The Known, the Unknown and the Future of the Pathophysiology of Endometriosis.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility, affecting 10% of women of reproductive age. A delay of up to 9 years is estimated between the onset of symptoms and the diagnosis of endometriosis. Endometriosis is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in research on endometriosis have some authors believing that endometriosis should be re-defined as "a fibrotic condition in which endometrial stroma and epithelium can be identified". There are several theories on the etiology of the disease, but the origin of endometriosis remains unclear. This review addresses the role of microRNAs (miRNAs), which are naturally occurring post-transcriptional regulatory molecules, in endometriotic lesion development, the inflammatory environment within the peritoneal cavity, including the role that cytokines play during the development of the disease, and how animal models have helped in our understanding of the pathology of this enigmatic disease.

Addressing Sexually Transmitted Infections Due to Neisseria gonorrhoeae in the Present and Future.

It was in the 1800s when the first public publications about the infection and treatment of gonorrhoea were released. However, the first prevention programmes were only published a hundred years later. In the 1940s, the concept of vaccination was introduced into clinical prevention programmes to address early sulphonamide resistance. Since then, tons of publications on Neisseria gonorrhoeae are undisputed, around 30,000 publications today. Currently, the situation seems to be just as it was in the last century, nothing has changed or improved. So, what are we doing wrong? And more importantly, what might we do? The review presented here aims to review the current situation regarding the resistance mechanisms, prevention programmes, treatments, and vaccines, with the challenge of better understanding this special pathogen. The authors have reviewed the last five years of advancements, knowledge, and perspectives for addressing the Neisseria gonorrhoeae issue, focusing on new therapeutic alternatives.

Assessment of the quality of life of patients with inflammatory bowel disease. / Evaluación de la calidad de vida de los pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Ulcerative colitis (UC) and Crohn's disease (CD) are diseases that cause a significant impact on patients' quality of life. The aim of this study is to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQoL). MATERIAL AND METHODS: Observational, descriptive, cross-sectional study, carried out at Torrecárdenas Hospital (Almería). Patients over 14 years of age diagnosed with CD or UC were included. For the assessment of HRQoL, the reduced 9-item IBDQ-9 questionnaire was used. RESULTS: 106 patients with a mean age of 44 years were included, with a female predominance. Forty-five percent of the patients in the sample had UC compared to 55% with CD. Of the patients, 69.8% were in clinical remission. The median questionnaire score was 60.8 points out of 100. Statistically significant differences were observed between sexes, with worse HRQoL for females. No differences were observed between patients with UC and CD. Differences were also detected between patients who underwent surgery and those who did not. A negative association was observed between the number of flares and the questionnaire score. CONCLUSIONS: In our study population, there is an acceptable HRQoL, with no differences observed between CD and UC. Female sex, absence of clinical remission, number of previous outbreaks, and surgery have a negative association with HRQoL.

Influence of fumarate on interspecies electron transfer and the metabolic shift induced in Clostridium pasteurianum by Geobacter sulfurreducens.

AIMS: In previous studies, it was demonstrated that co-culturing Clostridium pasteurianum and Geobacter sulfurreducens triggers a metabolic shift in the former during glycerol fermentation. This shift, attributed to interspecies electron transfer and the exchange of other molecules, enhances the production of 1,3-propanediol at the expense of the butanol pathway. The aim of this investigation is to examine the impact of fumarate, a soluble compound usually used as an electron acceptor for G. sulfurreducens, in the metabolic shift previously described in C. pasteurianum. METHODS AND RESULTS: Experiments were conducted by adding along with glycerol, acetate, and different quantities of fumarate in co-cultures of G. sulfurreducens and C. pasteurianum. A metabolic shift was exhibited in all the co-culture conditions. This shift was more pronounced at higher fumarate concentrations. Additionally, we observed G. sulfurreducens growing even in the absence of fumarate and utilizing small amounts of this compound as an electron donor rather than an electron acceptor in the co-cultures with high fumarate addition. CONCLUSIONS: This study provided evidence that interspecies electron transfer continues to occur in the presence of a soluble electron acceptor, and the metabolic shift can be enhanced by promoting the growth of G. sulfurreducens.

Unraveling the Molecular Landscape of Uterine Fibroids, Insights into HMGA2 and Stem Cell Involvement.

Uterine fibroids are prevalent benign tumors in women that exhibit considerable heterogeneity in clinical presentation and molecular characteristics, necessitating a deeper understanding of their etiology and pathogenesis. HMGA2 overexpression has been associated with fibroid development, yet its precise role remains elusive. Mutations in fibroids are mutually exclusive and largely clonal, suggesting that tumors originate from a single mutant cell. We explored a possible role for HMGA2 overexpression in differentiated myometrial cells, hypothesizing its potential to induce a stem cell-like or dedifferentiating phenotype and drive fibroid development. Myometrial cells were immortalized and transduced with an HMGA2 lentivirus to produce HMGA2hi cells. In vitro stem cell assays were conducted and RNA from HMGA2hi and control cells and fibroid-free myometrial and HMGA2 fibroid (HMGA2F) tissues were submitted for RNA-sequencing. HMGA2hi cells have enhanced self-renewal capacity, decreased proliferation, and have a greater ability to differentiate into other mesenchymal cell types. HMGA2hi cells exhibit a stem cell-like signature and share transcriptomic similarities with HMGA2F. Moreover, dysregulated extracellular matrix pathways are observed in both HMGA2hi cells and HMGA2F. Our findings suggest that HMGA2 overexpression drives myometrial cells to dedifferentiate into a more plastic phenotype and underscore a pivotal role for HMGA2 in fibroid pathogenesis.

Characterization of the oral microbiota and the relationship of the oral microbiota with the dental and periodontal status in children and adolescents with nonsyndromic cleft lip and palate. Systematic literature review and meta-analysis.

OBJECTIVE: To identify the characteristics of the oral microbiota and the relationship of the dental caries and periodontal status in patients aged 0 to 18 years with non-syndromic cleft lip and palate (CLP). MATERIALS AND METHODS: A systematic review of the literature was carried out. Five databases were consulted, including publications in English, Spanish and Portuguese. The evaluations of the quality of the observational studies and the experimental studies were carried out with the Newcastle-Ottawa scale and CONSORT guidelines, respectively. The risk of bias of the studies was determined using Rev Manager 5.4, and 5 publications were meta-analyzed. RESULTS: The cariogenic microbiota of children and adolescents with cleft lip and palate was similar to that of children without clefts, although with higher counts of Streptococcus mutans and Lactobacillus spp. The periodontopathogenic microbiota was related to the presence of Campylobacter spp, Fusobacterium spp, Fusobacterium nucleatum, Prevotella intermedia/nigrescens, Parvimonas micra and Porphyromonas gingivalis, considered microorganisms with high pathogenic capacity. Heterogeneity was shown in relation to the microbiota and the type of fissure, presenting numerous microorganisms associated with the pre- and post-surgical condition (cheilorrhaphy and palatorrhaphy) such as Staphylococcus aureus, Streptococcus beta hemolyticus, Klebsiella pneumoniae and Klebsiella oxytoca, Moraxella catarrhalis, Candida spp, Candida albicans, Candida krusei and Candida tropicalis. The meta-analysis revealed that patients with cleft lip and palate were 2.03 times more likely to have caries than the control group (p<0.005). CONCLUSION: In the microbiota, there was a great diversity of microorganisms that can vary according to the type of fissure and surgical interventions predisposing patients to a greater probability of dental caries, it is important to take into account the technique used to describe the oral microbiota in order to be able to compare the different studies. CLINICAL RELEVANCE: Studying the microbiota and the relationship of dental caries and periodontal status in children and adolescents with cleft lip and palate can facilitate the comprehensive care of patients with these conditions.

Mycoplasma pneumoniae at the rise not only in China: rapid increase of Mycoplasma pneumoniae cases also in Spain.

After the use of facemasks, other isolation measures enacted during the SARS-CoV-2 pandemic were lifted, respiratory pathogens, such as RSV, reappeared, but until the November 2023 WHO alert for China, M. pneumoniae had virtually disappeared. After observing a similar reappearance in our hospital, a retrospective analysis of the number of positive M. pneumoniae tests. Between 2018 and December 2023, 1619 PCR tests were ordered and 43 (2.6%) of them were positive. Two outbreaks, one in 2018 and one in 2023, accounted for the majority of cases. Tests were usually ordered in an outpatient setting (53.54%, n = 23) and most of them were paediatric patients with a mean age (sd) of 10.2 (6.2) years. As for the severity of the cases, in the 2018 outbreak, of 15 children who tested positive, 53.3% (n = 8) were admitted to the ward and 6.7% (n = 1) at the intensive care unit. Whereas in 2023, 2 patients were tested in the ward (10.5%) and one in the intensive care unit (5.2%) from a total of 19 patients. The positive rate in 2023 was significantly higher in comparison with years 2020, 2021 and 2022 and significantly lower in comparison with 2018 (P-value=0.003). The outbreak in late 2023 can be explained by the seasonality of Mycoplasma pneumonia alone, which has shown outbreaks every 3-5 years, and it does not appear to be more severe than the previous one.

Effectiveness of Virtual Reality and Feedback to Improve Gait and Balance in Patients with Diabetic Peripheral Neuropathies: Systematic Review and Meta-Analysis.

Diabetic peripheral neuropathy (DPN) is the primary complication in patients with diabetes mellitus, characterized by loss of sensation and function in the lower limbs. Virtual reality (VR) and/or sensory feedback (FB) therapy has shown positive effects in other neurologic conditions such as stroke. However, consensus regarding their effectiveness in the DPN population is lacking. This study aims to analyze existing scientific evidence about the effects of VR and/or FB on improving gait and balance and reducing the risk of falls in patients with DPN (pwDPN). A thorough search was conducted in scientific databases including PubMed, Scopus, and EMBASE, up until November 2023. CMSQ, the PEDro scale, and the Cochrane Collaboration's tool were used to assess the methodological quality and risk of bias of the studies. A total of 10 studies were selected for qualitative analysis, with three contributing information to the meta-analysis. The combined results suggest a positive trend in favor of VR and FB rehabilitation; however, significant differences were not observed in balance (SMD = -0.81, 95% CI = -1.90, 0.29; p = 0.15; I2 = 86%) or gait speed improvements (MD = -1.05, 95% CI = -2.96, 0.85; p = 0.28; I2 = 89%). Therefore, further randomized controlled studies are still needed to achieve stronger conclusions regarding the benefits of VR and/or FB in pwDPN.

Clinical complications after a traumatic brain injury and its relation with brain biomarkers.

We aimed to find out which are the most frequent complications for patients who suffer a traumatic brain injury (TBI) and its relation with brain biomarker levels. We conducted a hospital cohort study with patients who attended the Hospital Emergency Department between 1 June 2018 and 31 December 2020. Different variables were collected such as biomarkers levels after 6 h and 12 h of TBI (S100, NSE, UCHL1 and GFAP), clinical and sociodemographic variables, complementary tests, and complications 48 h and 7 days after TBI. Qualitative variables were analysed with Pearson's chi-square test, and quantitative variables with the Mann-Whitney U test. A multivariate logistic regression model for the existence of complications one week after discharge was performed to assess the discriminatory capacity of the clinical variables. A total of 51 controls and 540 patients were included in this study. In the TBI group, the mean age was 83 years, and 53.9% of the patients were male. Complications at seven days were associated with the severity of TBI (p < 0.05) and the number of platelets (p = 0.016). All biomarkers except GFAP showed significant differences in their distribution of values according to gender, with significantly higher values of the three biomarkers for women with respect to men. Patients with complications presented significantly higher S100 values (p < 0.05). The patient's baseline status, the severity of the TBI and the S100 levels can be very important elements in determining whether a patient may develop complications in the few hours after TBI.

Evaluating the impact of COVID-19 pandemic-related home confinement on the refractive error of school-aged children in Germany: a cross-sectional study based on data from 414 eye care professional centres.

OBJECTIVE: This study aimed at evaluating refractive changes in German school-aged children before and after the COVID-19 pandemic. DESIGN: Cross-sectional study. SETTING: 414 eye care professional centres from Germany. PARTICIPANTS: Refractive data from 59 926 German children aged 6-15 years were examined over a 7-year period (2015-2021). PRIMARY AND SECONDARY OUTCOME MEASURES: Spherical equivalent refraction was assessed as a function of year, age and gender. The refractive values concerning 2020 and 2021 were compared with those assigned to prior years (2015-2019). RESULTS: The refractive data associated with 2020 and 2021 showed a myopic refractive shift of approximately -0.20D compared with the 2015-2019 range. The refractive change was statistically considerable in the 6 to 11-year range (p<0.05), while from 12 to 15 years was negligible (p≥0.10). Percentage of myopes was also impacted in 2021 (p=0.002), but not in 2020 (p=0.25). From 6 to 11 years, the percentage of myopes in 2021 increased significantly by 6.02% compared with the 2015-2019 range (p≤0.04). The highest percentage increase occurred at 8 and 10 years of age, showing a rise of 7.42% (p=0.002) and 6.62% (p=0.005), respectively. From 12 to 15 years, there was no significant increase in the percentage of myopes in 2021 (p≥0.09). Percentage of myopes in 2020 was not influenced at any age (p≥0.06). CONCLUSION: Disruption of normal lifestyle due to pandemic-related home confinement appears to lead to a myopic refractive shift in children aged 6-11 years in Germany. The greater effect observed at younger ages seems to emphasise the importance of refractive development in this age group.

Prediction of refractive error and its progression: a machine learning-based algorithm.

OBJECTIVE: Myopia is the refractive error that shows the highest prevalence for younger ages in Southeast Asia and its projection over the next decades indicates that this situation will worsen. Nowadays, several management solutions are being applied to help fight its onset and development, nonetheless, the applications of these techniques depend on a clear and reliable assessment of risk to develop myopia. METHODS AND ANALYSIS: In this study, population-based data of Chinese children were used to develop a machine learning-based algorithm that enables the risk assessment of myopia's onset and development. Cross-sectional data of 12 780 kids together with longitudinal data of 226 kids containing age, gender, biometry and refractive parameters were used for the development of the models. RESULTS: A combination of support vector regression and Gaussian process regression resulted in the best performing algorithm. The Pearson correlation coefficient between prediction and measured data was 0.77, whereas the bias was -0.05 D and the limits of agreement was 0.85 D (95% CI: -0.91 to 0.80D). DISCUSSION: The developed algorithm uses accessible inputs to provide an estimate of refractive development and may serve as guide for the eye care professional to help determine the individual best strategy for management of myopia.

Thermal evaluation of plant biomass from the phytostabilisation of soils contaminated by potentially toxic elements.

The combination of phytoremediation of soils contaminated by potentially toxic elements with energy production by combustion of the generated biomass can be a sustainable land management option, combining the production of renewable bioenergy with soil restoration while minimising energy consumption and CO2 emission. In this work, plant biomass from phytoremediation of soils contaminated by potentially toxic elements was studied as solid biofuel for combustion by thermal analysis and biomass composition. Six plant species were grown in two soils with differing degrees of contamination: Brassica juncea, Cynara cardunculus, Atriplex halimus, Nicotiana glauca, Dittrichia viscosa, Retama sphaerocarpa and Salvia rosmarinus. The composition of the plant biomass was characterised chemically and thermogravimetric analyses were performed for the mass loss (TG), derivative curves of mass loss (DTG) and temperature difference (DTA) signal. The cellulose concentration correlated with the parameters of the thermal analysis in the low temperature range (150-350 °C), while lignin correlated with the thermal parameters of the second peak in the high temperature range. Salvia rosmarinus and R. sphaerocarpa showed the best combustion characteristics according to the thermal profile and mineral residue results. The accumulation of potentially toxic elements in B. juncea grown in heavily contaminated soil led to a higher amount of residue at 750 °C, with a global activation energy lower than the one obtained when this species was grown in a soil with lower contamination. Therefore, the most beneficial combination of soil phytoremediation and energy production (combustion) that can be suggested would depend on the level of soil contamination: in heavily contaminated soil, phytostabilisation using R. sphaerocarpa and S. rosmarinus; in slightly contaminated soil, B. juncea due to its high energy of activation, although the concentrations of potentially toxic elements in the residue must be controlled, as well as possible particulate matter emissions during combustion.

Effect of different industrialized acid beverages on the surface roughness of flowable composite resins: in vitro study.

Flowable composite resins are materials available for restorations in pediatric dentistry. However, these materials are subject to dangerous effects in the oral environment caused by acids that deteriorate and increase their roughness. Therefore it is important to evaluate the effect of different industrialized acid beverages on the roughness of flowable composite resins. An in vitro experimental study, was done using a convenience sample of 132 discs of 5 mm diameter by 2 mm depth of four flowable materials (FF (Filtek™ Z350 XT Flowable), TNF (Tetric® N-Flow), PF (PermaFlo®) and GF (Grandio® Flow)) exposed to three beverages (CC (Coca-Cola), AJ (apple juice), and FM (fermented milk)) and incubated at 37 ºC for 0, 15 and 30 days. The roughness (average roughness (Ra) and maximum height of profile (Rz) parameters) was measured at different intervals of time with a profilometer. For the data analysis, one-way analysis of variance (one-way ANOVA) and repeated measures analysis of variance (Repeated measures ANOVA) tests were applied (p < 0.05). In the roughness test before immersion, no differences were observed within the groups, with maximum roughness values for Filtek™ Z350 XT Flowable and minimum for PermaFlo®. However, at 15 and 30 days of immersion, the groups showed significant differences depending on the immersion drink, except Grandio® Flow in apple juice and fermented milk. The flowable materials studied presented specific behaviors according to the immersion period and drink used. The Filtek™ Z350 XT Flowable showed a similar increase in surface roughness independently of the drink used. Grandio® Flow was the most stable material against surface roughness changes after beverage immersion.

Detection of Endometriosis Lesions Using Gd-Based Collagen I Targeting Probe in Murine Models of Endometriosis.

PURPOSE: Endometriosis is a chronic condition characterized by high fibrotic content and affecting about 10% of women during their reproductive years. Yet, no clinically approved agents are available for non-invasive endometriosis detection. The purpose of this study was to investigate the utility of a gadolinium-based collagen type I targeting probe (EP-3533) to non-invasively detect endometriotic lesions using magnetic resonance imaging (MRI). Previously, this probe has been used for detection and staging of fibrotic lesions in the liver, lung, heart, and cancer. In this study we evaluate the potential of EP-3533 for detecting endometriosis in two murine models and compare it with a non-binding isomer (EP-3612). PROCEDURES: For imaging, we utilized two GFP-expressing murine models of endometriosis (suture model and injection model) injected intravenously with EP3533 or EP-33612. Mice were imaged before and after bolus injection of the probes. The dynamic signal enhancement of MR T1 FLASH images was analyzed, normalized, and quantified, and the relative location of lesions was validated through ex vivo fluorescence imaging. Subsequently, the harvested lesions were stained for collagen, and their gadolinium content was quantified by inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS: We showed that EP-3533 probe increased the signal intensity in T1-weighted images of endometriotic lesions in both models of endometriosis. Such enhancement was not detected in the muscles of the same groups or in endometriotic lesions of mice injected with EP-3612 probe. Consequentially, control tissues had significantly lower gadolinium content, compared to the lesions in experimental groups. Probe accumulation was similar in endometriotic lesions of either model. CONCLUSIONS: This study provides evidence for feasibility of targeting collagen type I in the endometriotic lesions using EP3533 probe. Our future work includes investigation of the utility of this probe for therapeutic delivery in endometriosis to inhibit signaling pathways that cause the disease.

MicroRNA-210-3p Regulates Endometriotic Lesion Development by Targeting IGFBP3 in Baboons and Women with Endometriosis.

MicroRNAs (miRs) play an important role in the pathophysiology of endometriosis; however, the role of miR-210 in endometriosis remains unclear. This study explores the role of miR-210 and its targets, IGFBP3 and COL8A1, in ectopic lesion growth and development. Matched eutopic (EuE) and ectopic (EcE) endometrial samples were obtained for analysis from baboons and women with endometriosis. Immortalized human ectopic endometriotic epithelial cells (12Z cells) were utilized for functional assays. Endometriosis was experimentally induced in female baboons (n = 5). Human matched endometrial and endometriotic tissues were obtained from women (n = 9, 18-45 years old) with regular menstrual cycles. Quantitative reverse transcript polymerase chain reaction (RT-qPCR) analysis was performed for in vivo characterization of miR-210, IGFBP3, and COL8A1. In situ hybridization and immunohistochemical analysis were performed for cell-specific localization. Immortalized endometriotic epithelial cell lines (12Z) were utilized for in vitro functional assays. MiR-210 expression was decreased in EcE, while IGFBP3 and COL8A1 expression was increased in EcE. MiR-210 was expressed in the glandular epithelium of EuE but attenuated in those of EcE. IGFBP3 and COL8A1 were expressed in the glandular epithelium of EuE and were increased compared to EcE. MiR-210 overexpression in 12Z cells suppressed IGFBP3 expression and attenuated cell proliferation and migration. MiR-210 repression and subsequent unopposed IGFBP3 expression may contribute to endometriotic lesion development by increasing cell proliferation and migration.

Platelet levels and age are determinants of survival after mild-moderate TBI: A prospective study in Spain.

Introduction: Traumatic brain injury (TBI) is a very important reason for consultation in emergency departments. Methods: A hospital cohort study with patients who attended a hospital emergency department between June 1, 2018 and December 31, 2020 due to TBI was studied. Clinical and sociodemographic variables were recorded. The levels of biomarkers and management variables were used. Qualitative variables were analyzed using Pearson's chi-square test, and quantitative variables using the Mann-Whitney U-test. Survival analyses were performed by fitting a multivariable Cox regression model for patient survival during the follow-up of the study in relation to the patient's characteristics upon admission to the emergency department. Results: A total of 540 patients were included. The mean age was 83 years, and 53.9% of the patients were men. Overall, 112 patients (20.7%) died during the study follow-up. The mortality rate per 100 person-years was 14.33 (11.8-17.24), the most frequent mechanism being falls in the home, with none caused on public roads. The multivariable Cox proportional hazards model showed that survival after TBI was significantly associated with age, S100 levels, Charlson index, patient's institutionalized status, the place where the TBI occurred, and hemoglobin and platelet levels. Discussion: The most common profile for a patient with a TBI was male and aged between 80 and 90 years. The combination of the variables age, Charlson index, place of TBI occurrence, and hemoglobin and platelet levels could offer early prediction of survival in our population independently of TBI severity. With the data obtained, a therapeutic algorithm could be established for patients suffering from mild TBI, allowing the patient to be supervised at home, avoiding futile referrals to emergency services.

Sequential dark fermentation and microbial electrolysis cells for hydrogen production: Volatile fatty acids influence and energy considerations.

Hydrogen production from food waste by coupling dark fermentation (DF) and microbial electrolysis cells (MEC) was studied. Metabolic patterns in DF, their effects on MECs efficiency, and the energy output of the coupling were investigated. Mesophilic temperature and acidic pH 5.5 resulted in 72 ± 20 mL H2/g CODin and a butyrate-enriched profile (C2/C4, 0.5-0.6) contrasting with an acetate-enriched profile (C2/C4, 1.8-1.9) and 36 ± 10 mL H2/g CODin at pH 7. Assessment in series of the DF effluents in MECs resulted in a higher hydrogen yield (566-733 mL H2/g CODin) and volatile fatty acids (VFAs) removal (84-95%) obtained from pH 7 effluents compared to pH 5.5 effluents (173-186 mL H2/g CODin and 29-59%). Finally, the output energy was lower in DF at pH 7, however, these effluents retrieved the highest energy in the MEC, showing the importance of process pH and VFAs profile to balance the coupling.

Do different robot appearances change emotion recognition in children with ASD?

Introduction: Socially Assistive Robotics has emerged as a potential tool for rehabilitating cognitive and developmental disorders in children with autism. Social robots found in the literature are often able to teach critical social skills, such as emotion recognition and physical interaction. Even though there are promising results in clinical studies, there is a lack of guidelines on selecting the appropriate robot and how to design and implement the child-robot interaction. Methods: This work aims to evaluate the impacts of a social robot designed with three different appearances according to the results of a participatory design (PD) process with the community. A validation study in the emotion recognition task was carried out with 21 children with autism. Results: Spectrum disorder results showed that robot-like appearances reached a higher percentage of children's attention and that participants performed better when recognizing simple emotions, such as happiness and sadness. Discussion: This study offers empirical support for continuing research on using SAR to promote social interaction with children with ASD. Further long-term research will help to identify the differences between high and low-functioning children.