Standard Quality Characteristics and Efficacy of a New Third-Generation Antivenom Developed in Colombia Covering Micrurus spp. Venoms.

In Colombia, Micrurus snakebites are classified as severe according to the national clinical care guidelines and must be treated with specific antivenoms. Unfortunately, these types of antivenoms are scarce in certain areas of the country and are currently reported as an unavailable vital medicine. To address this issue, La Universidad de Antioquia, through its spin-off Tech Life Saving, is leading a project to develop third-generation polyvalent freeze-dried antivenom. The goal is to ensure access to this therapy, especially in rural and dispersed areas. This project aims to evaluate the physicochemical and preclinical parameters (standard quality characteristics) of a lab-scale anti-elapid antivenom batch. The antivenom is challenged against the venoms of several Micrurus species, including M. mipartitus, M. dumerilii, M. ancoralis, M. dissoleucus, M. lemniscatus, M. medemi, M. spixii, M. surinamensis, and M. isozonus, following the standard quality characteristics set by the World Health Organization (WHO). The antivenom demonstrates an appearance consistent with standards, 100% solubility within 4 min and 25 s, an extractable volume of 10.39 mL, a pH of 6.04, an albumin concentration of 0.377 mg/mL (equivalent to 1.22% of total protein), and a protein concentration of 30.97 mg/mL. Importantly, it maintains full integrity of its F(ab')2 fragments and exhibits purity over 98.5%. Furthermore, in mice toxicity evaluations, doses up to 15 mg/mouse show no toxic effects. The antivenom also demonstrates a significant recognition pattern against Micrurus venoms rich in phospholipase A2 (PLA2) content, as observed in M. dumerilii, M. dissoleucus, and M. isozonus. The effective dose 50 (ED50) indicates that a single vial (10 mL) can neutralize 2.33 mg of M. mipartitus venom and 3.99 mg of M. dumerilii venom. This new anti-elapid third-generation polyvalent and freeze-dried antivenom meets the physicochemical parameters set by the WHO and the regulators in Colombia. It demonstrates significant efficacy in neutralizing the venom of the most epidemiologically important Micrurus species in Colombia. Additionally, it recognizes seven other species of Micrurus venom with a higher affinity for venoms exhibiting PLA2 toxins. Fulfilling these parameters represents the first step toward proposing a new pharmacological alternative for treating snakebites in Colombia, particularly in dispersed rural areas, given that this antivenom is formulated as a freeze-dried product.

Plasmid-mediated phenotypic noise leads to transient antibiotic resistance in bacteria.

The rise of antibiotic resistance is a critical public health concern, requiring an understanding of mechanisms that enable bacteria to tolerate antimicrobial agents. Bacteria use diverse strategies, including the amplification of drug-resistance genes. In this paper, we showed that multicopy plasmids, often carrying antibiotic resistance genes in clinical bacteria, can rapidly amplify genes, leading to plasmid-mediated phenotypic noise and transient antibiotic resistance. By combining stochastic simulations of a computational model with high-throughput single-cell measurements of blaTEM-1 expression in Escherichia coli MG1655, we showed that plasmid copy number variability stably maintains populations composed of cells with both low and high plasmid copy numbers. This diversity in plasmid copy number enhances the probability of bacterial survival in the presence of antibiotics, while also rapidly reducing the burden of carrying multiple plasmids in drug-free environments. Our results further support the tenet that multicopy plasmids not only act as vehicles for the horizontal transfer of genetic information between cells but also as drivers of bacterial adaptation, enabling rapid modulation of gene copy numbers. Understanding the role of multicopy plasmids in antibiotic resistance is critical, and our study provides insights into how bacteria can transiently survive lethal concentrations of antibiotics.

Measurement-induced collective vibrational quantum coherence under spontaneous Raman scattering in a liquid.

Spontaneous vibrational Raman scattering is a ubiquitous form of light-matter interaction whose description necessitates quantization of the electromagnetic field. It is usually considered as an incoherent process because the scattered field lacks any predictable phase relationship with the incoming field. When probing an ensemble of molecules, the question therefore arises: What quantum state should be used to describe the molecular ensemble following spontaneous Stokes scattering? We experimentally address this question by measuring time-resolved Stokes-anti-Stokes two-photon coincidences on a molecular liquid consisting of several sub-ensembles with slightly different vibrational frequencies. When spontaneously scattered Stokes photons and subsequent anti-Stokes photons are detected into a single spatiotemporal mode, the observed dynamics is inconsistent with a statistical mixture of individually excited molecules. Instead, we show that the data are reproduced if Stokes-anti-Stokes correlations are mediated by a collective vibrational quantum, i.e. a coherent superposition of all molecules interacting with light. Our results demonstrate that the degree of coherence in the vibrational state of the liquid is not an intrinsic property of the material system, but rather depends on the optical excitation and detection geometry.

A Survey of Cannabis Use among Patients with Inflammatory Bowel Disease (IBD).

Inflammatory bowel diseases (IBDs) are chronic conditions of unknown cause or cure. Treatment seeks to reduce symptoms and induce and maintain remission. Many patients have turned to alternatives, such as cannabis, to alleviate living with IBD. This study reports the demographics, prevalence, and perception on cannabis use of patients attending an IBD clinic. Patients agreed to participate and completed an anonymous survey during their visit or online. Descriptive analysis, Fisher's exact test, and Wilcoxon-Mann-Whitney rank-sum test were used. One hundred and sixty-two adults (85 males, 77 with CD) completed the survey. Sixty (37%) reported use of cannabis, of which 38 (63%) used it to relieve their IBD. A value of 77% reported low to moderate knowledge about cannabis, and 15% reported little to no knowledge. Among cannabis users, 48% had discussed use with their physician, but 88% said they would feel comfortable discussing medical cannabis for IBD. Most saw improvement of their symptoms (85.7%). A considerable number of patients with IBD use medical cannabis for their disease, unknown to their physician. The study reinforces the importance that physicians understand the role of cannabis in the treatment of IBD in order to appropriately counsel patients.

decoupleR: ensemble of computational methods to infer biological activities from omics data.

Summary: Many methods allow us to extract biological activities from omics data using information from prior knowledge resources, reducing the dimensionality for increased statistical power and better interpretability. Here, we present decoupleR, a Bioconductor and Python package containing computational methods to extract these activities within a unified framework. decoupleR allows us to flexibly run any method with a given resource, including methods that leverage mode of regulation and weights of interactions, which are not present in other frameworks. Moreover, it leverages OmniPath, a meta-resource comprising over 100 databases of prior knowledge. Using decoupleR, we evaluated the performance of methods on transcriptomic and phospho-proteomic perturbation experiments. Our findings suggest that simple linear models and the consensus score across top methods perform better than other methods at predicting perturbed regulators. Availability and implementation: decoupleR's open-source code is available in Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/decoupleR.html) for R and in GitHub (https://github.com/saezlab/decoupler-py) for Python. The code to reproduce the results is in GitHub (https://github.com/saezlab/decoupleR_manuscript) and the data in Zenodo (https://zenodo.org/record/5645208). Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Bell correlations between light and vibration at ambient conditions.

Time-resolved Raman spectroscopy techniques offer various ways to study the dynamics of molecular vibrations in liquids or gases and optical phonons in crystals. While these techniques give access to the coherence time of the vibrational modes, they are not able to reveal the fragile quantum correlations that are spontaneously created between light and vibration during the Raman interaction. Here, we present a scheme leveraging universal properties of spontaneous Raman scattering to demonstrate Bell correlations between light and a collective molecular vibration. We measure the decay of these hybrid photon-phonon Bell correlations with sub-picosecond time resolution and find that they survive over several hundred oscillations at ambient conditions. Our method offers a universal approach to generate entanglement between light and molecular vibrations. Moreover, our results pave the way for the study of quantum correlations in more complex solid-state and molecular systems in their natural state.

Impacto de una estrategia educativa en salud bucal en un hogar infantil de la ciudad de Medellín -Colombia* / Impact of an oral health educational strategy ina children's home in the city of Medellín-Colombia / Impacto de uma estratégia educacional de saúde bucal em um lar infantil na cidade de Medellín-Colômbia

Resumen Introducción y objetivo: la salud bucal de la primera infancia es importante para el buen desarrollo de los niños, siendo prioridad en las políticas de salud pública. evaluar el impacto de una intervención educativa en el estado de salud bucal de niños y niñas, pertenecientes a una institución educativa de la ciudad de Medellín. Materiales y métodos: se realizó un estudio de intervención entre los años 2015 y 2017, a partir de tres fases: a) tamización bucal a los menores y encuestas sobre su cuidado bucal a padres de familia o representantes, b) realización de actividades educativas y aplicación de barniz de flúor, c) evaluación de la estrategia. Se realizó un análisis descriptivo de la información recolectada y un análisis bivariado para la comparación de los hallazgos dentro del periodo de estudio. Resultados: se examinaron 479 escolares entre el 2015 y el 2017, se encontraron diferencias significativas en el índice COP modificado y el porcentaje de placa entre los periodos comparados, con disminución de lesiones cariadas con cavitación, mancha blanca e índice de placa después de la implementación de la estrategia. Conclusión: El fomento de prácticas respecto al cuidado bucal mejoró la calidad del cepillado dental y disminuyó la frecuencia de caries dental en la población de estudio. Se sugiere seguir con los programas de enseñanza y motivación para mejorar y mantener el buen estado de salud bucal en la primera infancia.

Introduction and objective: early childhood oral health is important for the good development of children, being a priority in public health policies. to evaluate the impact of an educational intervention on the state of oral health of children, belon- ging to an educational institution in the city of Medellin. Materials and methods: an intervention study was carried out between 2015 and 2017, based on three phases: a) oral screening of children and surveys of their oral care to parents or represen- tatives, b) carrying out educational activities and application of fluoride varnish, c) evaluation of the strategy. A descriptive analysis of the information collected and a bivariate analysis were performed to compare the findings within the study pe- riod. Results: 479 schoolchildren between 2015 and 2017 were examined, signifi- cant differences were found in the modified COP index and the percentage of plaque between the periods compared, with a decrease in carious lesions with cavitation, white spot and plaque index after implementation of the strategy. Conclusion: The promotion of practices regarding oral care improved the quality of tooth brushing and decreased the frequency of tooth decay in the study population. It is suggested to continue with the teaching and motivation programs to improve and maintain good oral health in early childhood.

Resumo Introdução y objetivo: a saúde bucal infantil é importante para o bom desenvolvimento da criança, sendo uma prioridade nas políticas públicas de saúde. Avaliar o impacto de uma intervenção educativa no estado de saúde bucal de meninos e meninas pertencentes a uma instituição educacional da cidade de Medellín. Materiais e métodos: foi realizado um estudo de intervenção entre 2015 e 2017, com base em três fases: a)triagem oral de menores e pesquisas de cuidados bucais para pais ou representantes, b) realização de atividades educativas e aplicação de verniz de flúor; c) avaliação da estratégia. Uma análise descritiva das informações coletadas e uma análise bivariada foram realizadas para comparar os achados no período do estudo. Resultados: 479 escolares foram examinados entre 2015 e 2017, foram encontradas diferenças significativas no índice de COP modificado e no percentual de placa entre os períodos comparados, com diminuição das lesões de cárie com cavitação, mancha branca e índice de placa após a implementação da estratégia. Conclusão: A promoção de práticas relacionadas à higiene bucal melhorou a qualidade da escovação e diminuiu a frequência de cárie na população estudada. Sugerese continuar comos programas de ensino e motivação para melhorar e manter uma boa saúde bucal na primeira infância.

Two-Color Pump-Probe Measurement of Photonic Quantum Correlations Mediated by a Single Phonon.

We propose and demonstrate a versatile technique to measure the lifetime of the one-phonon Fock state using two-color pump-probe Raman scattering and spectrally resolved, time-correlated photon counting. Following pulsed laser excitation, the n=1 phonon Fock state is probabilistically prepared by projective measurement of a single Stokes photon. The detection of an anti-Stokes photon generated by a second, time-delayed laser pulse probes the phonon population with subpicosecond time resolution. We observe strongly nonclassical Stokes-anti-Stokes correlations, whose decay maps the single phonon dynamics. Our scheme can be applied to any Raman-active vibrational mode. It can be modified to measure the lifetime of n≥1 Fock states or the phonon quantum coherences through the preparation and detection of two-mode entangled vibrational states.

Dinámica de flujo computacional en aneurismas cerebrales / Computational fluid dynamics in intracranial aneurysm

Los aneurismas cerebrales son lesiones arteriales caracterizadas por el debilitamiento y la dilatación de un segmento del vaso sanguíneo. Representan una gran amenaza para la vida del paciente debido al riesgo de ruptura, trombo-embolias o compresión del tejido adyacente. Los aneurismas cerebrales rotos son la causa más común de la hemorragia subaracnoidea y puede causar una significativa morbilidad y mortalidad. Con el fin de entender el comportamiento hemodinámico de los aneurismas cerebrales se han desarrollado estudios computacionales que simulan las condiciones y propiedades de dichas lesiones en modelos virtuales similares a la realidad; la mayoría de ellos se realizan en un sistema experimental conocido como dinámica de fluido computacional. Este artículo presenta una revisión del estado de la técnica aplicada a hemodinámica de flujo en aneurismas y pretende recopilar los avances más importantes del método que servirán en un futuro, para el desarrollo de una herramienta de apoyo al diagnóstico y tratamiento de estas dolencias.

Intracranial aneurysms are lesions of the arterial wall characterized by weakening and dilation of an arterial segment. These lesions are a major threat to the patient’s life because of the risk of rupture, thrombo-emboli, or compression of adjacent tissue. The rupture of an intracranial aneurysm causes subarachnoid hemorrhage associated with high mortality and morbidity rates. In order to understand the intracranial aneurysm hemodynamics, it has been developed computational studies, which simulate the boundary conditions and properties of these lesions in virtual models (models similar to reality), most of them are made in a computational fluid dynamic model (CFD). This study reviews the state of arts of the CFD technique applied to the aneurysm flow hemodynamics that claims to collect the most important progress of the method that will be useful in the tool’s developments that will become a rely on a diagnosis and treatment tool.

Resistencia de dientes restaurados con postes prefabricados ante cargas de máxima intercuspidación, masticación y bruxismo / Resistance of teeth restored with prefabricated posts to maximum intercuspidation loads, mastication and bruxism

Objetivo: determinar por el método de los elementos finitos la resistencia de dientes restaurados con postes prefabricados ante cargas estáticas de máxima intercuspidación y cargas cíclicas de masticación y bruxismo y analizar el efecto de la pérdida periodontal en la resistencia de las restauraciones. Métodos: se realizó una investigación in vitro mediante el método de los elementos finitos de dientes con pérdida periodontal, rehabilitados con postes prefabricados en fibra de vidrio, carbono y titanio. Los dientes fueron reconstruidos a partir de imágenes tomográficas de un paciente periodontalmente sano. Resultados: se muestra que ante cargas estáticas las rehabilitaciones no presentan tendencia a la falla, independientemente del material del poste o del grado de pérdida periodontal. En el caso de bruxismo y pérdida periodontal de 4 mm, la dentina presenta una durabilidad de 60 000 ciclos independiente del material del poste. Para cargas de masticación y periodonto sano, la falla en la dentina ocurre a los 100 000 ciclos con poste en titanio, 200 000 ciclos con poste en fibra de carbono y 1 100 000 ciclos con poste en fibra de vidrio. Para una pérdida periodontal de 2 mm la durabilidad de la dentina se reduce a 4 000 ciclos con poste en titanio, 5 000 ciclos con poste en fibra de carbono y 7 000 ciclos con poste en fibra de vidrio. Para pérdida periodontal de 4 mm, la durabilidad de la dentina se estima en 1 000 ciclos, independientemente del material del poste utilizado. Conclusiones: ante carga estática de máxima intercuspidación las rehabilitaciones con postes prefabricados en fibra de vidrio, carbono y titanio no presentan tendencia a la falla, independientemente del grado de pérdida periodontal. Ante cargas cíclicas, los postes prefabricados presentan una vida útil infinita, y es la dentina la estructura más afectada ante dichos eventos(AU)

Objective: using the finite element method, determine the resistance of teeth restored with prefabricated posts to maximum static intercuspidation loads, cyclical mastication loads and bruxism, and analyze the effect of periodontal loss on resistance by restorations. Methods: using the finite element method, an in vitro study was conducted of teeth with periodontal loss rehabilitated with prefabricated glass fiber, carbon and titanium posts. Reconstruction of the teeth was based on tomographic images from a periodontically healthy patient. Results: it was shown that rehabilitations did not tend to yield to static loads, irrespective of post material or the degree of periodontal loss. For bruxism and 4 mm periodontal loss, dentin durability was 60 000 cycles, irrespective of post material. For mastication loads and a healthy periodont, dentin failure occurs at 100 000 cycles with titanium posts, 200 000 cycles with carbon fiber posts, and 1 100 000 cycles with glass fiber posts. For 2 mm periodontal loss, dentin durability decreased to 4 000 cycles with titanium posts, 5 000 cycles with carbon fiber posts, and 7 000 cycles with glass fiber posts. For 4 mm periodontal loss, dentin durability is estimated at 1 000 cycles, irrespective of post material. Conclusions: restorations with glass fiber, carbon and titanium prefabricated posts do not yield to maximum static intercuspidation loads, irrespective of the degree of periodontal loss. Prefabricated posts exhibit endless resistance to cyclic loads. Dentin is the structure most severely affected by such events(AU)

Radiographical vignette: an apical lung density in an elderly man with hemoptysis.

An Aspergilloma is a "ball" of fungal mycelia composed of Aspergillus species developing in a pre-existing lung cavity. This uncommon entity may cause hemoptysis and may be a diagnostic challenge. We present imaging and review the literature of a recent case managed in our institution.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency.

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

Identification of Paracoccidioides brasiliensis in adrenal glands biopsies of two patients with paracoccidioidomycosis and adrenal insufficiency / Identificação do Paracoccidioides brasiliensis nas amostras de glândulas adrenais de dois doentes com paracoccidioidomicose e insuficiência adrenal

The authors report two cases of adrenal insufficiency secondary to infiltration of the adrenal glands by Paracoccidioides brasiliensis. The first patient had been treated for a chronic multifocal form of paracoccidiodomycosis 11 years ago. The diagnosis of the mycosis was done simultaneous with that of the adrenal insufficiency in the second patient. In both patients the diagnosis was done by direct visualization of fungus in adrenal biopsies. They were treated with hormonal supplements and itraconazol by 12 and six months, without relapses during the follow-up period.

Os autores apresentam dois casos de insuficiência supra-renal secundária à infiltração das adrenais pelo Paracoccidioides brasiliensis. O primeiro paciente tinha sido tratado de paracoccidioidomicose crônica multifocal 11 anos atrás. No segundo paciente, o diagnóstico da micose foi feito de forma simultânea com o da insuficiência adrenal. Em ambos os pacientes, o diagnóstico foi feito pela visualização direta do fungo nas biopsias adrenais. Eles foram tratados com suplementos hormonais com itraconazol por seis a 12 meses, sem recaídas durante o período de acompanhamento.

Diseño y construcción de un prototipo de ortesis para el tratamiento de la plagiocefalia occipital posicional / Design and construction of a prototype orthesis device for the positional occipital plagiocephaly treatment

Este artículo presenta el desarrollo de un prototipo de dispositivo ortésico para cráneo de pacientes con plagiocefalia occipital posicional, con el fin de aplicarlo en la rehabilitación de infantes entre los cuatro y doce meses de edad. La geometría del dispositivo se obtuvo a partir de las medidas estadísticas estándar de cráneo para infantes de 6 meses de edad de acuerdo con La Academia Americana de Pediatría y por medio del software GID 8. Los esfuerzos y las deformaciones sufridas por el dispositivo durante su aplicación fueron simuladas por medio de elementos finitos usando el software ANSYS® 10.0. Para estandarizar el tratamiento y conocer la presión aplicada por el dispositivo ortésico en el cráneo del paciente, se elaboró un sensor de presión de aire que trabaja en un intervalo de 0 mm Hg a 55 mm Hg. Los resultados muestran que el dispositivo cumple las especificaciones tanto desde el punto de vista de una validación matemática, como desde las especificaciones del diseño en cuanto a la resolución mínima para las medidas de presión sensadas, confort y resistencia...

This paper presents the development of a prototype orthesis device for the cranium of patientswith positional occipital plagiocephaly. This device will allow the rehabilitation of infants between four months and twelve months old. The device geometry was obtained from statistical cranium measurements evaluated in children of 6 months old by the American Academy of Pediatrics as well through software called GID 8. The stress and strain results were taken from the device during activity, or while the equipment applied some forces on the head; simulations were made by the software of finite element called ANSYS® 10.0. An implementation of air sensor to the device made it possible to know the levels of pressure in a range of 0mm Hg a 55mm Hg. This implementation was done in order to get the standardization of the treatment. The mathematic results as well as the design specifications (minimum resolution of the pressure measurements, comfort and resistance) showed that the device maybe used in rehabilitation.