Influence of state-of-the-art laboratory techniques on the phenotyping of women with polycystic ovary syndrome in the clinical setting.

PURPOSE: Evidence-based guidelines for the management of polycystic ovary syndrome (PCOS) recommend clinical laboratories use liquid chromatography-tandem mass spectrometry (LC-MS/MS) for diagnosing biochemical hyperandrogenism. However, automated immunoassays are still mostly used in routine laboratories worldwide. Another hurdle for PCOS phenotyping in the clinical setting is ultrasound assessment of polycystic ovarian morphology. We address the impact of using state-of-the-art (LC-MS/MS) and of an anti-müllerian hormone (AMH) assay on the diagnosis of PCOS in routine practice. METHODS: In a cross-sectional study, we included 359 premenopausal women consecutively evaluated because of symptoms of functional androgen excess or hyperandrogenemia, and finally diagnosed with PCOS. Patients were submitted to routine phenotyping based on serum androgen measurements by immunoassays and an ovarian ultrasound when necessary. Samples of all patients were also assayed by LC-MS/MS for hyperandrogenemia and for circulating AMH. RESULTS: The observed agreement between immunoassays and LC-MS/MS in identifying hyperandrogenemia was poor [78.0%; k(95%CI): 0.366 (0.283;0.449)]. The observed agreement between ultrasound and increased AMH was 27.3% [(95%CI): 0.060 (0.005; 0.115)]. Using LC-MS/MS changed PCOS phenotypes in 60(15.8%) patients. Fifty-two (18.3%) individuals with hyperandrogenemia by routine immunoassays no longer presented with androgen excess by LC-MS/MS. Overall diagnostic agreement between routine assessment using immunoassays and ultrasound and that derived from LC-MS/MS and the addition of AMH to US was moderate [weighted κ (linear weights): 0.512 (0.416;0.608)]. CONCLUSIONS: Immunoassays used in routine practice are unacceptably inaccurate for phenotyping women with PCOS. Our data cast some doubts upon the interchangeability of serum AMH and ultrasound examination for the diagnosis of PCOS.

Valorization of a by-product of the yerba mate industry by assembling with cassava starch adhesive for packaging material production.

Yerba mate industrial processing produces tons of powder as a by-product, this yerba mate powder (YMP) is an excellent source of biomass to develop biodegradable materials. Cassava starch modified with 1,2,3,4-butane tetracarboxylic acid (BA) in the presence of sodium propionate as a catalyst is an eco-friendly option to obtain bioadhesives. This work aimed to develop sustainable laminates from starch-based adhesives and yerba mate powder and to study their physico-chemical, structural, and mechanical properties. Blends of bioadhesive and YMP were prepared (1:1, adhesive:YMP). Monolayer materials were obtained by thermo-compression and later assembled with adhesive to obtain bilayer laminates. Bioadhesive was able to bind the yerba mate by-product fibers, as evidenced by SEM microstructure analysis, the interactions of adhesive:substrate were elucidated by ATR-FTIR and supported by chemometrics analysis. The incorporation of the catalyst decreased the rugosity of materials and their mechanical performance was improved by the action of both acid concentration and catalyst presence, requiring higher energy for puncture. Thus, it was feasible to obtain mono and bilayer laminates as an eco-compatible alternative for the design of sustainable tray-like materials based on the industrial by-product of yerba mate.

Reducing variability in nasal surgery outcomes through computational fluid dynamics and advanced 3D virtual surgery techniques.

Objectives: This study aims to delineate the specific impact of using computational fluid dynamics (CFD) and 3D virtual surgery techniques in otolaryngology surgery, focusing on their roles in enhancing the precision of nasal surgery and optimizing future patient outcomes. The central objective was to assess whether these advanced technologies could reduce variability in surgical approaches and decision-making among specialists, thereby improving the consistency and efficacy of patient care in cases of nasal obstruction. Methods and results: Our methodology involved a detailed analysis of pre- and post-operative scenarios using CFD feedback. Six otolaryngologists participated, employing virtual surgery techniques on two patients with diagnosed nasal obstruction. The CFD analysis focused on quantifying key airflow parameters: right nasal flow rate (QR), left nasal flow rate (QL), flow symmetry (Ф), and bilateral nasal resistance (R). These parameters were meticulously compared before and after the application of CFD feedback to evaluate changes in surgical planning and outcomes. Quantitative analysis revealed a notable decrease in the standard deviation of the measured parameters among the specialists post-CFD feedback, indicating reduced variability in surgical approaches. Specifically, for Patient #1 the standard deviation for QR values dropped from 0.694 L/min to 0.602 L/min, and for QL values from 0.676 L/min to 0.584 L/min, and for Patient #2, the standard deviation for QR values decreased from 2.204 L/min to 0.958 L/min, and for QL values from 2.295 L/min to 1.014 L/min. Moreover, the variability range, represented by the differences between the maximum and minimum values for Ф and R, diminished significantly. Post-operative average values for all parameters showed a convergence towards ideal basal levels, suggesting a more uniform and effective surgical strategy across different surgeons. Conclusions: Both integration of CFD and 3D virtual surgery techniques in otolaryngology can substantially reduce variability in surgical planning and decision-making, ultimately leading to improved patient outcomes. These advanced tools have the potential to standardize the diagnosis and treatment of nasal pathologies, contributing to more effective and consistent care. Future research in this area should focus on larger patient cohorts and further exploration of the potential benefits and applications of CFD and virtual surgery in otolaryngology.

Reliability of blood eosinophil count in steady-state bronchiectasis.

RATIONALE: The baseline value of eosinophils in peripheral blood (BEC) has been associated with different degrees of severity, prognosis and response to treatment in patients with bronchiectasis. It is not known, however, if this basal value remains constant over time. OBJECTIVES: The aim of this study was to assess whether the BEC remains stable in the long term in patients with bronchiectasis. METHODS AND MEASUREMENTS: Patients from the RIBRON registry of bronchiectasis diagnosed by computed tomography with at least 2 BEC measurements one year apart were included in the study. Patients with asthma and those taking anti-eosinophilic drugs were excluded. Reliability was assessed using the intra-class correlation coefficient (ICC). A patient with a BEC of at least 300 cells/uL or less than 100 cells/uL was considered eosinophilic or eosinopenic, respectively. Group changes over time were also calculated. MAIN RESULTS: Seven hundred and thirteen patients were finally included, with a mean age of 66.5 (13.2) years (65.8 % women). A total of 2701 BEC measurements were performed, with a median number of measurements per patient of 4 (IQR: 2-5) separated by a median of 12.1 (IQR: 10.5-14.3) months between two consecutive measurements. The ICC was good (>0.75) when calculated between two consecutive measurements (approximately one year apart) but had dropped significantly by the time of the next annual measurements. Similarly, the change from an eosinophilic or eosinopenic patient to a non-eosinophilic or non-eosinopenic patient, respectively, was less than 30 % during the first year with respect to the baseline value but was close to 50 % in later measurements. CONCLUSIONS: Given the significant changes observed in the baseline value of the BEC over time, its monitoring is necessary in patients with bronchiectasis in order to more reliably assess its usefulness.

Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.

Generation of a novel three-dimensional scaffold-based model of the bovine endometrium.

Bovine in vitro endometrial models that resemble tissue function in vivo are needed to study infertility, long-term uterine alterations induced by pathogens and impact of endocrine disruptor chemicals on reproductive function and other reproductive system complications that cause high economic losses in livestock species. The present study aimed to generate an innovative, reproducible, and functional 3D scaffold-based model of the bovine endometrium structurally robust for long term-culture. We developed a multicellular model containing both endometrial epithelial and stromal cells. Epithelial cells organized to form a luminal-like epithelial layer on the surface of the scaffold. Stromal cells produced their own extracellular matrix forming a stable subepithelial compartment that physiologically resembles the normal endometrium. Both cell types released prostaglandin E2 and prostaglandin F2α following a treatment with oxytocin and arachidonic acid. Additionally signal pathways mediating oxytocin and arachidonic acid stimulation of prostaglandin synthesis were analyzed by real time PCR (RT-PCR). Oxytocin receptor (OXTR), prostaglandin E2 receptor 2 (EP2), prostaglandin E2 receptor 4 (EP4), prostaglandin F receptor (PTGFR), prostaglandin E synthase (PTGES), PGF-synthase (PGFS) and prostaglandin-endoperoxide synthase 2 (COX-2) expression was detected in both control and treatment groups, however, only significant changes in abundance of OXTR mRNA transcripts were found. The results obtained by this study are a step forward in bovine in vitro culture technology. This 3D scaffold-based model provides a platform to study regulatory mechanisms involved in endometrial physiology and can set the basis for a broader tool for designing and testing novel therapeutic strategies for recurrent uterine pathologies.

Validation of circulating microRNAs miR-142-3p and miR-598-3p in women with polycystic ovary syndrome as potential diagnostic markers.

STUDY QUESTION: Circulating miRNAs previously associated with androgen excess in women might be used as diagnostic biomarkers for polycystic ovary syndrome (PCOS). SUMMARY ANSWER: Models based on circulating miR-142-3p and miR-598-3p expression show good discrimination among women with and without PCOS, particularly when coupled with easily available measurements such as waist-to-hip ratio (WHR) and circulating LH-to-FSH (LH/FSH) ratios. WHAT IS KNOWN ALREADY: The lack of standardization of the signs, methods, and threshold values used to establish the presence of the diagnostic criteria (hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology) complicates the diagnosis of PCOS. Certain biomarkers may help with such a diagnosis. We conducted a validation study to check the diagnostic accuracy for PCOS of several miRNAs that were associated with the syndrome in a small pilot study that had been previously carried out by our research group. STUDY DESIGN, SIZE, DURATION: This was a diagnostic test study involving 140 premenopausal women. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 71 women with PCOS and 69 healthy control women in the study. Both groups were selected as to be similar in terms of body mass index. We used miRCURY LNA™ Universal RT microRNA PCR to analyse the five miRNAs that had shown the strongest associations with PCOS in a much smaller pilot study previously conducted by our group. We studied diagnostic accuracy using receiver operating characteristics (ROC) curve analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Only the expression of two miRNAs, miR-142-3p and miR-598-3p, of the five studied, was different between the women with PCOS and the non-hyperandrogenic controls. The diagnostic accuracy of the combination of these circulating miRNAs was good (area under the ROC curve (AUC) 0.801; 95% CI: 0.72-0.88) and was further improved when adding WHR (AUC 0.834, 95% CI: 0.756-0.912), LH/FSH ratio (AUC = 0.869, 95% CI: 0.804-0.934) or both (AUC = 0.895, 95% CI: 0.835-0.954). We developed several models by selecting different threshold values for these variables favouring either sensitivity or specificity, with positive and negative predictive values as high as 88% or 85%, respectively. LIMITATIONS, REASONS FOR CAUTION: Patients included here had the classic PCOS phenotype, consisting of hyperandrogenism and ovulatory dysfunction; hence, the present results might not apply to milder phenotypes lacking androgen excess. WIDER IMPLICATIONS OF THE FINDINGS: If confirmed in larger studies addressing different populations and PCOS phenotypes, these biomarkers may be useful to simplify the clinical diagnosis of this prevalent syndrome. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (grants PI15/01686, PIE16/00050, PI18/01122 & PI21/00116) and co-funded by European Regional Development Fund 'A way to make Europe'. Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) are also initiatives of the Instituto de Salud Carlos III. The authors have no competing interests to disclose. TRIAL REGISTRATION NUMBER: N/A.

Post-TB bronchiectasis: from pathogenesis to rehabilitation.

The destruction of lung parenchyma caused by TB can result in pulmonary sequelae that are classified as bronchiectasis due to traction (radiological sequelae), and bronchiectasis persisting with an inflammatory bronchial component and opportunistic bronchial infection. There is a lack of studies that comprehensively analyse whether post-TB bronchiectasis differs in clinical, prognostic or therapeutic aspects from bronchiectasis arising from other aetiologies. However, it has been noted that post-TB bronchiectasis tends to appear more frequently in the upper lung lobes. In many countries, TB is the most frequent known cause of bronchiectasis, but there is currently no targeted management of bronchiectasis due to TB as opposed to other aetiologies. It is imperative to first prevent TB, and when that fails to provide early diagnosis and adequate treatment for TB disease. In addition, efforts should be made to limit additional lung insults such as tobacco use and provide management of post TB bronchiectasis to minimise further pulmonary sequelae. The objective of this minireview was to provide an update on post-TB bronchiectasis, its definition, epidemiological data, pathophysiology, and clinical, diagnosis and therapeutic aspects.

Assessment of the patient safety culture in the ICU of a second level hospital at the end of the third COVID-19 wave.

INTRODUCTION: Current healthcare settings and ICUs especially are complex, highly technical, and multidisciplinary, with interactions between healthcare professionals and users, in which there may be errors at different levels. Our objective was to assess the perception of patient safety in our unit at the end of the third wave of the COVID pandemic, with the intention of conducting subsequent improvement actions. METHODS: Observational, cross-sectional, and descriptive study. The perception of Safety Culture was estimated using the HSOPS questionnaire translated into Spanish. Some questions were posed in a positive sense, and others in a negative sense. The response was also rated as positive, negative, or neutral. Our findings were compared visually, not mathematically, with those found in the previous national study «Analysis of the culture on patient safety in the hospital setting of the Spanish National Health System¼ published in 2009. A subgroup analysis was performed according to professional group and seniority as a health worker. The Student's t, χ2 and ANOVA tests were used. RESULTS: Sixty-two professionals responded to the questionnaire, 73.90% of the total. The median time working in ICU 2 years (interquartile range 2-4.5 years). The rating for the degree of safety was 8.06 (SD 1.16). The majority (91.20%) had not reported any adverse event in the last year. A total of 30.90% had recently received patient safety training. The dimensions considered as weaknesses were 9 ("Staffing", with 27.57% of positive responses) and 10 ("Support of the hospital management in safety", with 17.64% of positive responses). The dimensions considered as strengths were 3 ("Expectation of actions by management/supervision of the service") with 85.29% of positive responses, and 5 ("Teamwork") with 95.58% of positive responses. The Cronbach's alpha index values suggest that the questionnaire has adequate internal consistency. In general, our data are more positive than those collected in the 2011 national survey, although the 2 dimensions considered weaknesses were already considered such in the previous work. CONCLUSIONS: The perception of patient safety in the ICU of our hospital after the end of the third wave of the COVID pandemic is adequate, with a more positive rating than that of the national study on safety culture at the hospital level carried out in 2009. The constant quest for patient safety should prioritize activity in the 2 dimensions considered weaknesses: staffing, and support from hospital management in everything related to patient safety.

Modelling the simultaneous chiral separation of a group of drugs by electrokinetic chromatography using mixtures of cyclodextrins.

Two mixtures of neutral cyclodextrins (CDs) were used in Electrokinetic Chromatography (EKC) to model and optimize the simultaneous enantiomeric separation of a group of seven drugs. Heptakis(2,6-di-O-methyl)-ß-CD (DM-ß-CD) combined with methyl-γ-CD (M-γ-CD) or with carboxyethyl-γ-CD (CE-γ-CD) was employed in a 25 mM formate buffer at pH 3.0 to have the drugs studied positively charged. Dubsky's model was applied to calculate the enantiomer effective electrophoretic mobilities for each combination of CDs at different averaged molar fractions and total CDs concentrations. The most adequate averaged molar fraction and total CDs concentration in terms of the simultaneous enantiomeric separation of the drug mixture were predicted by the model and results were experimentally corroborated. The model also foresaw interesting effects, derived from the combination of DM-ß-CD with M-γ-CD or with CE-γ-CD, on the individual chiral separation of some of the drugs studied. The observed reversal of the migration order for some compounds when changing the total CDs concentration was also predicted and the model showed its potential even at concentrations out of the experimental range of CD concentrations experimentally employed. The use of an averaged molar fraction of 0.8 for DM-ß-CD at a total CDs concentration of 40 mM in the DM-ß-CD/CE-γ-CD system predicted by the model enabled the simultaneous enantiomeric separation of six of the drugs studied (except verapamil) with resolutions ranging from 0.6 to 4.0.

Endarterectomy, Stenting, or Medical Treatment for Symptomatic Carotid Near-Occlusion: Results from CAOS, a Multicenter Registry Study.

BACKGROUND AND PURPOSE: The treatment of symptomatic carotid near-occlusion is controversial. Our aim was to analyze the results of carotid endarterectomy and carotid artery stent placement in patients with symptomatic carotid near-occlusion and to identify factors related to technical failure, periprocedural complications, and restenosis. MATERIALS AND METHODS: We conducted a multicenter, prospective nonrandomized study. Patients with angiography-confirmed carotid near-occlusion were included. We assessed the revascularization rate and periprocedural stroke or death. Twenty-four-month clinical and carotid imaging follow-up was performed, and rates of carotid restenosis or occlusion, ipsilateral stroke, and mortality were analyzed. Carotid artery stent placement, carotid endarterectomy, and medical treatment were compared. RESULTS: One hundred forty-one patients were included. Forty-four carotid artery stent placement and 23 carotid endarterectomy procedures were performed within 6 months after the event. Complete revascularization was achieved in 83.6%, 81.8% in the carotid artery stent placement group and 87% with carotid endarterectomy (P = .360). Periprocedural stroke or death occurred in 6% (carotid artery stent placement = 2.3%; carotid endarterectomy = 13%; P = .077) and was not related to revascularization failure. The carotid restenosis or occlusion rate was 8.3% (5% restenosis, 3.3% occlusion); with carotid artery stent placement it was 10.5%; and with carotid endarterectomy it was 4.5% (P = .419). The 24-month cumulative rate of ipsilateral stroke was 4.8% in the carotid artery stent placement group, 17.4% for carotid endarterectomy, and 13.1% for medical treatment (P = .223). Mortality was 12%, 4.5%, and 5.6%, respectively (P = .422). Revascularization failure and restenosis occurred more frequently in patients with full collapse compared with patients without full collapse (33.3% versus 5.6%, P = .009; 21.4% versus 2.9%, P = .032, respectively). CONCLUSIONS: Carotid artery stent placement and carotid endarterectomy are associated with high rates of failure and periprocedural stroke. Carotid near-occlusion with full collapse appears to be associated with an increased risk of technical failure and restenosis. Carotid near-occlusion revascularization does not seem to reduce the risk of stroke at follow-up compared with medical treatment.

PSCF and CWT methods as a tool to identify potential sources of 7Be and 210Pb aerosols in Granada, Spain.

This research is focused on studying the preferred source regions and the pathways of the air masses with high particulate concentrations impacting on the activity concentrations of 7Be and 210Pb aerosols in Granada atmosphere. For this purpose, three different source-receptor methods have been used: Cluster Analysis, Potential Source Contribution Function (PSCF), and Concentration Weighted Trajectory (CWT). Air filter samples were weekly collected and analysed in Granada university (Spain 37.177N, 3.598 W, 687m a.s.l.) during 12 years (2006-2017) for the activity concentration of 7Be, and during 5 years (2010-2014) for the one of 210Pb. The time series of the collected data indicate that the concentration of both radiotracers present a cyclical and seasonal pattern, in association with their origins and atmospheric conditions. Clustering analysis showed that the air masses arriving to Granada can be classified as: (1) tropical continental air masses coming from the Mediterranean Sea, (2) tropical and warm polar maritime air masses produced over the Atlantic Ocean, and (3) continental air masses originated over Europe and Northern Africa. The PSCF and CWT methods confirmed that the main source areas of 7Be are located in the Atlantic coast of southern Morocco, and Northern Africa. On the other hand, southern France and the Algerian desert were found to be the main region sources of 210Pb. In addition, the Mediterranean Basin has been postulated as a strong source region for 7Be and 210Pb. Furthermore, the PSCF and CWT models show that the regions with larger 7Be/210Pb ratios are located in the Atlantic Ocean, due to frequent stratospheric intrusions specially during the winter months.

Impact and treatment of exacerbations in adults with bronchiectasis.

Exacerbations have a negative impact on inflammatory diseases of the airways and, in patients with bronchiectasis, severe exacerbations are associated with increased morbidity and mortality. Exacerbations are also associated with a decline in quality of life and lung function, greater local and systemic inflammation and clinically more severe forms of the disease. As a consequence, the majority of therapeutic clinical trials carried out in patients with bronchiectasis are aimed at preventing exacerbations, but there is a scarcity of scientific evidence on the best treatment once they occur. All of these elements, combined with the great heterogeneity of bronchiectasis and the influence of geographical and microbiological factors on its clinical presentations and aetiologies, mean that the recommendations of therapeutic guidelines vary. An international group of experts has now reached agreement on the definition of exacerbation in bronchiectasis for the inclusion of patients in clinical trials, although its validity in clinical practice has yet to be demonstrated.

Evaluation of the microstructure, optical properties and hopping conduction mechanism of rare earth doped Ba0.85Ca0.12RE0.03Ti0.90Zr0.04Nb0.042O3 ceramics (RE = Ce3+ and Pr3+).

The current research work examines the impact of Rare Earth (RE3+) ion substitution on the structural, optical and conduction properties of a Ba0.85Ca0.12RE0.03Ti0.90Zr0.04Nb0.042O3 (BCRETZN) (RE = Ce, Pr) ceramic compound produced via a solid-state route. The Rietveld method of the X-ray data revealed a tetragonal (P4mm) structure at room temperature for our ceramic compound. The morphology of the compound was explored using Scanning Electron Microscopy (SEM) as well as optical response and conduction behavior. The photoluminescence properties revealed that the BCPrTZN sample results in green and red photoemissions under laser excitation at 450 nm at RT. Furthermore, for the BCCeTZN sample, the photoluminescence data demonstrated that strong violet emission bands were acquired, at RT upon an excitation at 350 nm. The electrical conduction process was verified via the correlated barrier Hopping method. The scaling behavior suggests that the electrical conduction mechanism is independent of temperature. The existence of Ce3+ and Pr3+ ions in these materials could have important technological potential in new multifunctional devices.