Early Disturbances Research Articles

The interplay of oxidative stress, apoptotic signaling, and impaired mitochondrial function in the pyrethroid-induced cardiac injury: Alleviative role of curcumin-loaded chitosan nanoparticle

This study assessed the consequence of exposure to a pyrethroid insecticide, fenpropathrin (FPN), on the heart and the probable underlying mechanisms in rats. Moreover, the probable protective effect of curcumin-loaded chitosan nanoparticles (CMN-CNP) was evaluated. Forty male Sprague Dawley rats were distributed into four groups orally given corn oil, CMN-CNP (50 mg/kg b.wt), FPN (15 mg/kg b.wt), or CMN-CNP+FPN for 60 days. The results revealed that FPN exposure increased serum cardiac damage indicators. In addition, a substantial increase in the reactive oxygen species and malondialdehyde content but reduced enzymatic and non-enzymatic antioxidants and altered architecture was recorded in the cardiac tissue of FPN-exposed rats. Additionally, a significant down-regulation of expression of the mitochondrial complexes I-V, mitochondrial dynamics, and antioxidants-related genes but up-regulation of apoptosis-related genes was detected in the FPN-exposed group. Immunofluorescence analyses revealed higher amounts of the harmful protein 4-hydroxynonenal in the heart tissue of FPN-exposed rats. Nevertheless, the earlier disturbances were significantly rescued in the FPN+CMN-CNP treated group. Conclusively, our findings reported the cardiotoxic activity of FPN and the involvement of several mitochondrial imbalances as a probable underlying mechanism. Also, the study findings proved the efficacy of CMN-CNP in combating FPN cardiotoxic effects.

Dysregulation of Regulatory T Cells and Autoimmune Sequelae in DRESS: Insights From Flow Cytometry and NanoString Analysis.

Drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse hypersensitivity reactions with distinct clinical manifestations. Regulatory T (Treg) cells may behave differently in these syndromes, contributing to their diverse clinical features and outcomes. This study compared Treg dynamics between DRESS and SJS/TEN patients during the acute and recovery phases. Flow cytometry quantitatively analysed and defined the immunophenotype of CD4+CD25+CD127-FoxP3+ Tregs in blood from DRESS and SJS/TEN patients indicated that Treg percentages were lowest in DRESS patients during the acute phase compared to those in the recovery phase in DRESS patients and the acute phase in SJS/TEN patients. During the acute phase, CTLA-4 expression in Tregs in both DRESS patients with and without autoimmune sequelae was significantly increased, while only DRESS patients without autoimmune sequelae had elevated OX40 expression compared to the healthy controls. High IL-10 expression in Tregs during the acute phase in SJS/TEN patients was also observed. The suppressive function of Tregs was lower in DRESS compared to SJS/TEN, which was determined using a suppression assay by co-culturing autologous Treg and effector T cells. Furthermore, NanoString technology explored mRNA profiles in Tregs. Genes associated with the JAK/STAT pathway were found to be downregulated during the acute phase in DRESS patients who later developed autoimmune sequelae. Our findings evidenced impaired Treg function in DRESS compared to SJS/TEN. The early disturbance of the JAK/STAT pathway may serve as a prognostic marker for autoimmune development in DRESS patients.

Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models

Snf7-3 is a crucial component of the endosomal sorting complexes required for transport (ESCRT) pathway, playing a vital role in endolysosomal functions. To elucidate the role of Snf7-3 in vivo, we developed conventional-like and conditional Snf7-3 knockout (KO) mouse models using a “Knockout-first” strategy. Conventional-like Snf7-3 KO mice showed significantly reduced Snf7-3 mRNA expression, and older mice (25–40 weeks) exhibited impaired social recognition and increased miniature excitatory postsynaptic currents (mEPSCs). Similarly, conditional KO mice aged 8–24 weeks, with Snf7-3 specifically deleted in forebrain excitatory neurons, displayed impaired object location memory and elevated mEPSC frequency. Consistently, Snf7-3 knockdown in cultured mouse hippocampal neurons led to increased densities of pre- and postsynaptic puncta, supporting the observed increase in mEPSC frequency. In addition, enhanced dendritic complexity was observed in the medial prefrontal cortex of these mice, indicating early synaptic disturbances. Our findings underscore the critical role of Snf7-3 in maintaining normal cognitive functions and social behaviors. The observed synaptic and behavioral deficits in both conventional-like and conditional KO mice highlight the importance of Snf7-3 in specific neuronal populations, suggesting that early synaptic changes could precede more pronounced cognitive impairments.

Taste Disturbance After Endoscopic Tympanoplasty with Tragal Cartilage Graft and Improvement Strategies.

Objectives: To explore the risk factors of early postoperative taste disturbance (EPTD) after type I endoscopic tympanoplasty and operative modification strategies to improve taste disturbance. Methods: This was a controlled study. One hundred and twenty-four patients who underwent type I endoscopic tympanoplasty with tragal cartilage graft were separated evenly into control and modified groups. The full-thickness tragus cartilage graft was placed close to the bony annulus to ensure drum integrity in the control group, and in the modified group, the cartilage graft was not in contact with the posterior-superior bony annulus, and the inferior-posterior of the scutum. Univariate and multivariate models were used to analyze the possible factors affecting EPTD and the prognosis of taste recovery. Results: The incidence of EPTD was significantly lower in the modification group (24.19%) than in the control group (56.45%) (OR: 4.24, 95% CI: 1.93-9.33, P < .001). Surgical manipulation of the chorda tympani nerve resulted in a higher incidence of EPTD (OR: 2.43; 95% CI: 1.06-5.57, P = .035). The size of the graft did not affect taste disturbance. No difference in the taste recovery rate was observed between the control and test groups (Z = -1.57, P = .116) after 3 months. The recovery rate of patients with manipulated chorda tympani nerves was still lower than that of patients without at 3 months (Z = -2.74, P = .006). Conclusion: Modified surgery and reduced manipulation of the chorda tympani nerve effectively reduce EPTD. Manipulated chorda tympani nerves may have a persistent effect on taste recovery.

Understanding the Impact of Childbirth: Postnatal Stress Symptoms in Psychologically Stable Mothers

This study examines the psychological impact of childbirth on first-time mothers, focusing on post-traumatic stress and depressive symptoms using the Impact of Event Scale (IES) and the Edinburgh Postnatal Depression Scale (EPDS). Many participants experienced intrusive thoughts, avoidance behaviors, and depressive symptoms within the first year postpartum. A strong correlation was found between mothers’ sense of safety and presence during childbirth and lower stress and EPDS scores. Additionally, the duration of Baby Blues was associated with higher IES and EPDS scores, suggesting that early emotional disturbances can have lasting effects on maternal mental health. The study also highlights how recounting birth experiences, either as reliving them or from a present perspective, influences stress levels. These findings underscore the importance of psychological support in postnatal care and advocate for routine screening for negative birth experiences and stress symptoms, emphasizing early intervention to improve maternal and family outcomes. Keywords: postnatal mental health, childbirth experience, maternal stress symptoms

Bark beetle detection method using electronic nose sensors. A possible improvement of early forest disturbance detection?

Bark beetle detection method using electronic nose sensors. A possible improvement of early forest disturbance detection?

Metabolic and Microbial Dysregulation in Preterm Infants with Neonatal Respiratory Distress Syndrome: An Early Developmental Perspective.

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.

Clinical characteristics and multimodal imaging can help diagnosing and treating mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently described, histopathologically and molecularly defined (SLC35A2-mutated) type of cortical malformation. Although increasingly recognized, the diagnosis of MOGHE remains a challenge. We present the characteristics of the first six patients diagnosed in Bulgaria, with the aim to facilitate identification, proper presurgical evaluation, and surgical treatment approach in this disease. Revision of histopathological specimens of 202 patients operated on for drug-resistant focal epilepsy identified four cases with MOGHE. Another two were suggested, based on clinical characteristics and subsequently, were histologically confirmed. Sanger SLC35A2 sequencing on paraffin-embedded or fresh-frozen brain tissue was performed. Analysis of seizure types, neuropsychological profiles, electroencephalographic (EEG), imaging features and epilepsy surgery outcomes was done. Three out of the six cases (50%) harbored pathogenic SLC35A2 mutations. One patient had a heterozygous somatic variant with uncertain significance. Clinical characteristics included epilepsy onset in infancy (in 100% under 3 years of age), multiple seizure types, and moderate or severe intellectual/developmental delay. Epileptic spasms with hypsarrhythmia on EEG were the initial seizure type in five patients. The subsequent seizure types resembled those in Lennox-Gastaut syndrome. The majority of the patients (n = 4) presented prominent and persisting autistic features. Magnetic resonance imaging (MRI) showed multilobar (n = 6) and bilateral (n = 3) lesions, affecting the frontal lobes (n = 5; bilaterally in three) and characterized by increased signal on T2/fluid-attenuated inversion recovery (FLAIR). Voxel-based morphometric MRI post-processing and positron emission tomography helped determining the localization and extent of the lesions and presumed epileptogenic zones. After surgery, four patients (66.7%) were seizure-free ≥2 years. Interestingly, all seizure-free patients carried somatic SLC35A2-alterations. Epileptic spasms, early prominent neuropsychological disturbances, MRI-T2/FLAIR hyperintense lesions with cortico-subcortical blurring, frequently multilobar and especially frontal, can preoperatively help to suspect MOGHE. Epilepsy surgery is still the only successful treatment option in MOGHE.

Human impacts overwhelmed climate as the dominant factor controlling lacustrine organic matter accumulation in Erhai Lake 2000 years ago, Southwest China

Climate and human activity are two important factors in regulating organic matter (OM) accumulation in the lake environment. However, when and how anthropogenic impacts have affected lacustrine OM accumulation in southwest China during the late Holocene have not yet been well defined. Here, a 16.3-kyr n-alkane record derived from Erhai Lake was used to trace OM sources and explore their connections to climate and human activity. The n-alkane distributions indicated that the dominant sediment sources shifted from terrestrial and aquatic plants to algae in the late Holocene. OM accumulation was closely related to catchment soil erosion, sediment transport, and deposition processes regulated by climate conditions before 5.0 cal. kyr B.P., following the patterns that stronger monsoon precipitation favoured more terrestrial and less aquatic OM input, and vice versa. From 5.0 to 2.0 cal. kyr B.P., the synchronous downwards trends in terrestrial OM input and precipitation intensity indicated that climate remained a major driving force for OM accumulation. However, sediment sources experienced large-magnitude and centennial-scale oscillations between allochthonous and autochthonous inputs, reflecting early human impacts appeared and lake ecosystems retained the self-regulated ability to recover from the basin-wide early moderate human disturbances. Afterwards, the increased (decreased) OM contributions from terrestrial (aquatic) plants contradicted the weakening monsoon precipitation since 2.0 cal. kyr B.P., indicating a dominant effect of human activities on OM accumulation. This change was accompanied by highly improved algae productivity and gradually elevated lacustrine trophic status, and the lake ecosystem eventually shifted into another state largely deviating from its climate-driven background due to intensified deforestation and agricultural cultivation. Regional comparison indicated that anthropogenic disturbances have temporal differences in southwest China. This study will further improve our understanding of past climate-human-environment interactions in southwest China.

Circulating asprosin concentrations in individuals with new-onset type 2 diabetes and prediabetes

AimsThis research aimed to clarify the relationship between serum asprosin levels and the occurrence of type 2 diabetes mellitus (T2DM) in light of mixed findings about the role of asprosin in T2DM and the lack of studies on its effects on prediabetic conditions. MethodsIn this observational analysis the cohort included 252 adults aged22–69 recruitedfromJinan Central Hospital were categorized into three groups, normal glucose tolerance (NGT), impaired glucose regulation (IGR) and T2DM groups. Serum asprosin levels were measured using enzyme linked immunosorbent assay (ELISA). Additionally, all participants underwent assessments of various anthropometric and biochemical markers. ResultsAnalysis revealed a notable increase in serum asprosin levels among individuals with newly diagnosed T2DM, with IGR subjects also demonstrating slightly elevated asprosin levels compared to the healthy group. Further stratification by quartiles of asprosin levels revealed a progressive increase in the proportions of IGR + T2DM patients, highlighting a potential association between elevated asprosin and increased T2DM risk. The Receiver Operating Characteristic (ROC) curve analysis for the efficacy of asprosin in identifying IGR + T2DM yielded an area under curve (AUC) of 0.853 (95 % CI: 0.808–0.899), pointing a threshold value of 4.95 ng/ml for asprosin. ConclusionsThis investigation revealed that individuals with prediabetes and those newly diagnosed with T2DM exhibit increased serum asprosin levels, suggesting that elevated asprosin concentrations are linked to early disturbances in glucose homeostasis.

Pancreatic neuroendocrine tumors: Are tumors smaller than 2 cm truly indolent?

Pancreatic neuroendocrine tumors (PNETs) are relatively rare but rank as the second most common pancreatic neoplasm. They can be functional, causing early metabolic disturbances due to hormone secretion, or non-functional and diagnosed later based on tumor size-related symptoms. Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management; some practitioners advocate for surgical removal and others suggest observation due to the tumors' lower potential for malignancy. However, it is unclear whether managing these small tumors expectantly is truly safe. To evaluate poor prognostic factors in PNETs based on tumor size (> 2 cm or < 2 cm) in surgically treated patients. This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín, Colombia. To assess patient survival, quarterly follow-ups were conducted during the first year after surgery, followed by semi-annual consultations at the hospital's hepatobiliary surgery department. Qualitative variables were described using absolute and relative frequencies, and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion. The presence of lymph node involvement, neural involvement, and lymphovascular invasion were all associated with an increased risk of mortality, with hazard ratios of 5.68 (95%CI: 1.26-25.61, P = 0.024), 6.44 (95%CI: 1.43-28.93, P = 0.015), and 24.87 (95%CI: 2.98-207.19, P = 0.003), respectively. Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter. The recurrence rates between the two tumor groups were furthermore similar: 18.2% for tumors smaller than 2 cm and 21.4% for tumors larger than 2 cm. Patient survival was additionally comparable between the two tumor groups. Tumor size does not dictate prognosis; lymph node and lymphovascular involvement affect mortality, which highlights that histopathological factors-rather than tumor size-may play a role in management.

Children’s heart and prematurity: a current view of the problem

Improved survival of children born with low, extremely low and very low body weight in modern conditions due to increased nursing capabilities, optimization of treatment and increased efficiency of resuscitation measures has led to the need for greater understanding of the importance of assessing the cardiovascular system’s state beyond the neonatal period. With approximately 10% of infants worldwide being born preterm, there is an increasing need for further research into optimal regimens, lifestyle and clinical interventions that can benefit and modify cardiovascular morphology and function in this growing population. Modern theoretical postulates on the physiology and pathophysiology of the child’s heart include ideas about the key process of cardiac biomechanics — diastole, during which the earliest disturbances, that precede the formation of systolic dysfunction, occur. Assessment of the pumping properties of the left ventricle in systole and diastole is a fundamental methodological technique for an in-depth understanding of the pathophysiological mechanisms of cardiovascular system’s emerging diseases, their early diagnosis and assessment of the complex therapy’s effectiveness. However, despite the widespread use of standard echocardiography to assess systolic and diastolic function, its traditional parameters have limitations in terms of diagnostic accuracy and effectiveness in practice. Expanding knowledge about new pathogenetic mechanisms of the cardiac dysfunction formation in conditions of prematurity at the current stage of cardiology development using the “trace spot” technology (two-dimensional speckle tracking echocardiography) will be very useful for scientists studying the mechanics formation of the child’s heart after premature birth, and for doctors of various specialties in early diagnosis of heart diseases.

Sleep Disturbance During Post-Traumatic Amnesia and Early Recovery After Traumatic Brain Injury.

After moderate to severe traumatic brain injury (TBI), sleep disturbance commonly emerges during the confused post-traumatic amnesia (PTA) recovery stage. However, the evaluation of early sleep disturbance during PTA, its recovery trajectory, and influencing factors is limited. This study aimed to evaluate sleep outcomes in patients experiencing PTA using ambulatory gold-standard polysomnography (PSG) overnight and salivary endogenous melatonin (a hormone that influences the sleep-wake cycle) assessment at two time-points. The relationships between PSG-derived sleep-wake parameters and PTA symptoms (i.e., agitation and cognitive disturbance) were also evaluated. In a patient subset, PSG was repeated after PTA had resolved to assess the trajectory of sleep disturbance. Participants with PTA were recruited from Epworth HealthCare's inpatient TBI Rehabilitation Unit. Trained nurses administered overnight PSG at the patient bedside using the Compumedics Somté portable PSG device (Compumedics, Ltd., Australia). Two weeks after PTA had resolved, PSG was repeated. On a separate evening, two saliva specimens were collected (at 24:00 and 06:00) for melatonin testing. Results of routine daily hospital measures (i.e., Agitated Behavior Scale and Westmead PTA Scale) were also collected. Twenty-nine patients were monitored with PSG (mean: 41.6 days post-TBI; standard deviation [SD]: 28.3). Patients' mean sleep duration was reduced (5.6 h, SD: 1.2), and was fragmented with frequent awakenings (mean: 27.7, SD: 15.0). Deep, slow-wave restorative sleep was reduced, or completely absent (37.9% of patients). The use of PSG did not appear to exacerbate patient agitation or cognitive disturbance. Mean melatonin levels at both time-points were commonly outside of normal reference ranges. After PTA resolved, patients (n = 11) displayed significantly longer mean sleep time (5.3 h [PTA]; 6.5 h [out of PTA], difference between means: 1.2, p = 0.005). However, disturbances to other sleep-wake parameters (e.g., increased awakenings, wake time, and sleep latency) persisted after PTA resolved. This is the first study to evaluate sleep disturbance in a cohort of patients as they progressed through the early TBI recovery phases. There is a clear need for tailored assessment of sleep disturbance during PTA, which currently does not form part of routine hospital assessment, to suggest new treatment paradigms, enhance patient recovery, and reduce its long-term impacts.

Lower Insulin Sensitivity Through 36 Months of Life With in Utero HIV and Antiretroviral Exposure in Botswana: Results From the Tshilo Dikotla Study.

There are little data on changes in insulin sensitivity during the first few years of life following in utero human immunodeficiency virus (HIV) and antiretroviral (ARV) exposure. The Tshilo Dikotla study enrolled pregnant persons with HIV (PWH) (receiving tenofovir/emtricitabine or lamivudine plus dolutegravir or efavirenz) and pregnant individuals without HIV, as well as their liveborn children. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was assessed at birth and 1, 18, 24, and 36 months of life. We fit linear mixed-effects models to evaluate the association between in utero HIV/ARV exposure and average HOMA-IR from birth through 36 months of life, adjusting for confounders. A total of 419 children were included (287 with in utero HIV/ARV exposure and uninfected [CHEU] and 132 without in utero HIV/ARV exposure [CHUU]). CHEU were born to older women (29.6 vs 25.3 years of age) with higher gravidity (3 vs 1). HOMA-IR was persistently higher in CHEU versus CHUU in adjusted analyses (mean difference of 0.07 in log10 HOMA-IR, P = .02) from birth through 36 months of life. Among CHEU, no differences in HOMA-IR were observed from birth through 36 months by in utero ARV exposure status or between AZT and NVP infant prophylaxis arms. In utero HIV/ARV exposure was associated with lower insulin sensitivity throughout the first 36 months of life, indicating persistent early life metabolic disturbances which may raise concern for poorer metabolic health later in life.

Leveraging past information and machine learning to accelerate land disturbance monitoring

Near real-time (NRT) monitoring of land disturbances holds great importance for delivering emergency aid, mitigating negative social and ecological impacts, and distributing resources for disaster recovery. Many past NRT techniques were built upon examining the overall change magnitude of a spectral anomaly with a predefined threshold, namely the unsupervised approach. However, their lack of fully considering spectral change direction, change date, and pre-disturbance conditions often led to low detection sensitivity and high commission errors, especially when only a few satellite observations were available at the early disturbance stage, eventually resulting in a longer lag to produce a reliable disturbance map. For this study, we developed a novel supervised machine learning approach guided by historical disturbance datasets to accelerate land disturbance monitoring. This new approach consisted of two phases. For the first phase, the supervised approach applied retrospective analysis on historical Harmonized Landsat Sentinel-2 (HLS) datasets from 2015 to 2021, combined with several open disturbance products. The disturbance model was constructed for each condition of consecutive anomaly number, with the aim of enhancing the specificity for delineating early-stage disturbance regions. Then, these stage-based models were applied for an NRT scenario to predict disturbance probabilities with 2022 HLS images incrementally on a weekly basis. To demonstrate the capability of this new approach, we developed an operational NRT system incorporating both the unsupervised and supervised approach. Latency and accuracy were evaluated against 3000 samples that were randomly selected from the five most influential disturbance events of the United States in 2022, based on labels and disturbance dates interpreted from daily PlanetScope images. The evaluation showed that the supervised approach required 15 days (since the start of the disturbance event) to reach the plateau of its F1 curve (where most disturbance pixels are detected with high confidence), seven days earlier with roughly 0.2 F1 score improvement compared to the unsupervised approach (0.733 vs. 0.546 F1 score). Further analysis showed the improvement was mainly due to the substantial decrease in commission errors (17.7% vs 44.4%). The latency component analysis illustrated that the supervised approach only took an average of 4.1 days to yield the first disturbance alert at its fastest daily updating speed, owing to its decreased sensitivity lag. This finding highlighted the importance of using past knowledge and machine learning to reduce detection delays for an NRT monitoring task.

Does Melatonin Improve Sleep Following Primary Total Knee Arthroplasty? A Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundSleep impairment following total knee arthroplasty (TKA) is common and may decrease patient satisfaction and recovery. Standardized postoperative recommendations for sleep disturbances have not been established. We aimed to assess whether melatonin use could promote healthy sleep and reduce sleep disturbance in the acute period following TKA. MethodsPatients undergoing primary, elective TKA between July 19, 2021 and January 4, 2024 were prospectively enrolled and randomized to receive either 5 mg of melatonin nightly or placebo for 14 days postoperatively. Participants recorded their nightly pain on the visual analog scale, the number of hours slept, and the number of night-time awakenings in a sleep diary starting the night of surgery (postoperative day [POD] 0). Sleep disturbance was assessed preoperatively and on POD 14 using the patient-reported outcome measurement information system sleep disturbance form. Epworth Sleepiness Scores were collected on POD 14 to assess sleep quality. ResultsOf the 138 patients enrolled, 128 patients successfully completed the study protocol, with 64 patients in each group. Melatonin patients trended toward more hours of sleep on POD 2 (placebo: 5.0 ± 2.4, melatonin: 5.8 ± 2.0, P = .084), POD 3 (placebo: 5.6 ± 2.2, melatonin: 6.3 ± 2.0, P = .075), and averaged over POD 1 to 3 (placebo: 4.9 ± 2.0, melatonin: 5.6 ± 1.8, P = .073), although no differences were observed on POD 4 or after. Fewer night-time awakenings in the melatonin group were observed on POD 1 (placebo: 4.4 ± 3.9, melatonin: 3.6 ± 2.4, P = .197), although this was not statistically significant. Preoperative and postoperative Patient-Reported Outcomes Measurement Information System Sleep Disturbance score increases were comparable for both groups (placebo: 4.0 ± 8.4, melatonin: 4.6 ± 8.2, P = .894). The melatonin (65.4%) and placebo (65%) groups demonstrated similar rates of increased sleep disturbance. ConclusionsMelatonin may promote longer sleep in the immediate postoperative period after TKA, although these benefits wane after POD 3. Disturbances in sleep should be expected for most patients, although melatonin may have an attenuating effect. Melatonin is safe and can be considered for TKA patients experiencing early sleep disturbances postoperatively.

Monitoring of Perioperative Microcirculation Dysfunction by Near-Infrared Spectroscopy for Neurological Deterioration and Prognosis of Aneurysmal Subarachnoid Hemorrhage: An Observational, Longitudinal Cohort Study.

No evidence has established a direct causal relationship between early microcirculation disturbance after aneurysmal subarachnoid hemorrhage (aSAH) and neurological function prognosis, which is the key pathophysiological mechanism of early brain injury (EBI) in patients with aSAH. A total of 252 patients with aSAH were enrolled in the Neurosurgical Intensive Care Unit of Southwest Hospital between January 2020 and December 2022 and divided into the no neurological deterioration, early neurological deterioration, and delayed neurological deterioration groups. Indicators of microcirculation disorders in EBI included regional cerebral oxygen saturation (rSO2) measured by near-infrared spectroscopy (NIRS), brain oxygen monitoring, and other clinical parameters for evaluating neurological function and determining the prognosis of patients with aSAH. Our data suggest that the rSO2 is generally lower in patients who develop neurological deterioration than in those who do not and that there is at least one time point in the population of patients who develop neurological deterioration where left and right cerebral hemisphere differences can be significantly monitored by NIRS. An unordered multiple-classification logistic regression model was constructed, and the results revealed that multiple factors were effective predictors of early neurological deterioration: reoperation, history of brain surgery, World Federation of Neurosurgical Societies (WFNS) grade4-5, Fisher grade3-4, SAFIRE grade 3-5, abnormal serum sodium and potassium levels, and reduced rSO2 during the perioperative period. However, for delayed neurological deterioration in patients with aSAH, only a history of brain surgery and perioperative RBC count were predictive indicators. The rSO2 concentration in patients with neurological deterioration is generally lower than that in patients without neurological deterioration, and at least one time point in the population with neurological deterioration can be significantly monitored via NIRS. However, further studies are needed to determine the role of microcirculation and other predictive factors in the neurocritical management of EBI after aSAH, as these factors can reduce the incidence of adverse outcomes and mortality during hospitalization.

Environmental change legacies attenuate disturbance response of desert soil microbiome and multifunctionality

Abstract Deserts are predicted to be one of the ecosystems most vulnerable to global climate change, with dramatic fluctuations of temperature and water, even over the span of a single day. These previous disturbances could influence the response of the soil microbiome and its functions to subsequent disturbances, which is known as legacy effect. However, how legacy effects shape the response of soil microbiome and its functions to environmental fluctuations (e.g. temperature and water availability) in desert ecosystems remains to be investigated. Here, we firstly exposed desert soils to drought, freezing or their combination, and then followed by a second disturbance, resulting in a temporally full factorial treatment. We found that environmental change legacies affected the response of soil multifunctionality, microbial abundance and richness to second drought and freezing, except for eukaryotic richness. Initial disturbances caused legacy effects on microbial composition and weakened their responses to later disturbances, and these effects were stronger for prokaryotes than eukaryotes. The attenuated response to later disturbances is largely due to that almost half of the taxa affected by the earlier disturbances were also affected by the second disturbances. The phylogenetic depth of these responses varied minimally among the types of disturbances but were more conserved for negative responses, indicating a result of historical adaptation. Moreover, the altered community composition was associated with functional changes in the disturbed soils. These findings will improve our understanding of the mechanisms underlying the legacy impacts of multiple environmental disturbances on desert microbial communities and strengthen our ability to develop management strategies for protection prior to disturbance events. Read the free Plain Language Summary for this article on the Journal blog.

P088 Single-cell transcriptomic analysis identifies early immune disturbances in preclinical Crohn's disease

Abstract Background Despite the increasing incidence of Crohn’s disease (CD), its early immune disturbances have not been described yet. The preclinical period provides an opportunity to gain insight into the initial processes involved in the pathogenesis of the disease. The main aim of our study was to describe how the subclinical inflammatory process is modifying the individual’s immunologic environment while the patient is still on preclinical period. Methods We analysed scRNASeq data from peripheral blood mononuclear cells (PBMC) of patients with incidentally-diagnosed CD according to ECCO criteria during the colorectal cancer screening programme, after histologic confirmation. Their gene expression profile was compared to healthy individuals acquired from publicly available datasets. The analytical pipeline included merging of the datasets followed by batch correction concerning integration from different studies, quality control and filtering, and finally cell-type annotation and differential gene expression analysis. Results Two patients with CD (mean age 53,5 years) and 2 healthy controls were included. We observed distinct transcriptomic profile in preclinical patients compared to controls, with small intragroup differences. The cell-type annotation identified B cells (B), CD4+ and CD8+ T-cells (CD4T, CD8T), dendritic cells (DC), monocytes (Mono) and natural killer cells (NK). The analytical pipeline included 17,021 cells (B:3,274, CD4T:5,798, CD8T:3,476, DC:315, 2, Mono:928, NK:3,230) and 3000 quantified genes. Considering each cell type individually, we identified 49 differentially expressed genes (DEG) between CD patients and controls (B:39, CD4T:37, CD8T:41, DC:42, Mono:37, NK:37), from which 30 were DEGs in all cell types. Building on the list of 49 detected DEGs, we report three insights into the preclinical period of the disease. First, pathway analysis revealed significant enrichment of the pathway that is related to immunoregulatory interactions between lymphoid and non-lymphoid cells, and functional annotation analysis identified gene products that are related to immunological defense. Second, we identified significant transcriptomic alterations in genes that have previously been related to the symptomatic phase of IBD, or reported as potential biomarkers. Third, after performing principal component analysis we observed greater separation between the patients groups in the CD8T cells compared to the other cell-types. Conclusion This study reveals the initial transcriptomic profiles and the main pathways that precede the onset of symptomatic inflammatory bowel disease. Our findings may help in identifying potential targets for early disease intervention.

Le microbiote pulmonaire, perspective d’innovation en microbiologie médicale

AbstractThe pulmonary niche represents a complex ecosystem influenced by various sources, in particular the oral and digestive tracts. Maintaining a dynamic balance between colonization factors (micro-aspiration, inhalation) and clearance factors (muco-cIilary elevator, innate immunity) is essential to preserve the lung microbiota. This microbiota is characterized by low bacterial concentration, high biodiversity and a notable abundance of anaerobic bacteria. The latter play a decisive role in the development of the pulmonary immune system. Early disturbances in the development of the lung microbiota can lead to an increased risk of later diseases, such as asthma. A common feature of chronic inflammatory diseases is pulmonary dysbiosis, often present before the onset of symptoms. The interaction between the gut microbiota and the lung microbiota is partly explained by the exchange of bacterial metabolites between these organs. Intestinal dysbiosis can thus have repercussions on the pulmonary niche. Conversely, modulation of the gut microbiota could serve as a strategy for improving respiratory health. In the context of personalized medicine, the lung microbiota is seen as a potential source of biomarkers for diagnosis and prognosis, and new therapies against respiratory diseases.