Diet and the risk of inflammatory bowel disease: A retrospective cohort study in Taiwan.

BACKGROUND/PURPOSE: The incidence of inflammatory bowel disease (IBD) rapidly increases in Asia, and western dietary pattern is suspected to be the major risk factor. Despite this, there has been a lack of studies analyzing the relationship between dietary patterns and IBD in Taiwan. This study examines the dietary habits of Taiwanese individuals with and without IBD to inform clinical dietary recommendations for IBD patients. METHODS: We collected baseline characteristics and dietary habits from both IBD patients and healthy controls from February and August 2022 in Chang Gung memorial hospital using a structured and validated food frequency questionnaire. The dietary habits of IBD patients in this study were focused on the six months leading up to their IBD diagnosis. RESULTS: Our study recruited 98 IBD patients and 184 healthy controls. In demographic characteristics, cigarette smoking is more common in IBD group. Besides, distinct dietary patterns were observed between groups. The healthy controls demonstrated a higher consumption of whole foods and antioxidants. By contrast, the IBD group consumed more western-style foods but the difference didn't reach statistical significance. CONCLUSION: Our study found that healthy controls in Taiwan embraced a dietary pattern rich in whole foods that may prevent IBD or reduce IBD disease activity. Nonetheless, a larger sample size is needed to further provide valuable dietary guidance for general population in Taiwan for IBD prevention or for patients with IBD for disease activity control.

In the fight against HIV/AIDS: the arduous implementation of government-funded pre-exposure prophylaxis programme in Taiwan.

INTRODUCTION: The government-funded pre-exposure prophylaxis (PrEP) programme was targeted to those aged under 30 years or serodiscordant couples and implemented in September 2018-October 2020 in Taiwan. The study aimed to examine the effectiveness of the programme and the relationship between sexually transmitted disease (STD) and HIV seroconversion. METHODS: This study was a retrospective cohort analysis with questionnaires designed for participants who joined the aforementioned programme in the PrEP-designated hospitals. The questionnaires included sociodemographic factors, sexual risk behaviours, number and types of sexual partners, and usage of narcotics filled in at the beginning of the programme and every 3 months. The McNemar test was used for the paired questionnaire analysis. The HIV seroconversion status among STD-notified patients nationwide was confirmed by using the data linkage method, followed up until October 2021 with stratification of PrEP programme participation or not. RESULTS: The programme recruited 2155 people. 11 participants (0.5%) had seroconversion within the programme, while 26 (1.2%) had seroconversion after withdrawing from the programme. Overall, 1892 subjects with repeated questionnaires were included in the analysis for behaviour changes with median follow-up of 289 days. After joining the programme, 94.7% of them claimed that they had sexual behaviours: the rate of those who had condomless sex rose to 5.5% (p<0.001) and the rate of those who used narcotics decreased to 2% (p<0.001), compared with their response in the pre-questionnaire. Notably, the frequency of non-use of narcotics in recent 3 months increased from 16.9% to 38.4% in the pre-questionnaire and post-questionnaire responses, among the 177 who had claimed narcotics usage in recent 12 months (p=0.003). More HIV seroconversion was found among patients with STD who did not join the programme than those who joined the programme (8.7% vs 4.9%, p=0.031). CONCLUSIONS: The government-funded programme showed HIV case reduction and positive changes in health behaviours except for condomless sex which had increased prevalence. The reduction of HIV cases was also observed among people with STD. More resources should be allocated to the PrEP programme.

Short-Term Outcomes of Conventional Laparoscopic versus Robot-Assisted Distal Pancreatectomy for Malignancy: Evidence from US National Inpatient Sample, 2005-2018.

BACKGROUND: The primary treatment for pancreatic cancer is surgical resection, and laparoscopic resection offers benefits over open surgery. This study aimed to compare the short-term outcomes of robot-assisted vs. conventional laparoscopic distal pancreatectomy. METHODS: Data of adults ≥ 20 years old with pancreatic cancer who underwent conventional laparoscopic or robot-assisted laparoscopic distal pancreatectomy were extracted from the United States (US) Nationwide Inpatient Sample (NIS) 2005-2018 database. Comorbidities and complications were identified through the International Classification of Diseases (ICD) codes. Short-term outcomes were compared using logistic regression and included length of hospital stay (LOS), perioperative complications, in-hospital mortality, unfavorable discharge, and total hospital costs. RESULTS: A total of 886 patients were included; 27% received robot-assisted, and 73% received conventional laparoscopic surgery. The mean age of all patients was 65.3 years, and 52% were females. Multivariable analysis revealed that robot-assisted surgery was associated with a significantly reduced risk of perioperative complications (adjusted odds ratio (aOR) = 0.61, 95% confidence interval (CI): 0.45-0.83) compared to conventional laparoscopic surgery. Specifically, robot-assisted surgery was associated with a significantly decreased risk of VTE (aOR = 0.35, 95% CI: 0.14-0.83) and postoperative blood transfusion (aOR = 0.37, 95% CI: 0.23-0.61). Robot-assisted surgery was associated with a significantly shorter LOS (0.76 days shorter, 95% CI: -1.43--0.09) but greater total hospital costs (18,284 USD greater, 95% CI: 4369.03-32,200.70) than conventional laparoscopic surgery. CONCLUSIONS: Despite the higher costs, robot-assisted distal pancreatectomy is associated with decreased risk of complications and shorter hospital stays than conventional laparoscopic distal pancreatectomy.

Breaking the symmetry of cell contractility drives tubulogenesis via CXCL1 polarization.

The intricate interplay between biomechanical and biochemical pathways in modulating morphogenesis is an interesting research topic. How biomechanical force regulates epithelial cell tubulogenesis remains poorly understood. Here, we established a model of tubulogenesis by culturing renal proximal tubular epithelial cells on a collagen gel while manipulating contractile force. Epithelial cells were dynamically self-organized into tubule-like structures by augmentation of cell protrusions and cell-cell association. Reduction and asymmetric distribution of phosphorylated myosin light chain 2, the actomyosin contractility, in cells grown on soft matrix preceded tube connection. Notably, reducing matrix stiffness via sonication of collagen fibrils and inhibiting actomyosin contractility with blebbistatin promoted tubulogenesis, whereas inhibition of cytoskeleton polymerization suppressed it. CXC chemokine ligand 1 (CXCL1) expression was transcriptionally upregulated in cells undergoing tubulogenesis. Additionally, inhibiting actomyosin contractility facilitated CXCL1 polarization and cell protrusions preceding tube formation. Conversely, inhibiting the CXCL1-CXC receptor 1 pathway hindered cell protrusions and tubulogenesis. Mechanical property asymmetry with cell-collagen fibril interaction patterns at cell protrusions and along the tube structure supported the association of anisotropic contraction with tube formation. Furthermore, suppressing the mechanosensing machinery of integrin subunit beta 1 reduced CXCL1 expression, collagen remodeling, and impaired tubulogenesis. In summary, symmetry breaking of cell contractility on a soft collagen gel promotes CXCL1 polarization at cell protrusions which in turn facilitates cell-cell association and thus tubule connection.

Efficient Removal of Hazardous P-Nitroaniline from Wastewater by Using Surface-Activated and Modified Multiwalled Carbon Nanotubes with Mesostructure.

P-nitroaniline (PNA) is an aniline compound with high toxicity and can cause serious harm to aquatic animals and plants. Multiwalled carbon nanotubes (MWCNTs) are a multifunctional carbon-based material that can be applied in energy storage and biochemistry applications and semiconductors as well as for various environmental purposes. In the present study, MWCNTs (CO2-MWCNTs and KOH-MWCNTs) were obtained through CO2 and KOH activation. ACID-MWCNTs were obtained through surface treatment with an H2SO4-HNO3 mixture. Herein, we report, for the first time, the various MWCNTs that were employed as nanoadsorbents to remove PNA from aqueous solution. The MWCNTs had nanowire-like features and different tube lengths. The nanotubular structures were not destroyed after being activated. The KOH-MWCNTs, CO2-MWCNTs, and ACID-MWCNTs had surface areas of 487, 484, and 80 m2/g, respectively, and pore volumes of 1.432, 1.321, and 0.871 cm3/g, respectively. The activated MWCNTs contained C-O functional groups, which facilitate PNA adsorption. To determine the maximum adsorption capacity of the MWCNTs, the influences of several adsorption factors-contact time, solution pH, stirring speed, and amount of adsorbent-on PNA adsorption were investigated. The KOH-MWCNTs had the highest adsorption capacity, followed by the CO2-MWCNTs, pristine MWCNTs, and ACID-MWCNTs. The KOH-MWCNTs exhibited rapid PNA adsorption (>85% within the first 5 min) and high adsorption capacity (171.3 mg/g). Adsorption isotherms and kinetics models were employed to investigate the adsorption mechanism. The results of reutilization experiments revealed that the MWCNTs retained high adsorption capacity after five cycles. The surface-activated and modified MWCNTs synthesized in this study can effectively remove hazardous pollutants from wastewater and may have additional uses.

Assessment of Tilapia Skin Collagen for Biomedical Research Applications in Comparison with Mammalian Collagen.

Collagen is an important material for biomedical research, but using mammalian tissue-derived collagen carries the risk of zoonotic disease transmission. Marine organisms, such as farmed tilapia, have emerged as a safe alternative source of collagen for biomedical research. However, the tilapia collagen products for biomedical research are rare, and their biological functions remain largely unexamined. In this study, we characterized a commercial tilapia skin collagen using SDS-PAGE and fibril formation assays and evaluated its effects on skin fibroblast adhesion, proliferation, and migration, comparing it with commercial collagen from rat tails, porcine skin, and bovine skin. The results showed that tilapia skin collagen is a type I collagen, similar to rat tail collagen, and has a faster fibril formation rate and better-promoting effects on cell migration than porcine and bovine skin collagen. We also confirmed its application in a 3D culture for kidney cells' spherical cyst formation, fibroblast-induced gel contraction, and tumor spheroid interfacial invasion. Furthermore, we demonstrated that the freeze-dried tilapia skin collagen scaffold improved wound closure in a mouse excisional wound model, similar to commercial porcine or bovine collagen wound dressings. In conclusion, tilapia skin collagen is an ideal biomaterial for biomedical research.

Association between Air Pollution and Short-Term Outcome of ST-Segment Elevation Myocardial Infarction in a Tropical City, Kaohsiung, Taiwan.

ST-segment elevation myocardial infarction (STEMI), one of the primary factors leading to global mortality, has been shown through epidemiological studies to have a relationship with short-term exposure to air pollutants; however, the association between air pollutants and the outcome of STEMI has not been well studied. The aim of this study was to estimate the impact of air pollutants on the outcomes of STEMI. Data on particulate matter <2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3) at each of the 11 air monitoring stations in Kaohsiung City were collected between 1 January 2012 and 31 December 2017. Medical records of non-trauma patients aged > 20 years who had presented to the Emergency Department (ED) with a principal diagnosis of STEMI were extracted. The primary outcome measure was in-hospital mortality. After adjusting for potential confounders and meteorological variables, we found that an increase in the interquartile range (IQR) in NO2 was associated with an elevated risk of in-hospital mortality in patients with STEMI. Moreover, there was an observed higher risk of in-hospital mortality associated with an increase in the IQR of NO2 during the warm season, specifically in lag 3 (3 days prior to the onset, OR = 3.266; 95%CI: 1.203-8.864, p = 0.02). Conversely, an IQR increase in PM10 was associated with an increased risk of in-hospital mortality in patients with STEMI in lag 3 (OR = 2.792; 95%CI: 1.115-6.993, p = 0.028) during the cold season. Our study suggests that exposure to NO2 (during the warm season) and PM10 (during the cold season) may contribute to a higher risk of poor prognosis in patients with STEMI.

Selection of Essential Neural Activity Timesteps for Intracortical Brain-Computer Interface Based on Recurrent Neural Network.

Intracortical brain-computer interfaces (iBCIs) translate neural activity into control commands, thereby allowing paralyzed persons to control devices via their brain signals. Recurrent neural networks (RNNs) are widely used as neural decoders because they can learn neural response dynamics from continuous neural activity. Nevertheless, excessively long or short input neural activity for an RNN may decrease its decoding performance. Based on the temporal attention module exploiting relations in features over time, we propose a temporal attention-aware timestep selection (TTS) method that improves the interpretability of the salience of each timestep in an input neural activity. Furthermore, TTS determines the appropriate input neural activity length for accurate neural decoding. Experimental results show that the proposed TTS efficiently selects 28 essential timesteps for RNN-based neural decoders, outperforming state-of-the-art neural decoders on two nonhuman primate datasets (R2=0.76±0.05 for monkey Indy and CC=0.91±0.01 for monkey N). In addition, it reduces the computation time for offline training (reducing 5-12%) and online prediction (reducing 16-18%). When visualizing the attention mechanism in TTS, the preparatory neural activity is consecutively highlighted during arm movement, and the most recent neural activity is highlighted during the resting state in nonhuman primates. Selecting only a few essential timesteps for an RNN-based neural decoder provides sufficient decoding performance and requires only a short computation time.

Outcomes for Patients with Urinary Tract Infection After an Initial Intravenous Antibiotics Dose Before Emergency Department Discharge.

INTRODUCTION: To investigate the effect of single-dose intravenous antibiotics before emergency department (ED) discharge on the outcomes of patients with urinary tract infections (UTIs). METHODS: This is a retrospective study conducted at the EDs of three medical centers. Patients aged over 18 years who presented to the ED with UTI and were discharged without admission between January 1, 2016 and December 31, 2017 were evaluated. The study group received a single dose of effective intravenous antibiotics on the basis of urine culture during the index ED visit following oral antibiotics, while the comparison group received oral antibiotics only. The primary outcomes were ED revisit within 72 h and admission following the return visit. RESULTS: A total of 8168 patients were included. Of these, 20.9% received intravenous antibiotics before ED discharge. Patients who received effective intravenous antibiotics before ED discharge were associated with less than 72-h ED revisit (adjusted odds ratio [OR] 0.791, 95% confidence interval [CI] 0.640-0.979]), but not decreased admission following the return visit (adjusted OR 0.921, 95% CI [0.731-1.153]). In subgroup analysis, parenteral antibiotic use during the index ED visit was associated with decreased admission following ED revisit in patients who presented with fever (adjusted OR 0.605; 95% CI 0.443-0.932). CONCLUSION: For patients with UTI and clinically well to be discharged from the ED, a single dose of effective intravenous antibiotics before ED discharge was associated with decreased 72-h ED revisit. In patients with febrile UTI, initial intravenous antibiotics were associated with decreased revisit leading to admissions.

Impact of coronary risk scores on disposition decision in emergency patients with chest pain.

BACKGROUND: Coronary risk scores (CRS) including History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) score and Emergency Department Assessment of Chest pain Score (EDACS) can help identify patients at low risk of major adverse cardiac events. In the emergency department (ED), there are wide variations in hospital admission rates among patients with chest pain. OBJECTIVE: This study aimed to evaluate the impact of CRS on the disposition of patients with symptoms suggestive of acute coronary syndrome in the ED. METHODS: This retrospective cohort study included 3660 adult patients who presented to the ED with chest pain between January and July in 2019. Study inclusion criteria were age > 18 years and a primary position International Statistical Classification of Diseases and Related Health Problems-10th revision coded diagnosis of angina pectoris (I20.0-I20.9) or chronic ischemic heart disease (I25.0-I25.9) by the treating ED physician. If the treating ED physician completed the electronic structured variables for CRS calculation to assist disposition planning, then the patient would be classified as the CRS group; otherwise, the patient was included in the control group. RESULTS: Among the 2676 patients, 746 were classified into the CRS group, whereas the other 1930 were classified into the control group. There was no significant difference in sex, age, initial vital signs, and ED length of stay between the two groups. The coronary risk factors were similar between the two groups, except for a higher incidence of smokers in the CRS group (19.6% vs. 16.1%, p = 0.031). Compared with the control group, significantly more patients were discharged (70.1% vs. 64.6%) directly from the ED, while fewer patients who were hospitalized (25.9% vs. 29.7%) or against-advise discharge (AAD) (2.6% vs. 4.0%) in the CRS group. Major adverse cardiac events and mortality at 60 days between the two groups were not significantly different. CONCLUSIONS: A higher ED discharge rate of the group using CRS may indicate that ED physicians have more confidence in discharging low-risk patients based on CRS.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy.

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation-the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)-all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

Association between prehospital prognostic factors on out-of-hospital cardiac arrest in different age groups.

BACKGROUND: The prognosis of out-of-hospital cardiac arrest (OHCA) is very poor. While several prehospital factors are known to be associated with improved survival, the impact of prehospital factors on different age groups is unclear. The objective of the study was to access the impact of prehospital factors and pre-existing comorbidities on OHCA outcomes in different age groups. METHODS: A retrospective observational analysis was conducted using the emergency medical service (EMS) database from January 2015 to December 2019. We collected information on prehospital factors, underlying diseases, and outcome of OHCAs in different age groups. Kaplan-Meier type survival curves and multivariable logistic regression were used to analyze the association between modifiable pre-hospital factors and outcomes. RESULTS: A total of 4188 witnessed adult OHCAs were analyzed. For the age group 1 (age ≦75 years old), after adjustment for confounding factors, EMS response time (odds ratio [OR] = 0.860, 95% confidence interval [CI]: 0.811-0.909, p < 0.001), public location (OR = 1.843, 95% CI: 1.179-1.761, p < 0.001), bystander CPR (OR = 1.329, 95% CI: 1.007-1.750, p = 0.045), attendance by an EMT-Paramedic (OR = 1.666, 95% CI: 1.277-2.168, p < 0.001), and prehospital defibrillation by automated external defibrillator (AED)(OR = 1.666, 95% CI: 1.277-2.168, p < 0.001) were prognostic factors for survival to hospital discharge in OHCA patients. For the age group 2 (age > 75 years old), age (OR = 0.924, CI:0.880-0.966, p = 0.001), EMS response time (OR = 0.833, 95% CI: 0.742-0.928, p = 0.001), public location (OR = 4.290, 95% CI: 2.450-7.343, p < 0.001), and attendance by an EMT-Paramedic (OR = 2.702, 95% CI: 1.704-4.279, p < 0.001) were independent prognostic factors for survival to hospital discharge in OHCA patients. CONCLUSIONS: There were variations between younger and older OHCA patients. We found that bystander CPR and prehospital defibrillation by AED were independent prognostic factors for younger OHCA patients but not for the older group.

Association between prehospital prognostic factors and out-of-hospital cardiac arrest: Effect of rural-urban disparities.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is associated with a poor prognosis and a highly variable survival rate. Few studies have focused on outcomes in rural and urban groups while also evaluating underlying diseases and prehospital factors for OHCAs. OBJECTIVE: To investigate the relationship between the patient's underlying disease and outcomes of OHCAs in urban areas versus those in rural areas. METHODS: We reviewed the emergency medical service (EMS) database for information on OHCA patients treated between January 2015 and December 2019, and collected data on pre-hospital factors, underlying diseases, and outcomes of OHCAs. Univariate and multivariate logistic regression analyses were used to evaluate the prognostic factors for OHCA. RESULTS: Data from 4225 OHCAs were analysed. EMS response time was shorter and the rate of attendance by EMS paramedics was higher in urban areas (p < 0.001 for both). Urban area was a prognostic factor for >24-h survival (odds ratio [OR] = 1.437, 95% confidence interval [CI]: 1.179-1.761). Age (OR = 0.986, 95% CI: 0.979-0.993). EMS response time (OR = 0.854, 95% CI: 0.811-0.898), cardiac arrest location (OR = 2.187, 95% CI: 1.707-2.795), attendance by paramedics (OR = 1.867, 95% CI: 1.483-2.347), and prehospital defibrillation (OR = 2.771, 95% CI: 2.154-3.556) were independent risk factors for survival to hospital discharge, although the influence of an urban area was not significant (OR = 1.211, 95% CI: 0.918-1.584). CONCLUSIONS: Compared with rural areas, OHCA in urban areas are associated with a higher 24-h survival rate. Shorter EMS response time and a higher probability of being attended by paramedics were noted in urban areas. Although shorter EMS response time, younger age, public location, defibrillation by an automated external defibrillator, and attendance by Emergency Medical Technician-paramedics were associated with a higher rate of survival to hospital discharge, urban area was not an independent prognostic factor for survival to hospital discharge in OHCA patients.

Liver cirrhosis affects serum lactate level measurement while assessing disease severity in patients with sepsis.

BACKGROUND: Elevated serum lactate is associated with higher mortality in sepsis, whereas liver dysfunction is associated with higher serum lactate levels. We assessed the predictive ability of serum lactate in patients with liver cirrhosis and sepsis. METHODS: This retrospective study included 12 281 cases of suspected infection with initial serum blood lactate drawn during January 2007-December 2013. RESULTS: Using one-to-two propensity score matching analysis, 1053 and 2106 septic patients with and without underlying liver cirrhosis, respectively, were successfully matched. Lactate levels of survivors and nonsurvivors were 2.58 and 5.93 mmol/L, respectively, in patients without liver cirrhosis (WLC), 2.96 and 7.29 mmol/L, respectively, in patients with nondecompensated liver cirrhosis (NDLC), and 4.08 and 7.16 mmol/L, respectively, in patients with decompensated liver cirrhosis (DLC). In receiver operating characteristic curve analysis, the sensitivity and specificity for predicting mortality were 0.81 and 0.55, respectively, in the WLC group, 0.85 and 0.45, respectively, in the NDLC group, and 0.86 and 0.33, respectively, in the DLC group, using serum lactate levels >2.0 mmol/L. CONCLUSIONS: The serum lactate level can be used to predict the severity of sepsis in patients with liver cirrhosis; however, its specificity would be lower at a cutoff of 2.0 mmol/L.

Serum Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 Associated with the Severity and Outcome of Acute Ischemic Stroke.

Stroke is a neurological emergency, where the mechanism of the blood supply to the brain is impaired, resulting in brain cell ischemia and death. Neuroinflammation is a key component in the ischemic cascade that results in cell damage and death after cerebral ischemia. The triggering receptor expressed on myeloid cells-1 (TREM-1) modulates neuroinflammation after acute ischemic stroke. In the present study, 60 patients with acute ischemic stroke, who had been subjected to neurological examinations and National Institutes of Health Stroke Scale (NIHSS) and brain magnetic resonance imaging studies, were enrolled in the emergency room of Kaohsiung Chang Gung Memorial Hospital. Twenty-four healthy volunteers were recruited as controls. The serum levels of soluble TREM-1 (sTREM-1), human S100 calcium-binding protein B (S100B), and proinflammatory cytokines and chemokines, including tumor necrosis α (TNF-α), interleukin 1ß, interleukin 6 (IL-6), interleukin 8, and interferon-γ were measured immediately after acute ischemic stroke. The serum levels of sTREM-1, TNFα, IL-6, and S100B were correlated with the stroke volume and NIHSS, after acute ischemic stroke. Additionally, the serum levels of sTREM-1 were significantly positively correlated with S100B. The functional outcomes were evaluated 6 months after ischemic stroke by the Barthel index, which was correlated with the age and levels of sTREM-1 and S100B. We suggest that acute ischemic stroke induces neuroinflammation by the activation of the TREM-1 signaling pathway and the downstream inflammatory machinery that modulates the inflammatory response and ischemic neuronal cell death. From a translational perspective, our results may allow for the development of a new therapeutic strategy for acute ischemic stroke by targeting the TREM-1 signaling pathway.

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling.

Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1α. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1α pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotection as a consequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1α by siRNA against pgc-1α will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1α induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1α/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus.

Isokotomolide A from Cinnamomum kotoense Induce Melanoma Autophagy and Apoptosis In Vivo and In Vitro.

Melanoma is an aggressive cancer with high lethality. In order to find new anticancer agents, isokotomolide A (Iso A) and secokotomolide A (Sec A) isolated from Cinnamomum kotoense were identified to be potential bioactive agents against human melanoma but without strong antioxidative properties. Cell proliferation assay displayed Iso A and Sec A treated in the normal human skin cells showed high viabilities. It also verified that two of them possess strong antimelanoma effect in concentration-dependent manners, especially on B16F10, A2058, MeWo, and A375 cells. Wound healing assay presented their excellent antimigratory effects. Through 3-N,3-N,6-N,6-N-Tetramethylacridine-3,6-diamine (acridine orange, AO) staining and Western blot, the autophagy induced by treatment was confirmed, including autophagy-related proteins (Atgs). By using annexin V-FITC/PI double-stain, the apoptosis was confirmed, and both components also triggered the cell cycle arrest and DNA damage. We demonstrated the correlations between the mitogen-activated protein kinase (MAPK) pathway and antimelanoma, such as caspase cascade activations. To further evaluate in vivo experiments, the inhibition of tumor cell growth was verified through the histopathological staining in a xenograft model. In this study, it was confirmed that Iso A and Sec A can encourage melanoma cell death via early autophagy and late apoptosis processes.

Influence of physicians' seniority on head computed tomography use for patients with isolated vertigo/dizziness.

OBJECTIVE: Vertigo/dizziness is a common reason for emergency department (ED) visits. Emergency physicians (EPs) must distinguish patients with dizziness/vertigo owing to serious central nervous system (CNS) disorders. We aimed to evaluate the association between physician seniority and use of head computed tomography (CT) and ED length of stay (LOS) in patients presenting to the ED with isolated dizziness/vertigo. METHODS: This retrospective cohort study included adult patients with non-traumatic dizziness/vertigo in the ED. EPs were categorized according to seniority: junior (less than 6 years' clinical experience), intermediate (7-12 years), and senior (≥12 years). RESULTS: Among 2589 patients with isolated dizziness/vertigo, 460 (17.8%) received brain CT; 46 (1.78%) had CNS disorder as a final diagnosis. Junior and intermediate EPs ordered more CT examinations than senior EPs: (odds ratio [OR] = 1.329, 95% confidence interval [CI]: 1.002-1.769 and OR = 1.531, 95% CI: 1.178-2.001, respectively). Patients treated by junior and intermediate EPs had lower patient ED LOS (OR = -0.432, 95% CI: -0.887 to 0.024 and OR = -0.436, 95% CI: -0.862 to -0.011). CONCLUSIONS: We revealed different judgment strategies among senior, intermediate, and junior EPs. Senior EPs ordered fewer CT examinations for patients with isolated vertigo/dizziness but had longer patient LOS.

Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a congenital malformation of cortical development where the cortical neurons located in the brain area fail to migrate in the proper formation. Epilepsy, particularly medically refractory epilepsy, is the most common clinical presentation for all types of FCD. This study aimed to explore the expression change of circulating miRNAs in patients with FCD from serum exosomes. A total of nine patients with FCD and four healthy volunteers were enrolled in this study. The serum exosomes were isolated from the peripheral blood of the subjects. Transmission electron microscopy (TEM) was used to identify the exosomes. Both exosomal markers and neuronal markers were detected by Western blotting analysis to prove that we could obtain central nervous system-derived exosomes from the circulation. The expression profiles of circulating exosomal miRNAs were assessed using next-generation sequencing analysis (NGS). We obtained a total of 107 miRNAs with dominant fold change (>2-fold) from both the annotated 5p-arm and 3p-arm of 2780 mature miRNAs. Based on the integrated platform of HMDD v3.2, miRway DB and DIANA-miRPath v3.0 online tools, and confirmed by MiRBase analysis, four potentially predicted miRNAs from serum exosomes in patients with FCD were identified, including miR194-2-5p, miR15a-5p, miR-132-3p, and miR-145-5p. All four miRNAs presented upregulated expression in patients with FCD compared with controls. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway category of four target miRNAs, we found eight possible signaling pathways that may be related to FCD. Among them, we suggest that the mTOR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, and cell cycle regulation and TGF-beta signaling pathway are high-risk pathways that play a crucial role in the pathogenesis of FCD and refractory epilepsy. Our results suggest that the circulating miRNAs from exosomes may provide a potential biomarker for diagnostic, prognostic, and therapeutic adjuncts in patients with FCD and refractory epilepsy.

Inhibition of Long-Term Variability in Decoding Forelimb Trajectory Using Evolutionary Neural Networks With Error-Correction Learning.

Objective: In brain machine interfaces (BMIs), the functional mapping between neural activities and kinematic parameters varied over time owing to changes in neural recording conditions. The variability in neural recording conditions might result in unstable long-term decoding performance. Relevant studies trained decoders with several days of training data to make them inherently robust to changes in neural recording conditions. However, these decoders might not be robust to changes in neural recording conditions when only a few days of training data are available. In time-series prediction and feedback control system, an error feedback was commonly adopted to reduce the effects of model uncertainty. This motivated us to introduce an error feedback to a neural decoder for dealing with the variability in neural recording conditions. Approach: We proposed an evolutionary constructive and pruning neural network with error feedback (ECPNN-EF) as a neural decoder. The ECPNN-EF with partially connected topology decoded the instantaneous firing rates of each sorted unit into forelimb movement of a rat. Furthermore, an error feedback was adopted as an additional input to provide kinematic information and thus compensate for changes in functional mapping. The proposed neural decoder was trained on data collected from a water reward-related lever-pressing task for a rat. The first 2 days of data were used to train the decoder, and the subsequent 10 days of data were used to test the decoder. Main Results: The ECPNN-EF under different settings was evaluated to better understand the impact of the error feedback and partially connected topology. The experimental results demonstrated that the ECPNN-EF achieved significantly higher daily decoding performance with smaller daily variability when using the error feedback and partially connected topology. Significance: These results suggested that the ECPNN-EF with partially connected topology could cope with both within- and across-day changes in neural recording conditions. The error feedback in the ECPNN-EF compensated for decreases in decoding performance when neural recording conditions changed. This mechanism made the ECPNN-EF robust against changes in functional mappings and thus improved the long-term decoding stability when only a few days of training data were available.