Pleiotrophin modulates acute and long-term LPS-induced neuroinflammatory responses and hippocampal neurogenesis.

The hippocampus is one of the most vulnerable regions affected in disorders characterized by overt neuroinflammation such as neurodegenerative diseases. Pleiotrophin (PTN) is a neurotrophic factor that modulates acute neuroinflammation in different contexts. PTN is found highly upregulated in the brain in different chronic disorders characterized by neuroinflammation, suggesting an important role in the modulation of sustained neuroinflammation. To test this hypothesis, we studied the acute and long-term effects of a single lipopolysaccharide (LPS; 5 mg/kg) administration in Ptn+/+ and Ptn-/- mice, and in mice with Ptn-overexpression (Ptn-Tg). Endogenous PTN levels proportionally modulate LPS-induced increase in TNF-α plasma levels one hour after treatment. In the dentate gyrus (DG) of the hippocampus, a lower percentage of DCX+ cells were detected in saline-treated Ptn-/- mice compared to Ptn+/+ mice, suggesting a crucial role of PTN in the maintenance of hippocampal neuronal progenitors. The data show that PTN overexpression tends to potentiate acute microglial responses in the DG 16 hours after LPS treatment. Remarkably, a significant increase in the number of neuronal progenitors together with astrogliosis was detected 10 months after a single injection of LPS treatment in wild type mice. However, these LPS-induced long-term effects were prevented in Ptn-/- and Ptn-Tg mice, suggesting that PTN modulates LPS-induced long-term neurogenesis changes and astrocytic response in the hippocampus. The data presented here suggest that endogenous PTN levels are crucial in the regulation of acute LPS-induced systemic and hippocampal microglial responses in young mice. Furthermore, our findings provide evidence of the key role of PTN in the regulation of long-term LPS effects on astrocytic response and neurogenesis in the hippocampus.

New risk classification adapting SCAI shock stages to patients with pulmonary embolism (RISA-PE).

BACKGROUND: Pulmonary embolism (PE) treatment is based on risk stratification according to European Society of Cardiology (ESC) guidelines. However, emerging therapies in acute PE may require a more granular risk classification. Therefore, the objective of the present study was to propose a new RIsk claSsification Adapting the SCAI shock stages to right ventricular failure due to acute PE (RISA-PE). METHODS: This registry included consecutive intermediate-high risk (IHR) or high-risk (HR)-PE patients selected for catheter-directed interventions (CDI) from 2018 to 2023 in 15 Spanish centers (NCT06348459). Patients were grouped according to RISA-PE classification as A (right ventricular dysfunction and troponin elevation); B (A + serum lactate >2 mmol/L OR shock index ≥1); C (persistent hypotension); D (obstructive shock); and E (cardiac arrest). In-hospital adverse events were assessed to evaluate RISA-PE performance. RESULTS: A total of 334 patients were included (age 62.1±15.2 years, 55.7% males). The incidence of in-hospital all-cause death was progressively higher with increasing RISA-PE stage (1.2%, 6.4%, 19.0%, 25.6%, and 57.7% for stages A, B, C, D, and E, respectively, P value for linear trend<0.001). However, using the ESC classification, there was an abrupt difference between IHR- and HR-PE patients regarding mortality (4.3% vs. 29.3%, P<0.001). The incidence of in-hospital major bleeding and acute kidney injury followed a similar pattern. CONCLUSIONS: The user-friendly RISA-PE classification may improve the granularity in stratifying PE patients' risk and warrants evaluation in larger studies with different therapeutic approaches in order to detect its utility as a decision-making scale.

Impact of Uniaxial Static Strain on Myoblast Differentiation in Collagen-Coated PCL Microfilament Scaffolds: Role of Onset Time of Mechanical Stimulation.

Tissue engineering endeavors to create in vitro constructs that replicate the properties of native tissue, such as skeletal muscle. This study investigated the use of mechanical stimulation to promote myogenic differentiation and enhance the functionality of bioengineered tissues. Specifically, it aimed to facilitate the differentiation of myoblasts within a three-dimensional scaffold using a defined pattern of mechanical stimulation. C2C12 cells were cultured on a collagen-coated PCL microfilament scaffold and subjected to 24 h of uniaxial static strain using a biomechanical stimulation system. Two onset times of stimulation, 72 h and 120 h post-seeding, were evaluated. Cell proliferation, myogenic marker expression, and alterations in cell morphology and orientation were assessed. Results indicate that static strain on the scaffold promoted myoblast differentiation, evidenced by morphological and molecular changes. Notably, strain initiated at 72 h induced an early differentiation stage marked by MyoD expression, whereas stimulation beginning at 120 h led to a mid-stage differentiation characterized by the co-expression of MyoD and Myogenin, culminating in myotube formation. These results highlight the critical influence of myoblast maturity at the time of strain application on the differentiation outcome. This study provides insights that could guide the optimization of mechanical stimulation protocols in tissue engineering applications.

Abiotic Stress Effect on Agastache mexicana subsp. mexicana Yield: Cultivated in Two Contrasting Environments with Organic Nutrition and Artificial Shading.

Research on medicinal plants is essential for their conservation, propagation, resistance to environmental stress, and domestication. The use of organic nutrition has been demonstrated to improve soil fertility and plant quality. It is also important to study the effects of the Basic Cation Saturation Ratio (BCSR) approach, which is a topic where there is currently controversy and limited scientific information. Evaluating the growth and yields of Agastache mexicana subsp. mexicana (Amm) in different environments is crucial for developing effective propagation and domestication strategies. This includes examining warm and subhumid environments with rain in summer in comparison to mild environments with summer rain. Significant differences were observed in the effects of cold, waterlogging, and heat stresses on the plant's biomass yield and the morphometric-quantitative modeling by means of isolines. The biomass yield was 56% higher in environment one compared to environment two, 19% higher in environment one with organic nutrition, and 48% higher in environment two with organic nutrition compared to using only BCSR nutrition. In the second harvesting cycle, the plants in environment one did not survive, while the plants in environment two managed to survive without needing additional nutrition. Statistical and mathematical analyses provided information about the population or sample. Additionally, further analysis using isolines as a new approach revealed new insights into understanding phenology and growth issues.

Content, Behaviour Change Techniques, and Quality of Postpartum Depression Apps to Be Recommended by Midwives: Systematic Search and Evaluation.

BACKGROUND: Postpartum depression is a public health problem that affects a considerable percentage of women. Despite the proliferation of related apps, there are limited data available on the best apps to prevent postpartum depression. We identified which apps available in Spanish could be recommended by midwives based on their content, quality, and behaviour change techniques, as a complementary tool for preventing postpartum depression in women. METHODS: A systematic search was performed to identify apps available on iOS App Store and Google Play, which were used to replicate how patients' access "postpartum depression prevention" apps. Apps' quality, behaviour change potential, and contents were assessed. RESULTS: A total of 1408 apps were identified, of which 7 were retrieved for assessment (0.5%). The mean objective and subject quality were 3.1 (SD = 1.01) and 2.7 (SD = 1.27), respectively. A total of 24 topics were identified. The mean ABACUS score was 6.6 (SD = 3.64), and the mean number of topics addressed by the apps was 9.9 (SD = 5.90). CONCLUSION: The results of the present study suggest that a specific free app is not available in Spanish for the prevention of postpartum depression, and only a small percentage of free apps should be recommended based on their quality, BCTs, and contents. The systematic review protocol was not registered.

Gangliocytic paraganglioma: A case report.

Paragangliomas (PGLs) are rare and encapsulated neuroendocrine tumors (NET), located in the adrenal gland or the extra-adrenal paraganglia. Extra-adrenal PGLs may develop a gangliocytic component with ganglion cells which are called gangliocytic paragangliomas (GPs). The most common location is the duodenum, and they appear with digestive symptoms or as an incidental finding. We described a 43 years old patient, with epigastric pain, nausea and vomiting. The CT-scan reveals a nodular image in the duodenum. An ultrasound-guided FNA was performed and the pathological report revealed neuroendocrine cell groups and neural tissue. Surgery was the chosen treatment. As the patient did not present lymphatic or pancreatic parenchyma invasion, radiotherapy (RT) was not administered. The management of GPs is not well established and multidisciplinary team approach is recommended to lead to therapeutic options. Surgical resection is still key in the treatment, and adjuvant RT may be considered in cases of lymph node invasion.

Effectiveness of a hybrid closed-loop system for children and adolescents with type 1 diabetes during physical exercise: A cross-sectional study in real life.

OBJECTIVE: The aim of the study was to describe how physical exercise affects metabolic control, insulin requirements and carbohydrate intake in children who use hybrid closed-loop systems. METHODS: Cross-sectional study design. The sample included 21 children and adolescents diagnosed with type 1 diabetes. During the study, participants were monitored for a period of 7 days to gather comprehensive data on these factors. RESULTS: Nine participants (42.9%) had switched to exercise mode to raise the target glucose temporarily to 150 mg/dL. The HbA1c values ranged from 5.5% to 7.9% (median, 6.5%; IQR, 0.75). The percentage of time within the target range of 70-180 mg/dL was similar; however, there was an increased duration of hyperglycaemia and more autocorrections on exercise days. The time spent in severe hyperglycaemia (>250 mg/dL) increased by 2.7% in exercise compared to non-exercise days (P = .02). It is worth noting that hypoglycaemic episodes did not increase during the exercise days compared with non-exercise days. CONCLUSION: The hybrid closed-loop system was effective and safe in children and adolescents with type 1 diabetes during the performance of competitive sports in real life.

Impact of Breast Cancer on Cardiometabolic Health in Spanish Women ≥50 Years with Pre-Existing Type 2 Diabetes Mellitus.

During breast cancer (BC), cardiometabolic disorders can worsen prognosis, particularly in women with type 2 diabetes mellitus (T2DM). This study aimed to determine the impact of BC diagnosis on cardiometabolic parameters and the incidence of complication in women over 50 years of age (90% aged ≥ 65 years) with pre-existing T2DM. Using primary care registries from Asturias (Spain), a total of 106 women diagnosed with T2DM followed by BC were selected and matched with women with T2DM (n = 212) in a cohort study. Indicators of cardiometabolic health and microvascular complications associated with T2DM were collected. Women were monitored from two years prior to five years after BC diagnosis. Conditional logistic regressions were used to compare the adjusted odds of staying below each indicator's threshold. During follow-up, women with T2DM+BC had a higher risk of fasting blood glucose ≥126 mg/dL (adjusted odds ratio [aOR] = 1.83; 95% confidence interval [CI95%]: 1.01-3.32) and glycosylated hemoglobin (Hb1Ac) ≥ 48 mmol/mol or 6.5% (aOR: 2.44; IC95%: 1.21-4.91). There was no difference between the groups regarding the incidence of microvascular complications. BC incidence negatively impacted the glycemic control of Spanish women with pre-existing T2DM measured by basal blood glucose and HbA1c, but not cardiometabolic health indicators or T2DM complications.

Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in KIT and PDGFRA genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis. METHODS: Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed. RESULTS: Both patients harbouring low-risk GISTs with different mutations (PDGFRA and KIT) shared homozygous germline pathogenic deletions in both CFHR1 and CFHR3 genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as SLC25A24. No particular pathogenic SNV shared by both patients was detected. CONCLUSION: Our study provides new insights into germline variants that can be associated with the development of GISTs, namely, CFHR1 and CFHR3 deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.

Quantitative non-contrast perfusion MRI in the body using arterial spin labeling.

Arterial spin labeling (ASL) is a non-invasive magnetic resonance imaging (MRI) method that enables the assessment and the quantification of perfusion without the need for an exogenous contrast agent. ASL was originally developed in the early 1990s to measure cerebral blood flow. The utility of ASL has since then broadened to encompass various organ systems, offering insights into physiological and pathological states. In this review article, we present a synopsis of ASL for quantitative non-contrast perfusion MRI, as a contribution to the special issue titled "Quantitative MRI-how to make it work in the body?" The article begins with an introduction to ASL principles, followed by different labeling strategies, such as pulsed, continuous, pseudo-continuous, and velocity-selective approaches, and their role in perfusion quantification. We proceed to address the technical challenges associated with ASL in the body and outline some of the innovative approaches devised to surmount these issues. Subsequently, we summarize potential clinical applications, challenges, and state-of-the-art ASL methods to quantify perfusion in some of the highly perfused organs in the thorax (lungs), abdomen (kidneys, liver, pancreas), and pelvis (placenta) of the human body. The article concludes by discussing future directions for successful translation of quantitative ASL in body imaging.

A phase III randomized controlled trial of plitidepsin, a marine derived compound, in hospitalized adults with moderate COVID-19.

BACKGROUND: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients. METHODS: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety. FINDINGS: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated. INTERPRETATION: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted. FUNDING: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).

Investigating the physicochemical properties, sensory profile and consumer acceptability of beetroot dark chocolate.

BACKGROUND: The incorporation of functional food ingredients in chocolate that seek to eliminate, if not completely, most of the added sugar content, as well as the use of alternative chocolate production techniques, have gained popularity in recent years. This study aimed to incorporate red beetroot powder into dark chocolate and investigate the effect of red beetroot powder concentration and processing time in a melanger on the physicochemical properties, sensory profile and consumer acceptability of beetroot dark chocolate. RESULTS: The addition of red beetroot powder increased the moisture content, particle size distribution and hardness of the chocolates, while the opposite was true for processing time with no effect on the colour. Except for taste, which had an average score of 3.2 ± 1.8 on the 7-point hedonic scale, consumers scored all the other sensory attributes of the chocolates above 4.0. Among the chocolates with red beetroot powder, samples with a 15% red beetroot powder addition had a high average overall acceptability score of >5, while the 30% sample scored <4. CONCLUSION: Red beetroot powder can be used to replace sugar in dark chocolate without affecting its physicochemical properties, sensory profile or consumer acceptability. However, the target market should be considered when determining the level of red beetroot powder incorporation in terms of chocolate taste. This research has the potential to improve the overall health-promoting properties of dark chocolate by eliminating added sugar (partially or completely). It would also help to diversify beetroot utilization, allow small-scale processors to venture into chocolate production and expand the small-scale chocolate value chain. © 2024 Society of Chemical Industry.

The Association between Pressure Pain Thresholds, Conditioned Pain Modulation, Clinical Status, and Sleep Quality in Fibromyalgia Patients: A Clinical Trial Secondary Analysis.

Background: Fibromyalgia (FM) is a complex multidimensional disorder primarily characterized by chronic widespread pain, significantly affecting patients' quality of life. FM is associated with some clinical signs found with quantitative sensory testing (QST), sleep disturbance, or psychological problems. This study aims to explore the associations between pressure pain thresholds (PPTs), conditioned pain modulation (CPM), clinical status, and sleep quality in FM patients, offering insights for better clinical management and assessment tools. Methods: This secondary analysis utilized data from a clinical trial involving 129 FM patients. Various assessments, including the Fibromyalgia Impact Questionnaire (FIQ), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), and Jenkins Sleep Scale (JSS), were employed to evaluate the clinical and psychological status and sleep quality. PPTs and CPM were measured to understand their relationship with clinical parameters. Results: Our findings revealed that PPTs and CPM are not significantly associated with the clinical status or sleep quality of FM patients. Instead, pain catastrophizing and anxiety state showed a stronger correlation with the impact of fibromyalgia and sleep disturbances. These results highlight the importance of psychological and cognitive factors in managing FM. Conclusions: The study suggests that while PPTs and CPM may not be reliable biomarkers for clinical status in FM, the use of comprehensive assessments including FIQ, PCS, STAI, and JSS can provide a more accurate evaluation of patients' condition. These tools are cost-effective, can be self-administered, and facilitate a holistic approach to FM management, emphasizing the need for personalized treatment plans.

Sex differences in the association between social frailty and diet quality among older adults in Spain.

OBJECTIVE: The aim was to examine the association between social frailty and diet quality in adults over 65 years of age, and whether results differed by sex. DESIGN: Population-based cross-sectional study using data from the Spanish National Health Survey. PARTICIPANTS: 5,071 community-dwelling people ≥65 years from Spain. MEASUREMENTS: Social frailty was deemed to exist when the person both lived alone and had low social support, measured with the Duke-UNC scale. Diet was assessed with the Spanish Healthy Eating Index (S-HEI), ranging from 0 to 100 points (highest diet quality). Means and 95% confidence intervals of the S-HEI score for each social frailty group were calculated using linear regressions, with socially robust people as reference. Analyses were adjusted for main confounders, including sociodemographic, lifestyle and morbidity variables. RESULTS: There were no differences in the S-HEI adjusted mean of socially frail (74.3 points, 95%CI: 73.4-75.2) compared to socially robust older adults (75.4 points; 95%CI: 75.1-75.7). In sex-stratified analyses, the S-HEI adjusted mean of socially frail men (71.9 points; 95%CI: 70.6-73.2) was lower than robust men (74.8 points; 95%CI: 74.4-75.3). Specifically, social frailty was associated with lower consumption of vegetables, fruits, dairy and lower diet variety in men. Differences were not observed according to social frailty among older women. CONCLUSIONS: Social frailty was associated with poor diet quality in community-dwelling older men, but not in women in Spain. Gender differences in self-care could partly explain this association. Sex-specific interventions are required to minimize the impact of social frailty on diet quality.

Alginate coatings applied on apple cubes as a vehicle for Lacticaseibacillus casei: probiotic viability and overall quality of a new functional product.

BACKGROUND: Worldwide, vegan and vegetarian lifestyles, as well as food allergies and intolerance (e.g. lactose intolerance and milk protein allergy) demand the development of alternatives to dairy-based probiotic foods. In the present study, probiotic Lacticaseibacillus casei CECT 9104 was added to alginate-based edible coatings enriched with inulin and oligofructose and applied to fresh-cut apple. Microbiological, physicochemical and sensory quality parameters of the apple cubes were monitored during 8 days of refrigerated storage. Lacticaseibacillus casei was tested for its antagonistic effect against inoculated Listeria innocua and Escherichia coli O157:H7. The viability of the probiotic strain during refrigerated storage and after simulated gastrointestinal digestion (GID) was evaluated. RESULTS: After 8 days of storage, 9.52-9.64 log colony-forming units (CFU) g-1 of L. casei were detected in apple samples. The functional apple cubes retained 8.31-8.43 log CFU g-1 of the probiotic after GID, without a significant effect of prebiotic addition. The microbiological quality and nutritional properties were maintained by the use of active coatings, whereas the sensory quality decreased after 8 days of storage. A bactericidal effect was exerted by the probiotic strain loaded in the coating against L. innocua artificially inoculated on apple cubes. Escherichia coli O157:H7 counts were reduced by 2.5 log after 8 days. CONCLUSION: This study has demonstrated the suitability of apple cubes as an alternative matrix to milk for carrying probiotic L. casei CECT 9104 and prebiotics, offering a promising alternative for the development of plant-based functional foods. © 2024 Society of Chemical Industry.

Factors associated with discharge home in older patients admitted to emergency department observation units: Looking for a predictive scale.

BACKGROUND: The selection of patients who are going to be admitted to an emergency department observation unit (EDOU) is essential for the good management of these units, intended fundamentally to avoid unnecessary hospitalization of patients. This is especially important when dealing with older patients. It would be important to know what factors are associated with discharge home and to have a clinical predictive scale that appropriately selects older patients who are going to be admitted to an EDOU. METHODS: A retrospective cross-sectional study was conducted of all patients ≥65 years of age assisted in 48 Spanish Emergency Departments for 7 consecutive days and were admitted to the EDOU. Demographics-functional, vital signs data and initial laboratory results were analyzed to investigate its association with discharge home and develop and validate a prediction model for discharge home from EDOU. Multivariable logistic regression was performed to develop a prediction model, and a scoring system was created. RESULTS: Among 5457 patients admitted to the EDOU from the emergency room, 2508 (46%) patients were discharged home, and 2949 (54%) were admitted to the hospital. Five variables were strongly associated with discharge home: the absence of fever (adjusted OR: 3.61, 95% CI:1.53-8.54), Glasgow Coma Scale score of 15 points (2.80, 1.63-4.82), absence of tachypnea (2.51, 1.74-3.64) or leukocytosis (2.07, 1.70-2.52) and oxygen saturation >94% (2.00, 1.64-2.43). The final model achieved an area under the receiver operating characteristic curve of 0.648 (IC95% = 0.627-0.668) in the development cohort and 0.635 (0.614-0.656) in the validation cohort. CONCLUSIONS: There are factors associated with a greater probability of discharge home of older patients admitted to EDOUs. Prediction at the individual level remains elusive, as the best model obtained in this study did not have sufficient validity to be applied in the clinical setting.

Growth factor-loaded ovarian extracellular matrix hydrogels promote in vivo ovarian niche regeneration and enhance fertility in premature ovarian insufficiency preclinical models.

Premature ovarian insufficiency (POI) means menopause before 40 years of age affecting about 1 % of women. Approaches based on cell therapy and the paracrine effects of stem cells or bioproducts such as platelet-rich plasma have been proposed, but concerns remain about undesired systemic effects, as well as the need to optimize delivery methods through bioengineering methods. This study explores the efficacy of decellularized bovine ovarian cortex extracellular matrix (OvaECM) hydrogels alone and as a growth factor (GF) carrier (OvaECM+GF) in a chemotherapy-induced POI murine model. In vitro assays showed a gradual release of GF from the OvaECM sustained for two weeks. Chemotherapy drastically reduced follicle numbers, but OvaECM+GF treatment restored pre-antral follicle development. Moreover, this treatment notably regenerated the ovarian microenvironment by increasing cell proliferation and microvessel density while reducing chemotherapy-induced apoptosis and fibrosis. Whole-ovary RNA sequencing and gene set enrichment analysis revealed an upregulation of regeneration-related genes and a downregulation of apoptotic pathways. The OvaECM+GF treatment also yielded significantly better outcomes following ovarian stimulation and in vitro fertilization. After two consecutive crossbreeding cycles, OvaECM+GF-treated mice showed normal reproductive function. This research showcases the biocompatibility and efficacy of OvaECM to reverse POI in mice, setting a foundation to explore innovative bioengineering-based POI therapies. STATEMENT OF SIGNIFICANCE: Premature ovarian insufficiency (POI) affects about 1 % of women worldwide, causing early menopause before 40 years old. Current treatments alleviate symptoms but do not restore ovarian function. This study explores an innovative approach using ovarian cortex extracellular matrix hydrogels to deliver growth factors into the murine ovarian niche and reverse POI. In vitro release kinetic assays demonstrated a gradual and sustained release of growth factors. In a POI-induced mouse model, intraovarian injections of the hydrogel encapsulating growth factors restored pre-antral follicle development, increased cell proliferation, reduced apoptosis and fibrosis, and improved ovarian response and in vitro fertilization outcomes. Long-term benefits included larger litter sizes. This innovative technique shows promise in regenerating the ovarian environment and improving reproductive outcomes.

An artificial intelligence-assisted system versus white light endoscopy alone for adenoma detection in individuals with Lynch syndrome (TIMELY): an international, multicentre, randomised controlled trial.

BACKGROUND: Computer-aided detection (CADe) systems for colonoscopy have been shown to increase small polyp detection during colonoscopy in the general population. People with Lynch syndrome represent an ideal target population for CADe-assisted colonoscopy because adenomas, the primary cancer precursor lesions, are characterised by their small size and higher likelihood of showing advanced histology. We aimed to evaluate the performance of CADe-assisted colonoscopy in detecting adenomas in individuals with Lynch syndrome. METHODS: TIMELY was an international, multicentre, parallel, randomised controlled trial done in 11 academic centres and six community centres in Belgium, Germany, Italy, and Spain. We enrolled individuals aged 18 years or older with pathogenic or likely pathogenic MLH1, MSH2, MSH6, or EPCAM variants. Participants were consecutively randomly assigned (1:1) to either CADe (GI Genius) assisted white light endoscopy (WLE) or WLE alone. A centre-stratified randomisation sequence was generated through a computer-generated system with a separate randomisation list for each centre according to block-permuted randomisation (block size 26 patients per centre). Allocation was automatically provided by the online AEG-REDCap database. Participants were masked to the random assignment but endoscopists were not. The primary outcome was the mean number of adenomas per colonoscopy, calculated by dividing the total number of adenomas detected by the total number of colonoscopies and assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04909671. FINDINGS: Between Sept 13, 2021, and April 6, 2023, 456 participants were screened for eligibility, 430 of whom were randomly assigned to receive CADe-assisted colonoscopy (n=214) or WLE (n=216). 256 (60%) participants were female and 174 (40%) were male. In the intention-to-treat analysis, the mean number of adenomas per colonoscopy was 0·64 (SD 1·57) in the CADe group and 0·64 (1·17) in the WLE group (adjusted rate ratio 1·03 [95% CI 0·72-1·47); p=0·87). No adverse events were reported during the trial. INTERPRETATION: In this multicentre international trial, CADe did not improve the detection of adenomas in individuals with Lynch syndrome. High-quality procedures and thorough inspection and exposure of the colonic mucosa remain the cornerstone in surveillance of Lynch syndrome. FUNDING: Spanish Gastroenterology Association, Spanish Society of Digestive Endoscopy, European Society of Gastrointestinal Endoscopy, Societat Catalana de Digestologia, Instituto Carlos III, Beca de la Marato de TV3 2020. Co-funded by the European Union.

YouTube videos on lymphedema as an information source for Spanish speaking breast cancer survivors.

BACKGROUND: Breast cancer-related lymphedema in the upper limb remains one of the most distressful complications of breast cancer treatment. YouTube is considered a potential digital resource for population health and decision making. However, access to inadequate information or misinformation could have undesirable impacts. This cross-sectional study aimed to evaluate the reliability, quality and content of YouTube videos on lymphedema as an information source for Spanish-speaking breast cancer survivors. METHODS: A search of YouTube was conducted in January 2023 using the key words "breast cancer lymphedema" and "lymphedema arm breast cancer." Reliability and quality of the videos were evaluated using the Discern tool, content, source of production, number of likes, comments, views, duration, Video Power Index, likes ratio, view ratio and age on the platform. RESULTS: Amongst the 300 Spanish language videos identified on YouTube, 35 were selected for analysis based on the inclusion and exclusion criteria. Of the 35 selected videos, 82.9% (n = 29) were developed by healthcare or academic professionals and 17.1% (n = 9) by others. Reliability (p < 0.017) and quality (p < 0.03) were higher in the videos made by professionals. The Discern total score (r = 0.476; p = 0.004), reliability (r = 0.472; p = 0.004) and quality (r = 0.469; p = 0.004) were positively correlated with the duration of the videos. CONCLUSIONS: Our findings provide a strong rationale for educating breast cancer survivors seeking lymphedema information to select videos made by healthcare or academic professionals. Standardised evaluation prior to video publication is needed to ensure that the end-users receive accurate and quality information from YouTube.