RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma.

There is a higher expression level of epidermal growth factor receptor (EGFR) in up to 90% of advanced head and neck squamous cell carcinoma (HNSCC) tissue than in normal surrounding tissues. However, the role of RNA-binding proteins (RBPs) in EGFR-associated metastasis of HNSCC remains unclear. In this study, we reveal that RBPs, specifically nucleolin (NCL) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1), correlated with the mesenchymal phenotype of HNSCC. The depletion of RBPs significantly attenuated EGF-induced HNSCC metastasis. Intriguingly, the EGF-induced EMT markers, such as fibronectin, were regulated by RBPs through the ERK and NF-κB pathway, followed by the enhancement of mRNA stability of fibronectin through the 5' untranslated region (5'-UTR) of the gene. The upregulation of fibronectin triggered the integrin signaling activation to enhance tumor cells' attachment to endothelial cells and increase endothelial permeability. In addition, the concurrence of EGFR and RBPs or EGFR and fibronectin was associated with overall survival and disease-free survival of HNSCC. The in vivo study showed that depletion of NCL, hnRNPA2B1, and fibronectin significantly inhibited EGF-promoted extravasation of tumor cells into lung tissues. The depletion of fibronectin or treatment with integrin inhibitors dramatically attenuated EGF-induced HNSCC metastatic nodules in the lung. Our data suggest that the RBPs/fibronectin axis is essential for EGF-induced tumor-endothelial cell interactions to enhance HNSCC cell metastasis.

Risk of NSAID-associated anastomosis leakage after colorectal surgery: a large-scale retrospective study using propensity score matching.

PURPOSE: NSAIDs are commonly used as opioid-sparing analgesics in colorectal surgery. Many efforts are made to elucidate the risk of NSAID-associated anastomotic leakage after colorectal surgery. However, these results still remain controversial. In this study, we applied large-scale retrospective analysis using propensity score matching to fully clarify the association between risk of anastomotic leakage and use of NSAID after colorectal surgery. METHODS: All colorectal cancer patients receiving operation during February 2008 to August 2018 in our multi-institution medical organization research database were enrolled. It is worthy to mention that only patients requiring re-operation within 21 days after colorectal surgery due to anastomotic leakage were counted as anastomosis leakage. Furthermore, a propensity score TriMatch analysis was performed to prevent from interference of confounding factors. RESULTS: A total of 10,584 patients were included in this study and divided into three groups, no NSAIDs group, non-selective NSAIDs group, and selective COX-2 inhibitors group, respectively. Before tri-matching analysis, significant differences in anastomotic leakage rate were observed. After propensity score matching analysis, the ratio of anastomotic leakage requiring re-operation occurred in 2.0%, 3.6%, and 2.0% in no NSAIDs, non-selective NSAIDs, and selective COX-2 inhibitors group, respectively. No significant difference was observed in these three groups. CONCLUSION: These results suggest that NSAIDs are not associated with incidence of anastomosis leakage following colorectal surgery. To our knowledge, it is the first study demonstrating that NSAIDs is not associated with incidence of anastomosis leakage following colorectal surgery using propensity score matching at a larger-scale retrospective study.

Developmental trajectories of sensory patterns from infancy to school age in a community sample and associations with autistic traits.

This prospective study examined the latent growth trajectories of sensory patterns among a North Carolina birth cohort (N = 1517; 49% boys, 87% White) across infancy (6-19 months), preschool (3-4 years), and school years (6-7 years). Change rates of sensory hyper- and hyporesponsiveness better differentiated children with an autism diagnosis or elevated autistic traits from those with other developmental conditions, including non-autistic children with sensory differences. More sensory hyper- and hyporesponsiveness at infancy followed by steeper increases differentially predicted more autistic traits at school age. Further, children of parents with higher education tended to show stable or improving trajectories. These findings highlight the importance of tracking sensory patterns from infancy for facilitating early identification of associated challenges and tailored support for families.

Early developmental profiles of sensory features and links to school-age adaptive and maladaptive outcomes: A birth cohort investigation.

Sensory-based subtypes among autistic children have been well documented, but little is known about longitudinal sensory subtypes beyond autistic populations. This prospective study aimed to identify subtypes based on trajectories of parent-reported sensory features measured at 6-19 months, 3-4, and 6-7 years of age among a community-based birth cohort (N = 1,517), and to examine their associations with school-age clinical and adaptive/maladaptive outcomes on a subset sample (N = 389). Latent class growth analysis revealed five trajectory subtypes varying in intensity and change rates across three sensory domains. In contrast to an Adaptive-All Improving subtype (35%) with very low sensory features and overall better school-age outcomes, an Elevated-All Worsening subtype (3%), comprised of more boys and children of parents with less education, was associated with most elevated autistic traits and poorest adaptive/maladaptive outcomes. Three other subtypes (62% in total) were generally characterized by stable or improving patterns of sensory features at mild to moderate levels, and challenges in certain outcome domains. Our findings indicate that characterizing children based on early sensory trajectories may contribute to earlier detection of subgroups of children with sensory challenges who are more likely to experience developmental challenges by school age, followed by early targeted interventions for improved long-term outcomes.

Sensory Features of Young Children From a Large Community Sample: Latent Factor Structures of the Sensory Experiences Questionnaire (Version 2.1, Short Form).

IMPORTANCE: Although three sensory factors (hyperresponsiveness [HYPO]; hyporesponsiveness [HYPER]; and sensory interests, repetitions, and seeking behaviors [SIRS]) have been demonstrated among a wide age range of clinical populations, they have not been well validated in the general population, especially with a large community sample of young children. OBJECTIVE: To validate the factor structure of the Sensory Experiences Questionnaire (Version 2.1, Short Form; SEQv2.1) in a community sample and to confirm the factor structure's existence in this sample. DESIGN: Caregivers completed the SEQv2.1, a parent-reported questionnaire designed to capture children's everyday sensory experiences. The latent factors of the SEQv2.1 were examined using confirmatory factor analysis. SETTING: North Carolina. PARTICIPANTS: Caregivers of 2,195 children age 3 yr were initially recruited through state birth records and were eligible to participate if the child did not have a history of serious medical problems and English was the family's primary language. OUTCOMES AND MEASURES: SEQv2.1. RESULTS: The SEQv2.1 showed validity in the community sample. Similar to previous research with clinical populations, the three broad patterns of sensory responsiveness were also confirmed in this large community sample of young children, but associations among the factors differed. CONCLUSIONS AND RELEVANCE: Validation of the three-sensory-factor structure in the general population suggests that these constructs are similar to those found with samples of participants with autism spectrum disorder and developmental disabilities. This finding underscores the importance of understanding the normative development of sensory features across a wider age range to better delineate qualitative differences underlying sensory features between clinical and general populations. What This Article Adds: Occupational therapists seeking to assess children's sensory features can use the SEQv2.1 not only with clinical samples but also with children in the general population.

Cell-Free Virus-Host Chimera DNA From Hepatitis B Virus Integration Sites as a Circulating Biomarker of Hepatocellular Cancer.

BACKGROUND AND AIMS: Early recurrence of hepatocellular carcinoma (HCC) after surgical resection compromises patient survival. Timely detection of HCC recurrence and its clonality is required to implement salvage therapies appropriately. This study examined the feasibility of virus-host chimera DNA (vh-DNA), generated from junctions of hepatitis B virus (HBV) integration in the HCC chromosome, as a circulating biomarker for this clinical setting. APPROACH AND RESULTS: HBV integration in 50 patients with HBV-related HCC was determined by the Hybridization capture-based next-generation sequencing (NGS) platform. For individual HCC, the vh-DNA was quantified by specific droplet digital PCR (ddPCR) assay in plasma samples collected before and 2 months after surgery. HBV integrations were identified in 44 out of 50 patients with HBV-related HCC. Tumor-specific ddPCR was developed to measure the corresponding vh-DNA copy number in baseline plasma from each patient immediately before surgery. vh-DNA was detected in 43 patients (97.7%), and the levels correlated with the tumor sizes (detection limit at 1.5 cm). Among the plasma collected at 2 months after surgery, 10 cases (23.3%) still contained the same signature vh-DNA detected at baseline, indicating the presence of residual tumor cells. Nine of them (90%) experienced HCC recurrence within 1 year, supporting vh-DNA as an independent risk factor in predicting early recurrence. Analysis of circulating vh-DNA at recurrence further helped identify the clonal origin. A total of 81.8% of recurrences came from original HCC clones sharing the same plasma vh-DNA, whereas 18.2% were from de novo HCC. CONCLUSIONS: vh-DNA was shown to be a circulating biomarker for detecting the tumor load in majority of patients with HBV-related HCC and aided in monitoring residual tumor and recurrence clonality after tumor resection.

EARLY RETINAL MICROVASCULAR ABNORMALITIES IN YOUNG ADULTS WITH TYPE 1 DIABETES MELLITUS WITHOUT CLINICALLY EVIDENT DIABETIC RETINOPATHY.

PURPOSE: To characterize the early retinal microvascular changes in young adults (age: 22.69 ± 3.50 years) with Type 1 diabetes mellitus without clinically detectable diabetic retinopathy using optical coherence tomography angiography and investigate the associated factors. METHODS: A total of 36 participants with Type 1 diabetes mellitus (70 eyes) and 34 healthy controls (57 eyes) were retrospectively reviewed. The analyzed optical coherence tomography angiography indices included capillary vessel density, foveal avascular zone area/perimeter/acircularity index, and foveal vascular density, acquired in the 6 × 6-mm2 area centered on the fovea. The generalized estimation equations model was applied to compare the mean values and to study the associated factors. RESULTS: In subjects with diabetes, statistically significant decreases were observed in parafoveal vessel density in both superficial and deep capillary plexuses, foveal avascular zone area/perimeter, and foveal vascular density when compared with controls (all P < 0.05). Higher glycated hemoglobin level was independently associated with the decrease of parafoveal vessel density as well as the increase of foveal avascular zone area/perimeter (all P < 0.05). Prepubescent onset of diabetes mellitus was also independently associated with the decrease of superficial parafoveal vessel density, foveal avascular zone area/perimeter, and foveal vascular density (P = 0.015, 0.011, 0.015, and 0.001, respectively). CONCLUSION: In young adults with Type 1 diabetes mellitus lacking clinical signs of diabetic retinopathy, optical coherence tomography angiography revealed alterations in retinal microvasculature that were associated with glycated hemoglobin level and onset of diabetes mellitus related to puberty.

c-Met inhibition is required for the celecoxib-attenuated stemness property of human colorectal cancer cells.

Cyclooxygenase-2 (COX-2) is frequently overexpressed and enhances colorectal cancer (CRC) tumorigenesis, including cancer stem cell (CSC) regulation. Accordingly, nonsteroidal anti-inflammatory drugs (NSAIDs), inhibiting COX-1/2 activity, are viewed as potential drugs for CRC treatment. Accumulated evidence indicates that celecoxib has the most potency for antitumor growth among NSAIDs and the underlying mechanism is only partly dependent on COX-2 inhibition. However, the potency of these NSAIDs on CSC inhibition is still not known. In this study, we found that among these NSAIDs, celecoxib has the most potency for CSC inhibition of CRC cells, largely correlating to inhibition of c-Met, not COX-2. Further analysis reveals that c-Met activity was required for basal CSC property. Silence of c-Met blocked whereas overexpression of c-Met enhanced the celecoxib-inhibited CSC property. Collectively, these results not only first elucidate the mechanism underlying celecoxib-inhibited CSC but also indicate c-Met as a critical factor for the CSC property of CRC cells.

Correlation of anti-acetylcholine receptor antibody levels and long-term outcomes of juvenile myasthenia gravis in Taiwan: a case control study.

BACKGROUND: Myasthenia gravis is the most common disease affecting the neuromuscular junction. The most common etiology among patients with juvenile myasthenia gravis is the production of antibodies against the acetylcholine receptor. However, the clinical outcome in relation to serum levels of anti-acetylcholine receptor antibodies in juvenile myasthenia gravis has rarely been discussed. We aimed to analyze the correlation between the presence of anti-acetylcholine receptor antibodies and outcome in juvenile myasthenia gravis. METHODS: Patients diagnosed with juvenile myasthenia gravis younger than of 20 years of age were retrospectively recruited from January 1995 to February 2017 in a tertiary referral medical center. According to the Myasthenia Gravis Foundation of America outcome scale, the primary outcome was complete symptom remission and cessation of medications for at least 1 year measured 2 years after diagnosis. Secondary outcome was complete symptom remission at the last outpatient clinic. RESULTS: A total of 54 patients were followed up for over 2 years. Nine patients (9/54, 16.7%) achieved complete remission without medication use at 2 years after diagnosis. Thirteen (24.1%) patients achieved complete remission during longer follow-up periods. Those with negative anti-acetylcholine receptor antibodies were more likely to achieve complete remission at 2 years (6/15 [40%] vs. 3/39 [7.7%], 95% Confidence interval [CI] 1.670 to 38.323) and at the last outpatient clinic follow-up (8/15 [53.3%] vs. 5/39 [12.8%], 95% CI 2.367 to 20.704). Thirteen patients with comorbid autoimmune thyroid diseases were older than those without disease (11.8 ± 5.8 years old vs. 8.0 ± 6.3 years old, 95% CI 0.018 to 7.33). Moreover, patients negative for anti-acetylcholine receptor antibodies were less likely comorbid with autoimmune thyroid disease (1/35 [2.9%] vs. 12/71 [16.9%], 95% CI 0.018 to 1.161). CONCLUSIONS: Juvenile myasthenia gravis patients without anti-acetylcholine antibodies exhibited significantly increased complete remission rates and a reduced likelihood of comorbid autoimmune thyroid diseases compared with those with anti-acetylcholine receptor antibodies among Chinese.

Development of a Smart Helmet for Strategical BCI Applications.

Conducting electrophysiological measurements from human brain function provides a medium for sending commands and messages to the external world, as known as a brain-computer interface (BCI). In this study, we proposed a smart helmet which integrated the novel hygroscopic sponge electrodes and a combat helmet for BCI applications; with the smart helmet, soldiers can carry out extra tasks according to their intentions, i.e., through BCI techniques. There are several existing BCI methods which are distinct from each other; however, mutual issues exist regarding comfort and user acceptability when utilizing such BCI techniques in practical applications; one of the main challenges is the trade-off between using wet and dry electroencephalographic (EEG) electrodes. Recently, several dry EEG electrodes without the necessity of conductive gel have been developed for EEG data collection. Although the gel was claimed to be unnecessary, high contact impedance and low signal-to-noise ratio of dry EEG electrodes have turned out to be the main limitations. In this study, a smart helmet with novel hygroscopic sponge electrodes is developed and investigated for long-term usage of EEG data collection. The existing electrodes and EEG equipment regarding BCI applications were adopted to examine the proposed electrode. In the impedance test of a variety of electrodes, the sponge electrode showed performance averaging 118 kΩ, which was comparable with the best one among existing dry electrodes, which averaged 123 kΩ. The signals acquired from the sponge electrodes and the classic wet electrodes were analyzed with correlation analysis to study the effectiveness. The results indicated that the signals were similar to each other with an average correlation of 90.03% and 82.56% in two-second and ten-second temporal resolutions, respectively, and 97.18% in frequency responses. Furthermore, by applying the proposed differentiable power algorithm to the system, the average accuracy of 21 subjects can reach 91.11% in the steady-state visually evoked potential (SSVEP)-based BCI application regarding a simulated military mission. To sum up, the smart helmet is capable of assisting the soldiers to execute instructions with SSVEP-based BCI when their hands are not available and is a reliable piece of equipment for strategical applications.

Proteasome Inhibitors Suppress ErbB Family Expression through HSP90-Mediated Lysosomal Degradation.

Although dual EGFR/HER2 tyrosine kinase inhibitor lapatinib has provided effective clinical benefits for HER2-positive breast cancer patients, acquired resistance to this drug remains a major concern. Thus, the development of alternative therapeutic strategies is urgently needed for patients who failed lapatinib treatment. Proteasome inhibitors have been reported to possess high anti-tumor activity to breast cancer cells. Therefore, this study aims to examine whether and how proteasome inhibitor bortezomib can overcome lapatinib resistance. Treatments with several proteasome inhibitors, including Bortezomib, MG132, and proteasome inhibitor I (PSI), as well as the viabilities of both HER2-positive breast cancer cell lines and their lapatinib-resistant clones, were inhibited. Importantly, the expressions of ErbB family were downregulated at both transcriptional and translational levels. Also, our results further indicated that proteasome inhibitors decreased ErbB family expression through lysosomal degradation pathway in a heat shock protein 90 (HSP90)-dependent manner. In this study, our data supported a potential approach to overcome the acquired resistance of HER2-overexpressing breast cancer patients to lapatinib using proteasome inhibitors.

Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin.

Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.

Comparison of efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema.

PURPOSE: To compare the efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema (DME). STUDY DESIGN: A retrospective, nonrandomized, and comparative study. METHODS: From May 2013 to March 2016, 148 eyes of 148 patients with treatment-naïve center-involving DME were reviewed in one institution. Forty-six eyes underwent prior vitrectomy at least 3 months ago, and 102 eyes did not receive any vitrectomy. Three monthly then PRN intravitreal ranibizumab treatments were performed in all the patients with monthly follow-up for 6 months. Primary outcome measures included change in central foveal thickness (CFT) and best-corrected visual acuity (BCVA) at month 6. RESULTS: The CFT significantly reduced, and the BCVA significantly improved 6 months after ranibizumab injections in either vitrectomized or non-vitrectomized groups (p < 0.05). There was no difference between vitrectomized and non-vitrectomized eyes in baseline characteristics. Significantly better final BCVA and visual gain were found in non-vitrectomized eyes than in vitrectomized eyes (p = 0.01 and 0.03, respectively). Final CFT and CFT decrease were significantly greater in non-vitrectomized group than in vitrectomized group (p = 0.02 and 0.006, respectively). Injection number of ranibizumab was 4.12 ± 0.58 in non-vitrectomized eyes, significantly less than that in vitrectomized eyes (5.05 ± 0.71) during 6-month period (p < 0.001). There were no severe systemic/ocular adverse effects in both groups. CONCLUSIONS: Intravitreal ranibizumab was helpful for either vitrectomized or non-vitrectomized eyes with DME in short-term follow-up. Anatomical and functional improvements were greater in non-vitrectomized patients than in vitrectomized cases.

Daily weather generator with drought properties by copulas and standardized precipitation indices.

The weather generator is an essential process in water resource assessment. Most weather generators focus on extreme rainfall events and rainfall amounts in a relatively short time scale. However, drought events often last more than several months, which conventional weather generators hardly generate. Conventional weather generators assume that monthly rainfalls are independent, skewing drought event generation. The purpose of this study is to construct a weather generator with improved drought property generation, combining with monthly rainfall data from conventional weather generators and characteristics of standardized precipitation indices. The proposed weather generators employs four drought parameters, namely starting month, duration, average, and minimum standardized precipitation indices, generated using a copula method. Analytical results show that the four parameters generated by the copula method are consistent with historical records. The proposed weather generator overcomes the limitation of conventional weather generators and can generate both rainfall and drought properties. The results also indicate that the assumption of monthly independence in drought generation can cause underestimated occurrence and duration of drought events. The proposed generator is also demonstrated for climate change assessment. The analytical results show that the uncertainties from the selection of weather generators are even higher than those from the selections of global circulation models while applying to water shortage assessment. We therefore suggest that weather generators should consider drought characteristics which can be measured using the standardized precipitation index to reduce the uncertainty.

Chemical proteomics identifies heterogeneous nuclear ribonucleoprotein (hnRNP) A1 as the molecular target of quercetin in its anti-cancer effects in PC-3 cells.

Quercetin, a flavonoid abundantly present in plants, is widely used as a phytotherapy in prostatitis and prostate cancer. Although quercetin has been reported to have a number of therapeutic effects, the cellular target(s) responsible for its anti-cancer action has not yet been clearly elucidated. Here, employing affinity chromatography and mass spectrometry, we identified heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) as a direct target of quercetin. A specific interaction between quercetin and hnRNPA1 was validated by immunoblotting and in vitro binding experiments. We found that quercetin bound the C-terminal region of hnRNPA1, impairing the ability of hnRNPA1 to shuttle between the nucleus and cytoplasm and ultimately resulting in its cytoplasmic retention. In addition, hnRNPA1 was recruited to stress granules after treatment of cells with quercetin for up to 48 h, and the levels of cIAP1 (cellular inhibitor of apoptosis), an internal ribosome entry site translation-dependent protein, were reduced by hnRNPA1 regulation. This is the first report that anti-cancer effects of quercetin are mediated, in part, by impairing functions of hnRNPA1, insights that were obtained using a chemical proteomics strategy.

Association study between novel CYP26 polymorphisms and the risk of betel quid-related malignant oral disorders.

BQ chewing may produce significant amounts of reactive oxygen species (ROS), resulting in oral mucosa damage, and ROS may be metabolized by CYP26 families. Because the CYP26 polymorphisms associated with malignant oral disorders are not well known, we conducted an association study on the associations between the single nucleotide polymorphisms (SNP) of CYP26 families and the risks of malignant oral disorders. BQ chewers with the CYP26A1 rs4411227 C/C+C/G genotype and C allele showed an increased risk of oral and pharyngeal cancer (adjusted odds ratio (aOR) = 2.30 and 1.93, respectively). The CYP26B1 rs3768647 G allele may be associated with oral and pharyngeal cancer (aOR = 3.12) and OPMDs (aOR = 2.23). Subjects with the rs9309462 CT genotype and C allele had an increased risk of oral and pharyngeal cancer (aOR = 9.24 and 8.86, respectively) and OPMDs (aOR = 8.17 and 7.87, respectively). The analysis of joint effects between the CYP26A1 rs4411227 and CYP26B1 rs3768647/rs9309462 polymorphisms revealed statistical significance (aOR = 29.91 and 10.03, respectively). Additionally, we observed a significant mRNA expression of CY26A1 and CYP26B1 in cancerous tissues compared with adjacent noncancerous tissues. Our findings suggest that novel CYP26 polymorphisms are associated with an increased risk of malignant oral disorders, particularly among BQ chewers.

Thrombolytic therapy is an only determinant factor for stroke evolution in large anterior choroidal artery infarcts.

BACKGROUND: Large anterior choroidal artery (AChA) infarcts are frequently associated with stroke evolution. This study aimed to investigate the major determinants for stroke evolution in patients with large AChA infarcts. METHODS: We studied 118 consecutive adult patients with acute large AChA infarcts. The diagnosis was confirmed as abnormal hyperintensities in 3 or more rostracaudal magnetic resonance imaging slices (5 mm thickness) using diffusion-weighted imaging within typical AChA vascular regions. Stroke evolution was defined as neurologic deterioration with an increase in National Institutes of Health Stroke Scale (NIHSS) score by at least 4 or an increase of NIHSS score in motor function by at least 2 in 7 days after stroke onset. RESULTS: Forty-seven (39.8%) patients developed stroke evolution. Thrombolytic therapy was inversely associated with the occurrence of stroke evolution (P = .004). Using multivariate analysis, thrombolytic therapy was the only protective determinant for stroke evolution (adjusted odds ratio, .08; 95% confidence interval, .01 to .67). Patients with large AChA infarcts receiving thrombolytic therapy had less unfavorable long-term functional outcome than those not receiving thrombolytic therapy (adjusted odds ratio, .11; 95% confidence interval, .02-.75). CONCLUSIONS: Thrombolytic therapy is an only determinant factor for stroke evolution in large AChA infarcts, which reduced the risk of stroke evolution and improved functional outcome.

Collagen type II solution extracted from supercritical carbon dioxide decellularized porcine cartilage: regenerative efficacy on post-traumatic osteoarthritis model.

Osteoarthritis (OA) of the knee is a common degenerative articular disorder and is one of the main causes of pain and functional disability. Cartilage damage is frequently linked to elevated osteoarthritis incidence. Supercritical carbon dioxide (scCO2) decellularized cartilage graft produced from the porcine cartilage is an ideal candidate for cartilage tissue engineering. In the present study, we derived collagen type II (Col II) solution from the scCO2 decellularized porcine cartilage graft (dPCG) and compared its efficacy with hyaluronic acid (HA) in the surgical medial meniscectomy (MNX) induced post-traumatic osteoarthritis (PTOA) model. Dose-dependent attenuation of the OA (12.3 ± 0.8) progression was observed in the intra-articular administration of Col II solution (7.3 ± 1.2) which significantly decreased the MNX-induced OA symptoms similar to HA. The pain of the OA group (37.4 ± 2.7) was attenuated dose-dependently by Col II solution (45.9 ± 4.1) similar to HA (43.1 ± 3.5) as evaluated by a capacitance meter. Micro-CT depicted a dose-dependent attenuation of articular cartilage damage by the Col II solution similar to HA treatment. A significant (p < 0.001) dose-dependent elevation in the bone volume was also observed in Col II solution-treated OA animals. The protective competence of Col II solution on articular cartilage damage is due to its significant (p < 0.001) increase in the expression of type II collagen, aggrecan and SOX-9 similar to HA. To conclude, intra-articular administration of type II collagen solution and HA reestablished the injured cartilage and decreased osteoarthritis progression in the experimental PTOA model.

High-protein diet with immediate post-exercise protein drink: Impact on appetite in middle-aged obesity.

Successful management of obesity can be challenging if individuals constantly experience cravings. The present study investigated the effects of a high-protein diet, including a high-protein drink consumed immediately after high-intensity interval training (HIIT), on appetite and weight loss in obese middle-aged individuals. A total of 52 obese middle-aged individuals (58.2 ± 4.11 years old) were randomly assigned to one of three groups: the exercise group (E, n=19), exercise and high-protein diet group (ED, n=21), and a control group (n=12). The E and ED groups engaged in cycling HIIT (comprising 90 % of peak heart rate (HRpeak) for 3 min, followed by 70 % of HRpeak for 3 min, for a total of 5 cycles) three times a week for 3 months. The ED group consumed a high-protein drink immediately after HIIT and had a daily protein intake of 1.6g/kg. Body composition and eating behavior were assessed before and after the intervention. Additionally, appetite levels were measured before and after each exercise session, before dinner, and before bedtime during three phases of the intervention: the first phase (weeks 3-4), the second phase (weeks 5-8), and the third phase (weeks 9-12). Results showed that only the ED group experienced a decrease in body mass index (from 27.4 ± 4.28 to 26.8 ± 4.09 kg/m2, p=0.04). Appetite significantly increased after exercise in both E and ED groups (p values for the three phases ranged from 0.04 to 0.001 for the E group and from 0.042 to 0.003 for the ED group). The desire to eat significantly increased after exercise in the E group (phase 1: p = 0.026; phase 2: p = 0.011; phase 3: p = 0.003), but not in the ED group. Furthermore, the frequency of late-night snacking decreased in the ED group (the score changed from 2.4 ± 0.86 to 2.7 ± 0.80, p = 0.034). Notably, the E group tended to have a higher pre-dinner appetite score than the ED group in the third phase (p = 0.063). In summary, a high daily protein intake, combined with the consumption of high-protein drinks after exercise, resulted in reduced post-exercise appetite and a decrease in the frequency of late-night snacking.

The Utility of a Novel Neuropsychological Measurement to Analyze Event-Related Attentional Behaviors among Young Children with Attention Deficit Hyperactivity Disorder-a Pilot Study.

OBJECTIVE: The identification and diagnosis of children with attention deficit hyperactivity disorder (ADHD) traits is challenging during the preschool stage. Neuropsychological measures may be useful in early assessments. Furthermore, analysis of event-related behavior appears to be an unmet need for clinical treatment planning. Conners' Kiddie Continuous Performance Test (K-CPT) is the most popular well-established neuropsychological measurement but lacks event markers to clarify the heterogeneous behaviors among children. This study utilized a novel commercially available neuropsychological measure, the ΣCOG, which was more game-like and provided definite event markers of individual trial in the test. METHODS: Thirty-three older preschool children (14 were diagnosed with ADHD, mean age: 66.21 ± 5.48 months; 19 demonstrated typical development, mean age: 61.16 ± 8.11 months) were enrolled and underwent comprehensive medical and developmental evaluations. All participants underwent 2 versions of neuropsychological measures, including the K-CPT, Second Edition (K-CPT 2) and the ΣCOG, within a short interval. RESULTS: The study indicated the omissions and response time scores measured in this novel system correlated with clinical measurement of the behavioral scales in all participants and in the group with ADHD; additionally, associations with the traditional K-CPT 2 were observed in commissions and response time scores. Furthermore, this system provided a within-task behavioral analysis that identified the group differences in the specific trial regarding omission and commission errors. CONCLUSIONS: This innovative system is clinically feasible and can be further used as an alternative to the K-CPT 2 especially in research by revealing within-task event-related information analysis.