Condom use across casual and committed relationships: The role of relationship characteristics.

BACKGROUND: While the existence of a complex variety of casual sexual relationships (CSRs) has been acknowledged, studies rarely describe the prevalence of condom use across these relationships or how their hybrid nature, specifically relationship characteristics, affect condom use. This study aims to describe condom use within committed relationships and various types of casual sexual relationships (CSRs), examining the influence of relationship characteristics on condom use among culturally validated relationship types (committed, friends with benefits, hookups, booty call). METHODS: Emerging adults (N = 728, 18-29 years, M = 22.56; SD = 3.01) completed a survey with four blocks: sociodemographics; brief sexual history; relationships over the previous year; and current relationship, assessing relationship type, ten relationship characteristics (e.g., commitment, emotional and sexual exclusivity, partner acquaintance, sexual involvement) and condom use (vaginal, oral, and anal), operationalized by three measures (use at last encounter, likert-type scale and percentage of use). RESULTS: The results showed patterns in condom use by relationship type and illuminated how relationship characteristics-grouped into three factors: commitment, intimacy, and sexuality-mediate condom use. Condom use was more frequent in vaginal than anal and oral sex, and less frequent in committed relationships. No significant differences were found in condom use in vaginal sex between committed relationships and hookups, with condom in these relationships being significantly lower than in booty call. Intimacy mediated between all contrasts tested and condom use in vaginal sex, while sexuality mediated between committed vs. CSRs and condom use in anal and oral sex. CONCLUSIONS: Findings point to the need of considering the diversity of CSRs for understanding condom use and highlight the role of intimacy as a relevant mechanism associated with condom use in vaginal sex and of sexuality in oral and anal sex, which should be taken into consideration in the tailoring of health promoting efforts.

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.

Association of hepatitis B virus treatment with all-cause and liver-related mortality among individuals with HBV and cirrhosis: a population-based cohort study.

Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Effects of Per- and Polyfluoroalkylated Substances on Female Reproduction.

Per- and poly-fluoroalkylated substances (PFAS) are a large group of chemicals that persist both in the environment and in the body. Legacy PFAS, e.g., perfluorooctanoic acid and perfluorooctane sulfonic acid, are implicated as endocrine disruptors and reproductive and developmental toxicants in epidemiological and animal model studies. This review describes female reproductive outcomes of reported studies and includes where associative relationships between PFAS exposures and female reproductive outcomes have been observed as well as where those are absent. In animal models, studies in which PFAS are documented to cause toxicity and where effects are lacking are described. Discrepancies exist in both human and animal studies and are likely attributable to human geographical contamination, developmental status, duration of exposure, and PFAS chemical identity. Similarly, in animal investigations, the model used, exposure paradigm, and developmental status of the female are important and vary widely in documented studies. Taken together, support for PFAS as reproductive and developmental toxicants exists, although the disparity in study conditions and human exposures contribute to the variation in effects noted.

Development of desmoid tumours after ileorectal anastomosis versus ileal pouch-anal anastomosis in familial adenomatous polyposis.

BACKGROUND & AIMS: Desmoid tumours (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: We performed an international historical cohort study in FAP patients who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. RESULTS: We analysed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The post-operative risk was significantly higher after IPAA (p < 0.01) in multivariable analysis, while approach did not significantly influence the risk. CONCLUSIONS: The risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.

Arabidopsis DNA glycosylase MBD4L improves recovery of aged seeds.

DNA glycosylases initiate the base excision repair (BER) pathway by catalyzing the removal of damaged or mismatched bases from DNA. The Arabidopsis DNA glycosylase methyl-CpG-binding domain protein 4 like (MBD4L) is a nuclear enzyme triggering BER in response to the genotoxic agents 5-fluorouracil and 5-bromouracil. To date, the involvement of MBD4L in plant physiological processes has not been analyzed. To address this, we studied the enzyme functions in seeds. We found that imbibition induced the MBD4L gene expression by generating two alternative transcripts, MBD4L.3 and MBD4L.4. Gene activation was stronger in aged than in non-aged seeds. Seeds from mbd4l-1 mutants displayed germination failures when maintained under control or ageing conditions, while 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 seeds reversed these phenotypes. Seed nuclear DNA repair, assessed by comet assays, was exacerbated in an MBD4L-dependent manner at 24 h post-imbibition. Under this condition, the BER genes ARP, APE1L, and LIG1 showed higher expression in 35S:MBD4L.3/mbd4l-1 and 35S:MBD4L.4/mbd4l-1 than in mbd4l-1 seeds, suggesting that these components could coordinate with MBD4L to repair damaged DNA bases in seeds. Interestingly, the ATM, ATR, BRCA1, RAD51, and WEE1 genes associated with the DNA damage response (DDR) pathway were activated in mbd4l-1, but not in 35S:MBD4L.3/mbd4l-1 or 35S:MBD4L.4/mbd4l-1 seeds. These results indicate that MBD4L is a key enzyme of a BER cascade that operates during seed imbibition, whose deficiency would cause genomic damage detected by DDR, generating a delay or reduction in germination.

Knowledge and attitudes of physicians in Chile toward Do-Not-Attempt-Resuscitation orders: A cross-sectional nation-wide study.

Objective: Do-Not-Attempt-Resuscitation orders originated in the early 1960s with the establishment of advanced cardiopulmonary resuscitation. These orders aim to limit therapeutic efforts in cases where it may be futile. The decision not to resuscitate a patient is a process that involves a series of ethical, legal, and clinical considerations. Still, it also requires a process in which priority is given to the patients and their autonomy. The objective of this study was to describe the knowledge and attitudes of physicians working in Chile toward Do-Not-Attempt-Resuscitation orders. Methods: A cross-sectional study was conducted, in which a digital questionnaire was sent to physicians from different regions of Chile. Quantitative variables were analyzed using measures of central tendency and dispersion (e.g., median and interquartile range), while qualitative variables were evaluated using frequencies and percentages. Results: Four hundred and thirty-one physicians completed the survey. 85.4% were familiar with the ethical and legal guidelines for cardiopulmonary resuscitation and the rights and duties of the patient. 39.2% believed that patients should have the final decision Do-Not-Attempt-Resuscitation orders, especially if they themselves requested not to be resuscitated. 87.7% mentioned that the Do-Not-Attempt-Resuscitation orders should be reassessed if the patient's prognosis improves. In addition, it was found that the decision not to resuscitate was not always discussed with the patient or their family. Conclusions: The study revealed an ethical conflict regarding Do-Not-Attempt-Resuscitation orders and their management by Chilean physicians. Therefore, it is necessary to create recommendations and provide training to guide professionals in this process, which should also involve patients and their families.

New Protocol for Twinning of Raman Devices Toward a Raman Intensity Harmonization.

The use of Raman spectroscopy has rapidly been on the rise across a great number of industries where comparability, reproducibility, and reliability of the data are of paramount importance. However, controlling the intensity of the Raman signal depends on a large number of factors such as the wavelength of the laser light, the optical components of each device, or the number of molecules in the illuminated volume. For this reason, in this study, a new protocol has been applied to twin Raman devices to achieve a conversion of the signal between them, by pairing the intensity response of the units using a reference sample. The new reference material is a homogenous dispersion of a 0.5 wt% anatase (titanium dioxide, or TiO2) in an epoxy resin matrix, with deviations <2.5% in Raman intensity across the reference material. The proposed protocol for Raman-twinned devices takes a well-defined approach that leads to obtaining a correction factor that relates the differences in the signal intensity between the two Raman devices, in order to obtain the same Raman intensity counts. The performance of the proposed method was evaluated based on the data from the devices, which presented the most common user cases: twinning Raman devices of the non-confocal same model for two different wavelengths; and twinning confocal and non-confocal devices. The results obtained show that the protocol has worked for both of the Raman twinning cases, allowing the Raman intensity harmonization of Raman spectra between two different devices.

The dynamics of oligodendrocyte populations following permanent ischemia promotes long-term spontaneous remyelination of damaged area.

Stroke is a major public health concern, with limited clinically approved interventions available to enhance sensorimotor recovery beyond reperfusion. Remarkably, spontaneous recovery is observed in certain stroke patients, suggesting the existence of a brain self-repair mechanism not yet fully understood. In a rat model of permanent cerebral ischemia, we described an increase in oligodendrocytes expressing 3RTau in damaged area. Considering that restoration of myelin integrity ameliorates symptoms in many neurodegenerative diseases, here we hypothesize that this cellular response could trigger remyelination. Our results revealed after ischemia an early recruitment of OPCs to damaged area, followed by their differentiation into 3RTau+ pre-myelinating cells and subsequent into remyelinating oligodendrocytes. Using rat brain slices and mouse primary culture we confirmed the presence of 3RTau in pre-myelinating and a subset of mature oligodendrocytes. The myelin status analysis confirmed long-term remyelination in the damaged area. Postmortem samples from stroke subjects showed a reduction in oligodendrocytes, 3RTau+ cells, and myelin complexity in subcortical white matter. In conclusion, the dynamics of oligodendrocyte populations after ischemia reveals a spontaneous brain self-repair mechanism which restores the functionality of neuronal circuits long-term by remyelination of damaged area. This is evidenced by the improvement of sensorimotor functions in ischemic rats. A deep understanding of this mechanism could be valuable in the search for alternative oligodendrocyte-based, therapeutic interventions to reduce the effects of stroke.

Sinus fungal balls caused by Syncephalastrum spp.: 2 clinical cases and literature review.

INTRODUCTION: Syncephalastrum spp. is a mucoral that rarely produces pathology. Fungal balls caused by this genus are infrequent. It requires early diagnosis and treatment to avoid associated morbidity and mortality. METHODS: We describe two clinical cases of sinus fungus balls caused by Syncephalastrum spp. and review the literature. RESULTS: Two patients were treated for sinus fungus balls. When their samples were analysed, the aetiology was determined to be Syncephalastrum spp. A case of pulmonary fungus ball due to Syncephalastrum spp. is described in the literature. All cases, including these described in the present study, had a good evolution after treatment. CONCLUSIONS: Syncephalastrum spp. is a filamentous fungus that should be considered as an aetiology of sinus fungus ball.

HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Fighting thyrotoxicosis with therapeutic plasma exchange: A case report.

Thyrotoxicosis is the clinical condition resulting from an excess of thyroid hormones for any reason. The main causes are Graves-Basedow disease, toxic multinodular goitre and toxic adenoma. The medical treatment to control thyroid function includes antithyroid drugs, beta blockers, iodine solutions, corticosteroids and cholestyramine. Although therapeutic plasma exchange is not generally part of the therapy, it is an alternative as a preliminary stage before the definitive treatment. This procedure makes it possible to eliminate T4, T3, TSI, cytokines and amiodarone. In most cases, more than one cycle is necessary, either daily or every three days, until clinical improvement is observed. The effect on thyrotoxicosis is temporary, with an approximate duration of 24-48h. This approach has been proposed as a safe and effective alternative when the medical treatment is contraindicated or not effective, and when there is multiple organ failure or emergency surgery is required.

BraNet: a mobil application for breast image classification based on deep learning algorithms.

Mobile health apps are widely used for breast cancer detection using artificial intelligence algorithms, providing radiologists with second opinions and reducing false diagnoses. This study aims to develop an open-source mobile app named "BraNet" for 2D breast imaging segmentation and classification using deep learning algorithms. During the phase off-line, an SNGAN model was previously trained for synthetic image generation, and subsequently, these images were used to pre-trained SAM and ResNet18 segmentation and classification models. During phase online, the BraNet app was developed using the react native framework, offering a modular deep-learning pipeline for mammography (DM) and ultrasound (US) breast imaging classification. This application operates on a client-server architecture and was implemented in Python for iOS and Android devices. Then, two diagnostic radiologists were given a reading test of 290 total original RoI images to assign the perceived breast tissue type. The reader's agreement was assessed using the kappa coefficient. The BraNet App Mobil exhibited the highest accuracy in benign and malignant US images (94.7%/93.6%) classification compared to DM during training I (80.9%/76.9%) and training II (73.7/72.3%). The information contrasts with radiological experts' accuracy, with DM classification being 29%, concerning US 70% for both readers, because they achieved a higher accuracy in US ROI classification than DM images. The kappa value indicates a fair agreement (0.3) for DM images and moderate agreement (0.4) for US images in both readers. It means that not only the amount of data is essential in training deep learning algorithms. Also, it is vital to consider the variety of abnormalities, especially in the mammography data, where several BI-RADS categories are present (microcalcifications, nodules, mass, asymmetry, and dense breasts) and can affect the API accuracy model.

Evolution of biotechnological advances and regenerative therapies for endometrial disorders: a systematic review.

BACKGROUND: The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes. OBJECTIVE AND RATIONALE: This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed. SEARCH METHODS: A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches. OUTCOMES: From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested. WIDER IMPLICATIONS: Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis. REGISTRATION NUMBER: https://osf.io/th8yf/.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

Enriching Eggs with Bioactive Compounds through the Inclusion of Grape Pomace in Laying Hens Diet: Effect on Internal and External Egg Quality Parameters.

(1) Background: Grapes and their associated by-products (such as grape pomace, GP) stand out for their polyphenol content, which makes them a source of bioactive compounds with antioxidant capacity. The aim of this research was to determine if the inclusion of 50 g/kg of GP in the diet of hens could enrich eggs with antioxidants and to study its effect on internal and external egg quality parameters. (2) Methods: A trial was conducted with two genetic lines of hens, which were fed either a control diet or a diet containing 50 g/kg of GP. Performance, internal and external egg quality, and egg yolk content of vitamins E and A and gallic acid were determined. (3) Results: In eggs laid by hens fed a GP diet, Haugh units and yolk color scores were enhanced, and eggshells became thinner, but without affecting the breaking strength. No dietary effect was observed on the vitamin contents of the yolk. A higher gallic acid content was observed in the yolks of eggs laid by hens fed the GP diet, suggesting that some dietary phenolic compounds could be transferred to the eggs. Hen genetics influenced egg weight, albumen Haugh units, shell thickness, and α- and γ-tocopherol concentration in yolks. (4) Conclusions: Dietary inclusion of GP improved the internal quality of eggs, enriching yolks with a phenolic compound but reducing shell thickness.

Persistence in the Methadone Maintenance Program and Its Relationship with the Medication Regimen Complexity Index in Opioid-Dependent Patients.

It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has not been studied. The aim of this study is to calculate the Methadone Maintenance Program (MMP) persistence and the MRCI score in a ODP cohort. Second, to analyze its relationship and association with other variables. To accomplish this research, an observational study including adults with a confirmed diagnosis of opiate-dependency according to the DSM-5 in a MMP center was carried out. To define MMP-persistence, a group was created by the researchers who defined five weighted items according to their agreed importance. Our first contribution was to create a new definition of MMP-persistence. This study also identified age, comorbidities, and received methadone maintenance doses as successful predictors for MMP-persistence. We have also shown that the MRCI does not seem to be a useful tool to determine MMP-persistence, probably because there are multiple factors that influence it in addition to the CPR. It is necessary to continue searching for more precise selection and stratification tools for ODP to improve their persistence.

Comparison of Bone Mineral Density and Trabecular Bone Score in Patients with and without Vertebral Fractures and Differentiated Thyroid Cancer with Long-Term Serum Thyrotrophin-Suppressed Therapy.

INTRODUCTION: The study of BMD provides only partial information on bone health in patients undergoing TSH suppression therapy due to differentiated thyroid cancer (DTC). The trabecular bone score (TBS), a new parameter assessing bone microarchitecture, is proposed for studying bone in this context. This study aimed to analyze their long-term use in patients with DTC. METHODS: Bone mineral density (BMD) was measured by dual X-ray densitometry (DXA) and TBS was assessed with iNsigth software (version 2.0, MediImaps, France) in 145 postmenopausal patients with DTC. Vertebral fractures (VFs) were identified using a semi-quantitative X-ray method. RESULTS: The BMD at the end of this study did not differ from the initial measurement. However, the TBS decreased from 1.35 ± 0.1 to 1.27 ± 0.1 (p = 0.002). Increased levels of PTH, osteocalcin, and bone alkaline phosphatase (BAP) were observed, suggesting enhanced bone remodeling. There was an increase in the prevalence of osteoporosis and osteopenia (40.6% and 16.5% to 46.6% and 18.6%, respectively). The proportion of patients with partially degraded and totally degraded TBS increased from 31% and 15.1% to 48.9% and 24.8% by the end of this study. Among the 30 patients with VFs, there were no significant differences in age, body mass index (BMI), calcium intake, alcohol consumption, smoking, radioiodine, therapy, or thyroid parameters compared to those without VFs. The odds ratio for VFs increased with osteopenia (OR 2.63). Combining TBS with BMD did not improve discrimination. CONCLUSIONS: The TBS decreased while the BMD remained unchanged. The percentage of patients with osteoporosis and osteopenia, whether partially degraded or totally degraded, increased by the end of this study. The predominant discordance was found in partially degraded microarchitectures, with a higher proportion of osteopenic patients compared to those with normal or osteoporotic bone density. The AUC of the combination of TBS and BMD did not enhance discrimination. TBS, radioactive iodine therapy, and sedentary lifestyle emerged as the main distinguishing factors for DTC patients with VFs.