Indiscriminate activities of different henipavirus polymerase complex proteins allow for efficient minigenome replication in hybrid systems.

The henipaviruses, including Nipah virus (NiV) and Hendra virus (HeV), are biosafety level 4 (BSL-4) zoonotic pathogens that cause severe neurological and respiratory disease in humans. To study the replication machinery of these viruses, we developed robust minigenome systems that can be safely used in BSL-2 conditions. The nucleocapsid (N), phosphoprotein (P), and large protein (L) of henipaviruses are critical elements of their replication machinery and thus essential support components of the minigenome systems. Here, we tested the effects of diverse combinations of the replication support proteins on the replication capacity of the NiV and HeV minigenomes by exchanging the helper plasmids coding for these proteins among the two viruses. We demonstrate that all combinations including one or more heterologous proteins were capable of replicating both the NiV and HeV minigenomes. Sequence alignment showed identities of 92% for the N protein, 67% for P, and 87% for L. Notably, variations in amino acid residues were not concentrated in the N-P and P-L interacting regions implying that dissimilarities in amino acid composition among NiV and HeV polymerase complex proteins may not impact their interactions. The observed indiscriminate activity of NiV and HeV polymerase complex proteins is different from related viruses, which can support the replication of heterologous genomes only when the whole polymerase complex belongs to the same virus. This newly observed promiscuous property of the henipavirus polymerase complex proteins likely attributed to their conserved interaction regions could potentially be harnessed to develop universal anti-henipavirus antivirals.IMPORTANCEGiven the severity of disease induced by Hendra and Nipah viruses in humans and the continuous emergence of new henipaviruses as well as henipa-like viruses, it is necessary to conduct a more comprehensive investigation of the biology of henipaviruses and their interaction with the host. The replication of henipaviruses and the development of antiviral agents can be studied in systems that allow experiments to be performed under biosafety level 2 conditions. Here, we developed robust minigenome systems for the Nipah virus (NiV) and Hendra virus (HeV) that provide a convenient alternative for studying NiV and HeV replication. Using these systems, we demonstrate that any combination of the three polymerase complex proteins of NiV and HeV could effectively initiate the replication of both viral minigenomes, which suggests that the interaction regions of the polymerase complex proteins could be effective targets for universal and effective anti-henipavirus interventions.

Identification of distinct genotypes in circulating RSV A strains based on variants on the virus replication-associated genes.

Respiratory syncytial virus is a common cause of respiratory infection that often leads to hospitalization of infected younger children and older adults. RSV is classified into two strains, A and B, each with several subgroups or genotypes. One issue with the definition of these subgroups is the lack of a unified method of identification or genotyping. We propose that genotyping strategies based on the genes coding for replication-associated proteins could provide critical information on the replication capacity of the distinct subgroup, while clearly distinguishing genotypes. Here, we analyzed the virus replication-associated genes N, P, M2, and L from de novo assembled RSV A sequences obtained from 31 newly sequenced samples from hospitalized patients in Philadelphia and 78 additional publicly available sequences from different geographic locations within the US. In-depth analysis and annotation of the protein variants in L and the other replication-associated proteins N, P, M2-1, and M2-2 identified the polymerase protein L as a robust target for genotyping RSV subgroups. Importantly, our analysis revealed non-synonymous variations in L that were consistently accompanied by conserved changes in its co-factor P or the M2-2 protein, suggesting associations and interactions between specific domains of these proteins. These results highlight L as an alternative to other RSV genotyping targets and demonstrate the value of in-depth analyses and annotations of RSV sequences as it can serve as a foundation for subsequent in vitro and clinical studies on the efficiency of the polymerase and fitness of different virus isolates.

Unlocking Preclinical Alzheimer's: A Multi-Year Label-Free In Vitro Raman Spectroscopy Study Empowered by Chemometrics.

Alzheimer's disease is a progressive neurodegenerative disorder, the early detection of which is crucial for timely intervention and enrollment in clinical trials. However, the preclinical diagnosis of Alzheimer's encounters difficulties with gold-standard methods. The current definitive diagnosis of Alzheimer's still relies on expensive instrumentation and post-mortem histological examinations. Here, we explore label-free Raman spectroscopy with machine learning as an alternative to preclinical Alzheimer's diagnosis. A special feature of this study is the inclusion of patient samples from different cohorts, sampled and measured in different years. To develop reliable classification models, partial least squares discriminant analysis in combination with variable selection methods identified discriminative molecules, including nucleic acids, amino acids, proteins, and carbohydrates such as taurine/hypotaurine and guanine, when applied to Raman spectra taken from dried samples of cerebrospinal fluid. The robustness of the model is remarkable, as the discriminative molecules could be identified in different cohorts and years. A unified model notably classifies preclinical Alzheimer's, which is particularly surprising because of Raman spectroscopy's high sensitivity regarding different measurement conditions. The presented results demonstrate the capability of Raman spectroscopy to detect preclinical Alzheimer's disease for the first time and offer invaluable opportunities for future clinical applications and diagnostic methods.

Clinicians' perspectives on race-specific guidelines for hypertensive treatment.

Despite the general consensus that there is no biological basis to race, racial categorization is still used by clinicians to guide diagnosis and treatment plans for certain diseases. In medicine, race is commonly used as a rough proxy for unmeasured social, environmental, and genetic factors. The American College of Cardiology's Eighth Joint National Committee's (JNC 8) guidelines for the treatment of hypertension provide race-specific medication recommendations for Black versus non-Black patients, without strong evidence for race-specific physiological differences in drug response. Clinicians practicing family or geriatric medicine (n = 21) were shown a video of a mock hypertensive patient with genetic ancestry test results that could be viewed as discordant with their phenotype and self-identified race. After viewing the videos, we conducted in-depth interviews to examine how clinicians value and prioritize different cues about race -- namely genetic ancestry data, phenotypic appearance, and self-identified racial classifications - when making treatment decisions in the context of race-specific guidelines, particularly in situations when patients claim mixed-race or complex racial identities. Results indicate that clinicians inconsistently follow the race-specific guidelines for patients whose genetic ancestry test results do not match neatly with their self-identified race or phenotypic features. However, many clinicians also emphasized the importance of clinical experience, side effects, and other factors in their decision making. Clinicians' definitions of race, categorization of the patient's race, and prioritization of racial cues greatly varied. The existence of the race-specific guidelines clearly influences treatment decisions, even as clinicians' express uncertainty about how to incorporate consideration of a patient's genetic ancestry. In light of widespread debate about removal of race from medical diagnostics, researchers should revisit the clinical justification for maintaining these race-specific guidelines. Based on our findings and prior studies indicating a lack of convincing evidence for biological differences by race in medication response, we suggest removing race from the JNC 8 guidelines to avoid risk of perpetuating or exacerbating health disparities in hypertension.

Doxycycline as Postsexual Exposure Prophylaxis: Use, Acceptability, and Associated Sexual Health Behaviors Among a Multi-Site Sample of Clinical Trial Participants.

Doxycycline postexposure prophylaxis (doxy-PEP) reduces sexually transmitted infections (STIs) in men who have sex with men (MSM) and transgender women (TGW). In a clinical trial of doxy-PEP, we sought to assess acceptability, impact, and meaning of doxy-PEP use among MSM/TGW. We conducted semistructured, in-depth 1:1 interviews with MSM and TGW enrolled in the intervention arm of the Doxy-PEP study. We queried motivations for and meaning of use, attitudes, beliefs, adherence, effect on sexual behaviors, and partner, community, and structural factors related to use. We coded interview transcripts into content areas, followed by thematic analysis. We interviewed 44 participants (median age 38), 2% were TGW, 17% Black, 61% White, 30% Hispanic, and 45% persons with HIV. We identified three overarching themes. First, participants found doxy-PEP acceptable, and believed it was effective based on their history of STIs, easy to adhere to, and acceptable to sex partners. Second, doxy-PEP benefited their quality of life and mental health, offering "peace of mind" by reducing their anxiety about acquisition or unwitting transmission of STIs. Participants reported feeling more "in control" of preventing STIs, and positive about supporting their personal, partner, and community health. Third, impact on sexual behavior was variable, with most reporting no change or a brief initial change. Participants in a multi-site clinical trial of doxycycline for STI prevention perceived it to be efficacious, and that it provided quality-of-life benefits, including reduced anxiety and sense of control over sexual health. Doxy-PEP had limited impact on sexual behavior. Clinicaltrials.gov: NCT03980223.

Impact of Pre-Gestational BMI and Gestational Weight Gain on Fetal Development Outcomes in Adolescent Pregnant Women.

Background. Gestational weight gain (GWG) constitutes an essential aspect of the gestational process. Due to factors such as pregestational body mass index (BMI), nutritional intake, level of physical activity, and psychological aspects, the recommended GWG may not be achieved, leading to adverse neonatal outcomes. Adolescents, due to their physiological and mental developmental stage, are at a higher risk of inappropriate GWG. Our aim is to highlight the importance of GWG in our population and to determine the correlation with perinatal outcomes. Methods. Pregnant adolescents who attended a tertiary care institution for prenatal care were included; maternal data such as preBMI and GWG were used to determine maternal and neonatal outcomes using the chi-square test and OR determination. Results. A total of 202 adolescent pregnant patients were included, comprising those with inadequate GWG (n = 70), adequate GWG (n = 85), and excessive GWG (n = 47). A statistically significant association was found between low BMI and inadequate GWG. Patients with inadequate GWG demonstrated a correlation with IUGR and low birth weight, while patients with excessive GWG gave birth to macrosomic neonates. Conclusion. We concluded that previous habits play a significant role in determining weight gain throughout pregnancy. GWG has a direct impact on neonatal growth and development.

An Event-based Neural Compressive Telemetry with >11× Loss-less Data Reduction for High-bandwidth Intracortical Brain Computer Interfaces.

Intracortical brain-computer interfaces offer superior spatial and temporal resolutions, but face challenges as the increasing number of recording channels introduces high amounts of data to be transferred. This requires power-hungry data serialization and telemetry, leading to potential tissue damage risks. To address this challenge, this paper introduces an event-based neural compressive telemetry (NCT) consisting of 8 channel-rotating Δ-ADCs, an event-driven serializer supporting a proposed ternary address event representation protocol, and an event-based LVDS driver. Leveraging a high sparsity of extracellular spikes and high spatial correlation of the high-density recordings, the proposed NCT achieves a compression ratio of >11.4×, while consumes only 1 µW per channel, which is 127× more efficient than state of the art. The NCT well preserves the spike waveform fidelity, and has a low normalized RMS error <23% even with a spike amplitude down to only 31 µV.

Fallo de medro en Pediatría de Atención Primaria: recomendaciones para su abordaje y seguimiento / Failure to Thrive in Primary Care pediatrics: recommendations for its approach and follow-up

El fallo de medro representa la dificultad para mantener un ritmo de crecimiento adecuado, tanto en peso como en talla, en menores de tres años. Se trata de una entidad actualmente infradiagnosticada que puede repercutir en el desarrollo físico, intelectual, emocional y social de los niños. El pediatra de Atención Primaria es clave en la identificación precoz y en la prevención de su morbilidad. Este documento representa una herramienta útil para el desarrollo de la labor conjunta del pediatra y la enfermería pediátrica, realizando una intervención precoz, individualizada y eficiente en estos niños. (AU)

Failure to thrive is poor physical growth, both in weight and height, in children under three years of age. This underdiagnosed entity can affect children’s physical, intellectual, emotional and social development. Paediatric Primary Care is crucial in early diagnosis and prevention of their morbidity. This document represents a useful tool for the teamwork between paediatricians and paediatric nursing. Its objective is to carry out an early, individualized and efficient approach in these children. (AU)

Association Between Rental Assistance Programs and Undiagnosed Diabetes Among U.S.

BACKGROUND: Rental assistance programs have been linked to better housing quality, stability, healthcare access, and reduced likelihood of uncontrolled diabetes. However, its direct association with diabetes screening is uncertain. OBJECTIVE: To determine whether federal rental assistance programs are associated with lower odds of undiagnosed diabetes. DESIGN: We used a quasi-experimental approach, comparing outcomes among adults receiving rental assistance to those who entered assisted housing within 2 years after their health data were collected. We test the a priori hypothesis that rental assistance will be associated with decreased odds of undiagnosed diabetes. PARTICIPANTS: Participants in the National Health and Nutrition Examination Survey 1999-2018 who received rental assistance and who had diabetes. INTERVENTION: Current rental assistance participation, including specific housing programs. MAIN MEASURES: Undiagnosed diabetes based on having hemoglobin A1c ≥ 6.5% but answering no to the survey question of being diagnosed with diabetes. KEY RESULTS: Among 435 eligible adults (median age 54.5 years, female 68.5%, non-Hispanic white 32.5%), 80.7% were receiving rental assistance programs at the time of the interview, and 19.3% went on to receive rental assistance within 2 years. The rates of undiagnosed diabetes were 15.0% and 25.3% among those receiving rental assistance programs vs. those in the future assistance group (p-value = 0.07). In an adjusted logistic regression model, adults receiving rental assistance had lower odds of undiagnosed diabetes (OR 0.52, 95% CI 0.28-0.94) than those in future assistance groups. Sex, race and ethnic group, educational level, and poverty ratio were not significantly associated with having undiagnosed diabetes, but individuals aged 45-64 years had significantly lower odds of undiagnosed diabetes (OR 0.21, 95% CI 0.08-0.53) compared with those aged 18-44. CONCLUSIONS: Rental assistance was linked to lower odds of undiagnosed diabetes, suggesting that affordable housing programs can aid in early recognition and diagnosis, which may improve long-term outcomes.

Cáncer incidental de vesícula: incidencia y factores asociados en pacientes de una institución de la ciudad de Medellín / Incidental gallbladder cancer: Incidence and associated factors in patients from an institution in the city of Medellín

Introducción. El cáncer de vesícula biliar es una de las neoplasias más frecuentes de la vía biliar y la mayoría de los casos se diagnostican de forma incidental o en estadios avanzados. En Colombia existen pocas publicaciones acerca de la prevalencia y características clínicas de pacientes con cáncer insospechado de vesícula biliar. El objetivo de este trabajo fue actualizar la información existente. Métodos. Estudio de tipo transversal basado en registros médicos. Como variable de resultado se definió el hallazgo incidental de patología maligna reportado por un patólogo y el subtipo histológico. Se midieron variables demográficas, clínicas y quirúrgicas. Se calcularon OR con sus respectivos intervalos de confianza (IC95%). Resultados. De los 2630 casos analizados, en cuatro se hizo diagnóstico de cáncer incidental de vesícula, con una prevalencia del 0,15 %. Se encontraron como características asociadas al cáncer incidental de vesícula, la edad, el antecedente de cáncer y la presencia de pólipos. Conclusiones. Esta es una patología poco frecuente en la población evaluada, lo que permite afirmar que no es necesario realizar estudios prequirúrgicos más amplios de forma rutinaria, a menos que el paciente presente alguno de los factores asociados.

Introduction. Gallbladder cancer is one of the most common neoplasms of the bile duct and most cases are diagnosed incidentally or in advanced stages. In Colombia, there are few publications about the prevalence and clinical characteristics of patients with unsuspected gallbladder cancer. The objective of this work was to update the existing information. Methods. Cross-sectional study based on medical records. The incidental finding of malignant pathology reported and the histological subtype were defined as the outcome variable. Demographic, clinical and surgical variables were measured. ORs were calculated with their respective 95% CI. Results. Of the 2630 cases analyzed, four were diagnosed with incidental gallbladder cancer, with a prevalence of 0.15%. Characteristics associated with incidental gallbladder cancer were age, history of cancer and the presence of polyps. Conclusions. This is a rare pathology in the population evaluated, which allows us to recommend that it is not necessary to routinely perform more extensive presurgical studies, unless the patient presents any of the associated factors.

Rotator cuff tear patterns: MRI appearance and its surgical relevance.

A new perspective on rotator cuff anatomy has allowed a better understanding of the patterns of the different rotator cuff tears. It is essential for radiologists to be aware of these different patterns of tears and to understand how they might influence treatment and surgical approach. Our objective is to review the arthroscopy correlated magnetic resonance imaging appearance of the different types of rotator cuff tears based on current anatomical concepts.Critical relevance statement Knowledge of the characteristics of rotator cuff tears improves our communication with the surgeon and can also make it easier for the radiologist to prepare a report that guides therapeutic conduct and serves as a prognosis for the patient.Key points• There is no universally accepted classification for RC tears.• New patterns such as delamination or myotendinous junction tears have been defined.• The most difficult feature to assess in full thickness tears on MRI is the pattern.• Fatty infiltration of the RC tendons is crucial in the prognosis and outcome.• The radiological report is an effective way of communication with the surgeon.

ATM Variant as a Cause of Hereditary Cutaneous Melanoma in a Spanish Family: Case Report.

Introduction: Ataxia-Telangiectasia Mutated (ATM) is a cancer predisposition gene; carriers of germline pathogenic variants have an increased risk of developing malignancies, including breast, prostate, pancreatic, and ovarian cancer. Most ATM variants are of uncertain significance. Findings from genome-wide association studies (GWAS) suggest that ATM may be a low-risk melanoma susceptibility locus. Case Report: We report the case of a Hispanic family whose members who have presented cutaneous melanoma have been found to be carriers for the ATM pathogenic variant c.3747-1G>C (rs730881364), one of whom was diagnosed at 24 years old. Discussion: We describe for the first time the possible clinical association between ATM (c.3747-1G>C) and familial melanoma. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site, assuming a variant that entails loss of functionality that is probably pathogenic and related to oncogenesis. However, we cannot exclude that cutaneous melanoma in both members and at an early age is the result of chance, environmental interaction, other uncontrolled external factors, or the interaction of other genetic alterations other than the ATM variant described in this study.

Madrid Newborn Sickle Cell Disease Cohort: clinical outcomes, stroke prevention and survival.

In May 2003, Madrid established the universal newborn screening (NBS) for sickle cell disease (SCD). However, there are no studies resembling the evolution of a SCD neonate cohort followed according to national guidelines in Spain. The aim of this study is to describe the morbimortality and the stroke prevention programme in patients diagnosed by SCD NBS in Madrid. This is a multicentre, observational, prospective cohort study between 2003 and 2018; 187 patients diagnosed with SCD were included (151 HbSS, 6 HbSß0, 27 HbSC, 3 HbSß +), and median follow-up was 5.2 years (0.03-14.9). There were 5 deaths: 2 related to SCD in patients with severe genotype (HbSS/HbSß0). Overall survival reached 95% and SCD-related survival 96.8%. The most frequent events were fever without focus, vaso-occlusive crises and acute chest syndromes. Eight strokes occurred in 5 patients which led to a 90.7% stroke-free survival in severe genotype patients (first stroke rate, 0.54 per 100 patient-years). Transcranial Doppler (TCD) was performed in 95% of eligible patients; 75% of children with pathological TCD remained stroke-free. Regarding HbSS/HbSß0 patients, 50.1% received hydroxyurea and 9.5% haematopoietic stem cell transplantation. This study reflects the evolution of Madrid SCD cohort and provides morbimortality data similar to other developed countries.

Ultra-high density electrodes improve detection, yield, and cell type identification in neuronal recordings.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra (NP Ultra). This device samples neuronal activity at ultra-high spatial density (~10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron's electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ~3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior.

Multiplexed Surface Electrode Arrays Based on Metal Oxide Thin-Film Electronics for High-Resolution Cortical Mapping.

Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired. This work presents an active micro-electrocorticography (µECoG) implant that tackles this limitation by incorporating metal oxide thin-film transistors (TFTs) into a flexible electrode array, allowing to address multiple electrodes through a single shared readout line. By combining the array with an incremental-ΔΣ readout integrated circuit (ROIC), the system is capable of recording from up to 256 electrodes virtually simultaneously, thanks to the implemented 16:1 time-division multiplexing scheme, offering lower noise levels than existing active µECoG arrays. In vivo validation is demonstrated acutely in mice by recording spontaneous activity and somatosensory evoked potentials over a cortical surface of ≈8×8 mm2 . The proposed neural interface overcomes the wiring bottleneck limiting ECoG arrays, holding promise as a powerful tool for improved mapping of the cerebral cortex and as an enabling technology for future brain-machine interfaces.

Atypical Presentation of Spitz Nevus: A Case Report.

Introduction: The Spitz nevus (SN) is an acquired melanocytic neoplasm composed of epithelioid and/or spindle cells, which tends to develop in childhood. In pediatric patients, it is usually located on the face and neck. Unusual locations have been found in the literature, such as the penis, mouth, and tongue, as well as 2 cases of ungual SN. Case Report: A 15-year-old male evaluated for dark brown-black longitudinal melanonychia that covered 40% of the nail, with pseudo-Hutchinson's sign, of 1 year of evolution. Discussion: The SN accounts for 1% of the melanocytic neoplasms. In the present paper, we show the third case of ungual SN never previously disclosed, which presents a zigzag pattern reported in the literature for its association with the pediatric population.

Caracterización sociodemográfica y alimentaria de personas vegetarianas chilenas en el año 2022

Actualmente, en Chile se ha evidenciado un aumento de la población vegetariana, sin embargo, existen escasos datos sociodemográficos, por lo cual, el objetivo del presente estudio es caracterizar, según antecedentes sociodemográficos y alimentarios a personas vegetarianas chilenas en el año 2022. Se utilizó el paradigma cuantitativo y el diseño metodológico fue no experimental, descriptivo, exploratorio de corte transversal. Se aplicó una encuesta de caracterización mediante Google Forms a 504 personas y para el análisis de la información se utilizó el programa SPSS v. 24. El 85,7% declaró ser de género femenino, la edad promedio fue 26,3 ± 5,7 años, 45,5% de los encuestados se declararon ovolactovegetarianos, seguido por vegetarianos estrictos (38,7%) y la principal motivación fue principios animalistas (68,7%). El 87,8% cursó educación superior y el 36,5% correspondió al área de salud. El principal motivo de asistencia al nutricionista fue el asesoramiento con un 80%. Se destacó que la población vegetariana consideró que es fundamental la asistencia a un profesional nutricionista para practicar este estilo de vida de forma óptima, por lo que es fundamental que los profesionales de salud se involucren en conocer a esta población, con el objetivo de otorgar una atención más cercana e integral. Finalmente, la presente investigación corresponde al primer estudio que permite caracterizar a la población vegetariana en Chile.

Currently, in Chile there has been an increase in the vegetarian population; however, there are few sociodemographic data, therefore, the objective of this study is to characterise, according to sociodemographic and dietary background, Chilean vegetarians in the year 2022. The quantitative paradigm was used and the methodological design was non-experimental, descriptive, exploratory cross-section. A characterisation survey was applied using Google Forms to 504 people and SPSS v. 24. 85.7% declared to be female, the average age was 26.3 ± 5.7 years, 45.5% of those surveyed declared themselves lacto-ovo vegetarians, followed by strict vegetarians (38.7%) and the main motivation was animalistic principles (68.7%). 87.8% attended higher education and 36.5% corresponded to the health area. The main reason for helping the nutritionist was the advice with 80%. It was highlighted that the vegetarian population considered that it is essential to assist a professional nutritionist in practising this lifestyle optimally, so it is essential that health professionals get involved in getting to know this population, with the aim of providing closer and more comprehensive care. Finally, this research corresponds to the first study that allows characterising the vegetarian population in Chile.

Single-Stage Immediate Breast Reconstruction with Acellular Dermal Matrix after Breast Cancer: Comparative Study and Evaluation of Breast Reconstruction Outcomes.

We evaluate postoperative complications, aesthetic results and satisfaction outcomes in patients with breast cancer after intervening with a skin-sparing or nipple-sparing mastectomy with an immediate prosthetic reconstruction with or without a biological mesh. Patients with multifocal breast cancer, ductal carcinoma in situ with an indication for a mastectomy and cT2 tumors with no response to primary systemic treatment were included, whereas patients aged >75 years, with inflammatory carcinoma, and severe circulatory disorders were excluded. Patients in the control group were reconstructed using a prosthesis, whereas the study group included patients reconstructed using a prosthesis and biological acellular porcine dermal mesh (Strattice™). In both groups, the result was assessed using the BREAST-Q instrument. A total of 51 patients (62 intervened breasts) were included in the study group and 38 patients (41 intervened breasts) in the control group. Implant loss and removal occurred in three patients in the study group (5.9%) and nine patients in the control group (24.3%; p = 0.030). Infections appeared in three patients in the study group (4.8%) and three patients in the control group (7.3%; p = 1.00). Skin necrosis appeared in 5 patients in the study group (12.2%) and 11 patients in the control group (21.6%; p = 0.367). Seroma appeared in five patients in the study group (12.2%) and five patients in the control group (8.1%; p = 0.514). The BREAST-Q questionnaire is a comparison between both groups regarding "satisfaction with breasts after surgery" (p = 0.026), "sexual well-being after intervention" (p = 0.010) and "satisfaction with the information received" (p = 0.049). We have noted a statistically significant decrease in implant loss in women receiving an implant with a biological mesh. A higher satisfaction was observed in patients reconstructed using Strattice™, with statistically significant differences in three items.

Copy-back viral genomes induce a cellular stress response that interferes with viral protein expression without affecting antiviral immunity.

Antiviral responses are often accompanied by translation inhibition and formation of stress granules (SGs) in infected cells. However, the triggers for these processes and their role during infection remain subjects of active investigation. Copy-back viral genomes (cbVGs) are the primary inducers of the mitochondrial antiviral signaling (MAVS) pathway and antiviral immunity during Sendai virus (SeV) and respiratory syncytial virus (RSV) infections. The relationship between cbVGs and cellular stress during viral infections is unknown. Here, we show that SGs form during infections containing high levels of cbVGs, and not during infections with low levels of cbVGs. Moreover, using RNA fluorescent in situ hybridization to differentiate accumulation of standard viral genomes from cbVGs at a single-cell level during infection, we show that SGs form exclusively in cells that accumulate high levels of cbVGs. Protein kinase R (PKR) activation is increased during high cbVG infections and, as expected, is necessary for virus-induced SGs. However, SGs form independent of MAVS signaling, demonstrating that cbVGs induce antiviral immunity and SG formation through 2 independent mechanisms. Furthermore, we show that translation inhibition and SG formation do not affect the overall expression of interferon and interferon stimulated genes during infection, making the stress response dispensable for global antiviral immunity. Using live-cell imaging, we show that SG formation is highly dynamic and correlates with a drastic reduction of viral protein expression even in cells infected for several days. Through analysis of active protein translation at a single-cell level, we show that infected cells that form SGs show inhibition of protein translation. Together, our data reveal a new cbVG-driven mechanism of viral interference where cbVGs induce PKR-mediated translation inhibition and SG formation, leading to a reduction in viral protein expression without altering overall antiviral immunity.