Autoimmune Liver Disease Associated Uveitis: An Extrahepatic Manifestation or a Polyautoimmunity Phenomenon? Case Reports.

PURPOSE: To report two cases of non-granulomatous unilateral anterior uveitis in two female patients associated with autoimmune liver diseases (ALD), emphasizing the possibility of this rare coexistence as a polyautoimmunity phenomenon. CASE DESCRIPTIONS: Case 1: An 18-year-old female with a history of congenital renal hypoplasia and metabolic syndrome presented with anterior uveitis in OS and a history of jaundice, blood elevated hepatic enzymes, and cholangioresonance compatible with primary sclerosing cholangitis (PSC). Laboratory work-up for additional autoimmune and infective causes were within normal limits. Case 2: An 58-year-old female presented an episode of anterior uveitis in OD and a history of Sjögren syndrome diagnosed at the age of 53, primary biliary cholangitis (PBC), systemic sclerosis, Raynaud's phenomenon, bilateral sacroiliitis, and vitiligo, consistent with polyautoimmunity and multiple autoimmune syndrome. CONCLUSIONS: Uveitis rarely coexists with ALD. However, it is essential to recognize the possibility of polyautoimmunity in patients presenting with ophthalmic manifestations and a previous diagnosis of ALD, such as PSC or PBC.

Early detection of optic nerve head changes using optical coherence tomography after using mesenchymal stromal cells as intravitreal therapy in rabbit models of ocular hypertension.

Background and Aim: Stem cell therapy is considered a promising treatment for several neurodegenerative diseases. However, there are very few studies on the use of this therapy in glaucoma models. By detecting the changes produced by glaucoma early, cell therapy could help prevent the events that lead to blindness. In this study, early changes in the optic nerve head (ONH) as detected by optical coherence tomography (OCT) after the application of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) in an experimental model of ocular hypertension (OH) were evaluated. Materials and Methods: Fifteen New Zealand rabbits were randomly divided into the following three groups: G1: OH, G2: hWJ-MSCs, and G3: OH + hWJ-MSCs. An OH model was constructed, and the intraocular pressure (IOP) was measured regularly. At week 7, 105/100 µL hWJ-MSCs were intravitreally injected. Retinography and OCT were used to evaluate structural changes in ONH. Results: IOP increased significantly in G1 and G3 from week 3 onward. Retinography revealed more significant optic nerve changes, that is, papillary asymmetry suggestive of optic nerve excavation, vascular alterations, and irregular hypopigmentation peripheral to the optic disk margin, in G1 compared with G3. OH locates the hWJ-MSCs solution in the vitreous in front of the optic nerve. OCT revealed retinal nerve fiber layer (RNFL) reduction in all groups, reduced optic cup volume in G2 and G3 between weeks 1 and 9, and significant ganglion cell layer thickness reduction in G1 and a slight increase in G3. Conclusion: Intravitreal hWJ-MSCs injection produced changes in optic cup volume, which were detected early on by OCT; however, RNFL could not be restored in this OH model.

Systemic and Bilateral Severe Ocular Toxoplasmosis Resembling Autoimmune Phenomena: A Case Report.

PURPOSE: To present an atypical case of severe bilateral ocular toxoplasmosis with systemic involvement that initially mimicked an autoimmune etiology, posing challenges to its diagnosis and treatment. CASE REPORT: A 39-year-old immunocompetent male was admitted to the hospital due to a presumed pulmonary thromboembolism concomitant with an abrupt onset of vision loss. Initial differential diagnoses included antiphospholipid syndrome and systemic lupus erythematosus, prompting the administration of corticosteroid pulses and rituximab. Despite observing a partial systemic response, there was no improvement in visual acuity. Subsequent aqueous humor polymerase chain reaction confirmed Toxoplasma gondii infection, leading to the introduction of oral antibiotic therapy. The patient's condition showed a partially favorable response; however, the treatment could not reverse the permanent retinal damage. CONCLUSION AND IMPORTANCE: This case underscores the importance of ruling out an infectious etiology in all cases of uveitis. Additionally, it alerts clinicians to the possibility that elevated positive autoantibodies may result from a severe inflammatory reaction caused by pathogens rather than an autoimmune or autoinflammatory disease, particularly in instances of poor treatment response or atypical clinical presentation.

Surgical stabilization of rib fractures under extracorporeal membrane oxygenation: A case report.

A 47-year-old male patient was referred to a level 1 trauma center with refractory acute respiratory distress syndrome, bilateral lung contusions, and flail chest after initial management for injuries sustained 5 days prior from an 8-m fall from a tower crane. Surgical stabilization of the rib fractures was achieved under extracorporeal membrane oxygenation support, with successful decannulation 4 days after surgery. The patient was discharged after 42 days and following multidisciplinary interventions. Use of extracorporeal membrane oxygenation support in blunt chest trauma patients presents a valuable opportunity as it may enable earlier surgical intervention and reduce in-hospital complications.

Conocimientos y prácticas sobre sífilis materna y congénita en adolescentes embarazadas en un Hospital General de Paraguay: estudio cualitativo

Introducción: La sífilis en embarazadas, sigue siendo un gran problema de salud pública en todo el mundo, y en Paraguay, no es la excepción. La sífilis congénita puede provocar abortos, muertes fetales y neonatales, peso bajo al nacer, prematuridad y otras anomalías congénitas, el conocimiento general de la población en edad fértil es fundamental. Objetivo: Analizar los conocimientos y prácticas sobre sífilis materna y sífilis congénita en adolescentes embarazadas en un Hospital General de Paraguay. Metodología: Se realizó un estudio cualitativo, fenomenológico descriptivo. Para la recolección de datos se utilizó la entrevista, simple que fue grabada con previa autorización del participante, la conclusión y recomendación serán entregados a la institución y a las adolescentes embarazadas. Resultados: Participaron diez adolescentes, en su mayoría de 19 años de edad, cinco conocen que la sífilis se transmite a través de las relaciones sexuales, sin embargo, desconocen acerca de cómo se transmite la sífilis congénita. Cinco de las adolescentes menciona haber iniciado las relaciones sexuales a los 16 años. Dos adolescentes a los 15 años, dos a los 14 años y una a los 17 años, nueve de las adolescentes embarazadas mencionan acudir a sus controles prenatales de forma periódica. Dos aún no se han realizado el test de VDRL. Discusión: Se concluye en cuanto al conocimiento, que solo cinco de diez adolescentes conocen acerca de la sífilis, sin embargo, no conocen sobre la sífilis congénita. En cuanto a las prácticas preventivas, 10 acuden de forma periódica a sus controles prenatales.

Introduction: Syphilis in pregnant women continues to be a major public health problem throughout the world, and in Paraguay, it is no exception. Congenital syphilis can cause abortions, fetal and neonatal deaths, low birth weight, prematurity, and other congenital anomalies; general knowledge of the population of childbearing age is essential. Objective: To analyze the knowledge and practices about maternal syphilis and congenital syphilis in pregnant adolescents in a General Hospital in Paraguay. Methodology: A qualitative, descriptive phenomenological study was carried out. A simple interview was used to collect data, which was recorded with prior authorization from the participant. The conclusion and recommendation will be delivered to the institution and to the pregnant adolescents. Results: Ten adolescents participated, mostly 19 years of age, five know that syphilis is transmitted through sexual relations, however, they do not know how congenital syphilis is transmitted. Five of the adolescent's mention having started sexual relations at the age of 16. Two adolescents at 15 years old, two at 14 years old and one at 17 years old, nine of the pregnant adolescent's mention attending their prenatal check-ups periodically. Two have not yet been tested for VDRL. Discussion: It is concluded in terms of knowledge that only five out of ten adolescents know about syphilis; however, they do not know about congenital syphilis. Regarding preventive practices, 10 attend their prenatal check-ups periodically.

Salud en la Frontera: Desafíos y Oportunidades para el Bienestar de las Comunidades Fronterizas

La salud en la frontera presenta una serie de desafíos y oportunidades para el bienestar de las comunidades fronterizas. Estas zonas geográficas, donde los límites políticos y territoriales se entrelazan, enfrentan problemas de salud únicos que requieren enfoques innovadores y colaborativos. Uno de los desafíos principales es el acceso limitado a servicios de atención médica de calidad. Las comunidades fronterizas a menudo carecen de infraestructuras de salud adecuadas, incluyendo hospitales y clínicas, lo que dificulta el acceso a servicios esenciales. Además, las barreras lingüísticas y culturales pueden dificultar aún más la comunicación entre los proveedores de salud y los pacientes, lo que limita la calidad de la atención. A pesar de estos desafíos, también existen oportunidades para mejorar la salud en la frontera. La colaboración transfronteriza puede ser una herramienta poderosa para abordar los problemas de salud comunes. Los países vecinos pueden compartir recursos, conocimientos y mejores prácticas para fortalecer los sistemas de salud en ambos lados de la frontera. Esto incluye la promoción de la formación y capacitación conjunta de profesionales de la salud, el intercambio de información epidemiológica y la armonización de políticas de salud. Además, las comunidades fronterizas pueden aprovechar su diversidad cultural y su conocimiento tradicional para mejorar la atención médica.

Border health presents a series of challenges and opportunities for border communities' well-being. These geographic areas, where political and territorial boundaries are intertwined, face unique health issues that require innovative and collaborative approaches. One of the main challenges is limited access to quality health care services. Border communities often lack adequate health infrastructure, including hospitals and clinics, which makes it difficult to access essential services. In addition, language and cultural barriers can further hinder communication between healthcare providers and patients, thereby limiting the quality of care. Despite these challenges, there are opportunities to improve border health. Cross-border collaboration can be a powerful tool for addressing common health problems. Neighboring countries can share resources, knowledge, and best practices to strengthen their health systems on both sides of their borders. This includes the promotion of joint education and training of health professionals, exchange of epidemiological information, and harmonization of health policies. In addition, border communities can take advantage of cultural diversity and traditional knowledge to improve healthcare.

Colombian Ocular Diseases Epidemiology Study (CODES): Prevalence and Sociodemographic Characterization of Refractive Errors in Colombian Eye Care Consultations.

PURPOSE: To estimate the prevalence and demographic characteristics of uncorrected refractive errors (URE) in people who attended eye care consultations in Colombia between 2015 and 2019, using the National Health Registry data. METHODS: We identified ICD codes for myopia (H-52.1), degenerative myopia (H-44.2), hyperopia (H-52.0), and astigmatism (H-52.2) from the Integrated Social Protection Information System. Crude prevalence rates by age and sex were calculated for the population attending eye care services during these years. Additionally, we developed a standardized morbidity map across county departments. RESULTS: In Colombia, the prevalence of URE among eye care consultations was 30.26%, increasing from 30.39% in 2015 to 35.14% in 2019. Of the 1,579,778 cases analyzed, 60.9% were females. Astigmatism emerged as the most prevalent URE, predominantly seen in individuals under 40 years old. Myopia showed the highest prevalence in the 10-30 age group, whereas hyperopia was most prevalent in the first decade of life. Geographically, the Andean region recorded most of URE cases, while more remote areas have seen a rising morbidity risk in recent years. CONCLUSIONS: The rising trend of URE in Colombia and its demographic and geographical variations underscores the urgent need for health professionals and government authorities to acknowledge and address this issue. This study provides crucial insights into the refractive error landscape across the country, highlighting the necessity for prevention programs specifically designed to cater to the country's unique needs.

Real-world experience with pertuzumab and trastuzumab combined with chemotherapy in neoadjuvant treatment for patients with early-stage HER2-positive breast cancer: the NEOPERSUR study.

PURPOSE: HER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC. METHODS: A retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR). RESULTS: A total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3-7.7) and 7.3 (95% CI 7.1-7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3-4 anti-HER2 related toxicities were reported in six (1.9%) patients. CONCLUSION: Neoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.

(Alternative) transcription start sites as regulators of RNA processing.

Alternative transcription start site usage (ATSS) is a widespread regulatory strategy that enables genes to choose between multiple genomic loci for initiating transcription. This mechanism is tightly controlled during development and is often altered in disease states. In this review, we examine the growing evidence highlighting a role for transcription start sites (TSSs) in the regulation of mRNA isoform selection during and after transcription. We discuss how the choice of transcription initiation sites influences RNA processing and the importance of this crosstalk for cell identity and organism function. We also speculate on possible mechanisms underlying the integration of transcriptional and post-transcriptional processes.

Challenging frontiers: Canine sporotrichosis due to Sporothrix brasiliensis, first case in Chile.

We report the first case of Sporothrix brasiliensis in a dog at Santiago, Chile. From an initial biopsy obtained from the patient, a histopathological study was performed that oriented a fungal infection. The molecular diagnosis from the isolated colony confirmed the identity of the S. brasiliensis agent. Although the literature indicates itraconazole as the first treatment option, the patient was treated with terbinafine followed by itraconazole, without achieving a clinical cure. S. brasiliensis that spread rapidly in Latin America, hence highlight the importance of timely diagnosis that contribute to maintaining human and animal health. 2012 Elsevier Ltd. All rights reserved.

In-cell NMR suggests that DNA i-motif levels are strongly depleted in living human cells.

I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites with i-motif formation propensity (iMFPS) in human cells, yet their specific contributions remain unclear. Using in-cell NMR with oligonucleotide iMFPS models, we monitor iM-associated structural equilibria in asynchronous and cell cycle-synchronized HeLa cells at 37 °C. Our findings show that iMFPS displaying pHT < 7 under reference in vitro conditions occur predominantly in unfolded states in cells, while those with pHT > 7 appear as a mix of folded and unfolded states depending on the cell cycle phase. Comparing these results with previous data obtained using an iM-specific antibody (iMab) reveals that cell cycle-dependent iM formation has a dual origin, and iM formation concerns only a tiny fraction (possibly 1%) of genomic sites with iM formation propensity. We propose a comprehensive model aligning observations from iMab and in-cell NMR and enabling the identification of iMFPS capable of adopting iM structures under physiological conditions in living human cells. Our results suggest that many iMFPS may have biological roles linked to their unfolded states.

Sustainable Silk-Based Particulate Systems for the Controlled Release of Pharmaceuticals and Bioactive Agents in Wound Healing and Skin Regeneration.

The increasing demand for innovative approaches in wound healing and skin regeneration has prompted extensive research into advanced biomaterials. This review focuses on showcasing the unique properties of sustainable silk-based particulate systems in promoting the controlled release of pharmaceuticals and bioactive agents in the context of wound healing and skin regeneration. Silk fibroin and sericin are derived from well-established silkworm production and constitute a unique biocompatible and biodegradable protein platform for the development of drug delivery systems. The controlled release of therapeutic compounds from silk-based particulate systems not only ensures optimal bioavailability but also addresses the challenges associated with conventional delivery methods. The multifaceted benefits of silk proteins, including their inherent biocompatibility, versatility, and sustainability, are explored in this review. Furthermore, the intricate mechanisms by which controlled drug release takes place from silk-based carriers are discussed.

Adoptive T cell therapy for solid tumors: current landscape and future challenges.

Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate the antitumor immune response, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene-modified T cells, and therapy with tumor-infiltrating lymphocytes (TILs). The outstanding results of CAR-T cells in some hematologic malignancies have launched the investigation of ACT in patients with refractory solid malignancies. However, certain characteristics of solid tumors, such as their antigenic heterogeneity and immunosuppressive microenvironment, hamper the efficacy of antigen-targeted treatments. Other ACT modalities, such as TIL therapy, have emerged as promising new strategies. TIL therapy has shown safety and promising activity in certain immunogenic cancers, mainly advanced melanoma, with an exciting rationale for its combination with immune checkpoint inhibitors. However, the implementation of TIL therapy in clinical practice is hindered by several biological, logistic, and economic challenges. In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell therapy in patients with solid tumors.

Using global remote camera data of a solitary species complex to evaluate the drivers of group formation.

The social system of animals involves a complex interplay between physiology, natural history, and the environment. Long relied upon discrete categorizations of "social" and "solitary" inhibit our capacity to understand species and their interactions with the world around them. Here, we use a globally distributed camera trapping dataset to test the drivers of aggregating into groups in a species complex (martens and relatives, family Mustelidae, Order Carnivora) assumed to be obligately solitary. We use a simple quantification, the probability of being detected in a group, that was applied across our globally derived camera trap dataset. Using a series of binomial generalized mixed-effects models applied to a dataset of 16,483 independent detections across 17 countries on four continents we test explicit hypotheses about potential drivers of group formation. We observe a wide range of probabilities of being detected in groups within the solitary model system, with the probability of aggregating in groups varying by more than an order of magnitude. We demonstrate that a species' context-dependent proclivity toward aggregating in groups is underpinned by a range of resource-related factors, primarily the distribution of resources, with increasing patchiness of resources facilitating group formation, as well as interactions between environmental conditions (resource constancy/winter severity) and physiology (energy storage capabilities). The wide variation in propensities to aggregate with conspecifics observed here highlights how continued failure to recognize complexities in the social behaviors of apparently solitary species limits our understanding not only of the individual species but also the causes and consequences of group formation.

Mesenchymal Stromal Cells from Human Wharton's Jelly Modulate the Intraocular Immune Response in a Glucocorticoid Hypertension Model: An Exploratory Analysis.

INTRODUCTION: Glaucoma is a neurodegenerative disease characterized by the loss of retinal ganglion cells. Recent research suggests immunological changes such as cytokine imbalance may affect its pathophysiology. This implies that immunomodulation, like that of mesenchymal cells, could be a potential therapeutic avenue for this disease. However, the effects of intravitreal injections of human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) on intraocular immune response have not been assessed in ocular hypertension (OH) models. METHODS: We explored this by measuring cytokine levels and expression of other markers, such as glial fibrillary acidic protein (GFAP) and T cells, in 15 randomly divided New Zealand rabbits: G1: OH, G2: hWJ-MSCs, and G3: OH+hWJ-MSCs. We analyzed the aqueous humor (IL-6, IL-8, and TNF-α) and vitreous humor (IFN-γ, IL-10, and TGF-ß) using ELISA and flow cytometry (cell populations), as well as TCD3+, TCD3+/TCD4+, and TCD3+/TCD8+ lymphocytes, and GFAP in the retina and optic nerve through immunohistochemistry. RESULTS: We found a decrease in TNF-α, IL-6, IFN-γ, IL-10, and IL-8 in G3 compared to G1 and an increase in TGF-ß in both G2 and G3. TCD3+ retinal infiltration in all groups was primarily TCD8+ rather than TCD4+ cells, and strong GFAP expression was observed in both the retina and optic nerves in all groups. CONCLUSION: Our results suggest that cellular and humoral immune responses may play a role in glaucomatous optic neuropathy and that intravitreal hWJ-MSCs can induce an immunosuppressive environment by inhibiting proinflammatory cytokines and enhancing regulatory cytokines.

Reptile Identification for Endemic and Invasive Alien Species Using Transfer Learning Approaches.

The Canary Islands are considered a hotspot of biodiversity and have high levels of endemicity, including endemic reptile species. Nowadays, some invasive alien species of reptiles are proliferating with no control in different parts of the territory, creating a dangerous situation for the ecosystems of this archipelago. Despite the fact that the regional authorities have initiated actions to try to control the proliferation of invasive species, the problem has not been solved as it depends on sporadic sightings, and it is impossible to determine when these species appear. Since no studies for automatically identifying certain species of reptiles endemic to the Canary Islands have been found in the current state-of-the-art, from the Signals and Communications Department of the Las Palmas de Gran Canaria University (ULPGC), we consider the possibility of developing a detection system based on automatic species recognition using deep learning (DL) techniques. So this research conducts an initial identification study of some species of interest by implementing different neural network models based on transfer learning approaches. This study concludes with a comparison in which the best performance is achieved by integrating the EfficientNetV2B3 base model, which has a mean Accuracy of 98.75%.

Modularity Implications of an Overground Exoskeleton on Plantar Pressures, Strength, and Spasticity in Persons with Acquired Brain Injury.

This study explored the effects of a modular overground exoskeleton on plantar pressure distribution in healthy individuals and individuals with Acquired Brain Injury (ABI). The research involved 21 participants, including ABI patients and healthy controls, who used a unique exoskeleton with adaptable modular configurations. The primary objective was to assess how these configurations, along with factors such as muscle strength and spasticity, influenced plantar pressure distribution. The results revealed significant differences in plantar pressures among participants, strongly influenced by the exoskeleton's modularity. Notably, significant distinctions were found between ABI patients and healthy individuals. Configurations with two modules led to increased pressure in the heel and central metatarsus regions, whereas configurations with four modules exhibited higher pressures in the metatarsus and hallux regions. Future research should focus on refining and customizing rehabilitation technologies to meet the diverse needs of ABI patients, enhancing their potential for functional recovery.

Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA).

PURPOSE: To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. METHODS: Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitis from January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. RESULTS: The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. CONCLUSION: This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patterns of uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation.

Additive Manufacturing of Nanocellulose Aerogels with Structure-Oriented Thermal, Mechanical, and Biological Properties.

Additive manufacturing (AM) is widely recognized as a versatile tool for achieving complex geometries and customized functionalities in designed materials. However, the challenge lies in selecting an appropriate AM method that simultaneously realizes desired microstructures and macroscopic geometrical designs in a single sample. This study presents a direct ink writing method for 3D printing intricate, high-fidelity macroscopic cellulose aerogel forms. The resulting aerogels exhibit tunable anisotropic mechanical and thermal characteristics by incorporating fibers of different length scales into the hydrogel inks. The alignment of nanofibers significantly enhances mechanical strength and thermal resistance, leading to higher thermal conductivities in the longitudinal direction (65 mW m-1  K-1 ) compared to the transverse direction (24 mW m-1  K-1 ). Moreover, the rehydration of printed cellulose aerogels for biomedical applications preserves their high surface area (≈300 m2  g-1 ) while significantly improving mechanical properties in the transverse direction. These printed cellulose aerogels demonstrate excellent cellular viability (>90% for NIH/3T3 fibroblasts) and exhibit robust antibacterial activity through in situ-grown silver nanoparticles.

Nucleotide metabolism, leukodystrophies, and CNS pathology.

The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to "TORCH" infections (Toxoplasma gondii, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications. AGS was first described in the early 1980s as familial clusters of "TORCH" infections, with severe neurology impairment, microcephaly, and basal ganglia calcifications (Aicardi & Goutières, Ann Neurol, 1984;15:49-54) and was associated with chronic cerebrospinal fluid (CSF) lymphocytosis and elevated type I interferon levels (Goutières et al., Ann Neurol, 1998;44:900-907). Since its first description, the clinical spectrum of AGS has dramatically expanded from the initial cohorts of children with severe impairment to including individuals with average intelligence and mild spastic paraparesis. This broad spectrum of potential clinical manifestations can result in a delayed diagnosis, which families cite as a major stressor. Additionally, a timely diagnosis is increasingly critical with emerging therapies targeting the interferon signaling pathway. Despite the many gains in understanding about AGS, there are still many gaps in our understanding of the cell-type drivers of pathology and characterization of modifying variables that influence clinical outcomes and achievement of timely diagnosis.