Constraints on Neutrino Natal Kicks from Black-Hole Binary VFTS 243.

The recently reported observation of VFTS 243 is the first example of a massive black-hole binary system with negligible binary interaction following black-hole formation. The black-hole mass (≈10M_{⊙}) and near-circular orbit (e≈0.02) of VFTS 243 suggest that the progenitor star experienced complete collapse, with energy-momentum being lost predominantly through neutrinos. VFTS 243 enables us to constrain the natal kick and neutrino-emission asymmetry during black-hole formation. At 68% confidence level, the natal kick velocity (mass decrement) is ≲10 km/s (≲1.0M_{⊙}), with a full probability distribution that peaks when ≈0.3M_{⊙} were ejected, presumably in neutrinos, and the black hole experienced a natal kick of 4 km/s. The neutrino-emission asymmetry is ≲4%, with best fit values of ∼0-0.2%. Such a small neutrino natal kick accompanying black-hole formation is in agreement with theoretical predictions.

Wiring between close nodes in molecular networks evolves more quickly than between distant nodes.

As species diverge, a wide range of evolutionary processes lead to changes in protein-protein interaction networks and metabolic networks. The rate at which molecular networks evolve is an important question in evolutionary biology. Previous empirical work has focused on interactomes from model organisms to calculate rewiring rates, but this is limited by the relatively small number of species and sparse nature of network data across species. We present a proxy for variation in network topology: variation in drug-drug interactions (DDIs), obtained by studying drug combinations (DCs) across taxa. Here, we propose the rate at which DDIs change across species as an estimate of the rate at which the underlying molecular network changes as species diverge. We computed the evolutionary rates of DDIs using previously published data from a high throughput study in gram-negative bacteria. Using phylogenetic comparative methods, we found that DDIs diverge rapidly over short evolutionary time periods, but that divergence saturates over longer time periods. In parallel, we mapped drugs with known targets in protein-protein interaction and co-functional networks. We found that the targets of synergistic DDIs are closer in these networks than other types of DCs and that synergistic interactions have a higher evolutionary rate, meaning that nodes that are closer evolve at a faster rate. Future studies of network evolution may use DC data to gain larger-scale perspectives on the details of network evolution within and between species.

Impact of Recombinant VSV-HIV Prime, DNA-Boost Vaccine Candidates on Immunogenicity and Viremia on SHIV-Infected Rhesus Macaques.

Currently, no effective vaccine to prevent human immunodeficiency virus (HIV) infection is available, and various platforms are being examined. The vesicular stomatitis virus (VSV) vaccine vehicle can induce robust humoral and cell-mediated immune responses, making it a suitable candidate for the development of an HIV vaccine. Here, we analyze the protective immunological impacts of recombinant VSV vaccine vectors that express chimeric HIV Envelope proteins (Env) in rhesus macaques. To improve the immunogenicity of these VSV-HIV Env vaccine candidates, we generated chimeric Envs containing the transmembrane and cytoplasmic tail of the simian immunodeficiency virus (SIV), which increases surface Env on the particle. Additionally, the Ebola virus glycoprotein was added to the VSV-HIV vaccine particles to divert tropism from CD4 T cells and enhance their replications both in vitro and in vivo. Animals were boosted with DNA constructs that encoded matching antigens. Vaccinated animals developed non-neutralizing antibody responses against both the HIV Env and the Ebola virus glycoprotein (EBOV GP) as well as systemic memory T-cell activation. However, these responses were not associated with observable protection against simian-HIV (SHIV) infection following repeated high-dose intra-rectal SHIV SF162p3 challenges.

Assessing Ecogeographic Rules in Two Sigmodontine Rodents along an Elevational Gradient in Central Chile.

Bergmann's and Allen's rules are two classic ecogeographic rules concerning the physiological mechanisms employed by endotherm vertebrates for heat conservation in cold environments, which correlate with adaptive morphological changes. Thus, larger body sizes (Bergmann's rule) and shorter appendages and limbs (Allen's rule) are expected in mammals inhabiting cold environments (higher latitudes). Both rules may also apply to elevational gradients, due to the decrease in external temperature as elevation increases. In this study, we evaluated whether these patterns were true in two coexisting sigmodontine rodents across an elevational gradient in central Chile. We analyzed whether the size of the skull, body, and appendages of Abrothrix olivacea (n = 70) and Phyllotis darwini (n = 58) correlated with elevation, as predicted by these rules in a range between 154 and 2560 m. Our data revealed weak support for the Bergmann and Allen predictions. Moreover, we observed opposite patterns when expectations of Bergmann's rules were evaluated, whereas Allen's rule just fitted for ear size in both rodent species. Our results suggest that morphological changes (cranial, body, and appendage sizes) may play a minor role in the thermoregulation of these two species at high elevations, although behavioral strategies could be more critical. Other ecological and environmental variables could explain the morphological trends observed in our study. These hypotheses should be assessed in future studies to consider the relative contribution of morphology, behavior, and physiological mechanisms to the thermal adaptation of these two rodent species at high elevations.

Autokinesis Reveals a Threshold for Perception of Visual Motion.

In natural viewing conditions, the brain can optimally integrate retinal and extraretinal signals to maintain a stable visual perception. These mechanisms, however, may fail in circumstances where extraction of a motion signal is less viable such as impoverished visual scenes. This can result in a phenomenon known as autokinesis in which one may experience apparent motion of a small visual stimulus in an otherwise completely dark environment. In this study, we examined the effect of autokinesis on visual perception of motion in human observers. We used a novel method with optical tracking in which the visual motion was reported manually by the observer. Experiment results show at lower speeds of motion, the perceived direction of motion was more aligned with the effect of autokinesis, whereas in the light or at higher speeds in the dark, it was more aligned with the actual direction of motion. These findings have important implications for understanding how the stability of visual representation in the brain can affect accurate perception of motion signals.

Injectable Nanoengineered Adhesive Hydrogel for Treating Enterocutaneous Fistulas.

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15-20%, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECF. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECF. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECF. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECF.

Gastric outlet obstruction due to an intragastric balloon in a patient returning from the Caribbean.

Key Clinical Message: Gastric outlet obstruction can be a dangerous complication of intragastric balloons, as it can result in severe metabolic alkalosis. As weight loss procedures and medical tourism become more popular, physicians should have a high index of suspicion for complications of invasive procedures, particularly in returning travelers. Abstract: Intragastric balloons for weight loss have decreased in frequency in the United States. However, they are still frequent in low- and middle-income countries. Severe complications occur in less than 3% of patients who undergo this procedure. Herein, we present a case of gastric outlet obstruction, severe metabolic alkalosis, and refeeding syndrome in a patient returning from the Dominican Republic. She presented with 2 weeks of emesis and obstipation, followed by a pre-syncope and altered mental status. An intragastric mass was observed on computerized tomography, which was characterized as an intragastric balloon and retrieved endoscopically. All metabolic derangements were corrected, and the patient improved without sequelae. As weight loss procedures and medical tourism become more popular, physicians should have a high index of suspicion for complications of invasive procedures, particularly in returning travelers.

Outcomes after surgical revascularization in diabetic patients.

OBJECTIVES: Patients with diabetes mellitus (DM) undergoing coronary artery bypass grafting (CABG) have been repeatedly demonstrated to have worse clinical outcomes compared to patients without DM. The objective of this study was to evaluate the impact of DM on 1-year clinical outcomes after isolated CABG. METHODS: The European DuraGraft registry included 1130 patients (44.6%) with and 1402 (55.4%) patients without DM undergoing isolated CABG. Intra-operatively, all free venous and arterial grafts were treated with an endothelial damage inhibitor. Primary end point in this analysis was the incidence of a major adverse cardiac event (MACE), a composite of all-cause death, repeat revascularization or myocardial infarction at 1 year post-CABG. To balance between differences in baseline characteristics (n = 1072 patients in each group), propensity score matching was used. Multivariable Cox proportional hazards regression was performed to identify independent predictors of MACE. RESULTS: Diabetic patients had a higher cardiovascular risk profile and EuroSCORE II with overall more comorbidities. Patients were comparable in regard to surgical techniques and completeness of revascularization. At 1 year, diabetics had a higher MACE rate {7.9% vs 5.5%, hazard ratio (HR) 1.43 [95% confidence interval (CI) 1.05-1.95], P = 0.02}, driven by increased rates of death [5.6% vs 3.5%, HR 1.61 (95% CI 1.10-2.36), P = 0.01] and myocardial infarction [2.8% vs 1.4%, HR 1.99 (95% CI 1.12-3.53) P = 0.02]. Following propensity matching, no statistically significant difference was found for MACE [7.1% vs 5.7%, HR 1.23 (95% CI 0.87-1.74) P = 0.23] or its components. Age, critical operative state, extracardiac arteriopathy, ejection fraction ≤50% and left main disease but not DM were identified as independent predictors for MACE. CONCLUSIONS: In this study, 1-year outcomes in diabetics undergoing isolated CABG were comparable to patients without DM.

Interatrial Septum Stenting for Hypoplastic Left Heart Syndrome in Ex Utero Intrapartum Therapy.

Patients with hypoplastic left heart syndrome (HLHS) with intact atrial septum have an increased mortality rate. This presentation occurs in 6% to 10% of cases. We present a patient with fetal diagnosis of HLHS with restrictive atrial septum. We performed a cesarean section at 37 weeks of gestation, and under ex utero intrapartum treatment proceeded with a median sternotomy and transatrial stenting for left atrial decompression due to findings of intact atrial septum on the fetal echocardiogram performed during the procedure. Subsequently, the patient underwent hybrid stage I palliation followed by a comprehensive stage II procedure at five months of age, but unfortunately died from postoperative complications.

Amphotericin B-loaded natural latex dressing for treating Candida albicans wound infections using Galleria mellonella model.

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.

Anti-Citrullinated Protein Antibodies With Multiple Specificities Ameliorate Collagen Antibody-Induced Arthritis in a Time-Dependent Manner.

OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and have long been regarded as pathogenic. Despite substantial in vitro evidence supporting this claim, reports investigating the proinflammatory effects of ACPAs in animal models of arthritis are rare and include mixed results. Here, we sequenced the plasmablast antibody repertoire of a patient with RA and functionally characterized the encoded ACPAs. METHODS: We expressed ACPAs from the antibody repertoire of a patient with RA and characterized their autoantigen specificities on antigen arrays and enzyme-linked immunosorbent assays. Binding affinities were estimated by bio-layer interferometry. Select ACPAs (n = 9) were tested in the collagen antibody-induced arthritis (CAIA) mouse model to evaluate their effects on joint inflammation. RESULTS: Recombinant ACPAs bound preferentially and with high affinity (nanomolar range) to citrullinated (cit) autoantigens (primarily histones and fibrinogen) and to auto-cit peptidylarginine deiminase 4 (PAD4). ACPAs were grouped for in vivo testing based on their predominant cit-antigen specificities. Unexpectedly, injections of recombinant ACPAs significantly reduced paw thickness and arthritis severity in CAIA mice as compared with isotype-matched control antibodies (P ≤ 0.001). Bone erosion, synovitis, and cartilage damage were also significantly reduced (P ≤ 0.01). This amelioration of CAIA was observed for all the ACPAs tested and was independent of cit-PAD4 and cit-fibrinogen specificities. Furthermore, disease amelioration was more prominent when ACPAs were injected at earlier stages of CAIA than at later phases of the model. CONCLUSION: Recombinant patient-derived ACPAs ameliorated CAIA. Their antiinflammatory effects were more preventive than therapeutic. This study highlights a potential protective role for ACPAs in arthritis.

Pllans-II: Unveiling the Action Mechanism of a Promising Chemotherapeutic Agent Targeting Cervical Cancer Cell Adhesion and Survival Pathways.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient's quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans-II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans-II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α5ß1 integrins and fibronectin of the extracellular matrix. Pllans-II reduces the cells' ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans-II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

Exploring the Safety of Pllans-II and Antitumoral Potential of Its Recombinant Isoform in Cervical Cancer Therapy.

The antitumor potential of proteins from snake venoms has been studied in recent decades, and evidence has emerged that phospholipases A2 can selectively attack cells of various types of tumors. Previous results have shown that phospholipase A2 "Pllans-II," isolated from Porthidium lansbergii lansbergii snake venom, displayed antitumoral activity on cervical cancer and did not alter the viability of non-tumorigenic cells. However, until now, there was no evidence of its safety at the local and systemic levels, nor had experiments been developed to demonstrate that its production using recombinant technology allows us to obtain a molecule with effects similar to those generated by native phospholipase. Thus, we evaluated the impact caused by Pllans-II on murine biomodels, determining whether it induced local hemorrhage or increased pro-inflammatory and liver damage markers and histological alterations in the liver and kidneys. Additionally, the protein was produced using recombinant technology using a pET28a expression vector and the BL21 (DE3) Escherichia coli strain. Equally, its enzymatic activity and anticancer effect were evaluated on cervical cancer lines such as HeLa and Ca Ski. The results demonstrated that Pllans-II did not generate hemorrhagic activity, nor did it increase the pro-inflammatory cytokines IL-6, IL-1B, or TNF-α at doses of 3.28, 1.64, and 0.82 mg/kg. There was also no evidence of organ damage, and only ALT and AST increased in mild levels at the two highest concentrations. Additionally, the recombinant version of Pllans-II showed conservation in its catalytic activity and the ability to generate death in HeLa and Ca Ski cells (42% and 23%, respectively). These results demonstrate the innocuity of Pllans-II at the lowest dose and constitute an advance in considering a molecule produced using recombinant technology a drug candidate for selective attacks against cervical cancer.

Seroprevalencia del SARS-CoV-2 en los pacientes con enfermedades inmunomediadas en tratamiento con terapias biológicas y sintéticos dirigidos

Introducción: La seroprevalencia del SARS-CoV-2 en las enfermedades inflamatorias inmunomediadas (IMID) sigue siendo fuente de controversia. Objetivo: Comparar la seroprevalencia de anticuerpos (Ac) anti SARS-CoV-2 en pacientes con IMID en tratamientos con fármacos antirreumáticos modificadores de la enfermedad biológicos (FAMEb) o sintéticos dirigidos (FAMEsd) frente a un grupo de personas sin IMID. Métodos: Estudio de pacientes con IMID y tratamientos con FAMEb y FAMEsd y de individuos sin IMID. Mediante la técnica de inmunoensayo por quimioluminiscencia indirecta, se determinaron las serologías IgG frente al SARS-CoV-2 entre octubre/2020 y mayo/2021. Resultados: Se estudiaron 1.100 sujetos, 550 pacientes con IMID y 550 personas sin IMID. Se observó una seroprevalencia de 16% (88/550) en los pacientes frente a 19,3% (106/550) en el grupo de personas sin IMID, sin significación estadística (OR 0,790 [IC 95% 0,558-1,118]). Comparando los tratamientos con FAMEb o FAMEsd, se observó una tendencia a una menor seroprevalencia con rituximab, en relación con los individuos sin IMID (OR 0,296 [IC 95% 0,0871,007]). Asimismo, se encontró menor seroprevalencia en los pacientes que además de su FAMEb recibían tratamiento con metotrexato, en comparación con el grupo de personas sin IMID (OR 0,432 [IC 95% 0,223-0,835]). Conclusiones: Las IMID en tratamiento con FAMEb o FAMEsd no influyen en la seroprevalencia frente al SARS-CoV-2 de los pacientes. El tratamiento concomitante con metotrexato disminuye de forma significativa la seroprevalencia en estos pacientes.

Background: The seroprevalence of SARS-CoV-2 in immunemediated inflammatory diseases (IMID) remains controversial. Aim: To compare the seroprevalence of antibodies (Ab) to SARS-CoV-2 in patients with IMID receiving treatment with biological diseasemodifying antirheumatic drugs (bDMARD) or targeted synthetic (tsDMARD) versus a group of people without IMID. Methods: Study of patients with IMID and treatments with bDMARD and tsDMARD and individuals without IMID. IgG serology against SARS-CoV-2 was measured using the two-step sandwich immunoassay technique by indirect chemiluminescence between October 2020 and May 2021. Results: A total of 1100 subjects were studied, 550 patients with IMID and 550 persons without IMID. A seroprevalence of 16% (88/550) was observed in patients versus 19.3% (106/550) in the group of people without IMID, without statistical significance (OR 0.790 [95% CI 0.558-1.118]). Comparing the treatments with bD- MARD or tsDMARD, there was a tendency to lower seroprevalence with rituximab, in relation to individuals without IMID (OR 0.296 [95% CI 0.087-1.007]). In addition, lower seroprevalence was found in patients who received methotrexate treatment in addition to their bDMARD, compared to the group of individuals without IMID (OR 0.432 [95% CI 0.223-0.835]). Conclusions: IMIDs in treatment with bDMARDs or tsDMARDs do not influence the seroprevalence against SARS-CoV-2 in patients. Concomitant treatment with methotrexate significantly decreased seroprevalence in these patients.

Robotic Navigation Autonomy for Subretinal Injection via Intelligent Real-Time Virtual iOCT Volume Slicing.

In the last decade, various robotic platforms have been introduced that could support delicate retinal surgeries. Concurrently, to provide semantic understanding of the surgical area, recent advances have enabled microscope-integrated intraoperative Optical Coherent Tomography (iOCT) with high-resolution 3D imaging at near video rate. The combination of robotics and semantic understanding enables task autonomy in robotic retinal surgery, such as for subretinal injection. This procedure requires precise needle insertion for best treatment outcomes. However, merging robotic systems with iOCT introduces new challenges. These include, but are not limited to high demands on data processing rates and dynamic registration of these systems during the procedure. In this work, we propose a framework for autonomous robotic navigation for subretinal injection, based on intelligent real-time processing of iOCT volumes. Our method consists of an instrument pose estimation method, an online registration between the robotic and the iOCT system, and trajectory planning tailored for navigation to an injection target. We also introduce intelligent virtual B-scans, a volume slicing approach for rapid instrument pose estimation, which is enabled by Convolutional Neural Networks (CNNs). Our experiments on ex-vivo porcine eyes demonstrate the precision and repeatability of the method. Finally, we discuss identified challenges in this work and suggest potential solutions to further the development of such systems.

Heart Transplantation in a Patient With a Heterotopic Percutaneous Tricuspid Valve Prosthesis: A Case Report.

The bicaval transcatheter prosthesis (TricValve) allows the treatment of cava reflux in patients with severe tricuspid regurgitation and high surgical risk. It consists of the implantation of 2 self-expanding valves in both vena cava without directly approaching the native tricuspid valve. Heart transplantation in this setting may require some modifications compared with the conventional bicaval technique. We describe the clinical case of a 69-year-old woman with a background of rheumatic mitral valve disease who required a mitral valve replacement a few decades before. Ongoing clinical deterioration with biventricular dysfunction and severe tricuspid regurgitation was treated with a percutaneous bicaval heterotopic self-expanding valve system, with no clinical benefit. The patient underwent an elective heart transplantation. For the surgical approach, venous cannulation was performed percutaneously for both the right internal jugular and right femoral vein. Due to the impossibility of extracting percutaneous caval valves, the biatrial technique was selected for heart implantation. The postoperative course was difficult, but the patient was successfully discharged home 2 months postoperatively. She remains in good clinical condition with normal heart function 1 year after the transplant. To our knowledge, this is the first report describing a heart transplant in a patient with a bicaval transcatheter prosthesis.

Heart Transplantation and Thromboembolic Risk In Patients With Percutaneous Aortic Valve Prosthesis and Left Ventricular Assist Device: A Case Report.

Transcatheter aortic valve replacements have become a good option for patients with aortic valve disease and high surgical risk. Thromboembolism is reported as a relatively common complication of Transcatheter aortic valve replacement. This risk may be increased in patients who have left ventricular assist devices, as valve motion is drastically reduced. We present the case of a 65-year-old man with a history of alcoholism and valvular cardiomyopathy (severe chronic aortic insufficiency) with severe left ventricular dysfunction. Improvement in ventricular function followed the cessation of alcohol consumption, but still in poor clinical condition. Due to his high surgical risk, it was decided to implant a percutaneous aortic valve to treat the valve deficiency. Two months later, he suffered from a first episode of embolic stroke, which he successfully recovered. Despite the treatment, his clinical status did not improve (INTERMACS 3-4), and he was referred for heart transplantation. A left ventricular assist device was implanted as a bridge to the transplant. While on the waiting list, he suffered from other 3 episodes of stroke, 2 of them requiring mechanical thrombectomy. Finally, his transplant was performed with a favorable postoperative clinical course. Heart transplantation may be feasible in patients with multiple intracardiac devices in left chambers, although we must be aware of the increased thromboembolic risk, especially when used in combination.

Management of the axial modulation of the illumination pattern in structured illumination microscopy using an extended illumination source.

We have designed and implemented an approach for three-dimensional (3D) structured illumination (SI) microscopy (SIM) based on a quasi-monochromatic extended source illuminating a Wollaston prism to improve robustness, light efficiency and flexibility over our previous design. We show through analytical and experimental verification of the presented theoretical framework for our proposed tunable structured illumination microscopy (TSIM) system, that a simple and accurate determination of the axial modulation of the SI pattern is achieved, enabling a realistic characterization of the system's effective optical transfer function (OTF). System performance as a function of the extended source size is investigated with simulations. Results from a comparative performance analysis of the proposed TSIM system and traditional SIM systems show some advantages over the traditional two-wave and three-wave interference SIM systems. We show that by controlling the source size and thereby the axial modulation of the 3D SI pattern, the TSIM scheme offers increased OTF compact support and improved optical sectioning capability, quantified by the integrated intensity, under certain conditions, which may be desirable when imaging optically thick samples. The additional tunability of the 3D SI pattern, provides a unique opportunity for OTF engineering in our TSIM system.

SER recommendations for the treatment of uveitis.

OBJECTIVE: To develop evidence-based expert-consensus recommendations for the management of non-infectious, non-neoplastic, non-demyelinating disease associated uveitis. METHODS: Clinical research questions relevant to the objective of the document were identified, and reformulated into PICO format (patient, intervention, comparison, outcome) by a panel of experts selected based on their experience in the field. A systematic review of the available evidence was conducted, and evidence was graded according to GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria. Subsequently, recommendations were developed. RESULTS: Three PICO questions were constructed referring to uveitis anterior, non-anterior and complicated with macular edema. A total of 19 recommendations were formulated, based on the evidence found and/or expert consensus. CONCLUSIONS: Here we present the first official recommendations of the Spanish Society of Rheumatology for the treatment of non-infectious and non-demyelinating disease associated uveitis. They can be directly applied to the Spanish healthcare system as a tool for assistance and therapeutic homogenisation.

Impact of environmental factors on the epidemiology of eosinophilic esophagitis in southwestern Europe (2007-2020).

Background: Eosinophilic esophagitis (EoE) is a disease characterized by symptoms of esophageal dysfunction and at least 15 eosinophils/hpf in the esophagus. Other systemic and local causes of esophageal eosinophilia should be excluded. Objectives: The study objectives were to examine the annual epidemiology of EoE for 14 consecutive years, investigate whether there is a relationship between the count of aeroallergens and the incidence of EoE for 12 years, evaluate whether there are family ties between the patients with EoE, and determine whether there are cases of EoE that are triggered or exacerbated by pollens. Methods: We conducted a prospective, descriptive, and analytic study in patients with EoE for 14 years (2007-2020). The study variables were age, sex, relatives with EoE, time of evolution of the symptoms until diagnosis of the disease, and symptoms. We examined incidence and prevalence, annual counts of aeroallergens for 12 years, and number of diagnoses per year (in 2007-2020). We studied patients with active EoE (in April-July) and EoE in remission (in August-March) for 2 consecutive years. Exacerbations were investigated by measuring symptoms using a visual analog scale of 1 to 10. Results: Of the 366 patients with EoE (studied from 2007 to 2020), 83.5% were atopic, with respiratory allergy and 28% had a food allergy. Their mean age was 35 years. The time of evolution of the symptoms was more than 6 years. Only 11% of the patients had a degree of kinship. Of the 366 patients, 87% had dysphagia, 27% had had impactions, and 12.5% had other symptoms of esophageal dysfunction. We found a positive correlation between the incidence of EoE and Platanaceae pollens. We did not detect any case of EoE triggered or exacerbated by pollens. Conclusions: The epidemiology of EoE in southwestern Europe continues to grow. We have corroborated the relevant impact of the environment on genetics. Future studies will clarify the possible relevance of Platanaceae pollens in the increased epidemiology of EoE. The role of grass and Oleaceae pollens in triggering EoE is limited by having a short pollination in time.