Sculpting photoproducts with DNA origami.

Natural light-harvesting systems spatially organize densely packed dyes in different configurations to either transport excitons or convert them into charge photoproducts, with high efficiency. In contrast, artificial photosystems like organic solar cells and light-emitting diodes lack this fine structural control, limiting their efficiency. Thus, biomimetic multi-dye systems are needed to organize dyes with the sub-nanometer spatial control required to sculpt resulting photoproducts. Here, we synthesize 11 distinct perylene diimide (PDI) dimers integrated into DNA origami nanostructures and identify dimer architectures that offer discrete control over exciton transport versus charge separation. The large structural-space and site-tunability of origami uniquely provides controlled PDI dimer packing to form distinct excimer photoproducts, which are sensitive to interdye configurations. In the future, this platform enables large-scale programmed assembly of dyes mimicking natural systems to sculpt distinct photophysical products needed for a broad range of optoelectronic devices, including solar energy converters and quantum information processors.

The roles of gene duplications in the dynamics of evolutionary conflicts.

Evolutionary conflicts occur when there is antagonistic selection between different individuals of the same or different species, life stages or between levels of biological organization. Remarkably, conflicts can occur within species or within genomes. In the dynamics of evolutionary conflicts, gene duplications can play a major role because they can bring very specific changes to the genome: changes in protein dose, the generation of novel paralogues with different functions or expression patterns or the evolution of small antisense RNAs. As we describe here, by having those effects, gene duplication might spark evolutionary conflict or fuel arms race dynamics that takes place during conflicts. Interestingly, gene duplication can also contribute to the resolution of a within-locus evolutionary conflict by partitioning the functions of the gene that is under an evolutionary trade-off. In this review, we focus on intraspecific conflicts, including sexual conflict and illustrate the various roles of gene duplications with a compilation of examples. These examples reveal the level of complexity and the differences in the patterns of gene duplications within genomes under different conflicts. These examples also reveal the gene ontologies involved in conflict and the genomic location of the elements of the conflict. The examples provide a blueprint for the direct study of these conflicts or the exploration of the presence of similar conflicts in other lineages.

Residential proximity to oil and gas developments and childhood cancer survival.

BACKGROUND: Environmental toxicants may impact survival in children with cancer, but the literature investigating these associations remains limited. Because oil and gas developments emit several hazardous air pollutants, the authors evaluated the relationship between residential proximity to oil or gas development and survival across 21 different pediatric cancers. METHODS: The Texas Cancer Registry had 29,730 children (≤19 years old) diagnosed with a primary cancer between 1995 to 2017. Geocoded data were available for 285,266 active oil or gas wells and 109,965 horizontal wells. The authors calculated whether each case lived within 1000 m (yes/no) from each type of oil or gas development. Survival analyses were conducted using Cox regression, adjusting for potential confounders. RESULTS: A total of 14.2% of cases lived within 1000 m of an oil or gas well or horizontal well. Living within 1000 m of an oil or gas well was associated with risk of mortality in cases with acute myeloid leukemia (AML) (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.01-1.84) and hepatoblastoma (aHR, 2.13; 95% CI, 1.03-4.39). An inverse association was observed with Ewing sarcoma (aHR, 0.35; 95% CI, 0.13-0.95). No associations were observed with horizontal well. There was evidence of a dose-response effect in children with AML or hepatoblastoma and residential proximity to oil or gas wells. In general, the magnitude of association increased with decreasing distance and with higher number of wells across the three distances. CONCLUSIONS: Residential proximity to oil or gas wells at diagnosis is associated with the risk of mortality in children with AML or hepatoblastoma.

Nectar and floral morphology differ in evolutionary potential in novel pollination environments.

Plants can evolve rapidly after pollinator changes, but the response of different floral traits to novel selection can vary. Floral morphology is often expected to show high integration to maintain pollination accuracy, while nectar traits can be more environmentally sensitive. The relative role of genetic correlations and phenotypic plasticity (PP) in floral evolution remains unclear, particularly for nectar traits, and can be studied in the context of recent pollinator changes. Digitalis purpurea shows rapid recent evolution of corolla morphology but not nectar traits following a range expansion with hummingbirds added as pollinators. We use this species to compare PP, heritability, evolvability and integration of floral morphology and nectar in a common garden. Morphological traits showed higher heritability than nectar traits, and the proximal section of the corolla, which regulates access to nectar and underwent rapid change in introduced populations, presented lower integration than the rest of the floral phenotype. Nectar was more plastic than morphology, driven by highly plastic sugar concentration. Nectar production rate showed high potential to respond to selection. These results explain the differential rapid evolution of floral traits previously observed in this species and show how intrafloral modularity determines variable evolutionary potential in morphological and nectar traits.

M. tuberculosis Infection Attributable to Exposure in Social Networks of Tuberculosis Cases in an Urban African Community.

Background: The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas. Methods: To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis. Results: Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3-1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure. Conclusions: This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.

Ultrathin-strut versus thin-strut stent healing and outcomes in preclinical and clinical subjects.

BACKGROUND: Compared with thin-strut durable-polymer drug-eluting stents (DP-DES), ultrathin-strut biodegradable-polymer sirolimus-eluting stents (BP-SES) improve stent-related clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). Reduced stent strut thickness is hypothesised to underlie these benefits, but this conjecture remains unproven. AIMS: We aimed to assess the impact of strut thickness on stent healing and clinical outcomes between ultrathin-strut and thin-strut BP-SES. METHODS: First, we performed a preclinical study of 8 rabbits implanted with non-overlapping thin-strut (diameter/thickness 3.5 mm/80 µm) and ultrathin-strut (diameter/thickness 3.0 mm/60 µm) BP-SES in the infrarenal aorta. On day 7, the rabbits underwent intravascular near-infrared fluorescence optical coherence tomography (NIRF-OCT) molecular-structural imaging of fibrin deposition and stent tissue coverage, followed by histopathological analysis. Second, we conducted an individual data pooled analysis of patients enrolled in the BIOSCIENCE and BIOSTEMI randomised PCI trials treated with ultrathin-strut (n=282) or thin-strut (n=222) BP-SES. The primary endpoint was target lesion failure (TLF) at 1-year follow-up, with a landmark analysis at 30 days. RESULTS: NIRF-OCT image analyses revealed that ultrathin-strut and thin-strut BP-SES exhibited similar stent fibrin deposition (p=0.49) and percentage of uncovered stent struts (p=0.63). Histopathological assessments corroÂborated these findings. In 504 pooled randomised trial patients, TLF rates were similar for those treated with ultrathin-strut or thin-strut BP-SES at 30-day (2.5% vs 1.8%; p=0.62) and 1-year follow-up (4.3% vs 4.7%; p=0.88). CONCLUSIONS: Ultrathin-strut and thin-strut BP-SES demonstrate similar early arterial healing profiles and 30-day and 1-year clinical outcomes.

Beneficios de la descompresión y enucleación en lesiones quísticas de gran tamaño en la mandíbula / Benefits of decompression and enuclation in large cystic lesions in the jaw / Benefícios da descompressão e enuclação nas grandes lesões císticas na mandíbula

Las lesiones quísticas ocurren en los maxilares, por la presencia de células remanentes del neuroectodermo embrionario. La descompresión es una técnica conservadora para disminuir la presión intraquística mediante drenaje constante, permitiendo el crecimiento de nuevo hueso centrípeto de las paredes óseas del quiste. Objetivo: determinar los beneficios de la descompresión y enucleación en lesiones quísticas mandibulares, tomando como base la metodología de un caso clínico. Descripción del caso: se diagnosticó una lesión quística mandibular en paciente masculino de 27 años, que acudió a consulta mostrando secreción purulenta en mucosa trígono retromolar de UD 37, inicialmente asintomática. Se utilizaron como materiales la tomográfica computarizada de haz cónico, artefacto de drenaje autocurado, hemiarcada izquierda elaborada con Metil Metacrilato y aparato a base de cilindro. Como resultados se reveló imagen hipodensa de bordes definidos localizada en el límite posterior de cuerpo mandibular, borde anterior y parte de la rama ascendente mandibular del lado izquierdo; extendida en sentido cefálico caudal desde la cresta alveolar y borde anterior de la rama hasta la cortical superior del conducto mandibular. Conclusión: Se confirmó diagnóstico de quiste periapical, quiste residual y ameloblastoma. Se realizó biopsia incisional de la lesión para estudio histopatológico y la descompresión con dispositivo personalizado a enucleación conminada con solución de Carnoy, resultando el tratamiento conservador efectivo complementado por la enucleación de una membrana quística más gruesa y menos friable.

Cystic lesions occur in the jaws due to the presence of remnant cells of the embryonic neuroectoderm. Decompression is a conservative technique to decrease intracystic pressure by constant drainage, allowing the growth of new centripetal bone from the bony walls of the cyst. Objective: to determine the benefits of decompression and enucleation in mandibular cystic lesions, based on the methodology of a clinical case. Case description: a cystic mandibular lesion was diagnosed in a 27 year old male patient, who came for consultation showing purulent secretion in the trigone retromolar mucosa of UD 37, initially asymptomatic. The materials used were cone beam computed tomography, self-curing drainage device, left hemiarch made with Methyl Methacrylate and cylinder based apparatus. The results revealed a hypodense image with defined borders located in the posterior limit of the mandibular body, anterior border and part of the ascending mandibular branch on the left side; extended in a caudal cephalic direction from the alveolar crest and anterior border of the branch to the superior cortical of the mandibular duct. Conclusion: Diagnosis of periapical cyst, residual cyst and ameloblastoma was confirmed. An incisional biopsy of the lesion was performed for histopathological study and decompression with a customized device to enucleation with Carnoy's solution, resulting in effective conservative treatment complemented by enucleation of a thicker and less friable cystic membrane.

As lesões císticas ocorrem nos maxilares, devido à presença de células remanescentes da neuroectoderme embrionária. A descompressão é uma técnica conservadora que visa reduzir a pressão intracística por meio de drenagem constante, permitindo o crescimento de novo osso centrípeto a partir das paredes ósseas do cisto. Objetivo: determinar os benefícios da descompressão e da enucleação em lesões císticas mandibulares, com base na metodologia de um caso clínico. Descrição do caso: foi diagnosticada uma lesão cística mandibular em um paciente do sexo masculino, 27 anos, que se apresentou para consulta apresentando secreção purulenta na mucosa do trígono retromolar do UD 37, inicialmente assintomática. Os materiais utilizados foram tomografia computadorizada de feixe cônico, dispositivo de drenagem autopolimerizável, hemiarco esquerdo confeccionado com metacrilato de metila e aparelho de base cilíndrica. Os resultados revelaram uma imagem hipodensa com limites definidos localizada no limite posterior do corpo mandibular, bordo anterior e parte do ramo mandibular ascendente do lado esquerdo; estendendo-se em direção cefálica caudal desde a crista alveolar e bordo anterior do ramo até ao córtex superior do ducto mandibular. Conclusão: Foi confirmado o diagnóstico de quisto periapical, quisto residual e ameloblastoma. Foi efectuada uma biopsia incisional da lesão para estudo histopatológico e descompressão com um dispositivo adaptado à enucleação cominutiva da solução de Carnoy, resultando num tratamento conservador eficaz complementado pela enucleação de uma membrana quística mais espessa e menos friável.

Microfilaremic infection in canine filariosis in Colombia: a challenge in morphological and molecular diagnostics.

Canine filariosis is caused by filiform nematodes and affects several species of animals as well as humans. The disease produces a wide range of symptoms that can often be confused with other diseases, which increases the complexity of its diagnosis. The search for methodologies to facilitate its diagnosis is a challenge, and specific and differential identification of the parasite species causing the disease holds key to a successful diagnosis. In Colombia, there is a problem of underdiagnosis of filariosis in microfilaremic dogs infected by Dirofilaria immitis and Acanthocheilonema reconditum, and of microfilaremias not related to heartworm disease. The highest prevalences have been reported for D. immitis infections, although new cases of A. reconditum infections are beginning to appear. The aim of this study was to differentiate the microfilariae infections caused by D. immitis and A. reconditum by a morphological and molecular characterization of microfilariae so as to facilitate an accurate diagnosis of canine filariosis in the metropolitan area of Bucaramanga (Colombia). For this purpose, 400 blood samples with anticoagulants were collected from the dogs and analyzed with the help of a commercial immunochromatography kit for the detection of D. immitis circulating antigen. The Woo, Knott, and polymerase chain reaction (PCR) techniques were employed for determining the parasite count, morphological observation, and molecular identification of microfilariae present in the dogs respectively. The prevalence of microfilaremic dogs in Bucaramanga metropolitan area was 18.75% (75/400). The prevalence of dogs that tested positive for D. immitis in the antigen and in PCR tests was 1.25% (5/400) and 1% (4/400), respectively. Furthermore, the PCR test revealed that 17.75% of the microfilaremic dogs tested positive for A. reconditum (71/400) (first report in the metropolitan area of Bucaramanga), with one animal co-infected by both species, and 0% for D. repens (0/400). However, by morphological characterization, 4% of the microfilariae (3/75) corresponded to D. immitis, 20% (15/75) to D. repens, and 76% (57/75) to A. reconditum. The use of molecular diagnostic methods such as PCR aids in the specific identification of the parasite, thus making it a more accurate method than the morphological characterization of microfilariae. The identification of the parasites by PCR helps improve the veterinary diagnosis of canine filariosis in Colombia, which would lead to the establishment of an appropriate treatment protocol for each species of filaria and also to the generation of reliable data to be used at the clinical and epidemiological levels.

Documento de consenso de la Sociedad Española de Obstetricia y Ginecologia (SEGO)y el Comité Español Interdisciplinario para la Prevención Vascular (CEIPV). Ventanade oportunidad: prevención del riesgo vascular en la mujer. Resultados adversos delembarazo y riesgo de enfermedad vascular* / Consensus document from the Spanish Society of Obstetrics and Gynecology (SEGO) and the Spanish Interdisciplinary Committee for Vascular Prevention (CEIPV). Window of opportunity: vascular risk prevention in women. Adverse pregnancy outcomes and risk of vascular diseas

Este documento resume la evidencia que existe entre los resultados adversos del embarazo (RAE) y el riesgo que tiene una persona gestante de desarrollar factores de riesgo vascular (RV) que pueden terminar provocando enfermedad vascular (EV) futura. Asimismo, este documento destaca la importancia de saber reconocer los RAE cuando se evalúa el RV en mujeres. Un antecedente de RAE es un indicador suficiente para hacer una prevención primaria de EV. De hecho, adoptar una dieta saludable y aumentar la actividad física entre las mujeres con RAE, de inicio en el embarazo o en el posparto y manteniéndolas a lo largo de la vida, son intervenciones importantes que permiten disminuir el RV. Por otro lado, la lactancia materna también puede disminuir el RV posterior de la mujer, incluyendo menos riesgo de mortalidad. Estudios futuros que evalúen el uso del ácido acetilsalicílico, las estatinas y la metformina, entre otros, en las mujeres con antecedentes de RAE podrían reforzar las recomendaciones sobre el uso de la farmacoterapia en la prevención primaria de la EV entre estas pacientes. Existen diferentes opciones dentro de los sistemas de salud para mejorar la transición de la atención de las mujeres con RAE entre los diferentes profesionales e implementar estrategias para reducir su RV a largo plazo. Una posible estrategia podría ser la incorporación del concepto del cuarto trimestre en las recomendaciones clínicas y las políticas de atención de la salud.(AU)

This document summarises the evidence regarding the association between adverse pregnancy outcomes (APOs),such as hypertensive disorders, preterm birth, gestational diabetes, fetal growth defects (small for gestational ageand/or fetal growth restriction), placental abruption, fetal loss, and the risk that a pregnant individual in developingvascular risk factors (VR) that may lead to future vascular disease (VD): coronary heart disease, stroke, peripheralvascular disease, and heart failure. Furthermore, this document emphasises the importance of recognising APOswhen assessing VR in women. A history of APOs serves as a sufficient indicator for primary prevention of VD. In fact,adopting a healthy diet and increasing physical activity among women with APOs, starting during pregnancy and/or postpartum, and maintaining it throughout life are significant interventions that can reduce VR. On the otherhand, breastfeeding can also reduce the future VR of women, including a lower risk of mortality. Future studies evaluating the use of aspirin, statins, and metformin, among others, in women with a history of APOscould strengthen recommendations regarding pharmacotherapy for primary prevention of VD in these patients.Various healthcare system options exist to improve the transition of care for women with APOs between differenthealthcare professionals and implement long-term VR reduction strategies. One potential process could involveincorporating the fourth-trimester concept into clinical recommendations and healthcare policies.(AU)

Next-generation vaccines for tropical infectious diseases.

Tropical infectious diseases inflict an unacceptable burden of disease on humans living in developing countries. Although anti-pathogenic drugs have been widely used, they carry a constant threat of selecting for resistance. Vaccines offer a promising means by which to enhance the global control of tropical infectious diseases; however, these have been difficult to develop, mostly because of the complex nature of the pathogen lifecycles. Here, we present recently developed vaccine candidates for five tropical infectious diseases in the form of a catalog that have either entered clinical trials or have been licensed for use. We deliberate on recently licensed dengue vaccines, provide evidence why combination vaccination could have a synergistic impact on schistosomiasis, critically appraise the value of typhoid conjugate vaccines, and discuss the potential of vaccines in the efforts to eliminate vivax malaria and hookworms.

Morphological Characterization of Self-Amplifying mRNA Lipid Nanoparticles.

The mRNA technology has emerged as a rapid modality to develop vaccines during pandemic situations with the potential to protect against endemic diseases. The success of mRNA in producing an antigen is dependent on the ability to deliver mRNA to the cells using a vehicle, which typically consists of a lipid nanoparticle (LNP). Self-amplifying mRNA (SAM) is a synthetic mRNA platform that, besides encoding for the antigen of interest, includes the replication machinery for mRNA amplification in the cells. Thus, SAM can generate many antigen encoding mRNA copies and prolong expression of the antigen with lower doses than those required for conventional mRNA. This work describes the morphology of LNPs containing encapsulated SAM (SAM LNPs), with SAM being three to four times larger than conventional mRNA. We show evidence that SAM changes its conformational structure when encapsulated in LNPs, becoming more compact than the free SAM form. A characteristic "bleb" structure is observed in SAM LNPs, which consists of a lipid-rich core and an aqueous RNA-rich core, both surrounded by a DSPC-rich lipid shell. We used SANS and SAXS data to confirm that the prevalent morphology of the LNP consists of two-core compartments where components are heterogeneously distributed between the two cores and the shell. A capped cylinder core-shell model with two interior compartments was built to capture the overall morphology of the LNP. These findings provide evidence that bleb two-compartment structures can be a representative morphology in SAM LNPs and highlight the need for additional studies that elucidate the role of spherical and bleb morphologies, their mechanisms of formation, and the parameters that lead to a particular morphology for a rational design of LNPs for mRNA delivery.

Incidence and risk factors for travellers' diarrhoea among short-term international adult travellers from high-income countries: a systematic review with meta-analysis of cohort studies.

BACKGROUND: Travellers' Diarrhoea (TD) continues to be the most common travel-related medical event in international travellers. Updated incidence and risk factor data will improve pre-travel medical advice for travellers from high-income countries (HIC), providing an opportunity for disease prevention, and appropriate disease management. METHODS: A systematic search for cohort studies of TD incidence published between 1 January 1997 and 2 March 2023 was performed using Ovid Medline, SCOPUS, and Google Scholar databases. Study quality was assessed with a modified Newcastle-Ottawa scale (NOS). We extracted incidence data for adults travelling less than 100 days from HIC and available risk factor data. The overall random-effects pooled incidence and the corresponding 95% confidence intervals (95% CI) were estimated. Heterogeneity was assessed using the I2 statistic, tau and the 95% prediction intervals. Subgroup analyses were conducted to identify sources of heterogeneity. Risk factor studies were reviewed qualitatively and described. RESULTS: Ten studies were included in the meta-analysis, containing 8478 participants. Two of the studies measured as high quality and eight as good quality as assessed by the modified NOS. The TD incidence was 36.1% (95% CI 24-41%; I2 94%), with a prediction interval ranging from 20.3% to 55.8%. The pooled incidence of mild, moderate, and severe TD was 23.6%, 8.1% and 2.9%, respectively. Subgroup analysis showed that the incidence increased with increasing average data collection period. Risk factors for TD in travellers from HIC identified include younger age, longer travel periods, low and middle-income destinations, travelling for tourism, backpacking travel styles and pre-travel health status. CONCLUSION: It is estimated that between 20 to 56% of international travellers can expect to develop TD in travel of under 100 days. While most cases are mild, approximately 3% of all travellers will experience a disease that prevents usual activities or requires medical attention.

Effect of COVID-19 on infections associated with medical devices in critical care.

OBJECTIVES: This study explores the hypothesis that COVID-19 patients are at a heightened risk of healthcare-associated infections (HAIs) associated with medical device usage compared to non-COVID-19 patients. Our primary objective was to investigate the correlation between COVID-19 infection in ICU patients and subsequent HAIs following invasive medical device insertion. Additionally, we aim to assess the impact of SARS-CoV-2 infection on onset times concerning specific microorganisms and the type of medical device, providing valuable insights into this intricate relationship in intensive care settings. METHODOLOGY: A retrospective cohort study was conducted using ICU patient records at our hospital from 2020 to 2022. This investigation entailed evaluating the timing of HAIs while distinguishing between patients with and without SARS-CoV-2 infection. We identified and analyzed the type of isolation and infection attributed to the medical device while controlling for ICU duration and ventilator days using Cox regression. RESULTS: Our study included 127 patients without SARS-CoV-2 infection and 140 patients with SARS-CoV-2 infection. The findings indicated a higher incidence of HAI caused by various microorganisms associated with any medical device in patients with SARS-CoV-2 (HR = 6.86; 95% CI-95%: 3.26-14.43; p < 0.01). After adjusting for ICU duration and ventilator days, a heightened frequency of HAIs persisted in SARS-CoV-2-infected individuals. However, a detailed examination of HAIs revealed that only ventilation-associated pneumonia (VAP) displayed a significant association (HR = 6.69; 95% CI: 2.59-17.31; p < 0.01). A statistically significant correlation between SARS-CoV-2 infection and the isolation of S. aureus was also observed (p = 0.034). The prevalence of S. aureus infection was notably higher in patients with SARS-CoV-2 (RR = 8.080; 95% CI: 1.052-62.068; p < 0.01). CONCLUSIONS: The frequency of pathogen isolates in invasive medical devices exhibited an association with SARS-CoV-2 infection. Critically ill patients with SARS-CoV-2 are more prone to developing early-onset VAP than those without SARS-CoV-2 infection.

A multitrait genetic study of hemostatic factors and hemorrhagic transformation after stroke treatment.

BACKGROUND: Thrombolytic recombinant tissue plasminogen activator (r-tPA) treatment is the only pharmacologic intervention available in the ischemic stroke acute phase. This treatment is associated with an increased risk of intracerebral hemorrhages, known as hemorrhagic transformations (HTs), which worsen the patient's prognosis. OBJECTIVES: To investigate the association between genetically determined natural hemostatic factors' levels and increased risk of HT after r-tPA treatment. METHODS: Using data from genome-wide association studies on the risk of HT after r-tPA treatment and data on 7 hemostatic factors (factor [F]VII, FVIII, von Willebrand factor [VWF], FXI, fibrinogen, plasminogen activator inhibitor-1, and tissue plasminogen activator), we performed local and global genetic correlation estimation multitrait analyses and colocalization and 2-sample Mendelian randomization analyses between hemostatic factors and HT. RESULTS: Local correlations identified a genomic region on chromosome 16 with shared covariance: fibrinogen-HT, P = 2.45 × 10-11. Multitrait analysis between fibrinogen-HT revealed 3 loci that simultaneously regulate circulating levels of fibrinogen and risk of HT: rs56026866 (PLXND1), P = 8.80 × 10-10; rs1421067 (CHD9), P = 1.81 × 10-14; and rs34780449, near ROBO1 gene, P = 1.64 × 10-8. Multitrait analysis between VWF-HT showed a novel common association regulating VWF and risk of HT after r-tPA at rs10942300 (ZNF366), P = 1.81 × 10-14. Mendelian randomization analysis did not find significant causal associations, although a nominal association was observed for FXI-HT (inverse-variance weighted estimate [SE], 0.07 [-0.29 to 0.00]; odds ratio, 0.87; 95% CI, 0.75-1.00; raw P = .05). CONCLUSION: We identified 4 shared loci between hemostatic factors and HT after r-tPA treatment, suggesting common regulatory mechanisms between fibrinogen and VWF levels and HT. Further research to determine a possible mediating effect of fibrinogen on HT risk is needed.

Displasia fibrosa maxilar. Del diagnóstico al tratamiento. Reporte de caso / Maxillary fibrous dysplasia. From diagnosis to treatment: Case report / Displasia fibrosa maxilar. Do diagnóstico ao tratamento: Relato de caso

La displasia fibrosa se puede presentar, en cualquier persona, por una mutación en los primeros meses de gestación. Se trata de lesiones óseas benignas en pacientes jóvenes, en las que el tejido óseo normal es sustituido por tejido conectivo fibroso, debido a una alteración funcional de las células, siendo esta la antesala de una neoplasia. El objetivo de éste artículo es presentar un caso local de Displasia Fibrosa Maxilar, enfatizando el manejo clínico, radiográfico, pre y postoperatorio más pertinente. Por lo tanto, se describe el caso de un paciente adolescente de género masculino, afectado por displasia fibrosa en hemimaxilar derecho, a quien le fueron realizados los estudios imagenológicos e histopatológicos necesarios para obtener el diagnóstico definitivo y decidir el abordaje menos invasivo posible cumpliendo con estándares de estética facial; se realizó abordaje intrabucal para shaving óseo, con sedación consciente bajo estricta vigilancia de la especialista en anestesiología y reanimación. Una vez logrado el contorno deseado mediante el uso de piezas de mano de alta y baja velocidad, se realizó la sutura de los tejidos y el paciente egresó ambulante y con buen estado general de salud.

Fibrous dysplasia can occur in any person due to a mutation in the first months of gestation. These are benign bone lesions in young patients, in which the normal bone tissue is replaced by fibrous connective tissue, due to a functional alteration of the cells, being this the prelude to a neoplasm. The aim of this article is to present a local case of Maxillary Fibrous Dysplasia, emphasizing the most relevant clinical, radiographic, pre and postoperative management. Therefore, we describe the case of an adolescent male patient, affected by fibrous dysplasia in the right hemimaxillary, who underwent the necessary imaging and histopathological studies to obtain the definitive diagnosis and decide the least invasive approach possible in compliance with facial aesthetic standards; an intraoral approach was performed for bone shaving, with conscious sedation under strict supervision of the specialist in anesthesiology and resuscitation. Once the desired contour was achieved through the use of high and low speed handpieces, the tissues were sutured and the patient was discharged ambulatory and in good general health.

A displasia fibrosa pode ocorrer em qualquer pessoa devido a uma mutação nos primeiros meses de gestação. São lesões ósseas benignas em pacientes jovens, nas quais o tecido ósseo normal é substituído por tecido conjuntivo fibroso, devido a uma alteração funcional das células, sendo esse o prelúdio de uma neoplasia. O objetivo deste artigo é apresentar um caso local de Displasia Fibrosa Maxilar, enfatizando o manejo clínico, radiográfico, pré e pós-operatório mais pertinente. Portanto, descrevemos o caso de um paciente adolescente do sexo masculino, afetado por displasia fibrosa no hemimaxilar direito, que foi submetido aos exames de imagem e histopatológicos necessários para obter um diagnóstico definitivo e decidir sobre a abordagem menos invasiva possível, em conformidade com os padrões estéticos faciais; foi realizada uma abordagem intraoral para raspagem óssea, com sedação consciente sob estrita supervisão do especialista em anestesiologia e ressuscitação. Depois que o contorno desejado foi obtido com o uso de peças de mão de alta e baixa velocidade, os tecidos foram suturados e o paciente recebeu alta ambulatorial em bom estado geral de saúde.

Escroto agudo en el lactante / Acute scrotum in infants

El escroto agudo consiste en un cuadro clínico de dolor testicular asociado a signos inflamatorios locales, excepcional en neonatos y lactantes. Presentamos un caso de un lactante de 2 meses con tumefacción y eritema escrotal derecho de 48 horas de evolución y pico febril en Urgencias. A la exploración, teste doloroso a la palpación, con reflejo cremastérico presente. En la ecografía testicular se objetiva orquiepididimitis derecha. La analítica muestra leucocitosis, neutrofilia y mínima elevación de reactantes de fase aguda. En el urocultivo se aísla Escherichia coli. Recibe antibioterapia durante 2 semanas con buena evolución. La orquiepididimitis es la inflamación aguda del testículo y epidídimo, patología muy infrecuente en neonatos y lactantes. La diseminación hematógena es la causa más frecuente en este grupo de edad, siendo el germen más frecuente el E. coli. Por tanto, en neonatos y lactantes con orquiepididimitis, considerando el riesgo de bacteriemia asociada, resulta fundamental optimizar el diagnóstico, incluyendo un estudio completo de sepsis junto con la ecografía Doppler y el inicio precoz de la antibioterapia empírica (AU)

Acute scrotum consists of testicular pain associated with local inflammatory signs and is very unsual in neonates and infants.We present a case of a 2-month-old infant with right scrotal swelling and erythema of 48 hours' evolution. Peak fever in the emergency department. On examination, the teste was painful on palpation, with cremasteric reflex present. Testicular ultrasound showed right orchiepididymitis with associated hydrocele. Laboratory tests show leukocytosis, neutrophilia and minimal elevation of acute phase reactants. Urine culture isolated Escherichia coli. He received antibiotherapy for 2 weeks with good evolution.Orchiepididymitis is an acute inflammation of the testicle and epididymis, and it is a very rare pathology in neonates and infants. Haematogenous dissemination is the most frequent cause in this age group, with E. coli being the most frequently isolated germ. Therefore, in neonates and infants with orchiepididymitis, considering the risk of associated bacteraemia, it is essential to optimize the diagnosis by including a complete sepsis study together with Doppler ultrasound and the early initiation of empirical antibiotherapy. (AU)

Role of Domain-Domain Interactions on the Self-Association and Physical Stability of Monoclonal Antibodies: Effect of pH and Salt.

Monoclonal antibodies (mAbs) make up a major class of biotherapeutics with a wide range of clinical applications. Their physical stability can be affected by various environmental factors. For instance, an acidic pH can be encountered during different stages of the mAb manufacturing process, including purification and storage. Therefore, understanding the behavior of flexible mAb molecules in acidic solution environments will benefit the development of stable mAb products. This study used small-angle X-ray scattering (SAXS) and complementary biophysical characterization techniques to investigate the conformational flexibility and protein-protein interactions (PPI) of a model mAb molecule under near-neutral and acidic conditions. The study also characterized the interactions between Fab and Fc fragments under the same buffer conditions to identify domain-domain interactions. The results suggest that solution pH significantly influences mAb flexibility and thus could help mAbs remain physically stable by maximizing local electrostatic repulsions when mAbs become crowded in solution. Under acidic buffer conditions, both Fab and Fc contribute to the repulsive PPI observed among the full mAb at a low ionic strength. However, as ionic strength increases, hydrophobic interactions lead to the self-association of Fc fragments and, subsequently, could affect the aggregation state of the mAb.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention.

We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69, ≥70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

CMC Strategies and Advanced Technologies for Vaccine Development to Boost Acceleration and Pandemic Preparedness.

This review reports on an overview of key enablers of acceleration/pandemic and preparedness, covering CMC strategies as well as technical innovations in vaccine development. Considerations are shared on implementation hurdles and opportunities to drive sustained acceleration for vaccine development and considers learnings from the COVID pandemic and direct experience in addressing unmet medical needs. These reflections focus on (i) the importance of a cross-disciplinary framework of technical expectations ranging from target antigen identification to launch and life-cycle management; (ii) the use of prior platform knowledge across similar or products/vaccine types; (iii) the implementation of innovation and digital tools for fast development and innovative control strategies.