervention (folic acid, iron, vitamin D, omega 3 fatty acids, myo-inositol and micronutrients) in pregnant women with obesity on the prevention of GDM, other perinatal outcomes, maternal and newborn nutritional status, and infant growth, adiposity, and neurodevelopment compared to usual care. Given the absence of established nutritional guidelines for managing obesity during pregnancy, there is a pressing need to develop and implement new nutritional programs to enhance perinatal outcomes.

Los sonidos de la ciudad son cambiantes, nos movemos por ella sin prestar atención y su análisis –las cartografías– reflejan sólo una parte. Es por ello que es necesario considerar otros aspectos: como el diseño y las formas de la ciudad, pero sobre todo la experiencia que narran quienes la escuchan y la viven.