Attitudes, concerns, and perceptions of patients undergoing fertility treatments in an abortion restrictive state in the aftermath of the Roe v. Wade reversal.

PURPOSE: To investigate the abortion views and reproductive concerns of current in vitro fertilization patients after the US Supreme Court Dobbs v. Jackson decision, which overturned the Roe v. Wade decision guaranteeing abortion access. METHODS: This is a cross-sectional survey of English-speaking patients undergoing in vitro fertilization from January to November 2022 at a large academic institution in a state with restricted abortion care. Participants completed a 43-question electronic survey which measured feelings about abortion, future fertility treatments, and embryo disposition both quantitatively and qualitatively. RESULTS: Of 543 eligible patients, 267 (49%) consented to participate when called and were sent the survey. Of those, 180 (67%) completed it, resulting in a total completion rate of 33%. The majority believe abortion should be legal in the case of birth defects (90.8%) or rape or incest (90.3%). A significant proportion (91.4%) expressed concerns about abortion being illegal in the state that they receive infertility care. They reported some concern about making embryos (89.6%), controlling what happens to them (95.4%), and discarding them (94.4%). Patients wrote about their concerns with pursuing fertility treatments, fear of not having access to needed medical care, and the desire to remain close to states with less restrictive abortion laws. CONCLUSIONS: The evolving political landscape surrounding access to reproductive care has created significant concerns regarding legal regulation of these treatments and the disposition of embryos. By understanding patients' concerns, health care providers can more effectively advocate for the protection of fertility treatments and patients' autonomy in embryo disposition.

Neuronal and astrocytic tetraploidy is increased in drug-resistant epilepsy.

AIMS: Epilepsy is one of the most prevalent neurological diseases. A third of patients with epilepsy remain drug-resistant. The exact aetiology of drug-resistant epilepsy (DRE) is still unknown. Neuronal tetraploidy has been associated with neuropathology. The aim of this study was to assess the presence of tetraploid neurons and astrocytes in DRE. METHODS: For that purpose, cortex, hippocampus and amygdala samples were obtained from patients subjected to surgical resection of the epileptogenic zone. Post-mortem brain tissue of subjects without previous records of neurological, neurodegenerative or psychiatric diseases was used as control. RESULTS: The percentage of tetraploid cells was measured by immunostaining of neurons (NeuN) or astrocytes (S100ß) followed by flow cytometry analysis. The results were confirmed by image cytometry (ImageStream X Amnis System Cytometer) and with an alternative astrocyte biomarker (NDRG2). Statistical comparison was performed using univariate tests. A total of 22 patients and 10 controls were included. Tetraploid neurons and astrocytes were found both in healthy individuals and DRE patients in the three brain areas analysed: cortex, hippocampus and amygdala. DRE patients presented a higher number of tetraploid neurons (p = 0.020) and astrocytes (p = 0.002) in the hippocampus than controls. These results were validated by image cytometry. CONCLUSIONS: We demonstrated the presence of both tetraploid neurons and astrocytes in healthy subjects as well as increased levels of both cell populations in DRE patients. Herein, we describe for the first time the presence of tetraploid astrocytes in healthy subjects. Furthermore, these results provide new insights into epilepsy, opening new avenues for future treatment.

Effect of accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT-A) and carrier screening for patients undergoing in vitro fertilization.

This retrospective cohort study assessed the accessibility of a genetic counselor on uptake of preimplantation genetic testing for aneuploidy (PGT-A) and carrier screening in a single academic Reproductive Endocrinology and Infertility (REI) clinic. A total of 420 patients were evaluated with 219 patients counseled by a REI physician only and 201 patients after the addition of a genetic counselor (GC) to the REI clinic team. Cycles initiated before hiring of a GC (pre-GC) were assessed from June 2018 to December 2018 and after integration of a GC (post-GC) from March 2019 to August 2019. Additionally, information regarding carrier screening was collected if available in the medical record. Results showed more patients utilized PGT-A post-GC (9.5% vs. 5.5%), although the difference between groups did not reach statistical significance (p = 0.12). Individuals who were screened post-GC or who started screening pre-GC and continued screening post-GC were screened for a larger number of conditions than if they were only screened pre-GC (median pre-GC = 3, post-GC = 27, pre- and post-GC = 274; p < 0.0001). The change in practice from using physician-only counseling to counseling with accessibility to a GC did not change the utilization of PGT-A in a single clinic.

Evaluating IoT-Based Services to Support Patient Empowerment in Digital Home Hospitalization Services.

Hospitals need to optimize patient care, as, among other factors, life expectancy has increased due to improvements in sanitation, nutrition, and medicines. Hospitalization-at-home (HaH) could increase admission efficiency, moderate costs, and reduce the demand for beds. This study aimed to provide data on the feasibility, acceptability, and effectiveness of the integration of IoT-based technology to support the remote monitoring and follow-up of patients admitted to HaH units, as well as the acceptability of IoT-based solutions in healthcare processes. The need for a reduction in the number of admission days, the percentage of admissions after discharge, and the actions of the emergency services during admission were the most relevant findings of this study. Furthermore, in terms of patient safety and trust perception, 98% of patients preferred this type of digitally-supported hospitalization model and up to 95% were very satisfied. On the professional side, the results showed a reduction in work overload and an increase in trust when the system was adopted.

Doxorubicin and zoledronate treatment in a dog with hemophagocytic histiocytic sarcoma.

A 6-year-old castrated male greyhound dog was referred for hemophagocytic histiocytic sarcoma (HHS) diagnosed following splenectomy. Severe thrombocytopenia, mild hypoalbuminemia, mild hypocholesterolemia, and mild hyperbilirubinemia were present. Abdominal ultrasound findings were concerning for hepatic metastasis. Doxorubicin and zoledronate combination therapy was initiated. The dog improved clinically and its thrombocytopenia, hypoalbuminemia, and hyperbilirubinemia resolved. The dog appeared well for 147 d before tumor progression was noted. The dog was treated with lomustine as a final measure, with no response. The dog survived for 6 mo with chemotherapy. To the authors' knowledge, this is the first report of clinical benefit of chemotherapy for HHS. Key clinical message: Doxorubicin should be considered for treating canine HHS since this variant of the disease is historically refractory to lomustine. Further research regarding efficacy of doxorubicin and zoledronate should be pursued.

Traitement à la doxorubicine et au zolédronate chez un chien atteint de sarcome histiocytaire hémophagocytaire. Un lévrier mâle castré de 6 ans a été vu pour un sarcome histiocytaire hémophagocytaire (HHS) diagnostiqué à la suite d'une splénectomie. Une thrombopénie sévère, une hypoalbuminémie légère, une hypocholestérolémie légère et une hyperbilirubinémie légère étaient présentes. Les résultats de l'échographie abdominale étaient préoccupants quant aux métastases hépatiques. Un traitement associant doxorubicine et zolédronate a été instauré. Le chien s'est amélioré cliniquement et sa thrombocytopénie, son hypoalbuminémie et son hyperbilirubinémie ont disparu. Le chien semblait en bonne santé pendant 147 jours avant de constater une progression tumorale. Le chien a été traité avec de la lomustine comme mesure finale, sans réponse. Le chien a survécu 6 mois grâce à la chimiothérapie. À la connaissance des auteurs, il s'agit du premier rapport faisant état d'un bénéfice clinique de la chimiothérapie pour le HHS.Message clinique clé :La doxorubicine doit être envisagée pour traiter le HHS canin puisque cette variante de la maladie est historiquement réfractaire à la lomustine. Des recherches plus approfondies concernant l'efficacité de la doxorubicine et du zolédronate devraient être poursuivies.(Traduit par Dr Serge Messier).

Satisfaction with new patient telehealth visits for reproductive endocrinology patients in the era of COVID-19.

PURPOSE: To study patient satisfaction with new patient telehealth visits in a reproductive endocrinology and infertility (REI) office. METHODS: A cross-sectional study in a university-based fertility clinic was completed including all new patients seen via telehealth between March 1, 2021, and August 19, 2021. Primary outcomes were perceived patient satisfaction, access, and preferences to telehealth visits. RESULTS: A total of 351 participants were contacted, 61.8% (n = 217) agreed to participate in the study, and 28.8% (n = 101) completed the survey. There were no significant differences in age, BMI, distance from clinic, or length of infertility with response to survey. Ninety-three percent of responders would use telehealth services again and were satisfied with the telehealth system. Telehealth improved access to healthcare for 88% and travel time for 96%. The median distance from clinic was 24 miles, and there was no significance difference in preference for telehealth visits over in person visits (p = 0.696). CONCLUSIONS: In the era of COVID-19, healthcare implementation has dramatically changed with a drastic increase in telehealth services. Based on our survey, majority of patients were satisfied with telehealth visits and believed it saved travel time while improving access to REI care. Despite no differences in patient preference for in person versus telehealth depending on their distance from clinic, this is reassuring because patients are satisfied with telehealth for reasons other than distance from clinic.

Co-designing a remote rehabilitation tool for Parkinson's disease: exploratory values and challenges.

BACKGROUND: Impaired motor function is one of the early symptoms shown in patients with Parkinson Disease (PD). For this reason, rehabilitative interventions have been used for many years to improve motor and non-motor symptoms. Among them, the use of music therapy has shown benefits in helping to overcome some of the most common motor dysfunction. Addressing the challenge of providing access to this type of therapy, this document presents the collaborative design process to develop a remote training support tool for PD based on music therapy. METHODS: A qualitative study with creative co-design methods was used in which different groups of healthcare professionals, patients, and relatives participated in six iterative sessions. Workshops were designed and structured to incrementally discover requirements and needs and validate the proposed prototype ideas. RESULTS: The study provided key aspects that were used for the development and validation of the proposed prototypes for the remote music-based training support tool for PD. Up to 20 factors that had a positive and/or negative influence on patient access to training were detected. These factors were classified into three common themes: daily activities and independence, participation in treatment and barriers to daily treatment, and self-management and personalization of information and telecommunication technologies (ICT). CONCLUSIONS: This paper shows the results of a collaborative design process aimed at identifying the different factors, relevant to patients with PD, to improve their access to remote ICT-based training therapy and their expectations regarding alternative therapies, such as music. The participatory design methods and the iterative model used helped overcome many of the traditionally barriers that this type of technological support solutions usually have, facilitating the future participation.

Monitoring strategies for clinical intervention studies.

BACKGROUND: Trial monitoring is an important component of good clinical practice to ensure the safety and rights of study participants, confidentiality of personal information, and quality of data. However, the effectiveness of various existing monitoring approaches is unclear. Information to guide the choice of monitoring methods in clinical intervention studies may help trialists, support units, and monitors to effectively adjust their approaches to current knowledge and evidence. OBJECTIVES: To evaluate the advantages and disadvantages of different monitoring strategies (including risk-based strategies and others) for clinical intervention studies examined in prospective comparative studies of monitoring interventions. SEARCH METHODS: We systematically searched CENTRAL, PubMed, and Embase via Ovid for relevant published literature up to March 2021. We searched the online 'Studies within A Trial' (SWAT) repository, grey literature, and trial registries for ongoing or unpublished studies. SELECTION CRITERIA: We included randomized or non-randomized prospective, empirical evaluation studies of different monitoring strategies in one or more clinical intervention studies. We applied no restrictions for language or date of publication. DATA COLLECTION AND ANALYSIS: We extracted data on the evaluated monitoring methods, countries involved, study population, study setting, randomization method, and numbers and proportions in each intervention group. Our primary outcome was critical and major monitoring findings in prospective intervention studies. Monitoring findings were classified according to different error domains (e.g. major eligibility violations) and the primary outcome measure was a composite of these domains. Secondary outcomes were individual error domains, participant recruitment and follow-up, and resource use. If we identified more than one study for a comparison and outcome definitions were similar across identified studies, we quantitatively summarized effects in a meta-analysis using a random-effects model. Otherwise, we qualitatively summarized the results of eligible studies stratified by different comparisons of monitoring strategies. We used the GRADE approach to assess the certainty of the evidence for different groups of comparisons. MAIN RESULTS: We identified eight eligible studies, which we grouped into five comparisons. 1. Risk-based versus extensive on-site monitoring: based on two large studies, we found moderate certainty of evidence for the combined primary outcome of major or critical findings that risk-based monitoring is not inferior to extensive on-site monitoring. Although the risk ratio was close to 'no difference' (1.03 with a 95% confidence interval [CI] of 0.81 to 1.33, below 1.0 in favor of the risk-based strategy), the high imprecision in one study and the small number of eligible studies resulted in a wide CI of the summary estimate. Low certainty of evidence suggested that monitoring strategies with extensive on-site monitoring were associated with considerably higher resource use and costs (up to a factor of 3.4). Data on recruitment or retention of trial participants were not available. 2. Central monitoring with triggered on-site visits versus regular on-site visits: combining the results of two eligible studies yielded low certainty of evidence with a risk ratio of 1.83 (95% CI 0.51 to 6.55) in favor of triggered monitoring intervention. Data on recruitment, retention, and resource use were not available. 3. Central statistical monitoring and local monitoring performed by site staff with annual on-site visits versus central statistical monitoring and local monitoring only: based on one study, there was moderate certainty of evidence that a small number of major and critical findings were missed with the central monitoring approach without on-site visits: 3.8% of participants in the group without on-site visits and 6.4% in the group with on-site visits had a major or critical monitoring finding (odds ratio 1.7, 95% CI 1.1 to 2.7; P = 0.03). The absolute number of monitoring findings was very low, probably because defined major and critical findings were very study specific and central monitoring was present in both intervention groups. Very low certainty of evidence did not suggest a relevant effect on participant retention, and very low certainty evidence indicated an extra cost for on-site visits of USD 2,035,392. There were no data on recruitment. 4. Traditional 100% source data verification (SDV) versus targeted or remote SDV: the two studies assessing targeted and remote SDV reported findings only related to source documents. Compared to the final database obtained using the full SDV monitoring process, only a small proportion of remaining errors on overall data were identified using the targeted SDV process in the MONITORING study (absolute difference 1.47%, 95% CI 1.41% to 1.53%). Targeted SDV was effective in the verification of source documents, but increased the workload on data management. The other included study was a pilot study, which compared traditional on-site SDV versus remote SDV and found little difference in monitoring findings and the ability to locate data values despite marked differences in remote access in two clinical trial networks. There were no data on recruitment or retention. 5. Systematic on-site initiation visit versus on-site initiation visit upon request: very low certainty of evidence suggested no difference in retention and recruitment between the two approaches. There were no data on critical and major findings or on resource use. AUTHORS' CONCLUSIONS: The evidence base is limited in terms of quantity and quality. Ideally, for each of the five identified comparisons, more prospective, comparative monitoring studies nested in clinical trials and measuring effects on all outcomes specified in this review are necessary to draw more reliable conclusions. However, the results suggesting risk-based, targeted, and mainly central monitoring as an efficient strategy are promising. The development of reliable triggers for on-site visits is ongoing; different triggers might be used in different settings. More evidence on risk indicators that identify sites with problems or the prognostic value of triggers is needed to further optimize central monitoring strategies. In particular, approaches with an initial assessment of trial-specific risks that need to be closely monitored centrally during trial conduct with triggered on-site visits should be evaluated in future research.

Ageing-friendly cities for assessing older adults' decline: IoT-based system for continuous monitoring of frailty risks using smart city infrastructure.

BACKGROUND AND AIMS: Population ageing is a typical phenomenon of developed countries with a great influence in their economy and society, with an increment on age-related expenditures. Disruptive solutions are needed to deploy new cost-effective and sustainable solutions for aging well and independent living of our seniors. In this sense, new technological paradigms as IoT technologies and smart cities have the potential to become main drivers for innovation uptake. The purpose of this study is to describe a longitudinal cohort study in smart cities for assessing early frailty symptoms deploying an unobtrusive IoT-based system in the Madrid city. METHODS: A system was deployed in the Madrid city with the participation of 45 elderly users for an average of 71 weeks. Metrics were assessed by the available sensors in combination with the open data infrastructure of Madrid. Metrics include activity of the user, weekly visits pattern and transport daily usage pattern. System engagement was also monitored. Participants are assessed bimonthly with health and functional questionnaires. RESULTS: 45 older adults with a mean age of 79.1 years. Participants activity patterns monitor detected changes during potentially risky situations that usually were not reported by traditional assessment tools. Analysis of data collected enabled to identify absence of frailty (robust or post-robust status) DISCUSSION AND CONCLUSIONS: The results demonstrate the feasibility of engaging older adults with an IoT-based system and the successful collection of their activity metrics. Variation in the activity patterns may be a first sign of functional decline and enables to identify potential areas of early intervention.

Assessing Amphiphilic ABAB Zn(II) Phthalocyanines with Enhanced Photosensitization Abilities in In Vitro Photodynamic Therapy Studies Against Cancer.

We have previously demonstrated that singlet oxygen photosensitization abilities of Zn(II) phthalocyanines (Zn(II)Pcs) are enhanced through α-functionalization with bulky fluorinated substituents (i.e., bis(trifluoromethyl)phenyl units) at facing positions of ABAB Zn(II)Pcs, where A and B refer to differently functionalized isoindoles. In this work, we have prepared the Zn(II)Pc ABAB 1 endowed with hydrophilic triethylene glycol monomethyl ether (i.e., at the A isoindoles) to provide solubility in aqueous media, together with its A3B and A4 counterparts, and compared their ability to behave as photosensitizers for photodynamic therapy. All photophysical data, aggregation studies and preliminary in vitro biological assays in cell cultures of SCC-13 (squamous cell carcinoma) and HeLa (cervical cancer cells), have proved ABAB 1 as the best photosensitizer of the series.

Design of a Training Model for Remote Management of Patients Hospitalized at Home.

PURPOSE: Hospitalization at Home (HaH) has proven to be more efficient and effective than conventional one, but it also requires a higher number of resources and specialised personnel. Information technologies can make this process scalable and allow physicians and nurses to deliver remote healthcare services for patients hospitalized at home. However, a correct and satisfactory usage of technology requires an adequate training of professionals and patients. This paper describes a new model for training healthcare professionals on managing remote ICT-based services for Hospitalization at Home. METHODS: The model was defined based on mix-method that combined the PICO model and a User Centred Design methodology, oriented to identify and discover the healthcare professionals needs and the training instruments in the literature that directly involved these professionals. These aspects were used in the definition and development of the assessment framework of the proposed training model. RESULTS: A training model for healthcare professionals focused on achieving an effective uptake of complex digital interventions such as Hospitalization at Home was defined. The selected mix-method led to the identification of four different blocks, that were considered as the main areas to include in a training programme. The model identifies measurable elements for assessing acceptability, workability increment and integration into daily clinical practice outcomes, as well as for evaluating the proposed training content and its outcomes. CONCLUSIONS: The proposed training model highlights the key aspects of training health professionals to favour an effective and successful implementation of complex technological healthcare interventions in the context of ICT-based HaH ICT.

Correction to: Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial.

The original version of this article unfortunately contained mistakes. The complete list of corrections is given below.

Effect of endometrial mechanical stimulation in an unselected population undergoing in vitro fertilization: futility analysis of a double-blind randomized controlled trial.

PURPOSE: Implantation failure is a major limiting factor of successful in vitro fertilization (IVF). The objective of this study was to determine if endometrial mechanical stimulation (EMS) by endometrial biopsy in the luteal phase of the cycle prior to embryo transfer (ET) improves clinical outcomes in an unselected subfertile population. METHODS: Double-blind, randomized controlled trial of EMS versus sham biopsy and odds of clinical pregnancy after IVF and embryo transfer. Secondary outcomes included spontaneous miscarriage and live birth. RESULTS: One hundred women enrolled and were randomized from 2013 to 2017. Enrollment was terminated after futility analysis showed no difference in clinical pregnancy between EMS versus control, 47.2% vs 61.7% (OR 0.55, 95% CI 0.25-1.23, p = 0.15). There were no significant differences between women who underwent EMS and those who did not in terms of positive pregnancy test 54.7% vs 63.8% (OR 0.69, 95% CI 0.31-1.53, p = 0.36), miscarriage 7.5% vs 2.1% (OR 3.76 95% CI 0.41-34.85, p = 0.22), or live birth 43.4% vs 61.7% (OR 0.48 95% CI 0.21-1.06, p = 0.07). CONCLUSIONS: EMS in the luteal phase of the cycle preceding embryo transfer does not improve clinical outcomes in an unselected subfertile population and may result in a lower live birth rate. We caution the routine use of EMS in an unselected population.

Estrogen-regulated miRNA-27b is altered by bisphenol A in human endometrial stromal cells.

MicroRNAs (miRs) are small molecules important for regulation of transcription and translation. The objective was to identify hormonally regulated miRs in human endometrial stromal cells and to determine the impact of the endocrine disruptor, bisphenol A (BPA), on those miRs. miR microarray analysis and multiple confirmatory cell preparations treated with 17ß-estradiol (E2) and BPA altered miR-27b, let-7c, let-7e and miR-181b. Further, decidualization downregulated miR-27b. VEGFB and VEGFC were validated as targets of miR-27b. Identification of miR-27b target genes suggests that BPA and E2 downregulate miR-27b thereby leading to upregulation of genes important for vascularization and angiogenesis of the endometrium during the menstrual cycle and decidualization.

Histone modifications associated with biological drug response in moderate-to-severe psoriasis.

INTRODUCTION: Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate-to-severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies. OBJECTIVE: To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM-SPSS v.23. RESULTS AND CONCLUSIONS: Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Non-significant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non-responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and non-responders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients' response to biological drugs in psoriasis.

TallyHO obese female mice experience poor reproductive outcomes and abnormal blastocyst metabolism that is reversed by metformin.

Obese women experience worse reproductive outcomes than normal weight women, specifically infertility, pregnancy loss, fetal malformations and developmental delay of offspring. The aim of the present study was to use a genetic mouse model of obesity to recapitulate the human reproductive phenotype and further examine potential mechanisms and therapies. New inbred, polygenic Type 2 diabetic TallyHO mice and age-matched control C57BL/6 mice were superovulated to obtain morula or blastocyst stage embryos that were cultured in human tubal fluid (HTF) medium. Deoxyglucose uptake was determined for individual insulin-stimulated blastocysts. Apoptosis was detected by confocal microscopy using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay and Topro-3 nuclear dye. Embryos were scored for TUNEL-positive as a percentage of total nuclei. AMP-activated protein kinase (AMPK) activation, tumour necrosis factor (TNF)-α expression and adiponectin expression were analysed by western immunoblot and confocal immunofluorescent microscopy. Lipid accumulation was assayed by BODIPY. Comparisons were made between TallyHO morulae cultured to blastocyst embryos in either HTF medium or HTF medium with 25 µg mL(-1) metformin. TallyHO mice developed whole body abnormal insulin tolerance, had decreased litter sizes and increased non-esterified fatty acid levels. Blastocysts from TallyHO mice exhibited increased apoptosis, decreased insulin sensitivity and decreased AMPK. A possible cause for the insulin resistance and abnormal AMPK phosphorylation was the increased TNF-α expression and lipid accumulation, as detected by BODIPY, in TallyHO blastocysts and decreased adiponectin. Culturing TallyHO morulae with the AMPK activator metformin led to a reversal of all the abnormal findings, including increased AMPK phosphorylation, improved insulin-stimulated glucose uptake and normalisation of lipid accumulation. Women with obesity and insulin resistance experience poor pregnancy outcomes. Previously we have shown in mouse models of insulin resistance that AMPK activity is decreased and that activators of AMPK reverse poor embryo outcomes. Here, we show for the first time using a genetically altered obese model, not a diet-induced model, that metformin reverses many of the adverse effects of obesity at the level of the blastocyst. Expanding on this we determine that activation of AMPK via metformin reduces lipid droplet accumulation, presumably by eliminating the inhibitory effects of TNF-α, resulting in normalisation of fatty acid oxidation and HADH2 (hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit) activity. Metformin exposure in vitro was able to partially reverse these effects, at the level of the blastocyst, and may thus be effective in preventing the adverse effects of obesity on pregnancy and reproductive outcomes.

Assessing the health condition profile in the freshwater fish Astyanax aeneus in Champoton River, Mexico.

The use of biomarkers for monitoring aquatic environmental quality has gained considerable interest worldwide. The effects of the environmental conditions of Río Champotón, México, in the hotspot of Mesoamerica, were assessed in Astyanax aeneus, a native fish of the tropics of southwestern México. Pollution from agrochemical residues is a major problem in Río Champotón. Three study sites along the freshwater portion of the river were monitored in April, July, and November 2007 and February 2008. This study includes a water quality index, a set of biomarkers (hepatic glycogen levels and lipid peroxidation in liver, gills, and muscle) to assess the integrated biomarker response, and population bioindicators (gonadosomatic and hepatosomatic indices and Fulton's condition factor). Although the water quality index suggested low level of contamination in the Río Champotón, biomarkers indicated that A. aeneus is exposed to stressors that impair biological responses. The integrated biomarker response showed stress periods with higher biomarker response and recovery periods with decreasing biomarker values. The somatic indices did not indicate severe effects at the population level. This study illustrates the usefulness of lipid peroxidation evaluation in the assessment of aquatic health conditions and corroborates the suitability of A. aeneus as a sentinel species.

Enhancing worker-centred digitalisation in industrial environments: A KPI evaluation methodology.

Recently, the European Commission announced Industry 5.0 as a strategic initiative toward a value-driven industrial transformation. This new paradigm coexists with previous Industry 4.0 revolution that has guided the efforts towards technology driven industrial digitalisation in the past ten years. As part of this Industry 4.0 strategies, numerous KPI-driven evaluation methods were proposed to cover the multiple pillars of smart industry assessment. However, they do not incorporate human workers and actors in a systematic way as drivers for digitalisation processes, as the new Industry 5.0 paradigm argues. This paper addresses this gap by proposing an evaluation methodology that incorporates multiple human actors in the digitalisation process. The final objective of this methodology is to evaluate the direct and indirect benefits of the technology-driven transformation process to achieve the goals of human workers and other human stakeholders. To this end, our methodology provides the basis for proposing assessment tools and instruments for technological and infrastructure integration, process optimisation, new functionalities and human factors benefits, and four core indicators that have been applied to a real case comparing the digitalisation processes of three different companies.

Oxidative stress elicits the remodeling of vimentin filaments into biomolecular condensates.

The intermediate filament protein vimentin performs an essential role in cytoskeletal interplay and dynamics, mechanosensing and cellular stress responses. In pathology, vimentin is a key player in tumorigenesis, fibrosis and infection. Vimentin filaments undergo distinct and versatile reorganizations, and behave as redox sensors. The vimentin monomer possesses a central α-helical rod domain flanked by N- and C-terminal low complexity domains. Interactions between this type of domains play an important function in the formation of phase-separated biomolecular condensates, which in turn are critical for the organization of cellular components. Here we show that several oxidants, including hydrogen peroxide and diamide, elicit the remodeling of vimentin filaments into small particles. Oxidative stress elicited by diamide induces a fast dissociation of filaments into circular, motile dots, which requires the presence of the single vimentin cysteine residue, C328. This effect is reversible, and filament reassembly can occur within minutes of oxidant removal. Diamide-elicited vimentin droplets recover fluorescence after photobleaching. Moreover, fusion of cells expressing differentially tagged vimentin allows the detection of dots positive for both tags, indicating that vimentin dots merge upon cell fusion. The aliphatic alcohol 1,6-hexanediol, known to alter interactions between low complexity domains, readily dissolves diamide-elicited vimentin dots at low concentrations, in a C328 dependent manner, and hampers reassembly. Taken together, these results indicate that vimentin oxidation promotes a fast and reversible filament remodeling into biomolecular condensate-like structures, and provide primary evidence of its regulated phase separation. Moreover, we hypothesize that filament to droplet transition could play a protective role against irreversible damage of the vimentin network by oxidative stress.

Identification of distinct stool metabolites in women with endometriosis for non-invasive diagnosis and potential for microbiota-based therapies.

BACKGROUND: Endometriosis, a poorly studied gynecological condition, is characterized by the presence of ectopic endometrial lesions resulting in pelvic pain, inflammation, and infertility. These associated symptoms contribute to a significant burden, often exacerbated by delayed diagnosis. Current diagnostic methods involve invasive procedures, and existing treatments provide no cure. METHODS: Microbiome-metabolome signatures in stool samples from individuals with and without endometriosis were determined using unbiased metabolomics and 16S bacteria sequencing. Functional studies for selected microbiota-derived metabolites were conducted in vitro using patient-derived cells and in vivo by employing murine and human xenograft pre-clinical disease models. FINDINGS: We discovered a unique bacteria-derived metabolite signature intricately linked to endometriosis. The altered fecal metabolite profile exhibits a strong correlation with that observed in inflammatory bowel disease (IBD), revealing intriguing connections between these two conditions. Notably, we validated 4-hydroxyindole, a gut-bacteria-derived metabolite that is lower in stool samples of endometriosis. Extensive in vivo studies found that 4-hydroxyindole suppressed the initiation and progression of endometriosis-associated inflammation and hyperalgesia in heterologous mouse and in pre-clinical models of the disease. CONCLUSIONS: Our findings are the first to provide a distinct stool metabolite signature in women with endometriosis, which could serve as stool-based non-invasive diagnostics. Further, the gut-microbiota-derived 4-hydroxyindole poses as a therapeutic candidate for ameliorating endometriosis. FUNDING: This work was funded by the NIH/NICHD grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society to R.K.