Flow reduction due to arterial catheterization during stroke treatment - A computational study using a distributed compartment model.

The effectiveness of various stroke treatments depends on the anatomical variability of the cerebral vasculature, particularly the collateral blood vessel network. Collaterals at the level of the Circle of Willis and distal collaterals, such as the leptomeningeal arteries, serve as alternative avenues of flow when the primary pathway is obstructed during an ischemic stroke. Stroke treatment typically involves catheterization of the primary pathway, and the potential risk of further flow reduction to the affected brain area during this treatment has not been previously investigated. To address this clinical question, we derived the lumped parameters for catheterized blood vessels and implemented a corresponding distributed compartment (0D) model. This 0D model was validated against an experimental model and benchmark test cases solved using a 1D model. Additionally, we compared various off-center catheter trajectories modeled using a 3D solver to this 0D model. The differences between them were minimal, validating the simplifying assumption of the central catheter placement in the 0D model. The 0D model was then used to simulate blood flows in realistic cerebral arterial networks with different collateralization characteristics. Ischemic strokes were modeled by occlusion of the M1 segment of the middle cerebral artery in these networks. Catheters of different diameters were inserted up to the obstructed segment and flow alterations in the network were calculated. Results showed up to 45% maximum blood flow reduction in the affected brain region. These findings suggest that catheterization during stroke treatment may have a further detrimental effect for some patients with poor collateralization.

Neurosteroids in Glioma: A Novel Therapeutic Concept.

Glioma, a diverse group of brain and spinal cord tumors arising from glial cells, is characterized by varying degrees of malignancy, with some types exhibiting highly aggressive behavior, rapid proliferation, and invasive growth patterns, posing significant therapeutic challenges. This review delves into the complex interactions between glioma cells, neurotransmitters, and neurosteroids, emphasizing their potential as therapeutic targets. Key neurotransmitters, like glutamate and gamma-aminobutyric acid (GABA), play crucial roles in glioma growth, invasion, and treatment response. This review examines the involvement of neurosteroids in glioma biology and explores innovative therapeutic strategies targeting these systems. It encompasses the biosynthesis and mechanisms of neurosteroids, interactions between gliomas and neurotransmitters, the spatial distribution of neurosteroid synthesis in gliomas, the role of ion channels, hormonal influences, enzyme modulation, and the neuroimmune system in glioma progression. Additionally, it highlights the potential of neurosteroids to modulate these pathways for therapeutic benefit.

Chemical Characterization of Pruning Wood Extracts from Six Japanese Plum (Prunus salicina Lindl.) Cultivars and Their Antitumor Activity.

The Japanese plum tree (Prunus salicina Lindl.) is mainly cultivated in temperate areas of China and some European countries. Certain amounts of wood (from pruning works) are generated every year from this crop of worldwide commercial significance. The main objective of this work was to value this agricultural woody residue, for which the chemical composition of pruning wood extracts from six Japanese plum cultivars was investigated, and the antiproliferative activity of extracts and pure phenolics present in those extracts was measured. For the chemical characterization, total phenolic content and DPPH radical-scavenging assays and HPLC‒DAD/ESI‒MS analyses were performed, with the procyanidin (-)-ent-epicatechin-(2α→O→7,4α→8)-epicatechin (5) and the propelargonidin (+)-epiafzelechin-(2ß→O→7,4ß→8)-epicatechin (7) being the major components of the wood extracts. Some quantitative differences were found among plum cultivars, and the content of proanthocyanidins ranged from 1.50 (cv. 'Fortune') to 4.44 (cv. 'Showtime') mg/g of dry wood. Regarding the antitumoral activity, eight wood extracts and four phenolic compounds were evaluated in MCF-7 cells after 48 h of induction, showing the wood extract from cv. 'Songold' and (‒)-annphenone (3), the best antiproliferative activity (IC50: 424 µg/mL and 405 µg/mL, respectively).

LDL-Cholesterol-Lowering Effects of a Dietary Supplement Containing Onion and Garlic Extract Used in Healthy Volunteers.

Hypercholesterolemia plays a pivotal role in the development and progression of cardiovascular diseases, and its prevention seems to be a crucial healthcare strategy to ameliorate these conditions. Subjects with mild hypercholesterolemia are frequently advised against using cholesterol-lowering drugs due to potential side effects, with an emphasis instead on prioritizing dietary adjustments and lifestyle modifications as the primary strategy. In this context, the use of dietary supplements based on medicinal plants may be recommended as a complementary approach to managing elevated cholesterol levels. The aim of this study was to investigate the safety and potential therapeutic effectiveness of a standardized formulation containing extracts from garlic and onions in addressing the health concerns of individuals with slightly elevated cholesterol levels. A controlled, randomized, double-blind, two parallel-group study was conducted over 8 weeks, with clinical visits scheduled at baseline, weeks 2 and 4, as well as at the end of the study. The results revealed significant reductions in both low-density lipoprotein cholesterol and total cholesterol levels among participants who received the extract. Additionally, improvements in blood pressure, as well as in oxidative and inflammatory markers were observed, thus suggesting its potential as a valuable therapeutic intervention for managing mild hypercholesterolemia.

A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment.

Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a heterochromatin-switch phenomenon whereby constitutive heterochromatin loss is partially mitigated through gains in facultative heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.

Efficacy and Safety of Mirabegron Add-on Therapy After Failure With Solifenacin in Multiple Sclerosis Patients With Overactive Bladder: A Pilot Study.

OBJECTIVES: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative progressive disease of central nervous system that mostly affects young adults. (1) Because of involvement of spinal cord and brain, lower urinary dysfunction symptoms are commonly encountered. MS patients mostly show overactive bladder symptoms like urgency, frequent daytime urination, and urgency incontinence. Among MS patients, antimuscarinic therapy is the first-line treatment with overactive bladder symptoms as well as in general population yet 30% of the patients show insufficient improvement or intolerance to the treatment (2). In our study, our aim is to evaluate the efficacy and safety of mirabegron add-on treatment in MS patients after inadequate response to antimuscarinic monotherapy. METHODS: University of Kyrenia and Dr Burhan Nalbantoglu State hospital's databases were screened for the study. Seventy patients who were residents diagnosed with MS according to McDonald criteria were questioned. Among these patients, a total of 22 of them were included in the study. Inclusion criteria was at least 3 years of MS diagnosis, score of <6 at Expanded Disability Status Scale, and a score of ≥3 at Overactive Bladder Symptom Score Scale. RESULTS: Among selected patients, 10 mg solifenacin treatment was daily started and followed for 4 weeks. Mirabegron add-on treatment was initiated to the 11 patient who had inadequate improvement in overactive bladder symptom score. After mirabegron add-on treatment among 11 patient, there was a sufficient improvement in overactive bladder symptom score ( P < 0.008). CONCLUSIONS: In our study, we have found that antimuscarinic and mirabegron combination causes improved efficacy for overactive bladder in MS population.

Description of the local hemodynamic environment in intracranial aneurysm wall subdivisions.

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient-specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier-Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low-shear environments can contribute to aneurysm pathology through distinct mechanisms.

Augmented surgical decision-making for glioblastoma: integrating AI tools into education and practice.

Surgical decision-making for glioblastoma poses significant challenges due to its complexity and variability. This study investigates the potential of artificial intelligence (AI) tools in improving "decision-making processes" for glioblastoma surgery. A systematic review of literature identified 10 relevant studies, primarily focused on predicting resectability and surgery-related neurological outcomes. AI tools, especially rooted in radiomics and connectomics, exhibited promise in predicting resection extent through precise tumor segmentation and tumor-network relationships. However, they demonstrated limited effectiveness in predicting postoperative neurological due to dynamic and less quantifiable nature of patient-related factors. Recognizing these challenges, including limited datasets and the interpretability requirement in medical applications, underscores the need for standardization, algorithm optimization, and addressing variability in model performance and then further validation in clinical settings. While AI holds potential, it currently does not possess the capacity to emulate the nuanced decision-making process utilized by experienced neurosurgeons in the comprehensive approach to glioblastoma surgery.

Distribution of rupture sites and blebs on intracranial aneurysm walls suggests distinct rupture patterns in ACom and MCA aneurysms.

The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient-specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient-specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high-flow in ACom with thin blebs at impingement sites and low-flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure-high-flow and low-flow conditions-highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient-specific characteristics impact these processes, which need further investigation.

A one-dimensional computational model for blood flow in an elastic blood vessel with a rigid catheter.

Strokes are one of the leading causes of death in the United States. Stroke treatment involves removal or dissolution of the obstruction (usually a clot) in the blocked artery by catheter insertion. A computer simulation to systematically plan such patient-specific treatments needs a network of about 105 blood vessels including collaterals. The existing computational fluid dynamic (CFD) solvers are not employed for stroke treatment planning as they are incapable of providing solutions for such big arterial trees in a reasonable amount of time. This work presents a novel one-dimensional mathematical formulation for blood flow modeling in an elastic blood vessel with a centrally placed rigid catheter. The governing equations are first-order hyperbolic partial differential equations, and the hypergeometric function needs to be computed to obtain the characteristic system of these hyperbolic equations. We employed the Discontinuous Galerkin method to solve the hyperbolic system and validated the implementation by comparing it against a well-established 3D CFD solver using idealized vessels and a realistic truncated arterial network. The results showed clinically insignificant differences in steady flow cases, with overall variations between 1D and 3D models remaining below 10%. Additionally, the solver accurately captured wave reflection phenomena at domain discontinuities in unsteady cases. A primary advantage of this model over 3D solvers is its ease in obtaining a discretized geometry of complex vasculatures with multiple arterial branches. Thus, the 1D computational model offers good accuracy and applicability in simulating complex vasculatures, demonstrating promising potential for investigating patient-specific endovascular interventions in strokes.

Focused ultrasound as a treatment modality for gliomas.

Ultrasound waves were initially used as a diagnostic tool that provided critical insights into several pathological conditions (e.g., gallstones, ascites, pneumothorax, etc.) at the bedside. Over the past decade, advancements in technology have led to the use of ultrasound waves in treating many neurological conditions, such as essential tremor and Parkinson's disease, with high specificity. The convergence of ultrasound waves at a specific region of interest/target while avoiding surrounding tissue has led to the coined term "focused ultrasound (FUS)." In tumor research, ultrasound technology was initially used as an intraoperative guidance tool for tumor resection. However, in recent years, there has been growing interest in utilizing FUS as a therapeutic tool in the management of brain tumors such as gliomas. This mini-review highlights the current knowledge surrounding using FUS as a treatment modality for gliomas. Furthermore, we discuss the utility of FUS in enhanced drug delivery to the central nervous system (CNS) and highlight promising clinical trials that utilize FUS as a treatment modality for gliomas.

Concordancia entre SPECT portátil y la gammagrafía convencional para detección de ganglio centinela en cáncer de mama / Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer

Introducción: La SPECT portátil puede ser una técnica de imagen útil para la planificación preoperatoria de la biopsia selectiva del ganglio centinela (BSGC) ya que permite la localización del ganglio centinela (GC) mediante imágenes tomográficas en 3D y en tiempo real y determina su profundidad, después de unos minutos de exploración. El objetivo del estudio fue evaluar la correlación entre el número de GC detectados entre las imágenes de la SPECT portátil y la linfogammagrafía (LG). Materiales y métodos: Cien pacientes con diagnóstico de cáncer de mama infiltrante y sin evidencia clínica de afectación ganglionar, se sometieron prospectivamente a una BSGC. El estudio preoperatorio incluyó imágenes de SPECT portátil a los 15 min tras la inyección y de LG a los 25 y 60-90 min (precoz y tardía). Se analizó el acuerdo observado y se realizó un estudio de concordancia entre el número de GC detectados con SPECT portátil y LG. Resultados: El acuerdo observado en la detección de GC entre SPECT portátil y LG precoz fue del 72%; entre SPECT portátil y LG tardía del 85%, y entre la LG precoz y la tardía de un 87%. En el estudio de concordancia se registró una concordancia moderada entre la SPECT portátil y la LG precoz (coeficiente kappa: 0,42); una concordancia moderada-alta entre la SPECT portátil y la LG tardía (coeficiente kappa: 0,60), y una concordancia de moderada-alta entre la LG precoz y la tardía (coeficiente kappa: 0,70), sin diferencias significativas entre ellos (valor p=0,16). Conclusión: La SPECT portátil presentó una concordancia moderada-alta con los estudios de imagen convencional y podría ser una alternativa válida para el estudio prequirúrgico de la BSGC en el cáncer de mama.(AU)

Introduction: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods: One hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60–90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. Results: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). Conclusion: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.(AU)

Relationship between transient ischemic dilatation and changes in heart rate during gated SPECT acquisition in a low-risk population without perfusion defects.

OBJECTIVES: Transient ischemic dilatation (TID) in myocardial perfusion single photon emission computed tomography (SPECT) is considered a marker of poor prognosis. However, it has been suggested that some cases are due to apparent volumetric changes secondary to differences in heart rate (HR) at the time of acquisition. We assessed the correlation between transient dilatation and HR in low risk patients with no perfusion defects. METHODS: We retrospectively analyzed patients sent for 99mTc-MIBI SPECT using a 2-day protocol. We recorded the median HR during acquisition and the HR difference (HRD) between the rest and post-stress. We obtained the medium ventricular volume, end-diastolic volume (EDV), and end-systolic volume (ESV). We included patients in which TID using medium ventricular volume (TIDMV) was ≥1.2. TID was also calculated for the EDV and ESV (TIDEDV, TIDESV). We excluded patients with known coronary artery disease, perfusion defects, various ECG disorders, positive stress test, or ESV < 10 ml. RESULTS: From a total of 2006 patients, 63 (50 exercise, 13 dipyridamole) met the criteria for analysis (age 63.8 ±â€…9.7, 44 men). TIDMV was 1.29 ±â€…0.09 and HRD 9.8 beats per minute (BPM) (range -10 to 41). There was positive correlation between HRD and TIDMV ( r  = 0.51, P  < 0.001) and TIDEDV ( r  = 0.5, P  < 0.001), but not TIDESV ( r  = 0.23, P  = 0.07). Correlation was stronger when HRD was ≥10 BPM ( r  = 0.67, P  < 0.001). CONCLUSION: TID without perfusion defects should be interpreted with caution in the presence of HRD ≥ 10 BPM during post-stress acquisition.

South American Archaeological Isotopic Database, a regional-scale multi-isotope data compendium for research.

The South American Archaeological Isotopic Database (SAAID) is a comprehensive open-access resource that aggregates all available bioarchaeological stable and radiogenic isotope measurements, encompassing data from human individuals, animals, and plants across South America. Resulting from a collaborative effort of scholars who work with stable isotopes in this region, SAAID contains 53,781 isotopic measurements across 24,507 entries from individuals/specimens spanning over 12,000 years. SAAID includes valuable contextual information on archaeological samples and respective sites, such as chronology, geographical region, biome, and spatial coordinates, biological details like estimated sex and age for human individuals, and taxonomic description for fauna and flora. SAAID is hosted at the PACHAMAMA community within the Pandora data platform and the CORA repository to facilitate easy access. Because of its rich data structure, SAAID is particularly well-suited for conducting spatiotemporal meta-analyses. It serves as a valuable tool for addressing a variety of research topics, including the spread, adoption, and consumption intensification of food items, paleo-environmental reconstruction, as well as the exploration of mobility patterns across extensive geographic regions.

Cardiovascular testing recovery in Latin America one year into the COVID-19 pandemic: An analysis of data from an international longitudinal survey.

Background: The COVID-19 pandemic disproportionately impacted Latin America (LATAM), significantly disrupting cardiovascular testing. This study evaluated cardiac procedure recovery in LATAM one year after the outbreak. Methods: The International Atomic Energy Agency (IAEA) surveyed 669 centers in 107 countries worldwide, including 135 facilities in 19 LATAM countries, to assess cardiovascular procedure volumes in March 2019, April 2020, and April 2021, and changes in center practices and staffing conditions one year into the COVID-19 pandemic. Findings: LATAM centers reported a 21 % decrease in procedure volumes in April 2021 from pre-pandemic-baseline, vs. a 0 % change in the rest of the world (RoW), and greater volume reductions for almost all procedure types. Centers in Central America and Mexico reported the largest procedure reductions (47 % reduction) compared to the Caribbean (15 %), and South America (14 %, p = 0.01), and this LATAM region was a significant predictor of lower procedure recovery in multivariable regression. More LATAM centers reported reduced salaries and increased layoffs of clinical staff compared to RoW, and LATAM respondents estimated that half of physician and non-physician staff experienced excess psychological stress related to the pandemic, compared to 25 % and 30 % in RoW (p < 0.001). Conclusions: Cardiovascular testing recovery in LATAM trailed behind RoW for most procedure types, with centers in Central America and Mexico reporting the greatest volume reductions. This study found lasting impacts of COVID-19 on cardiovascular care in LATAM and the need for mental health support for LATAM healthcare workers in current and future pandemics.

Microsurgical anatomy of the olfactory filaments in the nasal mucosa.

OBJECTIVE: The aim of this study was to examine the distribution of olfactory filaments (OFs) in the nasal mucosa to facilitate preservation of olfactory function in endonasal approaches and preparation of a nasoseptal flap. METHODS: One formalin-fixed and 9 fresh cadaveric silicone-injected specimens with 20 total sides were studied to measure the distance of the OFs to the anatomical landmarks and compare the OF presence in the nasal septum mucosa (NSM) and ethmoidal mucosa (EM). RESULTS: The mean distance from the first to the last OF was 19.37 ± 2.16 mm in the NSM and 23.44 ± 5.42 mm in the EM. The NSM had a mean of 7.55 ± 1.31 OFs and the EM had 14.3 ± 1.78. Average OF lengths were measured at 6.44 ± 1.48 (range 3.75-12.40) mm in the NSM and 8.05 ± 1.76 (range 4.14-13.20) mm in the EM. The mean values of the EM measurements were compared with those of the NSM; the number of OFs, the distance between the first and last OF, the average OF length, and the number of OFs between anterior and posterior ethmoidal arteries in the NSM were significantly less (p < 0.05) than those in the EM. The distance between the first OF to the nasal bone on the NSM was greater than on the EM. CONCLUSIONS: Compared with the EM, the OFs are significantly fewer in number and smaller in size in the NSM. The uppermost edge of the nasoseptal flap incision in the NSM might be safer to start below 12 mm from the cribriform plate for OF protection.

Antibody Conjugated Nano-Enabled Drug Delivery Systems Against Brain Tumors.

The use of antibody-conjugated nanoparticles for brain tumor treatment has gained significant attention in recent years. Nanoparticles functionalized with anti-transferrin receptor antibodies have shown promising results in facilitating nanoparticle uptake by endothelial cells of brain capillaries and post-capillary venules. This approach offers a potential alternative to the direct conjugation of biologics to antibodies. Furthermore, studies have demonstrated the potential of antibody-conjugated nanoparticles in targeting brain tumors, as evidenced by the specific binding of these nanoparticles to brain cancer cells. Additionally, the development of targeted nanoparticles designed to transcytoses the blood-brain barrier (BBB) to deliver small molecule drugs and therapeutic antibodies to brain metastases holds promise for brain tumor treatment. While the use of nanoparticles as a delivery method for brain cancer treatment has faced challenges, including the successful delivery of nanoparticles to malignant brain tumors due to the presence of the BBB and infiltrating cancer cells in the normal brain, recent advancements in nanoparticle-mediated drug delivery systems have shown potential for enhancing the efficacy of brain cancer therapy. Moreover, the development of brain-penetrating nanoparticles capable of distributing over clinically relevant volumes when administered via convection-enhanced delivery presents a promising strategy for improving drug delivery to brain tumors. In conclusion, the use of antibody-conjugated nanoparticles for brain tumor treatment shows great promise in overcoming the challenges associated with drug delivery to the brain. By leveraging the specific targeting capabilities of these nanoparticles, researchers are making significant strides in developing effective and targeted therapies for brain tumors.

Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons.

Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a's function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.

Clinical Characteristics and Microorganisms Isolated in Community-Acquired Pneumonia in the COVID-19 Period.

Introduction: Community-acquired pneumonia is a leading cause of mortality and hospital admissions. The aetiology remains unknown in 30-65% of the cases. Molecular tests are available for multiple pathogen detection and are under research to improve the causal diagnosis. Methods: We carried out a prospective study to describe the clinical characteristics and aetiology of community-acquired pneumonia during the COVID-19 pandemic and to assess the diagnostic effectivity of the microbiological tests, including a molecular test of respiratory pathogens (FilmArray™ bioMérieux). Results: From the 1st of February 2021 until the 31st of March 2022, 225 patients were included. Failure in microorganism identification occurred in approximately 70% of patients. Streptococcus pneumoniae was the most common isolate. There were 5 cases of viral pneumonia. The tested FilmArray exhibited a low positivity rate of 7% and mainly aided in the diagnosis of viral coinfections. Conclusions: Despite our extensive diagnostic protocol, there is still a low rate of microorganism identification. We have observed a reduction in influenza and other viral pneumoniae during the COVID-19 pandemic. Having a high NEWS2 score on arrival at the emergency department, an active oncohematological disease or chronic neurological conditions and a positive microbiological test result were related to worse outcomes. Further research is needed to determine the role of molecular tests in the microbiological diagnosis of pneumonia.