Development of a single-domain antibody to target a G-quadruplex located on the hepatitis B virus covalently closed circular DNA genome.

To achieve a virological cure for hepatitis B virus (HBV), innovative strategies are required to target the covalently closed circular DNA (cccDNA) genome. Guanine-quadruplexes (G4s) are a secondary structure that can be adopted by DNA and play a significant role in regulating viral replication, transcription, and translation. Antibody-based probes and small molecules have been developed to study the role of G4s in the context of the human genome, but none have been specifically made to target G4s in viral infection. Herein, we describe the development of a humanized single-domain antibody (S10) that can target a G4 located in the PreCore (PreC) promoter of the HBV cccDNA genome. MicroScale Thermophoresis demonstrated that S10 has a strong nanomolar affinity to the PreC G4 in its quadruplex form and a structural electron density envelope of the complex was determined using Small-Angle X-ray Scattering. Lentiviral transduction of S10 into HepG2-NTCP cells shows nuclear localization, and chromatin immunoprecipitation coupled with next-generation sequencing demonstrated that S10 can bind to the HBV PreC G4 present on the cccDNA. This research validates the existence of a G4 in HBV cccDNA and demonstrates that this DNA secondary structure can be targeted with high structural and sequence specificity using S10.

Field Programmable Gate Array-Based Smart Switch to Avoid Inrush Current in PV Installations.

This paper introduces an FPGA-based implementation of a smart switch designed to avoid inrush currents occurring during the connection of single-phase transformers utilized in grid-connected photovoltaic (PV) systems. The magnitude of inrush currents is notably impacted by the residual flux within the transformer core and the precise moment of energization relative to the wave cycle. Alternative methods frequently hinge on intricate procedures to estimate residual flux. This challenge is adeptly circumvented by the innovative smart control system proposed herein, rendering it a cost-effective solution for grid-connected PV systems. The proposed solution for mitigating inrush current remains effective, even in the face of challenges with current and voltage sensors. This resilience arises from the system's ability to learn and adapt by leveraging information acquired from the network.

Evidence of validity and reliability of the environmental action scale in Peruvian university students.

Background: The environmental action scale is used to measure the degree of participation in collective environmental actions and has been shown to have adequate psychometric properties in developed countries. However, there are still no studies that have evaluated its performance in the Peruvian population. Methods: In this instrumental study, the environmental action scale (EAS) was translated, adapted, and validated. The EAS was administered to 352 university students between 18 and 35 years of age (Mage = 23.37, SD = 2.57) from different cities in Peru. A validity analysis was performed using two sources of evidence: content validity and internal structure, carrying out an exploratory factor analysis (EFA) and a confirmatory factor analysis (CFA). Results: The structure of the scale has been organized into three oblique factors. The findings confirmed the reliability and validity of the three dimensions of the EAS. Conclusion: Therefore, this scale is considered a valid option for assessing environmental action.

Collecting and communicating perishable data in a post-disaster context: rapid research and rapid dissemination.

Context: Puerto Rico experienced four natural disasters in 4 years (2017-2021): Hurricanes Irma and Maria, thousands of earthquakes reaching 6.4 magnitude, and the COVID-19 pandemic. In this context, our team sought to understand the impact of disaster aid distribution on poverty and economic inequality, and their relationship to the spread of COVID-19 across Puerto Rico. Rapid research was required to ensure we could collect perishable data within this ever-changing context. Challenges: Our mixed methods design relied on both secondary and primary data. Because analyses of the former were to inform where and how to collect the latter, timing was of the essence. The data sources identified were not readily available to the public, and thus required gaining access through direct requests to government agencies. The requests coincided with a transition between administrations after an election. This resulted in unexpected delays. Once in the field, the team had to balance the rapid nature of the research with the mindful work to avoid compounding traumas experienced by participants, heightened risk for re-traumatization and fatigue, the risk of COVID-19, the digital divide, and intermittent electrical and telecommunication services. Adaptations: In response to the delayed access to secondary data, we adjusted our research question. We continued to collect data as they became available, incorporating some immediately into analyses, and cleaning and storing others for future research opportunities. To overcome ongoing trauma challenges and prevent fatigue, we recruited and hired a large temporary team, including members of communities where we collected data. By recruiting participants and co-researchers at the same time and place, we both collapsed time between these activities and increased our team's contextual competency. To adapt to challenges presented by the pandemic, we created hybrid data collection procedures where some data were collected online, and some in person, while maintaining COVID-19 protections. We used similar adaptations for dissemination. Lessons: Rapid research needs to be agile. Working within a convergence framework to investigate wicked problems had the unexpected added benefit of providing our team with a variety of disciplinary approaches which proved helpful in adapting to the changing conditions in the field. In addition to the resourcefulness of a transdisciplinary team, it is important to be willing to pivot in response to changes and to collect data where and when you can. To increase participation, opportunities need to be designed with flexibility, mindful of competing demands faced by individuals willing to collaborate. Collecting and analyzing data iteratively and utilizing local resources can enable rapid research that is rigorous and yields rich data. Contributions: Our team applied the lessons learned to structure a rapid and iterative dissemination plan. We combined member-checking with community-level dissemination, enabling us to hone findings further before presenting to policy makers and media. Rapid research creates opportunities to make data-informed program and policy adjustments when they can be most impactful. Both the media and policy makers pay closer attention to research on current events. Hence, our recommendation is to do more rapid research! The more we do, the better we will get at it, and the more accustomed community leaders, policy makers, and program designers will become to using data to inform decisions.

A Large Segmental Mid-Diaphyseal Femoral Defect Sheep Model: Surgical Technique.

Background:There are numerous animal models available to study bone healing as well as test strategies to accelerate bone formation. Sheep are commonly used for evaluation of long bone fractures due to similar dimensions and weight bearing environments compared to patients. Large critical-size defects can be created in sheep to facilitate the study of implantable materials, osteogenic proteins, and stem cell treatments. Studies have been published using plates to stabilize large critical size defects in femoral, tibial, and metatarsal defects. External fixators have also been used to stabilize tibial defects in sheep.Methods: The purpose of the current paper is to detail the surgical technique for creation of a 42 mm mid-diaphyseal femoral defect stabilization with an intramedullary device in sheep. Additional surgical details are provided for dynamization, reverse dynamization, and device removal.Conclusion: The article provides multiple technical tips applicable to this and other ovine osteotomy models and concludes with a discussion comparing the use of each stabilization technique in clinically significant large critical-size bone defects.

Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol.

The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen.

Asociación entre edad gestacional, peso y valor de apgar en recién nacidos extraídos en presentación pélvica / Gestational age, newborn weight and apgar score asociation in breech presentation delivered newborns

Se analizó la morbimortalidad materna y neonatal temprana de 343 embarazos con presentación pélvica y se establecieron las variables asociadas con el valor de Apgar a los cinco minutos del nacimiento. La morbilidad materno-neonatal en los casos atendidos por cesárea es baja, independientemente de la modalidad de presentación pélvica. La mortalidad fue ausente. Las variables asociadas significativamente con el valor de Apgar a los cinco minutos de nacimiento fueron la edad gestacional y el peso al nacimiento. Esta asociación se demostró en la totalidad de pacientes y cuando fueron analizadas por separado de acuerdo a la vía de interrupción del embarazo. El resultado perinatal de los atendidos por vía vaginal con presentación pélvica completa e incompleta franca de nalgas no mostraron diferencias con los atendidos por cesárea.