Exploring structural and computational contrasts in Myoglobins: Implications for thermal treatment-induced Sulfmyoglobin formation.

Greening of tuna metmyoglobin (MetMb) by thermal treatment (TT) and free cysteine is associated with sulfmyoglobin (SulfMb) production. This greening reaction (GR) was once thought to occur only in tuna species. However, recent research has revealed that not all tuna species exhibit this behavior, and it can also occur in horse MetMb. Thus, the present study aimed to compare the GR-reactive (Katsuwonus pelamis and Equus caballus) and GR-unreactive (Sarda chiliensis and Euthynnus lineatus) MetMb using UV-vis spectrometry during TT (60 °C/30 min and free cysteine) to monitor the GR. We used molecular dynamics (MD) simulation to assess the stability of the heme group during TT. We discovered that using GR-unreactive MetMb resulted in an incomplete GR without producing SulfMb. Additionally, our MD simulations indicated that Met85 presence in the heme cavity from GR-unreactive is responsible for the heme group instability and displacement of distal His during TT.

Evaluating the Safety of the Intragastric Balloon: Spanish Multicenter Experience in 20,680 Cases and with 12 Different Balloon Models.

INTRODUCTION: Intragastric balloon (IGB) is a minimally invasive and reversible option for obesity treatment. There is a worldwide growing number of different IGB models. The efficacy and safety profile for each model must be demonstrated. We aim to evaluate IGB safety profile according to the experience of the Spanish Bariatric Endoscopy Group (GETTEMO). METHODS: A survey of 37 IGBs safety-related questions was sent to all GETTEMO members, to retrospectively collect a multicenter Spanish registry. Incidence, causes, and resolution of both major and minor complications and adverse events (AEs), including legal consequences, differentiated for each balloon model were evaluated. Secondary outcome was weight loss data to confirm efficacy. RESULTS: Twenty-one Spanish hospitals experienced in IGBs responded. The overall data encompassed 20,680 IGBs, including 12 different models. Mean %TBWL of 17.66 ± 2.5% was observed. Early removal rate due to intolerance was 3.62%. Mean major complications rate was 0.70% (> 1% in Spatz2, HB, and Spatz3 models), mainly complicated gastric ulcer. Minor AEs rate was 6.37%, mainly esophagitis. Nine cases (0.04%) required surgery. A single case of mortality (0.0048%) occurred. Seven lawsuits (0.0034%) were received, all with favorable resolution. CONCLUSIONS: In the Spanish experience accumulating 20,680 IGBs and including 12 different balloon models, a low incidence rate of major complications and minor AEs are observed (0.70% and 6.37%, respectively), mostly resolved with medical/endoscopic management. IGB shows good tolerance and efficacy profile. These safety data are within the accepted quality standards.

Longitudinal outcome over four decades of allogeneic stem cell transplantation: a single center experience.

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality.

Childhood-Onset Non-Infectious Uveitis in the "Biologic Era". Results From Spanish Multicenter Multidisciplinary Real-World Clinical Settings.

OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.

Incidence of hypopituitarism in adults undergoing radiotherapy for neck and head cancer: protocol for a systematic review and meta-analysis.

INTRODUCTION: When children with head and neck cancer receive radiation therapy as part of their treatment, a considerable frequency of hypopituitarism has been recognised. However, in adults, it has been little studied and it is possible that patients may be inadvertently affected. The objective is to estimate the incidence of anterior pituitary dysfunction in adults undergoing radiotherapy for head and neck cancer. METHODS AND ANALYSIS: A total of five databases will be used to perform the document search: PubMed, Scopus, Web of Science (Core Collection), Ovid-MEDLINE and Embase. Cohort studies will be included without restriction by language or date. The main outcome will be the incidence of adenohypophyseal dysfunction for each axis: prolactin, growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, luteinising hormone and follicle-stimulating hormone. Incidence meta-analysis will be performed using the Freeman-Tukey double arcsine method. In addition, a random-effects model will be used along with a 95% CI. Subgroup analyses will be performed according to tumour location, radiation dose and endocrine assessment time. Meta-regression will be applied according to patient's age and time elapsed until diagnosis. ETHICS AND DISCLOSURE: Since this will be a systematic review of published data, no ethics committee approval is required. The results will be presented at conferences and finally published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235163.

Cytomegalovirus Reactivations in Allogeneic Hematopoietic Stem Cell Transplantation from HLA-Matched and Haploidentical Donors with Post-Transplantation Cyclophosphamide.

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies.

Assessment of asbestos-cement roof distribution and prioritized intervention approaches through hyperspectral imaging.

The discernment of asbestos-cement (AC) roofs within urban areas stands as a pivotal concern pertinent to communal well-being and ecological oversight, particularly in emerging nations where asbestos continues to be extensively employed. Conventional methodologies entailing the recognition of asbestos-cement roofs and the characterization of their degradation status, such as tangible examinations and laboratory assays, prove to be temporally protracted, financially demanding, and arduous to extrapolate comprehensively across expansive urban domains. In this paper, it is presented a novel approach for identifying asbestos-cement roofs in urban areas using hyperspectral airborne acquisition and carry out a diagnosis that allows to identify the state of asbestos-cement roofs and thus provide a tool for the competent authorities to develop and prioritize intervention strategies to mitigate the problem. Four different methodologies were implemented and compared, three of which are new in the literature, to identify the deterioration of asbestos-cement (AC) roof state in large urban areas. This, in turn, furnishes a tool for competent authorities to identify the state of AC roofs, develop and prioritize intervention strategies to mitigate the problem. The control points in field allowed validating the classification and the proposed methodology for the prioritization of intervention in AC roofs. Some neighborhoods in the city showed peaks in the area of asbestos-cement roofs of 47% of the total area of the neighborhood, representing practically all of the roofs present in the neighborhood. On average around 20% of the total area of a neighborhood in Cartagena is covered by AC. Furthermore, it was found a total area of AC roofs throughout the city of more than 9 km2 (9 million square meters). On the other hand, two of the 4 methods used showed encouraging results that demonstrate their ability to identify covers in poor and good condition at a large scale from hyperspectral images. This academic novelty suggests that there is a possibility of practical application of these methods in other urban contexts with high concentrations of AC roofs, helping in the planning and optimization of intervention strategies to mitigate the risk in public and environmental health due to the presence of asbestos.

Uso preoperatorio de fármacos hemostáticos para disminuir la transfusión de hemocomponentes en histerectomía total abdominal / Preoperative use of hemostatic drugs to reduce hemocomponent transfusion in total abdominal hysterectomy

Resumen: Introducción: en la actualidad se usan fármacos para disminuir el sangrado transoperatorio, la transfusión de hemoderivados como el ácido tranexámico que es un antifibrinolítico análogo de la lisina y desmopresina que actúa incrementando de forma autóloga el factor VIII y el factor de Von Willebrand (FVW) en individuos sanos. Objetivo: demostrar la eficacia del uso y seguridad del ácido tranexámico vs desmopresina para disminuir la transfusión de hemocomponentes en pacientes sometidos a histerectomía total abdominal electiva. Material y métodos: se estudiaron 72 pacientes, los cuales se dividieron en dos grupos (36 pacientes cada uno) asignados al azar para recibir ácido tranexámico 10 mg/kg de peso o desmopresina 0.3 mg/kg de peso, ambos por vía intravenosa 20 minutos previo al evento quirúrgico. Resultados: en comparación del ácido tranexámico contra desmopresina para la disminución del sangrado transoperatorio, 100% de las pacientes a las que se les administró el ácido tranexámico no requirieron transfusión de hemoderivados y presentado el 100% de efectividad siendo estadísticamente significativos con un valor de p < 0.05. Conclusiones: la administración de ácido tranexámico resultó más eficaz para disminuir la administración de hemoderivados en pacientes sometidos a histerectomía total abdominal electiva. Además, no se presentaron efectos adversos graves durante su administración.

Abstract: Introduction: drugs are currently used to reduce intraoperative bleeding, transfusion of blood products such as tranexamic acid, which is an antifibinolytic lysine analogue, and desmopressin, which acts by autologously increasing factor VIII and VWF in healthy individuals. Objective: demonstrate the efficacy of the use and safety of tranexamic acid vs desmopressin to reduce the transfusion of blood components in patients undergoing elective total abdominal hysterectomy. Material and methods: 72 patients were studied, divided into two groups (36 patients each one) randomly assigned to receive tranexamic acid 10 mg/kg weight or desmopressin 0.3 mg/kg weight, both intravenously 20 minutes prior to the surgical event. Results: the comparison of tranexamic acid against desmopressin for the reduction of intraoperative bleeding, 100% of the patients who were administered tranexamic acid did not require transfusion of blood products and presented 100% effectiveness, being statistically significant with a value of p < 0.05. Conclusions: the administration of tranexamic acid was more effective in reducing the administration of blood products in patients undergoing elective total abdominal hysterectomy.

Review of the Greening Reaction by Thermal Treatment: New Insights Exploring the Structural Implications of Myoglobin.

Myoglobin is the main factor responsible for muscle pigmentation in tuna; muscle color depends upon changes in the oxidative state of myoglobin. The tuna industry has reported muscle greening after thermal treatment involving metmyoglobin (MetMb), trimethylamine oxide (TMAO), and free cysteine (Cys). It has been proposed that this pigmentation change is due to a disulfide bond between a unique cysteine residue (Cys10) found in tuna MetMb and free Cys. However, no evidence has been given to confirm that this reaction occurs. In this review, new findings about the mechanism of this greening reaction are discussed, showing evidence of how free radicals produced from Cys oxidation under thermal treatment participate in the greening of tuna and horse muscle during thermal treatment. In addition, the reaction conditions are compared to other green myoglobins, such as sulfmyoglobin, verdomyoglobin, and cholemyoglobin.

Effectiveness and safety of a cement-on-cement removal system for hip and knee arthroplasty revision surgery.

Cement removal during hip or knee arthroplasty revision is challenging and not exempt of complications. Cement-on-cement procedure is among techniques developed to safe removal of cement from bone, and it could be a realistic solution. This cement-on-cement devices can provide advantages in removing bone cement during hip and knee arthroplasty septic and non-septic revision surgeries, and can be regarded as an effective and safe alternative. We present our experience using the cement-on-cement technique in 34 cases between 2010 and 2021, including revision surgeries for 20 knee and 14 hip arthroplasties. In 3 out of 34 cases the technique failed, with a success of 91%. Mean surgical time was 2.77 (SD 0.93) hours and blood transfusion was required in 23 cases. Success was achieved in every aseptic case. Of all patients, 60% were septic cases. Infection was considered to be eradicated in 70% (14/20) of patients with a septic revision. Cement-on-cement is a safe and effective alternative for cement removal during hip and knee arthroplasty revision. Level of evidence: III, retrospective case series.

A MERS-CoV antibody neutralizes a pre-emerging group 2c bat coronavirus.

The repeated emergence of zoonotic human betacoronaviruses (ß-CoVs) dictates the need for broad therapeutics and conserved epitope targets for countermeasure design. Middle East respiratory syndrome (MERS)-related coronaviruses (CoVs) remain a pressing concern for global health preparedness. Using metagenomic sequence data and CoV reverse genetics, we recovered a full-length wild-type MERS-like BtCoV/li/GD/2014-422 (BtCoV-422) recombinant virus, as well as two reporter viruses, and evaluated their human emergence potential and susceptibility to currently available countermeasures. Similar to MERS-CoV, BtCoV-422 efficiently used human and other mammalian dipeptidyl peptidase protein 4 (DPP4) proteins as entry receptors and an alternative DPP4-independent infection route in the presence of exogenous proteases. BtCoV-422 also replicated efficiently in primary human airway, lung endothelial, and fibroblast cells, although less efficiently than MERS-CoV. However, BtCoV-422 shows minor signs of infection in 288/330 human DPP4 transgenic mice. Several broad CoV antivirals, including nucleoside analogs and 3C-like/Mpro protease inhibitors, demonstrated potent inhibition against BtCoV-422 in vitro. Serum from mice that received a MERS-CoV mRNA vaccine showed reduced neutralizing activity against BtCoV-422. Although most MERS-CoV-neutralizing monoclonal antibodies (mAbs) had limited activity, one anti-MERS receptor binding domain mAb, JC57-11, neutralized BtCoV-422 potently. A cryo-electron microscopy structure of JC57-11 in complex with BtCoV-422 spike protein revealed the mechanism of cross-neutralization involving occlusion of the DPP4 binding site, highlighting its potential as a broadly neutralizing mAb for group 2c CoVs that use DPP4 as a receptor. These studies provide critical insights into MERS-like CoVs and provide candidates for countermeasure development.

Bowel cleansing effectiveness and safety of 1L PEG + Asc in the real-world setting: Observational, retrospective, multicenter study of over 13000 patients.

Background and study aims Effective bowel cleansing is critical for detecting lesions during colonoscopy, highlighting the importance of bowel preparations. 1L polyethylene glycol (PEG) + ascorbate (Asc) is the only recommended 1L PEG product in Europe and the United States. Its efficacy was demonstrated in large-scale controlled trials and confirmed in smaller-scale real-world studies. However, no large-scale real-world data exist. Patients and methods This observational, retrospective, multicenter study, used outpatient follow-up data from medical records from 10 centers in Spain and two in Portugal. Outpatients aged ≥18 years using 1L PEG + Asc as bowel preparation were included. The main outcome measures were overall adequate colon cleansing (Boston Bowel Preparation Scale [BBPS] score ≥6 with BBPS score ≥2 in each segment) and high-quality cleansing of the right colon (BBPS score=3). Results Data from 13169 eligible patients were included. Overall cleansing success was achieved in 89.3% (95%CI 88.7%-89.8%) and high-quality cleansing in the right colon in 49.3% (95%CI 48.4%-50.2%) of patients. For the overnight split-dose and same-day regimens, overall adequate quality cleansing success rate was 94.7% and 86.7% ( P <0.0001) and high-quality cleansing of the right colon rate was 65.4% and 41.4% ( P <0.0001), respectively. Colonoscopy was completed in 97.3% of patients, with non-completion due to poor preparation in only 0.8%; 2.3% of patients experienced at least one adverse event (AE). Conclusions This large-scale, real-world study demonstrates the effectiveness of 1L PEG + Asc in the total and right colon, with a low percentage of patients with AEs in routine clinical practice.

Teorías subjetivas sobre el tiempo de espera y experiencias de la parentalidad adoptiva / Subjective theories about waiting time and experiences from adoptive parenting

Resumen El proceso de adopción comprende cambios importantes en las familias adoptivas, pues implica una reestructuración y adaptación a una nueva organización del sistema familiar. Durante este proceso los padres elaboran expectativas y creencias respecto a cómo comportarse frente a los cambios y adaptarse a sus hijos, desde donde dirigen sus prácticas de crianza. La percepción del tiempo que tenga cada persona posee un papel en cómo se desarrolla la identidad tanto individual como familiar, pues las experiencias pasadas, vivencias actuales y expectativas del futuro influyen en sus acciones. Por lo tanto, es posible decir que los padres adoptivos elaboran teorías subjetivas sobre este proceso y especialmente en relación con el tiempo de espera de la adopción, explicaciones que podrían incidir en la forma en que enfrentan este nuevo desafío y se preparan para la parentalidad. El presente estudio tuvo por objetivo comprender las teorías subjetivas sobre el tiempo de espera y las experiencias de la parentalidad adoptiva. Participaron diez madres y padres adoptivos mediante entrevistas episódicas individuales. Se analizaron los datos obtenidos utilizando técnicas de tres procedimientos de análisis: de contenido basado en la Teoría Fundamentada, específico para las teorías subjetivas y de la perspectiva temporal. De los hallazgos se destacan teorías subjetivas de contenido emocional ansioso durante el proceso de adopción. Además, contar con una red de apoyo, compartir experiencias con otros padres y el uso de estrategias personales son las principales estrategias de adaptación de los padres adoptivos que les permiten sobrellevar los sentimientos negativos durante el proceso.

Abstract The adoption process includes important changes in adoptive families, since it implies a restructuring and adaptation to a new organization of the family system. The path to parenthood entails changes at levels of mental, physical and social health, which in the case of adoptive parents, the challenges are greater or are altered in some way due to the unique characteristics of their experiences and the obstacles they face. To these challenges are added the usual stressors that parents face, such as changes in roles, increased stress, lack of sleep, alterations in the relationship and intimacy of the couple and difficulties that arise in raising their children. On the other hand, time is configured as a concrete dimension through which life develop. The relationship between objective time and subjective or psychological time will shape the perception of time that each person has, which has a role in how both individual and family identity develops. This is because people´s actions are influenced by past experiences, current experiences and future expectations. One of the areas of the adoption process that has not yet been deepened is the waiting time, the period of time between obtaining the suitability and assignment of the minor to the adoptive family, which can be considered important for the future family depending on how adoptive parents face it, this because the way in which the adoption process is experienced impacts both the path to parenthood and post-adoption adaptation. In fact, it confirms that waiting time influences the psychological well-being of adoptive parents. Therefore, it is possible to say that adoptive parents elaborate subjective theories about this process and especially in relation to the waiting time for adoption, explanations that could influence the way in which they face this new challenge and prepare for parenthood. The present study aimed to understand subjective theories about the waiting time and experiences of adoptive parenting. Ten adoptive mothers and fathers participated in this study through individual episodic interviews. The data obtained were analyzed using techniques of three analysis procedures: content based on Grounded Theory, specific for subjective theories and time perspective.

Phosphorylation by ATR triggers FANCD2 chromatin loading and activates the Fanconi anemia pathway.

The Fanconi anemia (FA) pathway repairs DNA interstrand crosslinks (ICLs) in humans. Activation of the pathway relies on loading of the FANCD2/FANCI complex onto chromosomes, where it is fully activated by subsequent monoubiquitination. However, the mechanism for loading the complex onto chromosomes remains unclear. Here, we identify 10 SQ/TQ phosphorylation sites on FANCD2, which are phosphorylated by ATR in response to ICLs. Using a range of biochemical assays complemented with live-cell imaging including super-resolution single-molecule tracking, we show that these phosphorylation events are critical for loading of the complex onto chromosomes and for its subsequent monoubiquitination. We uncover how the phosphorylation events are tightly regulated in cells and that mimicking their constant phosphorylation leads to an uncontrolled active state of FANCD2, which is loaded onto chromosomes in an unrestrained fashion. Taken together, we describe a mechanism where ATR triggers FANCD2/FANCI loading onto chromosomes.

Antibody-mediated immunity against lung cancer goes retro.

Endogenous retrovirus antibody responses contribute to survival after immune checkpoint blockade therapy against lung adenocarcinoma.

Endoscopically Assisted LeFort I Osteotomy for Minimally Invasive Orthognathic Surgery: A Technical Note.

Minimally invasive surgery in orthognathic surgery has gained popularity in recent years. This is mainly due to the benefit to the patient of achieving a better postoperative period and a faster recovery. However, one of the main difficulties is the lack of direct vision, which is a concern for the surgeon. For this reason, this technical note aims to propose endoscopically assisted LeFort I osteotomy for MI orthognathic surgery.

Structural insights into the bi-specific cross-over dual variable antibody architecture by cryo-EM.

Multi-specific antibodies (msAbs) are being developed as next generation antibody-based therapeutics. Knowledge of the three-dimensional structures, in the full antibody context, of their fragment antigen-binding (Fab) moieties with or without bound antigens is key to elucidating their therapeutic efficiency and stability. However, the flexibility of msAbs, a feature essential for their multi specificity, has hindered efforts in this direction. Cross-Over Dual Variable immunoglobulin (CODVIg) is a promising bispecific antibody format, designed to simultaneously target the interleukins IL4 and IL13. In this work we present the biophysical and structural characterisation of a CODVFab:IL13 complex in the full antibody context, using cryo-electron microscopy at an overall resolution of 4.2 Å. Unlike the 1:2 stoichiometry previously observed for CODVIg:IL4, CODVIg:IL13 shows a 1:1 stoichiometry. As well as providing details of the IL13-CODV binding interface, including the residues involved in the epitope-paratope region, the structure of CODVFab:IL13 also validates the use of labelling antibody as a new strategy for the single particle cryo-EM study of msAbs in complex with one, or more, antigens. This strategy reduced the inherent flexibility of the IL13 binding domain of CODV without inducing either structural changes at the epitope level or steric hindrance between the IL4 and IL13 binding regions of CODVIg. The work presented here thus also contributes to the development of methodology for the structural study of msAbs, a promising platform for cancer immunotherapy.

Magnetic resonance imaging findings of spontaneous pyomyoma in a premenopausal woman managed with myomectomy: A case report.

BACKGROUND: Acute fibroid complications are rare. However, failure to recognize and treat acute complications expeditiously when they occur can lead to catastrophic, even deadly, complications. Pyomyoma is a rare but potentially fatal condition resulting from infarction and infection of a fibroid through bacterial seeding and direct, hematogenous, or lymphatic dissemination. Even though the diagnosis is established through clinical and laboratory findings, imaging is an important complementary method to support the suspected diagnosis. CASE SUMMARY: Herein, we report a case of a pyomyoma in a nulliparous woman previously diagnosed with uterine leiomyomatosis according to ultrasound findings. The patient had previously attended the emergency room due to hypogastric pain unresponsive to analgesics. After a week of persistent pain, she developed sepsis without any identifiable foci. Magnetic resonance imaging revealed findings compatible with uterine myomatosis with red degeneration, and a possible diagnosis of a pyomyoma was made according to the imaging findings along with the patient's clinical features. We decided to perform myomectomy (which is an infrequently performed surgical treatment due to the procedure's intrinsic implications) due to the patient's desire to preserve fertility. Histopathologic results revealed a uterine leiomyoma with coagulative and liquefactive necrosis, while the tissue culture showed gram-negative cocci bacteria, which were successfully treated using antibiotic therapy. The patient's health status improved after several days. CONCLUSION: The main diagnostic tools to evaluate pyomyomas are the clinical and laboratory findings as well as tissue cultures. Nonetheless, magnetic resonance imaging can help to corroborate these findings as well as to better characterize myomas with its different complications.

Efficient capture of recombinant SARS-CoV-2 receptor-binding domain (RBD) with citrate-coated magnetic iron oxide nanoparticles.

Several vaccines against COVID-19 use a recombinant SARS-CoV-2 receptor-binding domain (RBD) as antigen, making the purification of this protein a key step in their production. In this work, citrate-coated magnetic iron oxide nanoparticles were evaluated as nano adsorbents in the first step (capture) of the purification of recombinant RBD. The nanoparticles were isolated through coprecipitation and subsequently coated with sodium citrate. The citrate-coated nanoparticles exhibited a diameter of 10 ± 2 nm, a hydrodynamic diameter of 160 ± 3 nm, and contained 1.9 wt% of citrate. The presence of citrate on the nanoparticles' surface was confirmed through FT-IR spectra and thermogravimetric analysis. The crystallite size (10.1 nm) and the lattice parameter (8.3646 Å) were determined by X-ray diffraction. In parallel, RBD-containing supernatant extracted from cell culture was exchanged through ultrafiltration and diafiltration into the adsorption buffer. The magnetic capture was then optimized using different concentrations of nanoparticles in the purified supernatant, and we found 40 mg mL-1 to be optimal. The ideal amount of nanoparticles was assessed by varying the RBD concentration in the supernatant (between 0.113 mg mL-1 and 0.98 mg mL-1), which resulted in good capture yields (between 83 ± 5% and 94 ± 4%). The improvement of RBD purity after desorption was demonstrated by SDS-PAGE and RP-HPLC. Furthermore, the magnetic capture was scaled up 100 times, and the desorption was subjected to chromatographic purifications. The obtained products recognized anti-RBD antibodies and bound the ACE2 receptor, proving their functionality after the developed procedure.

Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians.

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.