Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Topical insulin, a novel corneal epithelial regeneration agent in dry eye disease.

OBJECTIVE: To evaluate the efficacy of insulin eye drops for dry eye disease in reducing corneal staining and improving symptoms. METHODS: In this retrospective case series, patients with dry eye disease treated with off-label use of insulin eye drops were collected. The main inclusion criterion was diagnosis of dry eye disease with epithelial damage and acceptance of the off-label use of topical insulin. Age, sex, type of dry eye disease, time since diagnosis, previous ocular surgeries, concomitant treatment, best corrected visual acuity, symptoms, conjunctival hyperemia and corneal staining were recorded. Data from the 1 and 3-month visit were included. RESULTS: 16 patients (32 eyes) were treated with insulin (14 females and 2 males; mean age 61.3 ± 16.8 years). 12 patients (71%) were also on autologous serum and 10 patients (63%) on cyclosporine. Symptoms were 3.4 ± 1.3 (range 2-5) when scaled from 0 to 5. Mean hyperemia was 1.0 ± 0.9 (range 0-3) and corneal staining was 2.5 ± 1.3 (range 0-5). After 3 months, 5 patients (31%) referred to be much better, 6 (38%) better, 3 (19%) slightly better and 2 patients (13%) were subjectively similar, mean symptoms being 2.3 ± 1.0 (range 1-4; p = 0.001). Hyperemia was 0.3 ± 0.4 (range 0-1) and corneal staining was 1.1 ± 1.0 (range 0-3; both p < 0.001). Topical insulin was well tolerated with no adverse events. CONCLUSIONS: The excellent results presented in these case series illustrate topical insulin as a promising treatment in dry eye disease with refractory epithelial damage.

Challenges of DMEK Technique with Young Corneal Donors' Grafts: Surgical Keys for Success-A Pilot Study.

PURPOSE: To report on the surgical maneuvers recommended for a successful unfolding of very young donors in order to accomplish an uneventful Descemet Membrane Endothelial Keratoplasty (DMEK) surgery. METHODS: Five patients (three females and two males, mean age 71.2 ± 6.7 years) with Fuchs endothelial cell dystrophy who underwent DMEK with very young donors (between 20 and 30 years old) were included. The following demographic data were assessed: donor's age, donor's endothelial cell density (ECD), preservation time, recipient's age and sex and unfolding surgical time. Best-corrected visual acuity (BCVA; decimal system), ECD and corneal central thickness (CCT) were assessed preoperatively and at 6-month follow-up. RESULTS: Donors' mean age was 23.6 ± 3.6 years (range 21 to 30) and the mean ECD was 2748.6 ± 162.6 cells/mm2. All of them underwent an uneventful DMEK as a single procedure performed by one experienced surgeon (MAG) with a mean unfolding time of 7.2 ± 4.9 min (range 4 to 15). The essential steps, including patient preparation as well as DMEK graft implantation, orientation, unrolling and centering are detailed. At 6 months, BCVA was 0.6 ± 0.2, ECD was 1945.0 ± 455.5 cells/mm2 and CCT was 497.0 ± 19.7 microns. CONCLUSIONS: We hereby present the keys to overcome tightly scrolled grafts of very young donors, which prove perfectly suitable for DMEK surgery. The graft shape tends towards a double-roll and specific maneuvers are strongly recommended.

Recommendations for the Clinical Approach to Immune Thrombocytopenia: Spanish ITP Working Group (GEPTI).

Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management.

Structural Strategies for Supramolecular Hydrogels and Their Applications.

Supramolecular structures are of great interest due to their applicability in various scientific and industrial fields. The sensible definition of supramolecular molecules is being set by investigators who, because of the different sensitivities of their methods and observational timescales, may have different views on as to what constitutes these supramolecular structures. Furthermore, diverse polymers have been found to offer unique avenues for multifunctional systems with properties in industrial medicine applications. Aspects of this review provide different conceptual strategies to address the molecular design, properties, and potential applications of self-assembly materials and the use of metal coordination as a feasible and useful strategy for constructing complex supramolecular structures. This review also addresses systems that are based on hydrogel chemistry and the enormous opportunities to design specific structures for applications that demand enormous specificity. According to the current research status on supramolecular hydrogels, the central ideas in the present review are classic topics that, however, are and will be of great importance, especially the hydrogels that have substantial potential applications in drug delivery systems, ophthalmic products, adhesive hydrogels, and electrically conductive hydrogels. The potential interest shown in the technology involving supramolecular hydrogels is clear from what we can retrieve from the Web of Science.

Spontaneous Descemet Layer Dissection Without Pneumodissection in Femtosecond Laser-Assisted Mushroom-Type Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to describe a case of spontaneous Descemet layer dissection without pneumodissection in femtosecond laser-assisted mushroom-type deep anterior lamellar keratoplasty. METHODS: This study is a case report. RESULTS: A 46-year-old woman diagnosed with reticular dystrophy underwent, in her left eye, mushroom configuration femtosecond laser-assisted DALK (F-DALK). After laser trephination and removal of the superficial stroma using manual dissection, a type 2 BB formation was observed intraoperatively in the AS-OCT without signs of an associated microperforation. A deeper stromal removal was accomplished by layer-by-layer manual dissection, while the BB persisted. After stromal dissection, the donor cornea was secured with 8 interrupted 10-0 nylon sutures. The next day AS-OCT showed a detachment of DM. After 1 week, a spontaneous resolution of the DM detachment was observed. CONCLUSIONS: This unknown F-DALK intraoperative complication has been detected through intraoperative AS-OCT images which may improve our understanding of F-DALK surgery and possible complications associated with femtolaser-assisted procedures.

Efficacy and safety of topical 5-fluorouracil in conjunctival intraepithelial neoplasia refractory to interferon alpha-2b.

PURPOSE: To report the efficacy and safety of 5-fluorouracil as the second line of treatment for two cases of conjunctival intraepithelial neoplasia refractive to topical interferon alpha-2b. CASE REPORT: In the first case, a 77-year-old woman was evaluated because of a fleshy vascularized lesion in the temporal conjunctiva on her right eye with leukoplakia of the corneal epithelium from 10- to 5-o'clock limbus. In the second case, an 81-year-old man, a nodular lesion in the temporal conjunctiva on his RE, with corneal adjacent opalescence, one millimeter in extent, was observed. Both patients were initially treated with excisional surgery, the samples being reported as conjunctival intraepithelial neoplasia with high-grade dysplasia. Co-adjuvant treatment with topical interferon alpha-2b 1 mIU/mL was indicated 4 times/day uninterruptedly. In the first case, there was no response despite 8 months of treatment, while in the second, the corneal lesion progressed in an arboriform pattern after 4 months of topical chemotherapy. MANAGEMENT & OUTCOME: In the absence of efficacy, the treatment was then changed to topical 5-fluorouracil (1%), 4 times/day for 7 days with a time-lapse of 21 days off, which constitutes a course. Two and four courses of treatment with 5-fluorouracil 1% were completed in both cases in the absence of important side effects. After the first course, both patients showed complete remission of the lesions. No clinical signs of relapse were noted after 1 year of follow-up. DISCUSSION: The treatment with 5-fluorouracil is a good option as the second line of treatment for conjunctival intraepithelial neoplasia who are low-responders to interferon alpha-2b, with fewer side effects than other currently available alternatives.

Heroínas con capa de enfermera. Paralelismo entre los cuidados bélicos de Florence Nightingale y Carmen Angoloti / Heroines with a nurse's cape. Parallelism between the war care of Florence Nightingale and Carmen Angoloti

El objetivo de este trabajo es identificar similitudes entre la labor desarrollada y las competencias enfermeras que Florence Nightingale y Carmen Angoloti prestaron durante la Guerra de Crimea y la Guerra del Rif respectivamente. Se ha realizado una revisión documental incluyendo biografías, memorias y periódicos de la época. Según metodología histórica, resulta en un estudio original de interés por el método analítico-sintético. Se ha podido constatar la relevancia del papel de ambas profesionales en la evolución de la profesión enfermera y su implantación en España, así como la evolución de la imagen social y relevancia de la enfermería de una época a otra. Se aprecian semejanzas como la importancia del apoyo monárquico para desarrollar la misión sanitaria, el desorden encontrado en los hospitales, establecimiento de reglas básicas de salud pública, orientación de los cuidados para cubrir las necesidades básicas de los heridos o las labores desempeñadas de gestión y administración de recursos (AU)

The aim of this thesis is to identify similarities between the work and nursing skills of Florence Nightingale and Carmen Angoloti during the Crimean War and the Rif War. A documentary review has been carried out, including biographies, memoirs and newspapers of the time. According to the historical methodology, it is an original study of interest through the analytical-synthetic method. The relevance of the role of both professionals in the evolution of the nursing profession and its establishment in Spain has been confirmed, as well as the evolution of the social image and relevance of nursing from one period to another. Similarities can be identified, such as the importance of monarchical support in the development of the health mission, the disorder found in hospitals, the establishment of basic public health rules, the orientation of care to meet the basic needs of the wounded and the work carried out in the management and administration of resources (AU)

Heroínas con capa de enfermera. Paralelismo entre los cuidados bélicos de Florence Nightingale y Carmen Angoloti / Heroines with a nurse's cape. Parallelism between the war care of Florence Nightingale and Carmen Angoloti

El objetivo de este trabajo es identificar similitudes entre la labor desarrollada y las competencias enfermeras que Florence Nightingale y Carmen Angoloti prestaron durante la Guerra de Crimea y la Guerra del Rif respectivamente. Se ha realizado una revisión documental incluyendo biografías, memorias y periódicos de la época. Según metodología histórica, resulta en un estudio original de interés por el método analítico-sintético. Se ha podido constatar la relevancia del papel de ambas profesionales en la evolución de la profesión enfermera y su implantación en España, así como la evolución de la imagen social y relevancia de la enfermería de una época a otra. Se aprecian semejanzas como la importancia del apoyo monárquico para desarrollar la misión sanitaria, el desorden encontrado en los hospitales, establecimiento de reglas básicas de salud pública, orientación de los cuidados para cubrir las necesidades básicas de los heridos o las labores desempeñadas de gestión y administración de recursos. (AU)

The aim of this thesis is to identify similarities between the work and nursing skills of Florence Nightingale and Carmen Angoloti during the Crimean War and the Rif War. A documentary review has been carried out, including biographies, memoirs and newspapers of the time. According to the historical methodology, it is an original study of interest through the analytical-synthetic method. The relevance of the role of both professionals in the evolution of the nursing profession and its establishment in Spain has been confirmed, as well as the evolution of the social image and relevance of nursing from one period to another. Similarities can be identified, such as the importance of monarchical support in the development of the health mission, the disorder found in hospitals, the establishment of basic public health rules, the orientation of care to meet the basic needs of the wounded and the work carried out in the management and administration of resources. (AU)

Enhancing Solid-Phase Extraction of Tamoxifen and Its Metabolites from Human Plasma Using MOF-Integrated Polyacrylonitrile Composites: A Study on CuBTC and ZIF-8 Efficacy.

This study investigates electrospun fibers of metal-organic frameworks (MOFs), particularly CuBTC and ZIF-8, in polyacrylonitrile (PAN) for the solid-phase extraction (SPE) of Tamoxifen (TAM) and its metabolites (NDTAM, ENDO, and 4OHT) from human blood plasma. The focus is on the isolation, pre-concentration, and extraction of the analytes, aiming to provide a more accessible and affordable breast cancer patient-monitoring technology. The unique physicochemical properties of MOFs, such as high porosity and surface area, combined with PAN's stability and low density, are leveraged to improve SPE efficiency. The study meticulously examines the interactions of these MOFs with the analytes under various conditions, including elution solvents and protein precipitators. Results reveal that ZIF-8/PAN composites outperform CuBTC/PAN and PAN alone, especially when methanol is used as the protein precipitator. This superior performance is attributed to the physicochemical compatibility between the analytes' properties, like solubility and polarity, and the MOFs' structural features, including pore flexibility, active site availability, surface polarity, and surface area. The findings underscore MOFs' potential in SPE applications and provide valuable insights into the selectivity and sensitivity of different MOFs towards specific analytes, advancing more efficient targeted extraction methods in biomedical analysis.

A Systematic Review on Spinal Asymmetries in Case Studies of Unilateral Nephroptosis from a Viscerosomatic Point of View.

The assessment of posture and asymmetries is common in musculoskeletal clinical practice, and correction is a frequent goal. In this setting, posture and asymmetries are usually interpreted in terms of musculoskeletal issues. This study aimed to evaluate spinal asymmetries in case studies of unilateral nephroptosis. A systematic review was performed using PubMed, CINAHL, Scopus and Web of Science. We included case reports and case series of nephroptotic patients which showed diagnostic imaging that allowed us to assess the presence of spinal asymmetries in the frontal plane. The methodological quality of the selected studies was assessed by using Case Report (CARE) checklist. Nineteen studies were included, with a total number of 78 reported patients (69 women) ranging 22 to 44 years old (mean: 29). Only one patient presented with medial nephroptosis, while the rest presented with caudal migration. Ninety-one percent of the cases affected to the right kidney. All cases but two showed homolateral flank closure (lower rib descent, iliac crest raise and/or homolateral side-bending). The correction of nephroptosis, either by supine position or surgical treatment, removed asymmetries in some cases while other cases improved only partly. Manual therapists must consider visceral implications while assessing body posture. Further, since the most common symptom of nephroptosis is loin pain, and it has been claimed that loin pain is underdiagnosed, manual therapists should consider its potential presence during clinical practice. Finally, being that nephroptosis shares several features with idiopathic lumbar scoliosis (type of patient, postural adaptation), more research is needed regarding any possible relation between them.

[Preventive activities in women. PAPPS update 2022]. / Actividades preventivas en la mujer. Actualización PAPPS 2022.

In the 2022 PAPPS update we present those specific preventive activities for women's health, except those related to cancer prevention (which are included in another document) and those aspects related to differential gender morbidity, a cross-cutting aspect for all working groups. Contraception is an essential preventive activity, considering basic the right to decide both the number of children and the time to have them. We must inform about the possible contraceptive methods, guaranteeing the monitoring of their safety, efficacy and effectiveness (tables are included on changing from one method to another to preserve contraceptive protection). We must inform about emergency contraception and propose it in the event of unprotected intercourse. All this will be done through opportunistic screening without requiring screening for thrombophilia or dyslipidemia, but for arterial hypertension. Pregnancy is an important life experience and the family doctor should not remain oblivious. We must be competent both in the preconception consultation (recommending the intake of folic acid, avoiding exposure to occupational and environmental risks, screening for certain pathologies and assessing the intake of drugs not indicated during pregnancy) and in the monitoring of pregnancy. Whether or not we monitor the pregnancy, we must not disregard its control, taking advantage of this period to promote healthy lifestyles and participating in the intercurrent processes that may occur. Menopause in general and osteoporosis in particular exemplify the strategy of medicalization of vital processes that has been followed from different instances and organizations. In our update we address the prevention and treatment of symptoms secondary to estrogen deprivation. We also propose the prevention of osteoporosis, including carrying out densitometry based on the risk of fracture in the next 10 years, and therefore densitometric screening is not recommended in women under 60 years of age. In risk assessment we recommend the use of the frax tool or better, the calibration of the risk of hip fracture with prevalence data from our setting. We linked the indication for treatment with the Z-Score (bone mineral density compared with women of the same age), as it is a condition associated with aging.

Conjunctivitis in an Individual With Monkeypox.

This case report describes a case of monkeypox in a patient with HIV presenting with conjunctivitis.

Advances in the Structural Strategies of the Self-Assembly of Photoresponsive Supramolecular Systems.

Photosensitive supramolecular systems have garnered attention due to their potential to catalyze highly specific tasks through structural changes triggered by a light stimulus. The tunability of their chemical structure and charge transfer properties provides opportunities for designing and developing smart materials for multidisciplinary applications. This review focuses on the approaches reported in the literature for tailoring properties of the photosensitive supramolecular systems, including MOFs, MOPs, and HOFs. We discuss relevant aspects regarding their chemical structure, action mechanisms, design principles, applications, and future perspectives.

Assessment of pavement deflection under vehicle loads using a 3D-DIC system in the field.

This study aims to introduce the use of 3D-digital image correlation (DIC) to the in situ testing of pavements and to support the development of techniques for a rapid evaluation of the conservation status of existing roads. Little research was found on this topic. The passage of a car wheel on an asphalt pavement was adopted as a case study. The DIC measurements were compared to those gathered by contact sensors. From a qualitative point of view, the DIC measurements captured the realistic shape of a deflection basin. From a quantitative point of view, the deflection values provided by the DIC system had a mean error of 0.015 mm and a standard deviation of 0.011 mm. At the moment of highest load, these errors had a mean value and standard deviation of - 0.016 mm and 0.021 mm, respectively. Thus, to improve the accuracy of the system, we propose modifying the camera support, speckle pattern, and control of natural light.

An analysis of the competitiveness of the tourism industry in a context of economic recovery following the COVID19 pandemic.

Business activities within the tourism industry are especially suffering from the consequences of the COVID19 pandemic. Those countries whose economy depends largely on tourism will experience a troublesome situation for years to come. Their return to a normal situation will be conditioned by the competitiveness of their tourism sector. The study begins by pinpointing the countries that have been more hardly stricken by the pandemic and in which tourism accounts for a greater share of the GDP. A comparative analysis of the competitiveness of these countries with that of world-leading countries will be carried out so as to conclude which will face the recovery period in a more vulnerable situation. The measurement of tourism competitiveness will be supported by the creation of a synthetic indicator based on the P2 distance method. A group of 13 countries has been identified as the most vulnerable, and it is advisable to act urgently in the following areas: the promotion of cultural elements and the historical and artistic heritage, the protection of natural areas, the availability of information and communication technologies, the international openness of the destination, and the availability of transportation infrastructures and tourist services.