Comparative analysis of endometrial, vaginal, and gut microbiota in patients with and without adenomyosis.

INTRODUCTION: Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated. The aim of the present study was to compare the microbiota composition in the vagina, endometrium, and gut of individuals with and without adenomyosis. MATERIAL AND METHODS: Cross-sectional study including 38 adenomyosis patients and 46 controls, performed between September 2021 and October 2022 in a university hospital-based research center. The diagnosis of adenomyosis was based on sonographic criteria. Fecal, vaginal, and endometrial samples were collected. Study of the microbiota using 16S rRNA gene sequencing. RESULTS: Patients with adenomyosis exhibited a significant reduction in the gut microbial alpha diversity compared with healthy controls (Chao1 p = 0.012, Fisher p = 0.005, Observed species p = 0.005). Beta-diversity analysis showed significant differences in the compositions of both gut and vaginal microbiota between adenomyosis patients and the control group (Adonis p-value = 0.001; R2 = 0.03 and Adonis p-value = 0.034; R2 = 0.04 respectively). Specific bacterial taxa were found to be either overrepresented (Rhodospirillales, Ruminococcus gauvreauii group, Ruminococcaceae, and Actinomyces) or underrepresented in the gut and endometrial microbiota of adenomyosis patients compared with controls. Distinct microbiota profiles were identified among patients with internal and external adenomyosis phenotypes. CONCLUSIONS: The study revealed reduced gut microbiota diversity in adenomyosis patients, accompanied by distinct compositions in gut and vaginal microbiota compared with controls. Overrepresented or underrepresented bacterial taxa were noted in the gut and endometrial microbiota of adenomyosis patients, with variations in microbiota profiles among those with internal and external adenomyosis phenotypes. These findings suggest a potential association between microbiota and adenomyosis, indicating the need for further research to comprehensively understand the implications of these differences.

Sorptive tape-spray tandem mass spectrometry using aluminum foil coated with mixed-mode microparticles.

Direct mass spectrometry (MS) is an exciting strategy in bioanalysis, enabling rapid decision-making in different scenarios. Its application is usually hindered by matrix effects and the typically low concentration of the target compounds in the biofluids. In this sense, combining a previous sample preparation step minimizes or removes these shortcomings. This article describes sorptive tape-spray tandem mass spectrometry (STS-MS/MS) based on mixed-mode particles as a strategy to combine sample preparation and MS analysis in a single device. The technique uses a sorptive tape (ST) consisting of mixed-mode polymeric microparticles (combining ionic exchange and hydrophobic interactions) coated over aluminum foil in a spatial controlled way. The tapes act as the sorptive phases to isolate the analytes from the sample matrix and substrates for STS-MS/MS. The performance of the technique has been evaluated by developing a method to determine codeine in saliva as proof of concept. The affordability of the STs elements allows the preparation of many individual phases at low cost so that several samples can be extracted simultaneously, thus increasing the sample throughput. The extraction variables were optimized following a multivariate approach. Working under the optimum conditions, the limit of detection was 0.3 µg L-1, while the intraday precision, calculated as relative standard deviation (RSD) at three concentration levels, was better than 9.4 %. The accuracy, expressed as relative recovery, was in the range of 78-98 %. The method was also applied to the analysis of real samples. Despite being a powerful strategy, the direct combination of microextraction to MS is not always affordable in all laboratories. For this reason, the STs were also combined with commercial liquid chromatography-MS working under the direct infusion mode to demonstrate the usefulness of the ST in classical extraction workflows.

Basal characteristics of patients who responded to Ovarian Fragmentation for Follicular Activation (OFFA) or In Vitro Activation (IVA): a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.

Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation.

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.

Revealing the Origin of Fast Delayed Fluorescence in a Donor Functionalized Bisterpyridine.

A new carbazole-substituted bisterpyridine with pronounced delayed fluorescence is presented. While the molecular donor-acceptor-donor design suggests the origin of this to be thermally activated delayed fluorescence (TADF), results from various photophysical characterizations, OLED characteristics, temperature-dependent NMR spectroscopy, and DFT calculations all point against the involvement of triplet states. The molecule exhibits blue emission at about 440 nm with two or more fast decay channels in the lower nanosecond range in both solution and thin films. The delayed emission is proposed to be caused by rotational vibrational modes. We suggest that these results are generally applicable, especially for more complex molecules, and should be considered as alternative or competitive emissive relaxation pathways in the field of organic light emitting materials.

Dual photoresponsive & water-triggered nitric oxide releasing materials based on rhodium-based metal-organic polyhedra.

The exogenous administration of nitric oxide (NO) is considered a potential therapeutic treatment against a great variety of diseases due to its significant role in multiple physiological functions. Due to the gaseous nature, short lifetime and dose- and tissue-dependent activity of this molecule, the development of new administration procedures is required to control the NO delivery in terms of dosage, timing, and location. In this work, we propose a new molecular material based on robust metal-organic polyhedra (MOPs) for controlled NO release. We select dirhodium paddlewheel complex-based cuboctahedral MOPs (RhMOP), in which NO can chemically coordinate to the open-metal sites at the axial sites of dirhodium paddlewheel moieties. We further prepare amorphous coordination polymer particles (CPPs) by connecting RhMOP with bis(imidazole) linkers at the external axial sites. Both molecular MOPs and polymeric CPPs show relevant NO payloads and the release of NO can be triggered by two different stimuli: light and humidity. We show that imidazole ligands coordinating to the external axial sites of the paddlewheel moieties tune the light-triggered NO release property. We further demonstrate that the size and the extrinsic pores of CPPs are important for enhanced NO release.

A Mediterranean Diet-Based Metabolomic Score and Cognitive Decline in Older Adults: A Case-Control Analysis Nested within the Three-City Cohort Study.

SCOPE: Evidence on the Mediterranean diet (MD) and age-related cognitive decline (CD) is still inconclusive partly due to self-reported dietary assessment. The aim of the current study is to develop an MD- metabolomic score (MDMS) and investigate its association with CD in community-dwelling older adults. METHODS AND RESULTS: This study includes participants from the Three-City Study from the Bordeaux (n = 418) and Dijon (n = 422) cohorts who are free of dementia at baseline. Repeated measures of cognition over 12 years are collected. An MDMS is designed based on serum biomarkers related to MD key food groups and using a targeted metabolomics platform. Associations with CD are investigated through conditional logistic regression (matched on age, sex, and education level) in both sample sets. The MDMS is found to be inversely associated with CD (odds ratio [OR] [95% confidence interval (CI)] = 0.90 [0.80-1.00]; p = 0.048) in the Bordeaux (discovery) cohort. Results are comparable in the Dijon (validation) cohort, with a trend toward significance (OR [95% CI] = 0.91 [0.83-1.01]; p = 0.084). CONCLUSIONS: A greater adherence to the MD, here assessed by a serum MDMS, is associated with lower odds of CD in older adults.

Orientation distributions of vacuum-deposited organic emitters revealed by single-molecule microscopy.

The orientation of luminescent molecules in organic light-emitting diodes strongly influences device performance. However, our understanding of the factors controlling emitter orientation is limited as current measurements only provide ensemble-averaged orientation values. Here, we use single-molecule imaging to measure the transition dipole orientation of individual emitter molecules in a state-of-the-art thermally evaporated host and thereby obtain complete orientation distributions of the hyperfluorescence-terminal emitter C545T. We achieve this by realizing ultra-low doping concentrations (10-6 wt%) of C545T and minimising background levels to reliably measure its photoluminescence. This approach yields the orientation distributions of >1000 individual emitter molecules in a system relevant to vacuum-processed devices. Analysis of solution- and vacuum-processed systems reveals that the orientation distributions strongly depend on the nanoscale environment of the emitter. This work opens the door to attaining unprecedented information on the factors that determine emitter orientation in current and future material systems for organic light-emitting devices.

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.

Extraocular Rectus Muscle Stretching as a Weakening Procedure.

INTRODUCTION: Anterior segment ischemia may occur when three or more rectus muscles are operated in the same eye. Our purpose was to investigate the efficacy of rectus muscle stretching as a vessel-sparing weakening technique, in comparison with a retrospectively collected series of patients. METHODS: Non-operated patients with an indication of medial rectus muscle weakening surgery (deviation up to 20 PD, prism diopters) who could cooperate with topical or sub-Tenon's anesthesia. Clinical workup included routine complete ophthalmological evaluation. One double-needle 6/0 Mersilene suture was used on each side of the muscle at 4 mm distance of the insertion and pulled/stretched to insert in the sclera 3-5 mm posterior to the muscle locking passes. Main outcome measure was distance deviation at 2 months after surgery (alternate prism and cover test). RESULTS: Seven patients with esotropia of 12-20 PD, recruited in a 20-month period, were included. Preoperative median deviation was 20 PD, whereas postoperative median deviation was 4 PD (range 0-8 PD). On a visual pain scale (1-10) median pain score was 3 (range 2-5). Remarkable postoperative complications did not occur. Significant differences with a retrospectively collected series of patients' data, treated with standard medial rectus recession, were not observed. CONCLUSIONS: Preliminary data indicate that stretching of a rectus muscle has some weakening effect, that could be useful to correct small-angle strabismus, and may be suggested as a vessel-sparing technique when two rectus muscles have previously been operated in the same eye. TRIAL REGISTRATION: ClinicalTrials.gov NCT05778565.

Impact of Continuous Estroprogestin Treatment on Circulating Microparticle Levels in Deep Endometriosis Patients.

There has been increasing interest in the study of new pathogenic mechanisms in endometriosis (END), including the coagulation/fibrinolysis system and its link with inflammation and tissue remodeling. It has been suggested that END patients, especially with deep-infiltrating (DE) forms, could present a hypercoagulable state revealing higher levels of proinflammatory and procoagulant markers, such as total circulating microparticles (cMPs) and cMP-TF (tissue factor), released by cells in response to damage, activation, or apoptosis. However, no previous study has assessed the effect of END hormonal treatments on cMP and cMP-TF levels. Therefore, the aim of this study was to evaluate the impact of these treatments on cMP and cMP-TF levels in DE patients. Three groups were compared: DE patients receiving a continuous combined oral contraceptive regimen (CCOCR) (n = 41), DE patients without CCOCR (n = 45), and a control group (n = 43). cMP and cMP-TF levels were evaluated in platelet-free plasma. A significant decrease in the total cMP levels was found in the DE group with CCOCR versus the group without CCOCR, reflecting a higher chronic inflammatory status in DE patients that decreased with the treatment. cMP-TF levels were higher in DE patients receiving CCOCR versus those not receiving CCOCR, suggesting that treatments containing estrogens play a predominant role in suppressing the inhibitory pathway of TF.

Risk factors for irreversible unilateral loss of renal function in patients with deep endometriosis.

Deep endometriosis (DE) can be more aggressive than other types of endometriosis, and may even lead to irreversible severe complications such as complete unilateral loss of renal function. We aimed to describe the clinical and radiologic characteristics of DE patients diagnosed with irreversible unilateral loss of renal function due to unilateral ureteral stenosis and evaluate risk factors for developing this loss. This retrospective cohort study included 436 patients who underwent laparoscopic DE surgery. We evaluated two groups of patients according to preserved (Non-Renal Loss Group; n = 421) or irreversible unilateral damaged renal function (Renal Loss Group; n = 15). Preoperative epidemiologic variables, clinical characteristics, radiologic findings and surgical treatments of all the patients were collected. The Renal Loss Group had a higher infertility rate and a higher proportion of asymptomatic patients. The following radiological variables showed statistically significant differences between the two groups: mean endometrioma diameter, the presence of intestinal DE and negative sliding sign. Multivariate analysis showed that infertility, being asymptomatic, having intestinal DE or torus uterinus/uterosacral ligament DE and a negative sliding sign significantly increased the risk of loss of renal function. Therefore, among patients with these clinical and/or radiological variables, severe urinary tract obstruction should be specifically ruled out.

A mesoporous Zr-based metal-organic framework driven by the assembly of an octatopic linker.

Metal-organic frameworks (MOFs) based on high-connected nets are generally very attractive due to their combined robustness and porosity. Here, we describe the synthesis of BCN-348, a new high-connected Zr-MOF built from an 8-connected (8-c) cubic Zr-oxocluster and an 8-c organic linker. BCN-348 contains a minimal edge-transitive 3,4,8-c eps net, and combines mesoporosity with thermal and hydrolytic stability. Encouraging results from preliminary studies on its use as a catalyst for hydrolysis of a nerve-agent simulant suggest its potential as an agent for detoxification of chemical weapons and other pernicious compounds.

Evaluation of menstrual symptoms after Coronavirus disease 2019 vaccination in women with endometriosis.

BACKGROUND: Vaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis. OBJECTIVES: We aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes. DESIGN: A total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group). METHODS: Data regarding demographics, clinical characteristics, hormonal treatment, and menstrual-associated symptoms in the first and second cycle after vaccination were collected through an online survey. RESULTS: A similar percentage of patients in both the endometriosis and the non-endometriosis group self-reported menstrual-associated changes the first (52.6% versus 48.8%, respectively) and second cycle after vaccination (29.0% versus 28.1%, respectively). Although the total symptoms recorded were not different between the two groups, several specific symptoms were statistically more frequent in the endometriosis group. These were pain disorders and fatigue in the first cycle after vaccination and pain disorders, menstrual headache and fatigue in the second cycle after vaccination. Bleeding frequency/regularity disorders were found to be more frequent in the non-endometriosis group in the first cycle after vaccination. Patients under hormonal treatment reported fewer changes in menstrual symptoms in the first and second cycle after vaccination compared with those not receiving this treatment. Similarly, patients in the endometriosis group receiving hormonal treatment reported fewer changes in menstrual-associated symptoms compared with those not following any hormonal treatment in the first and second menstrual cycle after the last vaccination. CONCLUSION: Women with endometriosis immunized with mRNA-based SARS-CoV-2 vaccines did not perceive greater worsening or new menstrual-associated symptoms after complete COVID-19 vaccination compared with healthy controls. Hormonal treatment may have a protective effect against worsened or new menstrual symptoms induced by COVID-19 vaccination.

Saline Retention and Permeability of Nanofiltration Membranes Versus Resistance and Capacitance as Obtained from Impedance Spectroscopy under a Concentration Gradient.

Impedance spectroscopy has been widely used for the study of the electrical properties of membranes for their characterization. The most common use of this technique is the measure of the conductivity of different electrolyte solutions to study the behavior and movement of electrically charged particles inside the pores of membranes. The objective of this investigation was to observe if there is a relation present between the retention that a nanofiltration membrane possesses to certain electrolytic solutions (NaCl, KCl, MgCl2, CaCl2, and Na2SO4) and the parameters that are obtained through IS measurements of the active layer of the membrane. To achieve our objective, different characterization techniques were performed to obtain the permeability, retention, and zeta potential values of a Desal-HL nanofiltration membrane. Impedance spectroscopy measurements were performed when a gradient concentration was present between both sides of the membrane to study the variation that the electrical parameters had with the time evolution.

Short-Peptide Supramolecular Hydrogels for In Situ Growth of Metal-Organic Framework-Peptide Biocomposites.

The development of bio-MOFs or MOF biocomposites through the combination of MOFs with biopolymers offers the possibility of expanding the potential applications of MOFs, making use of more environmentally benign processes and reagents and giving rise to a new generation of greener and more bio-oriented composite materials. Now, with the increasing use of MOFs for biotechnological applications, the development of new protocols and materials to obtain novel bio-MOFs compatible with biomedical or biotechnological uses is needed. Herein, and as a proof of concept, we have explored the possibility of using short-peptide supramolecular hydrogels as media to promote the growth of MOF particles, giving rise to a new family of bio-MOFs. Short-peptide supramolecular hydrogels are very versatile materials that have shown excellent in vitro and in vivo biomedical applications such as tissue engineering and drug delivery vehicles, among others. These peptides self-assemble by noncovalent interactions, and, as such, these hydrogels are easily reversible, being more biocompatible and biodegradable. These peptides can self-assemble by a multitude of stimuli, such as changes in pH, temperature, solvent, adding salts, enzymatic activity, and so forth. In this work, we have taken advantage of this ability to promote peptide self-assembly with some of the components required to form MOF particles, giving rise to more homogeneous and well-integrated composite materials. Hydrogel formation has been triggered using Zn2+ salts, required to form ZIF-8, and formic acid, required to form MOF-808. Two different protocols for the in situ MOF growth have been developed. Finally, the MOF-808 composite hydrogel has been tested for the decontamination of water polluted with phosphate ions as well as for the catalytic degradation of toxic organophosphate methyl paraoxon in an unbuffered solution.