Early Window Research Articles

Sensory-Behavioral Deficits in Parkinson's Disease: Insights from a 6-OHDA Mouse Model.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the striatum, predominantly associated with motor symptoms. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remains poorly understood. In this study, we examined changes in tactile sensation within a Parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal dopamine (DA). Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and Parkinson-like states. Our findings reveal that DA depletion induces pronounced alterations in tactile sensation behavior, extending beyond expected motor impairments. We observed diverse behavioral deficits, spanning detection performance, task engagement, and reward accumulation, among lesioned individuals. While subjects with extreme DA depletion consistently showed severe sensory behavioral deficits, others with substantial DA depletion displayed minimal changes in sensory behavior performance. Moreover, some exhibited moderate degradation of behavioral performance, likely stemming from sensory signaling loss rather than motor impairment. The implementation of a sensory detection task is a promising approach to quantify the extent of impairments associated with DA depletion in the animal model. This facilitates the exploration of early non-motor deficits in PD, emphasizing the importance of incorporating sensory assessments in understanding the diverse spectrum of PD symptoms.

The role of microglial TREM2 in development: A path toward neurodegeneration?

The nervous and the immune systems undergo a continuous cross talk, starting from early development and continuing throughout adulthood and aging. Defects in this cross talk contribute to neurodevelopmental and neurodegenerative diseases. Microglia are the resident immune cells in the brain that are primarily involved in this bidirectional communication. Among the microglial genes, trem2 is a key player, controlling the functional state of microglia and being at the forefront of many processes that require interaction between microglia and other brain components, such as neurons and oligodendrocytes. The present review focuses on the early developmental window, describing the early brain processes in which TREM2 is primarily involved, including the modulation of synapse formation and elimination, the control of neuronal bioenergetic states as well as the contribution to myelination processes and neuronal circuit formation. By causing imbalances during these early maturation phases, dysfunctional TREM2 may have a striking impact on the adult brain, making it a more sensitive target for insults occurring during adulthood and aging.

The Role of Last-Mile Delivery Quality and Satisfaction in Online Retail Experience: An Empirical Analysis

The rise of the e-commerce industry has markedly changed the global economy, providing customers with unparalleled access to goods and services. This study empirically examines online shoppers’ perceptions and preferences, focusing on their experiences with last-mile delivery (LMD) services and its impact on their shopping behaviour. This research employs machine learning classification and regression models for a large-scale analysis of customers’ responses, collected using an online survey in the main cities in Saudi Arabia, which is experiencing rapid e-commerce growth amidst a broader digital transformation. The findings highlight a strong consumer preference for timely LMD services, typically within a day of purchase, while noting dissatisfaction with exceedingly early delivery windows. The research emphasises the need to address customer dissatisfaction with delivery services to retain clientele, as many may switch retailers without informing the retailers. Additionally, a considerable trend towards preferring digital over cash-on-delivery payment methods was observed among online shoppers. Overall, this study provides valuable insights into the significant influence of LMD services on customer satisfaction and behaviour in the e-commerce sector. The use of robust machine learning models has revealed critical factors that can guide retailers and LMD providers in enhancing service delivery and customer experience, contributing to the broader discourse on e-commerce logistics efficiency and customer satisfaction.

Comparison of vascular risk profile and clinical outcomes among patients with central (branch) retinal artery occlusion versus amaurosis fugax

BackgroundRetinal artery occlusions lead to sudden, painless vision loss, affecting millions globally. Despite their significance, treatment strategies remain unestablished, contrasting with acute ischemic stroke (AIS), where IVT has proven efficacy. Similar to AIS, retinal artery occlusions demand urgent evaluation and treatment, reflecting the principle "time is retina". Even for patients with transient monocular vision loss, also known as amaurosis fugax (AF), pertinent guidelines meanwhile recommend immediate emergency assessment in a specialized facility. However, data on the clinical benefit and comparability with persistent occlusions are missing. This study aimed to compare the results of a comprehensive stroke-workup among patients with persistent retinal artery occlusions (RAO), including both central retinal (CRAO) and branch retinal artery occlusion (BRAO) and those with AF.MethodsConducted at the University Hospital Giessen, Germany, this exploratory cross-sectional study enrolled patients with transient or permanent unilateral vision loss of non-arteritic origin. The primary outcome were differences between the two groups RAO and AF with regard to cardiovascular risk profiles and comorbidities, vascular and pharmacological interventions and clinical neurological and ophthalmological outcomes. Secondary outcome was a sub-group analysis of patients receiving IVT.ResultsOut of 166 patients assessed, 76 with RAO and 40 with AF met the inclusion criteria. Both groups exhibited comparable age, gender distribution, and cardiovascular risk profiles. Notably, RAO patients did not show significantly more severe vascular comorbidities than AF patients. However, AF patients received vascular interventions more frequently. Pharmacological intervention rates were similar across groups. RAO patients had slightly worse neurological outcomes, and IVT did not yield favorable ophthalmological outcomes within any observed patients.ConclusionThe study found similar vascular burden and risk factors in patients with RAO and AF, with implications for clinical workflows. IVT for RAO may only be effective in very early treatment windows. This emphasizes the need for public awareness and collaborative protocols between ophthalmologists and neurologists to improve outcomes.

Outcomes of Blood Flow Restriction Training After ACL Reconstruction in NCAA Division I Athletes.

Blood flow restriction training (BFRT) is a safe and potentially effective adjunctive therapeutic modality for postoperative rehabilitation related to various knee pathologies. However, there is a paucity of literature surrounding BFRT in high-performance athletes after anterior cruciate ligament reconstruction (ACLR). To (1) compare the overall time to return to sports (RTS) in a cohort of National Collegiate Athletic Association (NCAA) Division I athletes who underwent a standardized rehabilitation program either with or without BFRT after ACLR and (2) identify a postoperative time interval for which BFRT has the maximum therapeutic benefit. Cohort study; Level of evidence, 3. A total of 55 student-athletes who underwent ACLR between 2000 and 2023 while participating in NCAA Division I sports at a single institution were included in this study. Athletes were allocated to 1 of 2 groups based on whether they participated in a standardized postoperative rehabilitation program augmented with BFRT (BFRT group; n = 22) or completed the standardized protocol alone (non-BFRT group [control]; n = 33). Our primary outcome measure was time to RTS. The secondary outcome measure was handheld dynamometry quadriceps strength testing at various postoperative time points, converted to a limb symmetry index (LSI). Quadriceps strength was not tested between the BFRT and non-BFRT groups because of the limited amount of data on the control group. The mean age at the date of surgery was 18.59 ± 1.10 years for the BFRT group and 19.45 ± 1.30 years for the non-BFRT group (P = .011), and the mean RTS time was 409 ± 134 days from surgery for the BFRT group and 332 ± 100 days for the non-BFRT cohort (P = .047). For the BFRT group, the mean quadriceps strength LSI increased by 0.67% (95% CI, 0.53%-0.81%) for every week of rehabilitation, and there was a significantly positive rate of change in quadriceps strength in weeks 13-16 compared with weeks 9-12 (ΔLSI, 8.22%; P < .001). In elite NCAA Division I athletes, a statistically significant delay was observed in RTS with BFRT compared with standardized physical therapy alone after undergoing ACLR. There also appeared to be an early window during the rehabilitation period where BFRT had a beneficial impact on quadriceps strength.

Organic geochemical investigation of cretaceous source rocks with varying thermal maturity levels in the East Andes (Boyacá, Colombia)

This study encompasses a geochemical investigation of Cretaceous source rocks from the Eastern Cordillera (Colombia). This basin represents an interesting area for geochemical studies due to its abundance of organic matter-rich levels, some of which exhibit mild to extremely high thermal maturities, enabling discussion on long-term carbon sinks. This research work focuses on the study of organic-rich shaly sediments of Barremian to Campanian age from seven (7) outcrop locations in two areas of the Boyacá Department. A set of seventy (70) rock samples have been analysed using several organic geochemical techniques and have shown to cover thermal maturity ranges from the early oil window to the metagenesis stage (measured reflectance values from 0.6% to 2.1%). The OAE2 event was identified based on a 2.5‰–3‰ carbon isotopic excursion in the distal Guaguaquí Group from the section along the Guaquaquí River. Maturity was not found to correlate with depositional burial depths in the so-called distal study area, suggesting that other tectonic events may have played an important role in the genetic history of hydrocarbons particularly in this part of the Boyacá Department. During the mid-to late Cretaceous times, the two study areas consisted of a marine margin with a terrestrial input from the east, which is reflected in a higher terrestrial character of sediments in the eastern foothills (V/Ni < 0.7) compared to the others. Finally, fluorene- and diamondoid-based components were used for enhancing the characterization of the mid-to late Cretaceous organic matter in terms of source in the study sub-region (three-fluorenes and dimethyl-/trimethyl-adamantanes ratios above or below 0.25 and 0.85).

The influence of maternal prepregnancy weight and gestational weight gain on the umbilical cord blood metabolome: a case–control study

BackgroundMaternal overweight/obesity and excessive gestational weight gain (GWG) are frequently reported to be risk factors for obesity and other metabolic disorders in offspring. Cord blood metabolites provide information on fetal nutritional and metabolic health and could provide an early window of detection of potential health issues among newborns. The aim of the study was to explore the impact of maternal prepregnancy overweight/obesity and excessive GWG on cord blood metabolic profiles.MethodsA case control study including 33 pairs of mothers with prepregnancy overweight/obesity and their neonates, 30 pairs of mothers with excessive GWG and their neonates, and 32 control mother-neonate pairs. Untargeted metabolomic profiling of umbilical cord blood samples were performed using UHPLC‒MS/MS.ResultsForty-six metabolites exhibited a significant increase and 60 metabolites exhibited a significant reduction in umbilical cord blood from overweight and obese mothers compared with mothers with normal body weight. Steroid hormone biosynthesis and neuroactive ligand‒receptor interactions were the two top-ranking pathways enriched with these metabolites (P = 0.01 and 0.03, respectively). Compared with mothers with normal GWG, in mothers with excessive GWG, the levels of 63 metabolites were increased and those of 46 metabolites were decreased in umbilical cord blood. Biosynthesis of unsaturated fatty acids was the most altered pathway enriched with these metabolites (P < 0.01).ConclusionsPrepregnancy overweight and obesity affected the fetal steroid hormone biosynthesis pathway, while excessive GWG affected fetal fatty acid metabolism. This emphasizes the importance of preconception weight loss and maintaining an appropriate GWG, which are beneficial for the long-term metabolic health of offspring.

Current State of Evidence for Neuroimaging Paradigms in Management of Acute Ischemic Stroke.

Stroke is the chief differential diagnosis in patient presenting to the emergency room with abrupt onset focal neurological deficits. Neuroimaging, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI), vascular and perfusion imaging, is a cornerstone in the diagnosis and treatment decision-making. This review examines the current state of evidence behind the different imaging paradigms for acute ischemic stroke diagnosis and treatment, including current recommendations from the guidelines. Non-contrast CT brain, or in some centers MRI, can help differentiate ischemic stroke and intracerebral hemorrhage (ICH), a pivotal juncture in stroke diagnosis and treatment algorithm, especially for early window thrombolytics. Advanced imaging such as MRI or perfusion imaging can also assist making a diagnosis of ischemic stroke versus mimics such as migraine, Todd's paresis, or functional disorders. Identification of medium-large vessel occlusions with CT or MR angiography triggers consideration of endovascular thrombectomy (EVT), with additional perfusion imaging help identify salvageable brain tissue in patients who are likely to benefit from reperfusion therapies, particularly in the ≥6 h window. We also review recent advances in neuroimaging and ongoing trials in key therapeutic areas and their imaging selection criteria to inform the readers on potential future transitions into use of neuroimaging for stroke diagnosis and treatment decision making. ANN NEUROL 2024;95:1017-1034.

“Examining the link between tooth agenesis and papillary thyroid cancer: is there a risk factor?” Observational study

BackgroundMutations in one or multiple genes can lead to hypodontia and its characteristic features. Numerous studies have shown a strong genetic influence on the occurrence of hypodontia, and identified several genes, including AXIN2, EDA, FGF3, FGFR2, FGFR10, WNT10A, MSX1, and PAX9, that are directly associated with dental agenesis and carcinogenesis. The objective of this study was to investigate the occurrence and pattern of tooth agenesis, microdontia, and palatally displaced canine (PDC) in women diagnosed with papillary thyroid cancer (PTC), compared to a control group of women without any malignancy or thyroid disease.Materials and methodsThis case–control study was carried at the Department of Orthodontics, School of Dental Medicine University of Zagreb, and Department of Oncology and Nuclear Medicine Sestre Milosrdnice University Hospital Centre. The study involved a clinical examination and evaluation of dental status, panoramic X-ray analysis, and assessment of medical and family history of 116 female patients aged 20–40 with PTC, as well as 424 females in the control group who were of similar age.ResultsThe prevalence of hypodontia, microdontia, and PDC was statistically higher in women with PTC than in the control group. The prevalence rate of hypodontia was 11.3% in the experimental group and 3.5% in the control group. The experimental group showed a higher occurrence of missing upper lateral incisors, lower left central incisors, and all the third molars (except the upper left) compared to the control group. Women with PTC showed the prevalence of PDC significantly higher than the control group (3.5%, 0.7%, p = 0.002). The probability of hypodontia as a clinical finding increases 2.6 times, and microdontia occurs 7.7 times more frequently in women with PTC.ConclusionOur study suggests a possible link between odontogenesis and PTC. The absence of permanent teeth may increase the likelihood of PTC in women. Leveraging the age-7 orthopantomogram to identify women at high risk for PTC within a critical early detection window could significantly improve oral health outcomes and PTC prognosis through proactive interventions.

Early life imprinting of intestinal immune tolerance and tissue homeostasis.

Besides its canonical role in protecting the host from pathogens, the immune system plays an arguably equally important role in maintaining tissue homeostasis. Within barrier tissues that interface with the external microenvironment, induction of immune tolerance to innocuous antigens, such as commensal, dietary, and environmental antigens, is key to establishing immune homeostasis. The early postnatal period represents a critical window of opportunity in which parallel development of the tissue, immune cells, and microbiota allows for reciprocal regulation that shapes the long-term immunological tone of the tissue and subsequent risk of immune-mediated diseases. During early infancy, the immune system appears to sacrifice pro-inflammatory functions, prioritizing the establishment of tissue tolerance. In this review, we discuss mechanisms underlying early life windows for intestinal tolerance with a focus on newly identified RORγt+ antigen-presenting cells-Thetis cells-and highlight the role of the intestinal microenvironment in shaping intestinal immune system development and tolerance.

Infection induced inflammation impairs wound healing through IL-1β signaling

Wound healing is impaired by infection; however, how microbe-induced inflammation modulates tissue repair remains unclear. We took advantage of the optical transparency of zebrafish and a genetically tractable microbe, Listeria monocytogenes, to probe the role of infection and inflammation in wound healing. Infection with bacteria engineered to activate the inflammasome, Lm-Pyro, induced persistent inflammation and impaired healing despite low bacterial burden. Inflammatory infections induced il1b expression and blocking IL-1R signaling partially rescued wound healing in the presence of persistent infection. We found a critical window of microbial clearance necessary to limit persistent inflammation and enable efficient wound repair. Taken together, our findings suggest that the dynamics of microbe-induced tissue inflammation impacts repair in complex tissue damage independent of bacterial load, with a critical early window for efficient tissue repair.

Integrated analysis of source rock evaluation and basin modelling in the Abu Gharadig Basin, Western Desert, Egypt: Insights from pyrolysis data, burial history, and trap characteristics

Source rock evaluation and basin modelling play crucial roles in understanding hydrocarbon potential. In this study, pyrolysis data from 92 shale ditch samples were employed to assess the source rocks in the Abu Gharadig Basin (Western Desert, Egypt). The organic richness ranged from 0.53% to 4.1% by weight, indicating varying hydrocarbon‐generating capabilities. Specifically, kerogen types II and III exhibited the potential to generate hydrocarbons, ranging from fair to good oil sources. The burial history analysis provided insights into the sedimentation and subsidence rates during different geological periods. The Late Jurassic‐Early Cretaceous period witnessed modest rates of sedimentation and subsidence. In contrast, the Oligocene and Late Miocene periods experienced medium burial rates, while the Late Cretaceous‐Early Tertiary period exhibited high burial rates. Specific formations were examined in detail, with the Apollonia Formation standing out as a significant hydrocarbon reservoir. It entered the early oil window at approximately 17.87 Ma and the wet gas window at about 17.41 Ma in the ASSIL‐1X well. However, it didn't reach the GPAA‐4 well. The Abu Roash ‘D’ member also showed promise, entering the early oil window at 38.20 and 47.38 Ma, and the wet gas window at 37.40 and 43.64 Ma. Similarly, the Abu Roash ‘F’ member exhibited favourable hydrocarbon generation, entering the early oil window at 39.90 and 54.86 Ma, and the wet gas window at 39.70 and 51.62 Ma in both the ASSIL‐1X and GPAA‐4 wells. Based on the analysis, the Apollonia, Abu Roash ‘D’ and ‘F’ members were identified as source rocks, while the Kharita, ‘C’, ‘E’ and ‘G’ members were recognized as reservoir rocks. The Abu Roash Shale acted as an effective seal rock. The geological structure of the region revealed the presence of NW‐SE normal faults, forming a three‐way dip closure trap. This research substantially enhances our comprehension of the hydrocarbon system within this basin. It achieves this by thoroughly investigating source rock evaluation, basin modelling and delivering invaluable insights into the mechanisms that govern hydrocarbon generation, expulsion and trap age.

Abstract WP87: To Walk-In or Not to Walk-In: Effects of ED Mode of Arrival on Acute Stroke Treatment and Hospitalization Outcomes in a Large Integrated Healthcare System

Background: Prior studies reported that only half of stroke patients arrived at emergency departments (ED) via emergency medical services (EMS). We sought to assess predictors of ED mode of arrival and its effects on acute stroke care and inpatient outcomes in a large racial-ethnically diverse cohort. Methods: In 2016, we launched a system-wide standardized telestroke program for 21 certified stroke centers. Non-cancelled stroke alerts included those patients who were potential candidates for further workup for acute ischemic stroke treatment. This study cohort included non-cancelled stroke alerts seen by Telestroke in 2021. Assessment included demographics, ED arrival mode , initial NIH Stroke Scale (NIHSS), neuroimaging results, IV thrombolytic, door-to-needle (DTN) time, large vessel occlusion (LVO), thrombectomy referral, hospital length of stay and discharge disposition. Clustered logistic regression was used to evaluate ED arrival mode’s effects on short-term outcomes. Results: Of the 7744 stroke alerts seen by Telestroke in 2021, 3264 (42.2%) were non-canceled. Among these, 2014 (61.7%) were in the early window (0-4.5 hours from last seen well). More of those arriving in the early window came via EMS compared to those seen in the extended window [1625 (80.7%) versus 729 (58.3%) respectively]. Among non-canceled ED stroke alerts, compared to patients who arrived via EMS, walk-in patients were younger, more Hispanic, had lower initial NIHSS scores, longer times for ED to contact Telestroke, slower DTN times, but less mortality [Table]. In multivariate analysis, walk-in patients were less likely to have a DTN time within 30 minutes (OR=0.37, 95% CI 0.25-0.34; p=&lt;0.001). Conclusions: In our cohort, there were several differences between walk-in patients and those who arrived via EMS. Further research is needed to understand these differences, the reasons for choosing walk-in, and whether ED mode of arrival affects clinical outcomes.

Abstract WMP92: Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes After Acute Ischemic Stroke: An Analysis of the DAWN Trial

Introduction: In the early window, time to treatment with endovascular thrombectomy (EVT) is inversely associated with favorable clinical outcomes but this remains unclear in the extended window. We aimed to assess the impact of time to EVT on clinical outcomes in the DAWN trial. Methods: The association between every 1-hour treatment delay with 90-day functional independence (modified Rankin Scale [mRS] 0-2), symptomatic intracranial hemorrhage (SICH), and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs witnessed vs unwitnessed) considering both time from last seen well (TLSW) and time from symptoms first observed (TSFO). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6-12-hour and 12-24-hour time window, respectively. Considering all three modes of onset together, there was no statistically significant association between TLSW to randomization with either functional independence or mortality at 90 days in either the EVT (mRS0-2 OR 1-hour-delay:1.07;95%CI[0.93-1.24]; mRS6 OR:0.84;95%CI[0.65-1.03]) or medical management (mRS0-2 OR1-hour-delay:0.98;95%CI[0.80-1.14]; mRS6 OR 1-hour-delay:0.94;95%CI[0.79-1.09]) groups. Moreover, there was no significant interaction between treatment effect and time (p=0.439 and p=0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between TLSW to successful reperfusion (mTICI≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p=0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p=0.018) negative slope in wake-up patients. There was no association between treatment times and SICH. Comparable analysis using TSFO yielded similar results. Conclusion: In extended window patients, the association between time to treatment and clinical outcomes seems to be primarily driven by successfully perfused patients with wake-up rather than witnessed or unwitnessed strokes suggesting that wake-up strokes do not behave as “slow-progressors”.

Abstract 40: Relationship of Collateral Status With Clinical Outcomes in Endovascular Thrombectomy for Large Core Stroke: A SELECT2 Subanalysis

Background: Previous studies demonstrating association of collateral status with clinical outcomes after endovascular thrombectomy (EVT) excluded patients with large core infarcts. We analyzed the association of collateral status with clinical outcomes and EVT treatment effect in SELECT2. Methods: In SELECT2, a central core lab adjudicated CT-angiographic collateral status using collateral scores (CS) by Tan et al. Patients were stratified based on CS into poor (CS 0-1) vs good (CS 2-3) collaterals. The primary outcome was the distribution of modified Rankin Scale score at 90-day follow-up. Models were adjusted for core volume, ASPECTS in addition to age, stroke severity and time to randomization. Results: Of 352 patients, 180 received EVT. Median collateral status was 2(IQR 1-2). Patients presenting &lt;6h after last known well (LKW) (n=100) had poorer collaterals than those presenting at 6-24 hours (n=252), median 1 (1-2) vs 2 (1-2), p&lt;0.001. Collateral status inversely correlated with CTP core volume (Rho=-0.32, p&lt;0.0001), but not with CT ASPECTS (Rho=0.07, p=0.16). Overall, point estimates favored EVT in patients with poor (CS 0-1) [aGenOR: 1.32, 95% CI: 0.98-1.79, p=0.068] and good (CS 2-3) collaterals [aGenOR: 1.97, 95% CI: 1.43-2.72, p&lt;0.001] without significant heterogeneity [p-interaction=0.094]. However, in the earlier 0-6h time window, there was evidence of treatment effect hetermogeneity with a larger treatment effect when good collaterals were present [aGenOR: 4.10, 95% CI: 1.81-9.29] and an absent treatment effect when only poor collaterals were observed [aGenOR: 1.26, 95% CI: 0.79-1.99], p-interaction=0.023. In the late time window, (6-12h), the EVT treatment effect did not differ significantly between poor collaterals (aGenOR: 1.35, 95% CI: 0.91-2.01) and good collaterals (aGenOR: 1.78, 95% CI: 1.24-2.56, p-interaction=0.50). Conclusion: Collateral status was worse in large core patients presenting in early (&lt;6 hours) window; and correlated with ischemic core volume but not ASPECTS. Collaterals status modified EVT treatment effect in the early but not the late time window, in which both good and poor collaterals still benefited from EVT. Clinicaltrials.gov registration: NCT03876457

Association between prenatal and childhood PM2.5 exposure and preadolescent anxiety and depressive symptoms.

Fine particulate matter (PM2.5) exposure has been linked to anxiety and depression in adults; however, there is limited research in the younger populations, in which symptoms often first arise. We examined the association between early-life PM2.5 exposure and symptoms of anxiety and depression in a cohort of 8-11-year-olds in Mexico City. Anxiety and depressive symptoms were assessed using the Spanish versions of the Revised Children's Manifest Anxiety Scale and Children's Depression Inventory. Daily PM2.5 was estimated using a satellite-based exposure model and averaged over several early and recent exposure windows. Linear and logistic regression models were used to estimate the change in symptoms with each 5-µg/m3 increase in PM2.5. Models were adjusted for child's age, child's sex, maternal age, maternal socioeconomic status, season of conception, and temperature. Average anxiety and depressive symptom T-scores were 51.0 (range 33-73) and 53.4 (range 44-90), respectively. We observed consistent findings for exposures around the fourth year of life, as this was present for both continuous and dichotomized anxiety symptoms, in both independent exposure models and distributed lag modeling approaches. This window was also observed for elevated depressive symptoms. An additional consistent finding was for PM2.5 exposure during early pregnancy in relation to both clinically elevated anxiety and depressive symptoms, this was seen in both traditional and distributed lag modeling approaches. Both early life and recent PM2.5 exposure were associated with higher mental health symptoms in the child highlighting the role of PM2.5 in the etiology of these conditions.

Abstract TP141: Understanding Potential Limitations of CTP Imaging in Early Window Large Vessel Anterior Circulation Strokes

Background: Computerized tomography perfusion (CTP) imaging serves as a valuable modality for the assessment of individuals with a large vessel anterior circulation stroke. Current literature proposes that employing CTP imaging in patients within the initial time frame of less than 8 hours, may lead to an overestimation of the projected infarct core, specifically when utilizing cerebral blood flow (CBF) less than 30%. The hypoperfusion intensity ratio (HIR) may result in overestimation. We sought to further investigate the interplay of CTP parameters in patients presenting within 8 hours of symptom onset of stroke, to assess the accuracy of core infarct estimation. Methods: A retrospective cohort study analyzing patients with large vessel anterior occlusion (LVAO) who underwent CTP and mechanical thrombectomy within 24 hours of symptom onset between January 2017 to December 2022. RAPID software estimates the infarct core using CBF &lt;30%. DWI-MRI determined final infarct volume. A multivariate logistic regression model was employed to assess the impact of HIR and reperfusion success on outcomes. Results: Ninety-seven patients were identified within an 8-hour time window. CBF&lt;30% overestimated core infarct volume (mL) in 22 patients (22.6%) with a mean of 15.72 (range 4.4-37.7) and a median of 22.85. Of these, 2 patients experienced poor reperfusion (9%) while 20 had successful reperfusion (91%). Of the patients who did have successful reperfusion, an average of 13.57mL core was overpredicted compared to the DWI volumes. A multivariate logistic regression model adjusting for degree of reperfusion, administration of thrombolytic, and time from symptom onset showed that HIR strongly predicted the probability of core estimation with an odds ratio of 148.6, 95% CI [21.0-1048.8], (p&lt;0.001). Conclusion: HIR exceeding 0.4 demonstrates a predictive capacity for core overestimation in early-window LVAO patients. Our study affirms this observation with statistical significance. The integration of HIR as a parameter for early-window LVAO core computation shows promise, and has potential ramifications for patient selection for thrombectomy. In this context, utilization of further databases is imperative for validation and broader application of HIR.

Shaping Microbiota During the First 1000 Days of Life.

Given that the host-microbe interaction is shaped by the immune system response, it is important to understand the key immune system-microbiota relationship during the period from conception to the first years of life. The present work summarizes the available evidence concerning human reproductive microbiota, and also, the microbial colonization during early life, focusing on the potential impact on infant development and health outcomes. Furthermore, we conclude that some dietary strategies including specific probiotics and other-biotics could become potentially valuable tools to modulate the maternal-neonatal microbiota during this early critical window of opportunity for targeted health outcomes throughout the entire lifespan.

Micromotor-based electrochemical immunoassays for reliable determination of amyloid-β (1–42) in Alzheimer's diagnosed clinical samples.

Alzheimer's disease (AD), in addition to being the most common cause of dementia, is very difficult to diagnose, with the 42-amino acid form of Aβ (Aβ-42) being one of the main biomarkers used for this purpose. Despite the enormous efforts made in recent years, the technologies available to determine Aβ-42 in human samples require sophisticated instrumentation, present high complexity, are sample and time-consuming, and are costly, highlighting the urgent need not only to develop new tools to overcome these limitations but to provide an early detection and treatment window for AD, which is a top-challenge. In recent years, micromotor (MM) technology has proven to add a new dimension to clinical biosensing, enabling ultrasensitive detections in short times and microscale environments.To this end, here an electrochemical immunoassay based on polypyrrole (PPy)/nickel (Ni)/platinum nanoparticles (PtNPs) MM is proposed in a pioneering manner for the determination of Aβ-42 in left prefrontal cortex brain tissue, cerebrospinal fluid, and plasma samples from patients with AD. MM combines the high binding capacity of their immunorecognition external layer with self-propulsion through the catalytic generation of oxygen bubbles in the internal layer due to decomposition of hydrogen peroxide as fuel, allowing rapid bio-detection (15 min) of Aβ-42 with excellent selectivity and sensitivity (LOD = 0.06 ng/mL). The application of this disruptive technology to the analysis of just 25 μL of the three types of clinical samples provides values concordant with the clinical values reported, thus confirming the potential of the MM approach to assist in the reliable, simple, fast, and affordable diagnosis of AD by determining Aβ-42.

PALYNOFACIES AND ORGANIC GEOCHEMISTRY OF LACUSTRINE SOURCE ROCKS: THE POTRERILLOS – CACHEUTA SOURCE ROCK SYSTEM IN THE TRIASSIC CUYO BASIN, WEST‐CENTRAL ARGENTINA

This study presents an integrated investigation of the Upper Triassic Potrerillos – Cacheuta lacustrine source rock in the Cuyo Basin of western Argentina. Data came from palynofacies analyses, organic petrography, Rock‐Eval pyrolysis and mineralogical studies based on X‐ray diffraction analyses. An 80 m thick outcrop section was studied and is interpreted to represent the transition from shallow‐lacustrine sediments influenced by fluvial discharges (uppermost Potrerillos Formation) to the deposits of a deep, permanent lake (Cacheuta Formation). Three palynofacies were defined. Palynofacies I is characterized by shallowing‐upward cycles with abundant woody material, and was deposited under an oxic, disturbed water column. Palynofacies II and III occur in laminated shales rich in amorphous organic matter (AOM) and freshwater algal material (Botryococcus) respectively, which were deposited under oxygen‐depleted conditions. In general, the detrital material present suggests an input derived from fluvial discharges; however, interbedded tuffs altered to analcime and smectite suggest the transformation of vitric material in pyroclastic ash under saline to alkaline water conditions. Kerogen Types II/III and III with high total organic carbon values indicate a moderate oil‐ and gas‐prone source rock whose thermal maturity varies from immature to the early oil window (Tmax: 430‐438 °C; vitrinite reflectance: 0.59‐0.67 % VRo; and thermal alteration index: 2‐2+).This study demonstrates the importance of palynofacies analyses for the interpretation of depositional changes and associated controls in lacustrine shale successions. When integrated with data from organic geochemistry, palynofacies analysis is an important tool in the evaluation of a source rock's thermal maturity and hydrocarbon generation potential.