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Background: The postoperative course after surgery for primary brain tumours can be difficult to predict. We examined the time course of postoperative neurological deficits and analysed possible predisposing factors. Method: Hundred adults with a radiological suspicion of low- or high-grade glioma were prospectively included and the postoperative course analysed. Possible predictors of postoperative neurological deterioration were evaluated. Results: New postoperative neurologic deficits occurred in 37% of the patients, and in 4%, there were worsening of a preoperative deficit. In 78%, the deficits occurred directly after surgery. The probable cause of deterioration was EEG-verified seizures in 7, ischemic lesion in 5 and both in 1, resection of eloquent tissue in 6, resection close to eloquent tissue including SMA in 11 and postoperative haematoma in 1 patient. Seizures were the main cause of delayed neurological deterioration. Two-thirds of patients with postoperative deterioration showed complete regression of the deficits, and in 6% of all patients, there was a slight disturbance of the function after 3 months. Remaining deficits were found in 6% and only in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of postoperative neurological deterioration and preoperative neurological deficits of remaining deficits. Conclusions: Postoperative neurological deficits occurred in 41% and remained in 6% of patients. Remaining deficits were found in patients with preoperative neurological deficits and high-grade tumours with mainly eloquent locations. Eloquent tumour location was a predictor of neurological deterioration and preoperative neurological deficits of remaining deficits. [ABSTRACT FROM AUTHOR]

We were to investigate the time course of lesions for awakening in acute Percheron artery ischemic coma (PAIC), which was previously unknown. Patients who had newly identified acute PAIC events in 2012–2015 and had not received thrombolytic therapy were enrolled retrospectively. The time course of lesions in PAIC was investigated by diffusion-weighted imaging (DWI). Ninety-three patients met the inclusion criteria, of whom 63 and 30 had transient PAIC and persistent PAIC, respectively. The time course of awakening events in persistent PAIC decreased over time, with large lesions in the bilateral paramedian thalamus/ rostral midbrain on DWI almost in all patients who was either plus or minus a "top of basilar artery" strokes. Whereas awakening events in transient PAIC increased over time, with small or lacunar lesions in the unilateral or bilateral thalamus/rostral midbrain about in 30.2 % cases, and the rest in naturally recanalization of infarcts or TIA. Lesion volumes were larger for persistent PAIC than for transient PAIC (median, 2.4 cm3 vs. 0.03 cm3, P < 0.0001). In Cox hazards ratio (HR) analysis, a lower GCS score was associated with mortality (HR, 5.5; 95 % confidence interval [CI],1.427–21.45). Multivaliate analysis shown that the predictors of higher risk of persistent PAIC were only increased NIHSS scores (HR,1.3; 95 % CI,1.109–1.640) and large lesions in bilateral thalamus/rostral midbrain (HR,15.0; 95 % CI,1.440–58.13). The time course of acute PAIC included transient and persistent. Most persistent PAIC was associated with large lesions in bilateral paramedian thalamus/ rostral midbrain, and with high mortality. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effectiveness and time course for improvements in explosive actions through resistance training (RT) vs. plyometric training (PT) in prepubertal soccer players. Thirty-four male subjects were assigned to: a control group (n = 11); an RT group (5 regular soccer training sessions per week, n = 12); a PT group (3 soccer training sessions and 2 RT sessions per week, n = 11). The outcome measures included tests for the assessment of muscle strength (e.g., 1 repetition maximum half-squat test), jump ability (e.g., countermovement jump, squat jump, standing long jump, and multiple 5 bounds test), linear speed (e.g., 20 m sprint test), and change of direction (e.g., Illinois change of direction test). The RTG showed an improvement in the half-squat (Δ = 13.2%; d = 1.3, p < 0.001) and countermovement jump (Δ = 9.4%; d = 2.4, p < 0.001) at Week 4, whereas improvements in the 20-m sprint (Δ = 4.2%; d = 1.1, p < 0.01); change of direction (CoD) (Δ = 3.8%; d = 2.1, p < 0.01); multiple 5 bounds (Δ = 5.1%; d = 1.5, p < 0.05); standing long jump (Δ = 7.2%; d = 1.2, p < 0.01); squat jump (Δ = 19.6%; d = 1.5, p < 0.01); were evident at Week 8. The PTG showed improvements in CoD (Δ = 2.1%; d = 1.3, p < 0.05); standing long jump (Δ = 9.3%; d = 1.1, p < 0.01); countermovement jump (Δ = 16.1%; d = 1.2, p < 0.01); and squat jump (Δ = 16.7%; d = 1.4, p < 0.01); at Week 8 whereas improvements in the 20-m sprint (Δ = 4.1%; d = 1.3, p < 0.01); and multiple 5 bounds (Δ = 7.4%; d = 2.4, p < 0.001); were evident only after Week. The RT and PT groups showed improvements in all sprint, CoD, and jump tests (p < 0.05) and in half-squat performance, for which improvement was only shown within the RTG (p < 0.001). RT and PT conducted in combination with regular soccer training are safe and feasible interventions for prepubertal soccer players. In addition, these interventions were shown to be effective training tools to improve explosive actions with different time courses of improvements, which manifested earlier in the RTG than in the PTG. These outcomes may help coaches and fitness trainers set out clear and concise goals of training according to the specific time course of improvement difference between RT and PT on proxies of athletic performance of prepubertal soccer players. [ABSTRACT FROM AUTHOR]

Background: A genome-wide study identified de novo DNA methylation alterations in leukocytes of children at paediatric intensive care unit (PICU) discharge, offering a biological basis for their impaired long-term development. Early parenteral nutrition (early-PN) in PICU, compared with omitting PN in the first week (late-PN), explained differential methylation of 23% of the affected CpG-sites. We documented the time course of altered DNA methylation in PICU and the impact hereon of early nutritional management. Results: We selected 36 early-PN and 36 late-PN matched patients, and 42 matched healthy children. We quantified DNA methylation on days 3, 5 and 7 for the 147 CpG-sites of which methylation was normal upon PICU admission in this subset and altered by critical illness at PICU discharge. Methylation in patients differed from healthy children for 64.6% of the 147 CpG-sites on day 3, for 72.8% on day 5 and for 90.5% on day 7 as revealed by ANOVA at each time point. Within-patients methylation time course analyses for each CpG-site identified different patterns based on paired t test p value and direction of change. Rapid demethylation from admission to day 3 occurred for 76.2% of the CpG-sites, of which 67.9% remained equally demethylated or partially remethylated and 32.1% further demethylated beyond day 3. From admission to day 3, 19.7% of the CpG-sites became hypermethylated, of which, beyond day 3, 34.5% remained equally hypermethylated or partially demethylated again and 65.5% further hypermethylated. For 4.1% of the CpG-sites, changes only appeared beyond day 3. Finally, for the CpG-sites affected by early-PN on the last PICU day, earlier changes in DNA methylation were compared for early-PN and late-PN patients, revealing that 38.9% were already differentially methylated by day 3, another 25.0% by day 5 and another 13.9% by day 7. Conclusions: Critical illness- and early-PN-induced changes in DNA methylation occurred mainly within 3 days. Most abnormalities were at least partially maintained or got worse with longer time in PICU. Interventions targeting aberrant DNA methylation changes should be initiated early. [ABSTRACT FROM AUTHOR]

Previous psycholinguistic studies that compared the time course of interpretation for pragmatic some and literal all have returned mixed results. In particular, a delayed pragmatic some has been found in some studies but not in others. We explain these conflicting findings in terms of factors which are independent of incremental semantic/pragmatic interpretation. Two offline experiments provide evidence of the effect of these factors. Three visual-world studies showed that they influence participants' eye movements in online comprehension. We introduce a new measure for investigating the time course of scalar inference. This new measure allows us to reason about the time course question based on the difference in verification procedures between numbers and quantifiers. Results from our visual-world studies suggest that deriving the pragmatic interpretation is not delayed relative to the semantic interpretation. [ABSTRACT FROM AUTHOR]

Chronic pain is associated with persistent structural and functional changes throughout the neuroaxis, including in the prefrontal cortex (PFC). The PFC is important in the integration of sensory, cognitive, and emotional information and in conditioned pain modulation. We previously reported widespread epigenetic reprogramming in the PFC many months after nerve injury in rodents. Epigenetic modifications, including DNA methylation, can drive changes in gene expression without modifying DNA sequences. To date, little is known about epigenetic dysregulation at the onset of acute pain or how it progresses as pain transitions from acute to chronic. We hypothesize that acute pain after injury results in rapid and persistent epigenetic remodelling in the PFC that evolves as pain becomes chronic. We further propose that understanding epigenetic remodelling will provide insights into the mechanisms driving pain-related changes in the brain. Epigenome-wide analysis was performed in the mouse PFC 1 day, 2 weeks, 6 months, and 1 year after peripheral injury using the spared nerve injury in mice. Spared nerve injury resulted in rapid and persistent changes in DNA methylation, with robust differential methylation observed between spared nerve injury and sham-operated control mice at all time points. Hundreds of differentially methylated genes were identified, including many with known function in pain. Pathway analysis revealed enrichment in genes related to stimulus response at early time points, immune function at later time points, and actin and cytoskeletal regulation throughout the time course. These results emphasize the importance of considering pain chronicity in both pain research and in treatment optimization. [ABSTRACT FROM AUTHOR]

Since the emergence of the SARS-CoV-2 pandemic in December 2019 about 500,000 people died within the first 6 months. The virus itself, as well as the related political decisions, intensified an increasing feeling of fear in billions of people worldwide. However, while some people remained unperturbed, others experienced panic over the current situation. In order to investigate individual differences in the perceptions, emotions and behaviors in response to the Coronavirus pandemic, an online survey was conducted between 6th and 27th of March 2020. Participants included 7309 individuals from 96 countries, who provided information on socio-demographics, personality, political orientation and general life satisfaction. To determine the specificity of fear of Coronavirus, we also investigated fear related to two other current political issues: the refugee and the climate crises. Overall, in parallel with the escalation of the pandemic, fear of Coronavirus increased significantly over the 22-day period, with the strongest predictors being the personality variable neuroticism, as well as education, sex and being an at-risk person. A detailed longitudinal analysis of the largest sample, Germany, revealed that political orientation was also an important predictor of fear of Coronavirus. Specifically, conservatives were more afraid of Coronavirus than liberals. However, as the perceived threat of the virus increased, the influence of political orientation disappeared, whereas personality remained a stable predictor. The pattern of results regarding the perceived threat of the refugee and climate crises painted a different picture: political orientation was by far the best predictor, more important even than personality. Conservatives were more worried about the refugees, and liberals about climate change. Cross-cultural analyses showed pronounced differences between countries, dependent on the crisis. Nonetheless, the importance of personality for the prediction of fear of Coronavirus remained stable over time and across the world within the investigated 22-day period. [ABSTRACT FROM AUTHOR]

Background and Objectives: Individuals evaluate the demands and resources associated with a pressurized situation, which leads to distinct patterns of cardiovascular responses. While it is accepted that cognitive evaluations are updated throughout a pressurized situation, to date, cardiovascular markers have only been recorded immediately before, or averaged across, these situations. Thus, this study examined the influence of in-task performance-related feedback on cardiovascular markers of challenge and threat to explore fluctuations in these markers. Methods and Design: Forty participants completed a pressurized visual search task while cardiovascular markers of challenge and threat were recorded. During the task, participants received either positive or negative feedback via distinct auditory tones to induce a challenge or threat state. Following task completion, cardiovascular markers were recorded during a recovery phase. Results: Participants' cardiovascular responses changed across the experimental protocol. Specifically, while participants displayed a cardiovascular response more reflective of a challenge state following in-task performance-related feedback, participants exhibited a response more akin to a threat state later during the recovery phase. Conclusions: In-task auditory performance-related feedback promoted cardiovascular markers of a challenge state. These markers fluctuated over the experiment, suggesting that they, and presumably underlying demand and resource evaluations, are relatively dynamic in nature. [ABSTRACT FROM AUTHOR]

Key points: The present study showed that anodal and cathodal transcranial direct current stimulation (tDCS) can respectively increase and decrease the amplitude of visually evoked field potentials in the stimulated visual cortex of cats, with the effect lasting for ∼60–70 min.We directly measured tDCS‐induced changes in the concentration of inhibitory and excitatory neurotransmitters in the visual cortex using the enzyme‐linked immunosorbent assay method and showed that anodal and cathodal tDCS can selectively decrease the concentration of GABA and glutamate in the stimulated cortical area.Anodal and cathodal tDCS can selectively inhibit the synthesis of GABA and glutamate by suppressing the expression of GABA‐ and glutamate‐synthesizing enzymes, respectively. Transcranial direct current stimulation (tDCS) evokes long‐lasting neuronal excitability in the target brain region. The underlying neural mechanisms remain poorly understood. The present study examined tDCS‐induced alterations in neuronal activities, as well as the concentration and synthesis of GABA and glutamate (GLU), in area 21a (A21a) of cat visual cortex. Our analysis showed that anodal and cathodal tDCS respectively enhanced and suppressed neuronal activities in A21a, as indicated by a significantly increased and decreased amplitude of visually evoked field potentials (VEPs). The tDCS‐induced effect lasted for ∼60–70 min. By contrast, sham tDCS had no significant impact on the VEPs in A21a. On the other hand, the concentration of GABA, but not that of GLU, in A21a significantly decreased after anodal tDCS relative to sham tDCS, whereas the concentration of GLU, but not that of GABA, in A21a significantly decreased after cathodal tDCS relative to sham tDCS. Furthermore, the expression of GABA‐synthesizing enzymes GAD65 and GAD67 in A21a significantly decreased in terms of both mRNA and protein concentrations after anodal tDCS relative to sham tDCS, whereas that of GLU‐synthesizing enzyme glutaminase (GLS) did not change significantly after anodal tDCS. By contrast, both mRNA and protein concentrations of GLS in A21a significantly decreased after cathodal tDCS relative to sham tDCS, whereas those of GAD65/GAD67 showed no significant change after cathodal tDCS. Taken together, these results indicate that anodal and cathodal tDCS may selectively reduce GABA and GLU syntheses and thus respectively enhance and suppress neuronal excitability in the stimulated brain area. Key points: The present study showed that anodal and cathodal transcranial direct current stimulation (tDCS) can respectively increase and decrease the amplitude of visually evoked field potentials in the stimulated visual cortex of cats, with the effect lasting for ∼60–70 min.We directly measured tDCS‐induced changes in the concentration of inhibitory and excitatory neurotransmitters in the visual cortex using the enzyme‐linked immunosorbent assay method and showed that anodal and cathodal tDCS can selectively decrease the concentration of GABA and glutamate in the stimulated cortical area.Anodal and cathodal tDCS can selectively inhibit the synthesis of GABA and glutamate by suppressing the expression of GABA‐ and glutamate‐synthesizing enzymes, respectively. [ABSTRACT FROM AUTHOR]

Objective: To quantify wear‐off of the response to OnabotulinumtoxinA (OnabotA) treatment over the treatment cycle in chronic migraine at group and individual level. Background: OnabotA administered quarterly is an effective treatment for chronic migraine. However, some patients report that headache recurs before the scheduled follow‐up injection. Methods: In this retrospective chart review performed in 6 university outpatient centers or private practices specialized in headache treatment, 112 patients with a ≥30% response to OnabotA who completed headache diaries over 13 weeks after OnabotA treatment were included (age [mean ± SD] 45 ± 12 years, 82% female, headache days/month at baseline 24 ± 6). Results: Compared to weeks 5 to 8 after injection, headache days/week increased significantly in weeks 12 (+0.52 ± 1.96, 95% CI [0.15, 0.88], P <.009) and 13 (+1.15 ± 1.95, CI[0.79, 1.52], P <.001), demonstrating significant wear‐off of the OnabotA effect. Similarly, acute medication days/week significantly increased in weeks 12 (0.38±1.67, CI [0.06, 0.69], P ≤.027) and 13 (+0.83 ± 1.76, CI [0.49, 1.16], P <.001). At an individual level, 57 patients (51%) showed ≥30% wear‐off by weeks 12 and 13, and 28 patients (25%) showed ≥30% wear‐off already by weeks 10 and 11. Age, gender, OnabotA dose or cycle number, or headache center did not predict individual wear‐off. Conclusions: These data show that in clinical practice, on average the response of chronic migraine patients to OnabotA injection shows a clinically significant wear‐off from week 12 after treatment. About 25% of the patients experience wear‐off even by weeks 10 and 11. It must be noted that wear‐off detected in a real‐world study on OnabotA responders can be due to wear‐off of a pharmacological OnabotA effect or a placebo effect, or to regression to the mean effects. This wear‐off phenomenon may negatively affect quality of life of chronic migraine patients under OnabotA treatment. The best way to counteract wear‐off remains to be determined. [ABSTRACT FROM AUTHOR]

Patients suffering from painful post-traumatic trigeminal neuropathy (PTTN) often report circadian variations in pain. This pilot study aimed to assess the daily evolution of pain in patients fulfilling the following criteria: PTTN diagnosed based on ICHD-3 criteria; >18 years of age; no impairment in communication and signed informed consent. Primary study outcome was a self-declared quantitative assessment of pain intensity using an 11-point numerical scale (0–10) for 8 consecutive days. Impact on oral function and quality of life was also assessed, using psychometric questionnaires GOHAI and HADS. Eleven patients with PTTN were recruited (mean age: 66.1 ± 6.8 years old). Mean pain intensity was 3.6 ± 0.99. Mean pain intensity increased progressively and significantly during the day, from 1.8 ± 1.3 to 4.6 ± 2.3 (p < 0.0001). Mean HADS score was 7.8 ± 2.7. Mean GOHAI score was weak (35/60). In conclusion, PTTN seems to follow a circadian rhythm. [ABSTRACT FROM AUTHOR]

In the small intestine, localized innate mucosal immunity is critical for intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) infection induces villus injury and impairs digestive function. Moreover, the infection might comprise localized innate mucosal immunity. This study investigated specific enterocyte subtypes and innate immune components of weaned pigs during PEDV infection. Four-week-old pigs were orally inoculated with PEDV IN19338 strain (n = 40) or sham-inoculated (n = 24). At day post inoculation (DPI) 2, 4, and 6, lysozyme expression in Paneth cells, cellular density of villous and Peyer's patch microfold (M) cells, and the expression of polymeric immunoglobulin receptor (pIgR) were assessed in the jejunum and ileum by immunohistochemistry, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α were measured in the jejunum by ELISA. PEDV infection led to a decrease in the ratios of villus height to crypt depth (VH–CD) in jejunum at DPI 2, 4, and 6 and in ileum at DPI 4. The number of villous M cells was reduced in jejunum at DPI 4 and 6 and in ileum at DPI 6, while the number of Peyer's patch M cells in ileum increased at DPI 2 and then decreased at DPI 6. PEDV-infected pigs also had reduced lysozyme expression in ileal Paneth cells at DPI 2 and increased ileal pIgR expression at DPI 4. There were no significant changes in IL-1β and TNF-α expression in PEDV-infected pigs compared to controls. In conclusion, PEDV infection affected innate mucosal immunity of weaned pigs through alterations in Paneth cells, villous and Peyer's patch M cells, and pIgR expression. [ABSTRACT FROM AUTHOR]

Background: Kounis syndrome is a rare condition that is characterized by the coexistence of acute coronary syndrome and allergic reactions; however, its time course remains unclear. We report a case of anaphylactic shock with subsequent development of ST-segment elevation myocardial infarction.Case Report: A 47-year-old man with food allergies presented to the emergency department of our hospital with breathing difficulties after eating bread. He had a history of angina and underwent stent implantation 3 years earlier. On examination, he was lethargic, disoriented, and in shock. He had a rash on his face and anterior chest wall, as well as severe itching and sweating. Anaphylaxis was diagnosed and, 3 min after presentation, 0.5 mg epinephrine was injected intramuscularly into the right thigh. Electrocardiography, which was recorded 2 min after the administration of epinephrine, was normal; however, chest pain developed suddenly 18 min later. Repeat electrocardiography showed ST-segment elevations, and emergency coronary angiography revealed total occlusion of the left anterior descending coronary artery (i.e., the previous stenting site). Recanalization of the left anterior descending coronary artery was achieved after repeated thrombus aspiration with difficulty, followed by stent implantation inside of the stent under the support of intra-aortic balloon pumping. The clinical course was uneventful. He was discharged and advised to avoid eating wheat and carry an epinephrine self-injection kit for anaphylaxis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The present case highlights the importance of recognizing Kounis syndrome in the management of anaphylactic shock because treatment may be difficult, particularly in patients with type III Kounis syndrome. [ABSTRACT FROM AUTHOR]

The anterior temporal lobe (ATL) is considered a crucial area for the representation of transmodal concepts. Recent evidence suggests that specific regions within the ATL support the representation of individual object concepts, as shown by studies combining multivariate analysis methods and explicit measures of semantic knowledge. This research looks to further our understanding by probing conceptual representations at a spatially and temporally resolved neural scale. Representational similarity analysis was applied to human intracranial recordings from anatomically defined lateral to medial ATL sub-regions. Neural similarity patterns were tested against semantic similarity measures, where semantic similarity was defined by a hybrid corpus-based and feature-based approach. Analyses show that the perirhinal cortex, in the medial ATL, significantly related to semantic effects around 200 to 400 ms, and were greater than more lateral ATL regions. Further, semantic effects were present in low frequency (theta and alpha) oscillatory phase signals. These results provide converging support that more medial regions of the ATL support the representation of basic-level visual object concepts within the first 400 ms, and provide a bridge between prior fMRI and MEG work by offering detailed evidence for the presence of conceptual representations within the ATL. [ABSTRACT FROM AUTHOR]

In experiments on behavioral adaptation, hundreds or even thousands of trials per subject are often required in order to accurately recover the many psychometric functions that characterize adaptation's time course. More efficient methods for measuring perceptual changes over time would be beneficial to such efforts. In this article, we propose two methods to adaptively select the optimal stimuli sequentially in an experiment on adaptation: These are the minimum entropy (ME) method and the match probability (MP) method. The ME method minimizes the uncertainty about the joint posterior distribution of the function parameters at each trial and is mathematically equivalent to Zhao, Lesmes, and Lu's (2019) method, which efficiently measures time courses of perceptual change by maximizing information gain. The MP method selects the next stimulus that makes the value of the psychometric function closest to.5—that is, where the probability of choosing either one of the two options for each stimulus is closest to.5. We extended Zhao et al.'s (2019) work by evaluating the ME method in a new domain (contrast adaptation) with two simulation studies that compared it to MP and two other methods (i.e., traditional staircase and random methods), and also explored the optimal block length. ME outperformed the other three methods in general, and using fewer longer blocks generally produced better parameter recovery than using more shorter blocks. [ABSTRACT FROM AUTHOR]

Background: Usual clinical practice for arterial blood gas analysis (BGA) in conscious patients involves a one-time arterial puncture to be performed after a resting period of 20-30 min. The aim of this study was to evaluate the use of transcutaneous BGA for estimating this gold standard arterial BGA.Methods: Spontaneously breathing Asian adults (healthy volunteers and respiratory patients) were enrolled (n = 295). Transcutaneous PO2 (PtcO2) and PCO2 (PtcCO2) were monitored using a transcutaneous monitor (TCM4, Radiometer Medical AsP, Denmark) with sensors placed on the chest, forearm, earlobe or forehead. Transcutaneous BGA at 1-min intervals was compared with arterial BGA at 30 min. Reasonable steps to find severe hypercapnia with PaCO2 > 50 mmHg were evaluated.Results: Sensors on the chest and forearm were equally preferred and used because of small biases (n = 272). The average PCO2 bias was close to 0 mmHg at 4 min, and was almost constant (4-5 mmHg) with PtcCO2 being higher than PaCO2 at ≥8 min. The limit of agreement for PCO2 narrowed over time: ± 13.6 mmHg at 4 min, ± 7.5 mmHg at 12-13 min, and ± 6.3 mmHg at 30 min. The limit of agreement for PO2 also narrowed over time (± 23.1 mmHg at 30 min). Subgroup analyses showed that the PaCO2 and PaO2 levels, gender, and younger age significantly affected the biases. All hypercapnia subjects with PaCO2 > 50 mmHg (n = 13) showed PtcCO2 ≥ 50 mmHg for until 12 min.Conclusions: Although PtcCO2 is useful, it cannot completely replace PaCO2 because PCO2 occasionally showed large bias. On the other hand, the prediction of PaO2 using PtcO2 was unrealistic in Asian adults. PtcCO2 ≥ 50 mmHg for until 12 min can be used as a screening tool for severe hypercapnia with PaCO2 > 50 mmHg. [ABSTRACT FROM AUTHOR]

Introduction: Alterations in cell-free DNA concentration (cfDNA) over time have been studied in diseased or injured patients or analyzed in athletes during exhaustive exercise. However, no fluctuations have been examined over a short time course in healthy humans at rest so far, wherefore the aim of this study was to examine individual variations at different time points within 75 min. Methods: Serial blood drawing was performed in 14 healthy female volunteers at rest within 75 min. Plasma DNA was quantified by real-time qPCR, and absolute levels were analyzed together with relative variations. cfDNA alterations were moreover analyzed in consideration of potential volunteer-related impact factors (e.g., pulse) and were compared to alterations of plasma CK and AST. Results: Absolute cfDNA concentration ranged from 0.6 to 3.4 ng/ml. Regarding alterations over time, positive and negative variations were identified, whereby the interdecile range of fold changes was from 0.5 to 1.4. The maximum fold change was determined at 10 min. No relations were found between cfDNA levels and the analyzed individual factors. Conclusion: We evidenced the variability of cfDNA in healthy humans at rest within a short time course. The determined variations should serve in future studies to distinguish small cfDNA increases after minor trauma from natural fluctuations. Without such reference of intra-individual variation at rest, it would not be feasible to distinguish an injury from a fluctuation with certainty. Thus, a basis was established for the application of cfDNA as biomarker for the detection of mild injuries in forensic biomechanics. [ABSTRACT FROM AUTHOR]

Purpose: To assess the intraocular pressure (IOP) time response to change in body position from sitting to supine and from supine to sitting immediately and during rest in each position. Methods: Forty‐four visually healthy volunteers were recruited for the study. The experiment consisted of the initial sitting position (baseline state), the subsequent lying period and the final sitting period. Both periods were 30 min long. The IOP was measured in the baseline state, immediately after each position change and then in minutes 5, 15, 25 and 30 during each period. The Icare Pro® rebound tonometer was used. Results: The mean IOP increased after each position change (2.6 ± 2.4 mmHg after lying down and 2.1 ± 3.1 mmHg after sitting up) and then gradually decreased with time. The mean IOP was 1.41 ± 2.4 mmHg higher in the lying period than in the sitting period; the mean difference was smaller for the lower baseline (0.9 ± 2.2 mmHg) than the higher baseline (1.9 ± 2.5 mmHg). The mean IOP in the final sitting was significantly lower (2.5 ± 1.9 mmHg) than in the initial sitting position. The effect of sex was insignificant. Conclusions: There was an immediate increase in IOP as a response to both changes in the body position and the subsequent gradual decrease with time. The IOP difference between lying and sitting position was depended on baseline. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury is associated with high rates of mortality and morbidity. Trauma patients with a coagulopathy have a 10-fold increased mortality risk compared to patients without a coagulopathy. The aim of this study was to identify the incidence of coagulopathy and relate early coagulopathy to clinical outcome in patients with traumatic intracranial hemorrhages. Methods: Between September 2015 and December 2016, 108 consecutive cranial trauma patients with traumatic intracranial hemorrhages were included in this study. To assess the relationship between patients with a coagulopathy and outcome, a chi-squared test was performed. Results: A total of 29 out of the 108 patients (27%) with a traumatic intracranial hemorrhage developed a coagulopathy within 72 h after admission. Overall, a total of 22 patients (20%) died after admission of which ten were coagulopathic at emergency department presentation. Early coagulopathy in patients with traumatic brain injury is associated with progression of hemorrhagic injury (odds ratio 2.4 (95% confidence interval 0.8–8.0)), surgical intervention (odds ratio 2.8 (95% confidence interval 0.87–9.35)), and increased in-hospital mortality (odds ratio 23.06 (95% confidence interval 5.5–95.9)). Conclusion: Patients who sustained a traumatic intracranial hemorrhage remained at risk for developing a coagulopathy until 72 h after trauma. Patients who developed a coagulopathy had a worse clinical outcome than patients who did not develop a coagulopathy. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) is the most common and important pulmonary manifestation of rheumatoid arthritis (RA). A radiological honeycomb pattern has been described in diverse forms of ILD that can impact survival. However, the clinical course and sequential radiological changes in the formation of the honeycomb pattern in patients with RA-ILD is not fully understood.Methods: We evaluated the sequential changes in computed tomography findings in 40 patients with chronic forms of RA-ILD without the honeycomb pattern at initial diagnosis. We classified the patients into the Non-honeycomb group and Honeycomb group, and then analyzed the characteristics and prognosis of the two groups. The term "honeycomb formation" indicated a positive finding of honeycombing on any available follow-up CT.Results: Our RA-ILD cohort included patients with probable usual interstitial pneumonia (UIP) (35%), nonspecific interstitial pneumonia (NSIP) (20%), and mixed NSIP/UIP (45%). Among all RA-ILD patients, 16 (40%) showed honeycomb formation on follow-up CT (median time between initial and last follow-up CT was 4.7 years). Patient characteristics and prognosis were not significantly different between the Non-honeycomb and Honeycomb groups. However, Kaplan-Meier survival curve for the time from the date of honeycomb formation to death showed a poor median survival time of 3.2 years.Conclusions: A certain number of patients with RA-ILD developed a honeycomb pattern during long-term follow-up, regardless of whether they had UIP or NSIP. Prognosis in the patients with characteristics of both progressive ILD and honeycomb formation could be poor. Although radiological findings over the disease course and clinical disease behavior in RA-ILD are heterogenous, clinicians should be alert to the possibility of progressive disease and poor prognosis in patients with RA-ILD who form a honeycomb pattern during follow-up observation. [ABSTRACT FROM AUTHOR]

Adults process words that are rated as being learned earlier in life faster than words that are rated as being acquired later in life. This age-of-acquisition (AoA) effect has been observed in a variety of word-recognition tasks when word frequency is controlled. AoA has also previously been found to influence fixation durations when words are embedded into sentences and eye movements are recorded. However, the time course of AoA effects during reading has been inconsistent across studies. The current study further explored the time course of AoA effects on distributions of first-fixation durations during reading. Early and late acquired words were embedded into matched neutral sentence frames. Participants read the sentences while their eye movements were recorded. AoA effects were observed in both early and late fixation duration measures, suggesting that AoA has an early and long-lasting effect on word-recognition processes during reading. Survival analysis revealed that the earliest discernable effect of AoA on distributions of first-fixation durations emerged beginning at 158 ms. This rapid influence of AoA was confirmed through the use of Vincentile plots, which demonstrated that the effect of AoA occurred early and was relatively consistent across the distribution of fixations. This pattern of results provides support for the direct lexical-control hypothesis, as well as the viewpoint that AoA may exert an influence at multiple loci within the mental lexicon. [ABSTRACT FROM AUTHOR]

In an isolated and confined environment, leadership roles are important for mission success and harmonious interpersonal relationships. The task role benefits the achievement of mission goals and operational needs while the supportive role promotes emotional support and boosts morale. This study examined the effects of time on leadership roles and leadership influence among four crew members in a 180-day isolated and confined experiment. The crew members completed the Group Environment Scale around every two weeks to record their perceptions of leader support and leader control. Overall, perceived leader support decreased over the isolated and confined period, but the perception of leader control remained stable. Crew members perceived the role of leadership as providing support more than control. Leadership had a positive effect on the group climate by clarifying tasks and reducing aggression. Finally, the various functions of perceived leadership roles could be explained by crew composition and occupational features. The findings have implications that should be considered in future space missions and earth-based experiments when selecting leaders and arranging work duties with high autonomy. Further studies are needed to examine the generality of leadership roles in isolated and confined environments. • Perception of the supportive role diminished over time in isolation, and leadership roles enhanced the group climate and reduced conflict. • The leader's supportive role was perceived as higher than the task role in the small group. • Both the supportive role and the task role enhanced the group climate and reduced conflict. • There were individual differences in perceived support and control. [ABSTRACT FROM AUTHOR]

Objective: In this study, we compared in vitro and in vivo bioactivity of nitrogen-doped multi-walled carbon nanotubes (NDMWCNT) to MWCNT to test the hypothesis that nitrogen doping would alter bioactivity. Materials and Methods: High-resolution transmission electron microscopy (TEM) confirmed the multilayer structure of MWCNT with an average layer distance of 0.36 nm, which was not altered by nitrogen doping: the nanomaterials had similar widths and lengths. In vitro studies with THP-1 cells and alveolar macrophages from C57BL/6 mice demonstrated that NDMWCNT were less cytotoxic and stimulated less IL-1β release compared to MWCNT. For in vivo studies, male C57BL/6J mice received a single dose of dispersion medium (DM), 2.5, 10 or 40 µg/mouse of NDMWCNT, or 40 µg/mouse of MWCNT by oropharyngeal aspiration. Animals were euthanized between 1 and 7 days post-exposure for whole lung lavage (WLL) studies. Results and Discussion: NDMWCNT caused time- and dose-dependent pulmonary inflammation. However, it was less than that caused by MWCNT. Activation of the NLRP3 inflammasome was assessed in particle-exposed mice by determining cytokine production in WLL fluid at 1 day post-exposure. Compared to DM-exposed mice, IL-1β and IL-18 were significantly increased in MWCNT- and NDMWCNT-exposed mice, but the increase caused by NDMWCNT was less than MWCNT. At 56 days post-exposure, histopathology determined lung fibrosis in MWCNT-exposed mice was greater than NDMWCNT-exposed mice. Conclusions: These data indicate nitrogen doping of MWCNT decreases their bioactivity, as reflected with lower in vitro and in vivo toxicity inflammation and lung disease. The lower activation of the NLRP3 inflammasome may be responsible. Abbreviations: NDMWCNT: nitrogen-doped multi-walled carbon nanotubes; MWCNT: multi-walled carbon nanotubes; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; IL-1ß: interleukin-1ß; DM: dispersion medium; WLL: whole lung lavage; IL-18: interleukin-18; GSD: geometric standard deviation; XPS: X-ray photoelectron spectroscopy; SEM: standard error of the mean; PMA: phorbol 12-myristate 13-acetate; LPS: lipopolysacharride; LDH: lactate dehydrogenase; AM: alveolar macrophage; PMN: polymorphonuclear leukocyte [ABSTRACT FROM AUTHOR]

Context: Few reports have investigated the time course of fibrinogen (or fibrin) degradation product (FDP) levels for trauma patients in the subacute phase. Aims: This study aimed to investigate the time course of the FDP levels among patients with moderate and severe trauma in the subacute phase. Settings and Design: A retrospective medical chart review in a single hospital. Subjects and Methods: From September 2017 to March 2018, a medical chart review was retrospectively performed for all patients with trauma who were admitted to our department, and these patients were included as participants in the present study. We collected the data on each patient's sex, age, presence of head injury, mechanism of injury, Glasgow Coma Scale on arrival, systolic blood pressure, heart rate, type of injury (blunt versus penetrating), injury severity score, complication of infection, surgical procedure, duration of admission, survival rate, and FDP level from the 1st to 7th hospital day. The average level of FDP on each hospital day was compared with that on the previous day. Statistical Analysis Used: The statistical analyses were performed using a paired Student's t-test. P < 0.05 was considered to indicate a statistically significant difference. Results: From the 1st to 4th hospital day, the average level of FDP significantly diminished day by day. However, from the 5th hospital day, the average level significantly increased. This trend persisted even after excluding the complications of infection and surgical procedures performed between the 2nd and 7th hospital day. Conclusions: Among trauma patients, the average level of FDP significantly diminished day by day from the admission to the 4th hospital day; however, from the 5th hospital day, the average level significantly increased. Further studies are needed to determine the time course of FDP or D-dimer levels in the long term and when FDP levels return to normal limits. [ABSTRACT FROM AUTHOR]

Aims: To investigate the time courses of myofascial temporomandibular disorder (TMD) pain and mandibular function impairment (MFI), and to identify predictive factors associated with these time courses. Methods: During a 12-month period following conservative TMD treatment, the time courses of myofascial TMD pain and pain-related disabilities were assessed by questionnaires. Ninety-six myofascial TMD patients participated, of whom 70 completed the study. Before treatment (baseline data), Characteristic Pain Intensity (CPI), MFI, parafunctional activities, and psychological status were assessed, and at completion of treatment and at 3, 6, 9, and 12 months, CPI and MFI were scored again. Individual time courses in scores were analyzed using linear growth modeling. Results: Baseline values of CPI had a positive correlation with CPI during follow-up (P = .002), whereas the influences of reported parafunctions and of pain elsewhere on CPI scores were close to significance (P = .058 and .06, respectively). Patients with a low somatization score showed a further decline in CPI during follow-up (P = .027), whereas patients with a high score showed a gradual increase (P = .030). Baseline values of MFI were positively correlated with MFI scores during the follow-up period (P = .000). The influence of reported parafunctions on MFI was not significant (P = .174), but that of pain elsewhere was (P = .004). The trend for a further decline in MFI values during follow-up was close to significance (P = .063) for patients with low somatization scores. Patients with high somatization scores showed a significant increase in MFI values (P = .007). Conclusion: Baseline reports of pain and impairment, oral parafunctional activities, pain elsewhere in the body, and somatization are associated with the severity and time course of myofascial TMD complaints following treatment. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to clarify the dynamics (expression patterns) of mRNA expression up to 12 hours after resistance exercise. Methods: The tibialis anterior muscles of the right leg of male Wistar rats were electrically stimulated, and the muscles were extracted before exercise, immediately, 1, 3, 6, and 12 hours after exercise. Gene expressions were comprehensively measured by RNA-Seq and differentially expressed genes (DEGs) with resistance exercise were extracted. Gene Ontology (GO) analysis was performed for functional analysis. Results and Discussion: When the DEGs were divided into three groups (fast, medium, and slow) according to the rate of change, different GO terms were enriched in each group in significantly increased DEGs. Furthermore, skeletal muscle cell differentiation, response to mechanical stimulus, regulation of fat cell differentiation, and blood vessel development were enriched as significant GO terms for the 44 genes that decreased slowly after the peak in the increased DEGs. Thus, maintenance of increased mRNA levels may be important for resistance exercise-induced skeletal muscle adaptation. [ABSTRACT FROM AUTHOR]

Several theoretical studies on modal superposition methods to achieve tactile differentiation have been reported. However, there is still a lack of in-depth analysis and understanding of the regularity of the superposition of vibration modes and the resulting differences in tactile sensation. The touch beam vibrations are no longer in the form of standing waves after the modal superposition. The vibration points on the touch beam will present a periodic motion over time, instead of simply moving harmonically. The vibration response of the touch beam at high frequency, gave subjects a dramatically different tactile perception from that of a single inherent mode. Therefore, this paper reshapes the modal superposition theory of the haptic feedback technique to classify the vibration modes generated by the modal superposition of touch beams showing differences in tactile sensations considering the time course. The analysis and tactile texture prediction theories are improved compared to previous studies. The tactile sensation generated by the vibration patterns of left-right sway were found in the touch beam. Finally, the correctness of the tactile differentiation achieved by the modal superposition method was demonstrated by psychophysical assessment for different finger conditions. [ABSTRACT FROM AUTHOR]

The timing of the effects of botulinum toxin A on spastic muscles is not yet fully clarified. The goal of this study was to follow the temporal changes of surface electromyographic activity of lower limb muscles during walking, after a therapeutic dose of botulinum toxin A injected into the calf muscles of children with spastic cerebral palsy. A group of children with spastic equinus foot was administered botulinum toxin A into the gastrocnemius medialis and lateralis muscles. Surface electromyographic activity of the tibialis anterior, gastrocnemius medialis, rectus femoris and medial hamstrings, was recorded before botulinum toxin A injections and after 4, 8, and 16 weeks. Children walked on ground and on a treadmill at an incline of 0% and 12%. The area of electromyographic activity and the index of muscle co-contraction were calculated for specific segments of gait cycle. Botulinum toxin A did not modify the speed of gait on ground. ANOVA showed significant differences in electromyography during the stance phase segments with a maximum decrease between 4 and 8 weeks' post botulinum toxin A and a full recovery at 16 weeks. A significant co-contraction of rectus femoris/gastrocnemius medialis, between 0 and 20% and 35–50% of the gait cycle, was observed from the 4th to the 8th week post- botulinum toxin A for both treadmill settings. The temporal identification of deterioration/recovery of electromyographic activity as well as of muscle co-contractions, could be key elements in a rehabilitation program planning combined with botulinum toxin A. • Gastrocnemius shows a U shaped myoelectric trend after botulinum toxin (73 characters) • Before botulinum toxin, gastrocnemius adapts to different walking tasks (74 characters) • After botulinum toxin, gastrocnemius does not adapt to different walking tasks (81 characters) • Co-contraction of rectus femoris occurs when gastrocnemius is weakened (74 characters) • Resistance training should be started after the 8th week post botulinum toxin (81 characters) [ABSTRACT FROM AUTHOR]

Objective: To predict acidosis in fetus showing deceleration associated with non-reassuring fetal status during delivery, we examined the relationship between duration of the deceleration and umbilical arterial pH. Materials and methods: A total of 19,907 deliveries in eight facilities of the Juntendo Perinatal Care Group, 895 cases of vaginal deliveries with level 3 decelerations were selected for the subjects of this study. The cut-off point of time when the umbilical arterial pH fell below 7.20 in all cases of level 3 and for each deceleration type were examined. The explanatory variables were the pH and pO2 of umbilical arterial gas and the time from onset of the level 3 pattern to delivery. From receiver operating characteristic (ROC) analysis using these variables, the critical point indicating low Apgar score was set at an umbilical arterial pH

Abstract Background In citrus the transition from juvenility to mature phase is marked by the capability of a tree to flower and fruit consistently. The long period of juvenility in citrus severely impedes the use of genetic based strategies to improve fruit quality, disease resistance, and responses to abiotic environmental factors. One of the genes whose expression signals flower development in many plant species is FLOWERING LOCUS T (FT). Results In this study, gene expression levels of flowering genes CiFT1, CiFT2 and CiFT3 were determined using reverse-transcription quantitative real-time PCR in citrus trees over a 1 year period in Florida. Distinct genotypes of citrus trees of different ages were used. In mature trees of pummelo (Citrus grandis Osbeck) and ‘Pineapple’ sweet orange (Citrus sinensis (L.) Osbeck) the expression of all three CiFT genes was coordinated and significantly higher in April, after flowering was over, regardless of whether they were in the greenhouse or in the field. Interestingly, immature ‘Pineapple’ seedlings showed significantly high levels of CiFT3 expression in April and June, while CiFT1 and CiFT2 were highest in June, and hence their expression induction was not simultaneous as in mature plants. Conclusions In mature citrus trees the induction of CiFTs expression in leaves occurs at the end of spring and after flowering has taken place suggesting it is not associated with dormancy interruption and further flower bud development but is probably involved with shoot apex differentiation and flower bud determination. CiFTs were also seasonally induced in immature seedlings, indicating that additional factors must be suppressing flowering induction and their expression has other functions.

Background/Aims: To characterize the temporal profile of cold-induced angiogenesis in brown and white adipose tissues of mice in vivo and the temporal changes of angiogenic factors in primary mice brown (BA) and white adipocytes (WA) treated with β3-adrenoceptor agonist (CL316,243) in vitro. Methods: 8-week old male C57BL/6J mice were individually housed in conventional cages under cold exposure (4°C) for 1, 2, 3, 4 and 5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous (sWAT) and epididymal white adipose tissues (eWAT) were harvested for immunohistochemical and gene expression analysis. In vitro, primary mice BA and WA treated with or without CL316,243 were harvested for gene expression and protein secretion analysis. Results: A combination of morphological and genetic (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) analyses demonstrated depot-specific angiogenesis in response to cold exposure. Upon CL316,243 treatment, angiogenic factors (Vegfa, Vegfr2, Hif-1α, Pai1 and Pedf) and secreted protein VEGFA were transiently increased in both BA and WA. Conclusion: Our results show that iBAT is highly responsive to cold-induced angiogenesis that is mainly supported by sWAT with a lesser extent by eWAT. Moreover, the angiogenesis is a transient process with the angiogenic factors may work in an autocrine/paracrine manner.

Simultaneous profiling of biospecimens using different technological platforms enables the study of many data types, encompassing microbial communities, omics, and meta-omics as well as clinical or chemistry variables. Reduction in costs now enables longitudinal or time course studies on the same biological material or system. The overall aim of such studies is to investigate relationships between these longitudinal measures in a holistic manner to further decipher the link between molecular mechanisms and microbial community structures, or host-microbiota interactions. However, analytical frameworks enabling an integrated analysis between microbial communities and other types of biological, clinical, or phenotypic data are still in their infancy. The challenges include few time points that may be unevenly spaced and unmatched between different data types, a small number of unique individual biospecimens, and high individual variability. Those challenges are further exacerbated by the inherent characteristics of microbial communities-derived data (e.g., sparse, compositional). We propose a generic data-driven framework to integrate different types of longitudinal data measured on the same biological specimens with microbial community data and select key temporal features with strong associations within the same sample group. The framework ranges from filtering and modeling to integration using smoothing splines and multivariate dimension reduction methods to address some of the analytical challenges of microbiome-derived data. We illustrate our framework on different types of multi-omics case studies in bioreactor experiments as well as human studies.

The existence of two different types of sleep spindles (slow and fast) is well-established, according to their topographical distribution at scalp- and cortical-level. Our aim was to provide a systematic investigation focused on the temporal evolution of sleep spindle sources during non-rapid eye movement (NREM) sleep. Spindle activity was recorded and automatically detected in 20 healthy subjects. Low resolution brain electromagnetic tomography (LORETA) was applied for the EEG source localization. Aiming to evaluate the time course of the detected slow and fast spindle sources, we considered the first four NREM sleep cycles and divided each cycle into five intervals of equal duration. We confirmed the preferential localization in the frontal (Brodmann area 10) and parietal (Brodmann area 7) cortical regions, respectively for slow (11.0–12.5) and fast (13.0–14.5) spindles. Across subsequent NREM sleep episodes, the maximal source activation remained systematically located in Brodmann area 10 and Brodmann area 7, showing the topographical stability of the detected generators. However, a different time course was observed as a function of the type of spindles: a linear decrease across subsequent cycles was found for slow spindle but not for fast spindle source. The intra-cycle variations followed a “U” shaped curve for both spindle source, with a trough around third and fourth interval (middle part) and the highest values at the beginning and the end of the considered temporal window. We confirmed the involvement of the frontal and parietal brain regions in spindle generation, showing for the first time their changes within and between consecutive NREM sleep episodes. Our results point to a correspondence between the scalp-recorded electrical activity and the underlying source topography, supporting the notion that spindles are not uniform phenomena: complex region- and time-specific patterns are involved in their generation and manifestation.

Motor imagery refers to the phenomenon of imagining performing an action without action execution. Motor imagery and motor execution are assumed to share a similar underlying neural system that involves primary motor cortex (M1). Previous studies have focused on motor imagery of manual actions, but articulatory motor imagery has not been investigated. In this study, transcranial magnetic stimulation (TMS) was used to elicit motor-evoked potentials (MEPs) from the articulatory muscles [orbicularis oris (OO)] as well as from hand muscles [first dorsal interosseous (FDI)]. Twenty participants were asked to execute or imagine performing a simple squeezing task involving a pair of tweezers, which was comparable across both effectors. MEPs were elicited at six time points (50, 150, 250, 350, 450, 550 ms post-stimulus) to track the time course of M1 involvement in both lip and hand tasks. The results showed increased MEP amplitudes for action execution compared to rest for both effectors at time points 350, 450 and 550 ms, but we found no evidence of increased cortical activation for motor imagery. The results indicate that motor imagery does not involve M1 for simple tasks for manual or articulatory muscles. The results have implications for models of mental imagery of simple articulatory gestures, in that no evidence is found for somatotopic activation of lip muscles in sub-phonemic contexts during motor imagery of such tasks, suggesting that motor simulation of relatively simple actions does not involve M1.

Human has an exceptional ability for face recognition to keep up social network. However, it is unclear to understand the mechanisms of face recognition until now. Specifically, there is less research to examine the time course of part-based and holistic processing when these two routes trigger and finish. In the present experiments, the exposure time was manipulated to examine the time course of face processing and found evidence suggesting that holistic processing occurs shortly after part-based processing at about 200 ms, and can last for a relatively long duration up to 2,000 ms. These results may support to a dual-route model comprising holistic processing and part-based processing in face perception. Moreover, our findings were inconsistent with the previous study which suggests that no holistic processing was observed at the relatively long duration, and suspected that perceptual discriminability may have been responsible for the discrepancy.

Background: The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis., Methods: This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated., Results: In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674-0.823), and 0.601 (95% CI: 0.524-0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025-6.891) was an independent risk factor for 28-day mortality., Conclusions: The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality., (© 2024. The Author(s).)

Lung inflammation and fibrogenesis are the two main characteristics during the development of pulmonary fibrosis (PF), which are particularly associated with pulmonary macrophages. In this context, whether cryptotanshinone (CTS) could alleviate PF through regulating macrophage polarization were preliminarily demonstrated in vitro. Then the time course of PF and its relationship with macrophage polarization was determined in BLM-induced mice based on cytokine levels in bronchoalveolar lavage fluid (BALF), lung histopathology, flow cytometric analysis, mRNA and protein expression. CTS was loaded into macrophage-targeted and responsively released mannose-modified liposomes (Man-lipo), and the liposomes were then embedded into mannitol microparticles (M-MPs) using spray drying to achieve efficient pulmonary delivery. Afterwards, how CTS regulates macrophage polarization in vivo during different time courses of PF was probed. Furthermore, the molecular mechanisms of CTS against PF by regulating macrophage polarization were elucidated in vivo and in vitro. The full-course therapy group could achieve comparable therapeutic effects compared with the positive control drug PFD group. CTS can alleviate PF through regulating macrophage polarization, mainly by inhibiting NLRP3/TGF-β1 pathway during the inflammation course and modulating MMP-9/TIMP-1 balance during the fibrosis development course, providing new insights into chronic PF treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Postoperative nausea and vomiting (PONV) and pain are common and distressing complications in patients undergoing surgery. However, it remains uncertain whether timing of the postoperative course or the diel rhythm influences the occurrence of PONV or severe pain. Therefore, we aimed to explore the temporal distribution of PONV and severe pain., Material and Methods: In this prospective observational study, we enrolled patients aged 18-65 years with American Society of Anesthesiologists classifications I-III, who were scheduled for surgery under general anesthesia. Patients were visited postoperatively at regular intervals (every 6 h over a 24-h period). Incidence of PONV was recorded and categorized based on real-time divisions: before dawn (00:00-05:59), morning (06:00-11:59), afternoon (12:00-17:59), and evening (18:00-23:59) and as sequential periods (i.e., 0-6, 6-12, 12-18, and 18-24 h). Severe pain and use of additional remedies were also recorded., Results: A total of 724 patients were included in the final analysis. Of these, 14.92 % experienced PONV within the first 6 h, and 8.29 % received antiemetic therapy. Occurrence of PONV and administration of remedies declined over the 24-h postoperative period. The lowest rate of PONV was observed during the pre-dawn hours (5.66 %). There was no statistically significant difference in the incidence of PONV 24-h postoperatively between surgeries with different end times. Patients underwent orthopedic surgeries had the highest incidence of PONV during 18:00-23:59, gynecological surgery patients had the highest incidence at 12:00-17:59, and 6:00-11:59 for other surgery patients. All patients had the lowest incidence during 0:00-5:59. During the initial 6-h postoperative period, 24.59 % of patients experienced severe pain, which declined in the remaining episodes. Patients who underwent orthopedic and gynecological surgeries exhibited similar temporal patterns and distribution characteristics of PONV and severe pain., Discussion: Both PONV and severe pain declined within the 24-h postoperative period, particularly within the first 6 h. Additionally, the onset patterns of PONV vary among patients undergoing different types of surgeries, all patients demonstrated decreased susceptibility to PONV between 00:00-05:59. Our findings enhance prevention and treatment strategies within an optimized timeframe during the postoperative course., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Sleep inertia (SI) refers to a complex psychophysiological phenomenon, observed after awakening, that can be described as the gradual recovery of waking-like status. The time course of cognitive performance dissipation in an everyday life condition is still unclear, especially in terms of the sleep stage at awakening (REM or NREM-stage 2) and the relative effects on performance. The present study aimed to investigate the SI dissipation in different memory performances upon spontaneous morning awakening after uninterrupted nighttime sleep. Eighteen young adults (7 females; mean age 24.9 ± 3.14 years) spent seven non-consecutive nights (one baseline, three REM awakenings and three St2 awakenings) in the laboratory under standard polysomnographic (PSG) control. Participants were tested after three REM awakenings and three St2 awakenings, and three times at 11:00 a.m. as a control condition. In each testing session, participants filled in the Global Vigor and Affect Scale and carried out one memory task (episodic, semantic, or procedural task). For each condition, participants were tested every 10 min within a time window of 80 min. In accordance with previous studies, SI affected subjective alertness throughout the entire time window assessed. Moreover, SI significantly affected performance speed but not accuracy in the semantic task. With reference to this task, the SI effect dissipated within 30 min of awakening from REM, and within 20 min of awakening from St2. No significant SI effect was observed on episodic or procedural memory tasks.

Background: Bacterial cells during many replication cycles accumulate spontaneous mutations, which result in the birth of novel clones. As a result of this clonal expansion, an evolving bacterial population has different clonal composition over time, as revealed in the long-term evolution experiments (LTEEs). Accurately inferring the haplotypes of novel clones as well as the clonal frequencies and the clonal evolutionary history in a bacterial population is useful for the characterization of the evolutionary pressure on multiple correlated mutations instead of that on individual mutations. Results: In this paper, we study the computational problem of reconstructing the haplotypes of bacterial clones from the variant allele frequencies observed from an evolving bacterial population at multiple time points. We formalize the problem using a maximum likelihood function, which is defined under the assumption that mutations occur spontaneously, and thus the likelihood of a mutation occurring in a specific clone is proportional to the frequency of the clone in the population when the mutation occurs. We develop a series of heuristic algorithms to address the maximum likelihood inference, and show through simulation experiments that the algorithms are fast and achieve near optimal accuracy that is practically plausible under the maximum likelihood framework. We also validate our method using experimental data obtained from a recent study on long-term evolution of Escherichia coli. Conclusion: We developed efficient algorithms to reconstruct the clonal evolution history from time course genomic sequencing data. Our algorithm can also incorporate clonal sequencing data to improve the reconstruction results when they are available. Based on the evaluation on both simulated and experimental sequencing data, our algorithms can achieve satisfactory results on the genome sequencing data from long-term evolution experiments. Availability: The program (ClonalTREE) is available as open-source software on GitHub at https://github.com/COL-IU/ClonalTREE. [ABSTRACT FROM AUTHOR]

Background: Bud dormancy is a crucial stage in perennial trees and allows survival over winter to ensure optimal flowering and fruit production. Recent work highlighted physiological and molecular events occurring during bud dormancy in trees. However, they usually examined bud development or bud dormancy in isolation. In this work, we aimed to further explore the global transcriptional changes happening throughout bud development and dormancy onset, progression and release. Results: Using next-generation sequencing and modelling, we conducted an in-depth transcriptomic analysis for all stages of flower buds in several sweet cherry (Prunus avium L.) cultivars that are characterized for their contrasted dates of dormancy release. We find that buds in organogenesis, paradormancy, endodormancy and ecodormancy stages are defined by the expression of genes involved in specific pathways, and these are conserved between different sweet cherry cultivars. In particular, we found that DORMANCY ASSOCIATED MADS-box (DAM), floral identity and organogenesis genes are up-regulated during the pre-dormancy stages while endodormancy is characterized by a complex array of signalling pathways, including cold response genes, ABA and oxidation-reduction processes. After dormancy release, genes associated with global cell activity, division and differentiation are activated during ecodormancy and growth resumption. We then went a step beyond the global transcriptomic analysis and we developed a model based on the transcriptional profiles of just seven genes to accurately predict the main bud dormancy stages. Conclusions: Overall, this study has allowed us to better understand the transcriptional changes occurring throughout the different phases of flower bud development, from bud formation in the summer to flowering in the following spring. Our work sets the stage for the development of fast and cost effective diagnostic tools to molecularly define the dormancy stages. Such integrative approaches will therefore be extremely useful for a better comprehension of complex phenological processes in many species. [ABSTRACT FROM AUTHOR]

Crassulacean acid metabolism (CAM) has evolved as a water-saving strategy, and its engineering into crops offers an opportunity to improve their water use efficiency. This requires a comprehensive understanding of the regulation of the CAM pathway. Here, we use the facultative CAM species Talinum triangulare as a model in which CAM can be induced rapidly by exogenous abscisic acid. RNA sequencing and metabolite measurements were employed to analyse the changes underlying CAM induction and identify potential CAM regulators. Non-negative matrix factorization followed by k -means clustering identified an early CAM-specific cluster and a late one, which was specific for the early light phase. Enrichment analysis revealed abscisic acid metabolism, WRKY-regulated transcription, sugar and nutrient transport, and protein degradation in these clusters. Activation of the CAM pathway was supported by up-regulation of phosphoenolpyruvate carboxylase, cytosolic and chloroplastic malic enzymes, and several transport proteins, as well as by increased end-of-night titratable acidity and malate accumulation. The transcription factors HSFA2 , NF-YA9 , and JMJ27 were identified as candidate regulators of CAM induction. With this study we promote the model species T. triangulare , in which CAM can be induced in a controlled way, enabling further deciphering of CAM regulation. [ABSTRACT FROM AUTHOR]

Simultaneous profiling of biospecimens using different technological platforms enables the study of many data types, encompassing microbial communities, omics, and meta-omics as well as clinical or chemistry variables. Reduction in costs now enables longitudinal or time course studies on the same biological material or system. The overall aim of such studies is to investigate relationships between these longitudinal measures in a holistic manner to further decipher the link between molecular mechanisms and microbial community structures, or host-microbiota interactions. However, analytical frameworks enabling an integrated analysis between microbial communities and other types of biological, clinical, or phenotypic data are still in their infancy. The challenges include few time points that may be unevenly spaced and unmatched between different data types, a small number of unique individual biospecimens, and high individual variability. Those challenges are further exacerbated by the inherent characteristics of microbial communities-derived data (e.g., sparse, compositional). We propose a generic data-driven framework to integrate different types of longitudinal data measured on the same biological specimens with microbial community data and select key temporal features with strong associations within the same sample group. The framework ranges from filtering and modeling to integration using smoothing splines and multivariate dimension reduction methods to address some of the analytical challenges of microbiome-derived data. We illustrate our framework on different types of multi-omics case studies in bioreactor experiments as well as human studies. [ABSTRACT FROM AUTHOR]

Cough and wheezing are the predominant symptoms of acute bronchitis. Hitherto, the evaluation of respiratory symptoms was limited to subjective methods such as questionnaires. The main objective of this study was to objectively determine the time course of cough and wheezing in children with acute bronchitis. The impact of nocturnal cough on parent's quality of life was assessed as secondary outcome. In 36 children (2-8 years), the frequency of nocturnal cough and wheezing was recorded during three nights by automated lung sound monitoring. Additionally, parents completed symptom logs, i.e., the Bronchitis Severity Score (BSS), as well as the Parent-proxy Children's Acute Cough-specific Quality of Life Questionnaire (PAC-QoL). During the first night, patients had 34.4 ± 52.3 (mean ± SD) cough epochs, which were significantly reduced in night 5 (13.5 ± 26.5; p < 0.001) and night 9 (12.8 ± 28.1; p < 0.001). Twenty-two patients had concomitant wheezing, which declined within the observation period as well. All subjective parameters (BSS, Cough log and PAC-QoL) were found to be significantly correlated with the objectively assessed cough parameters.Conclusion: Long-term recording of cough and wheezing offers a useful opportunity to objectively evaluate the time course of respiratory symptoms in children with acute bronchitis. To assess putative effects of pharmacotherapy on nocturnal bronchitis symptoms, future studies in more homogeneous patient groups are needed. What is Known: • Cough and wheezing are the predominant symptoms of acute bronchitis. • There is a diagnostic gap in long-term assessment of these respiratory symptoms, which needs to be closed to optimize individual therapies. What is New: • Long-term recording of nocturnal cough and wheezing allows for objective evaluation of respiratory symptoms in children with acute bronchitis and provides a tool to validate the efficacy of symptomatic bronchitis therapies. [ABSTRACT FROM AUTHOR]

Biology relies on the central thesis that the genes in an organism encode molecular mechanisms that combine with stimuli and raw materials from the environment to create a final phenotypic expression representative of the genomic programming. While conceptually simple, the genotype-to-phenotype linkage in a eukaryotic organism relies on the interactions of thousands of genes and an environment with a potentially unknowable level of complexity. Modern biology has moved to the use of networks in systems biology to try to simplify this complexity to decode how an organism's genome works. Previously, biological networks were basic ways to organize, simplify, and analyze data. However, recent advances are allowing networks to move beyond description and become phenotypes or hypotheses in their own right. This review discusses these efforts, like mapping responses across biological scales, including relationships among cellular entities, and the direct use of networks as traits or hypotheses. After a number of years, systems biology and networks are being transitioned from generating hypotheses to being used to directly test hypotheses. Numerous statistical methods are now available to create predictive and testable hypotheses from a wide array of omics and systems data. Eigengenes allows the use, measuring, and testing of networks directly as any physiological, developmental trait. Community solutions surrounding sharing and visualizing networks are essential to allow the broader utilization of these approaches. [ABSTRACT FROM AUTHOR]

The existence of two different types of sleep spindles (slow and fast) is well-established, according to their topographical distribution at scalp- and cortical-level. Our aim was to provide a systematic investigation focused on the temporal evolution of sleep spindle sources during non-rapid eye movement (NREM) sleep. Spindle activity was recorded and automatically detected in 20 healthy subjects. Low resolution brain electromagnetic tomography (LORETA) was applied for the EEG source localization. Aiming to evaluate the time course of the detected slow and fast spindle sources, we considered the first four NREM sleep cycles and divided each cycle into five intervals of equal duration. We confirmed the preferential localization in the frontal (Brodmann area 10) and parietal (Brodmann area 7) cortical regions, respectively for slow (11.0–12.5) and fast (13.0–14.5) spindles. Across subsequent NREM sleep episodes, the maximal source activation remained systematically located in Brodmann area 10 and Brodmann area 7, showing the topographical stability of the detected generators. However, a different time course was observed as a function of the type of spindles: a linear decrease across subsequent cycles was found for slow spindle but not for fast spindle source. The intra-cycle variations followed a "U" shaped curve for both spindle source, with a trough around third and fourth interval (middle part) and the highest values at the beginning and the end of the considered temporal window. We confirmed the involvement of the frontal and parietal brain regions in spindle generation, showing for the first time their changes within and between consecutive NREM sleep episodes. Our results point to a correspondence between the scalp-recorded electrical activity and the underlying source topography, supporting the notion that spindles are not uniform phenomena: complex region- and time-specific patterns are involved in their generation and manifestation. [ABSTRACT FROM AUTHOR]