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We investigated whether type 2 diabetes mellitus (T2DM), a risk factor of stroke, affects the level of scavenger receptor CD36 and the uptake of its ligand, oxidized LDL (oxLDL); and whether pioglitazone, a drug that enhances CD36, promotes oxLDL uptake. Compared to normoglycemic db/+ mice, adult db/db mice showed a pronounced reduction in surface CD36 expression on myeloid cells from the blood, brain, and bone marrow as detected by flow cytometry, which correlated with elevated plasma soluble-CD36 as determined by ELISA. Increased CD36 expression was found in brain macrophages and microglia of both genotypes 7 days after ischemic stroke. In juvenile db/db mice, prior to obesity and hyperglycemia, only a mild reduction of surface CD36 was found in blood neutrophils, while all other myeloid cells showed no difference relative to the db/+ strain. In vivo, oral pioglitazone treatment for four weeks increased CD36 levels on myeloid cells in db/db mice. In vitro, uptake of oxLDL by bone marrow derived macrophages (BMDMs) of db/db mice was reduced relative to db/+ mice in normal glucose medium. OxLDL uptake inversely correlated with glucose levels in the medium in db/+ BMDMs. Furthermore, pioglitazone restored oxLDL uptake by BMDMs from db/db mice cultured in high glucose. Our data suggest that T2DM is associated with reduced CD36 on adult myeloid cells, and pioglitazone enhances CD36 expression in db/db cells. T2DM or high glucose reduces oxLDL uptake while pioglitazone enhances oxLDL uptake. Our findings provide new insight into the mechanism by which pioglitazone may be beneficial in the treatment of insulin resistance.

The linkage between reading for pleasure and language ability has been well established, but the relationship between content-based recreational reading and academic achievement in various subject areas has rarely been explored. To investigate whether reading literature, social studies, and science trade books for pleasure is related to students' growth in achievement for the subjects of Chinese, social studies, and science, respectively, this study used data from 4,730 students at a Taiwanese girls' high school. Based on students' high school entrance exam test scores in three subject areas as control variables, and their college entrance exam scores as the outcomes, the findings indicated that pleasure reading in a specific content area might lead to growth in achievement for that particular content area, and in some cases, reading in other content areas might help as well. A reading program that invites students to engage in self-sponsored reading can promote disciplinary literacy and academic achievement.

Background Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. Methods A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. Conclusion The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. ClinicalTrials.gov Identifier NCT03162510 [ABSTRACT FROM AUTHOR]

We present a subspace-based polynomial rooting algorithm to estimate the frequency bias (FB) of generalized frequency division multiplexing (GFDM) systems employing null subcarriers and repetitive sub-symbols. The estimation process is classified into fractional FB (FFB) and integer FB (IFB) estimation. The use of repetitive sub-symbols creates a quasi-periodic structure in the FB-distorted received signal, allowing the proposed algorithm to estimate the FFB using the root-MUSIC algorithm. Based on this, the proposed algorithm compensates for the FFB in the received signal and then estimates the null subcarrier pattern (NSP) in the frequency domain. As a result, the IFB estimate can be obtained in a maximum likelihood (ML) manner. Before the NSP estimation, this study uses a sub-symbol combiner to enhance signal strength of the FFB-aligned signal, ensuring the reliability of the IFB estimate. Computer simulations show that the proposed subspace-based algorithm has several advantages over traditional FB estimation methods: 1. Unlike some existing algorithms that use a training sequence to estimate FB, the proposed approach is a semi-blind algorithm because it can deliver information through repeated sub-symbols while estimating FB; 2. The proposed algorithm demonstrates excellent estimation accuracy compared to most traditional FB estimation algorithms; and 3. The proposed algorithm is computationally efficient, making it applicable to real-time applications in future communication systems. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, and cancer-associated fibroblasts (CAFs) play a major role in the tumor microenvironment (TME), which facilitates the progression of CRC. It is critical to understand how CAFs promote the progression of CRC for the development of novel therapeutic approaches. The purpose of this study was to understand how CAF-derived stromal-derived factor-1 (SDF-1) and its interactions with the corresponding C-X-C motif chemokine receptor 4 (CXCR4) promote CRC progression. Our study focused on their roles in promoting tumor cell migration and invasion and their effects on the characteristics of cancer stem cells (CSCs), which ultimately impact patient outcomes. Here, using in vivo approaches and clinical histological samples, we analyzed the influence of secreted SDF-1 on CRC progression, especially in terms of tumor cell behavior and stemness. We demonstrated that CAF-secreted SDF-1 significantly enhanced CRC cell migration and invasion through paracrine signaling. In addition, the overexpression of SDF-1 in CRC cell lines HT29 and HCT-116 triggered these cells to generate autocrine SDF-1 signaling, which further enhanced their CSC characteristics, including those of migration, invasion, and spheroid formation. An immunohistochemical study showed a close relationship between SDF-1 and CXCR4 expression in CRC tissue, and this significantly affected patient outcomes. The administration of AMD3100, an inhibitor of CXCR4, reversed the entire phenomenon. Our results strongly suggest that targeting this signaling axis in CRC is a feasible approach to attenuating tumor progression, and it may, therefore, serve as an alternative treatment method to improve the prognosis of patients with CRC, especially those with advanced, recurrent, or metastatic CRC following standard therapy. [ABSTRACT FROM AUTHOR]

Unilateral brain injury is known to disrupt the balance between the two cortices, as evidenced by an abnormally high interhemispheric inhibitory drive from motor cortex M1intact to M1lesioned transmitted transcallosally. Our previous work has shown that the deletion of homeobox gene Emx1 not only led to the agenesis of the corpus callosum (cc), but also to reduced hippocampal neurogenesis. The current study sought to determine whether lacking the cc affected the recovery of forelimb function and hippocampal plasticity following training of the affected limb in mice with unilateral traumatic brain injuries (TBI). One week after TBI, produced by a controlled cortical impact to impair the preferred limb, Emx1 wild type (WT) and knock out (KO) mice were subjected to the single-pellet reaching task with the affected limb for 4 weeks. Both TBI and Emx1 deletion had overall adverse effects on the successful rate of reaching. However, TBI significantly affected reaching performance only in the WT mice and not in the KO mice. Both TBI and Emx1 gene deletion also negatively affected hippocampal neurogenesis, demonstrated by a reduction in doublecortin (DCX)-expressing immature neurons, while limb training enhanced DCX expression. However, limb training increased DCX cells in KO mice only in the TBI-treated group, whereas it induced neurogenesis in both WT mice groups regardless of the treatment. Our finding also suggests that limb training enhances neuroplasticity after brain injury at functionally remote regions including the hippocampus, which may have implications for promoting overall recovery of function after TBI.

Hereditary angioedema (HAE) is an autosomal dominant disease characterized clinically by recurrent episodes of swelling in the tissues of the extremities, face, abdomen, and respiratory tract. It is most often caused by C1 esterase inhibitor (C1 INH) gene mutation. This swelling may lead to bradykinin release, resulting in recurrent, paroxysmal, painful angioedema. Blister formation is an uncommon cutaneous manifestation of HAE. Herein, we report a case of a patient with HAE who developed linear wrist blisters on her skin, with swelling, as a rare complication of HAE. She was treated with attenuated androgens (Danazol) for two weeks at our clinic, after which the blisters showed dramatic improvement. To date, only a few HAE cases have been reported across the world. Therefore, it is important to focus on and recognize the development of edema blisters as a flare of HAE, which could consequently avoid unnecessary dermatological diagnostic workup and treatment.

Background and purposeThe presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion.MethodsWe examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in db/+ and db/db mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters.ResultsAfter unilateral CCAO, db/db mice exhibited diminished leptomeningeal collateral flow compensation compared with db/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO. db/db mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with db/+ mice.ConclusionsType 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.

Abstract Background Traumatic dislocation of laser-assisted in situ keratomileusis (LASIK) corneal flaps is an uncommon postoperative complication that could occur any time after LASIK, and could be visually devastating. We evaluated the visual outcomes, corneal sensation, tear function, and dry eye questionnaire results of patients with traumatic dislocation of LASIK flaps, including one LASIK flap amputation. Methods This is a retrospective case series. Seven patients who were diagnosed with traumatic displacement of the LASIK flap and underwent flap replacement surgery between August 2014 and January 2019 were included.Patient’s visual acuity, refraction, corneal sensitivity, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH), and ocular surface disease index (OSDI) results were evaluated. Results The patients’ mean age was 35.86 ± 5.84 years, and 42.9 % (3/7) were male. The mean duration from LASIK to trauma was 8.86 ± 2.48 years.The mean preoperative and postoperative six-month corrected distance visual acuity (CDVA) were 0.55 ± 0.34 and 0.02 ± 0.03, respectively. The mean spherical equivalent and astigmatism at six months postoperatively was − 1.0 ± 0.95 D and − 0.5 ± 0.25 D, respectively. The corneal flap was clear and well-positioned at the final follow-up (mean: 28.57 ± 6.9 months). 85.71 % (6/7) of the patients showed worse corneal sensation in the injured eye. Interocular OSDI discrepancy was less in those whose last visit was more than 30 months after the trauma. Conclusions Postoperative CDVAat six months was improved, and the refractive data also showed some improvement. The corneal nerve and tear function recovery peaked before 30 months, while the OSDI continued to show a strong trend of improvement beyond 30 months.

Although videos are now used pervasively in English as a Foreign Language settings, most existing literature centers on learners as knowledge receivers or passive video viewers (Lialikhova, 2014; Fisher & Frey, 2015; Bakar et al., 2019). Rarely do studies involving videos engaged learners as knowledge generators or active, self-directed learners. To fill this research gap, the current study examined the effects of the online-video pronunciation dictionary YouGlish, which employs a lexical approach on learners' speaking skills, including pronunciation, intonation, word usage, and strategies that learners applied while using YouGlish as well as their reactions to it. The results revealed that YouGlish can help learners make progress in their oral skills, especially in terms of word usage, by providing meaningful context that helps them comprehend how oral English is used in real life. The findings revealed the process of using YouGlish generated students to become more active and self-directed learners, rather than remained as passive receivers of knowledge.

Chlorich®EnergyBoost, a water extract obtained from Chlorella sorokiniana, has been proposed to enhance physical performance and provide anti-fatigue effects. This study assessed the impact of Chlorich®EnergyBoost supplementation on physical performance and its anti-fatigue properties. Twenty-four mice were allocated into four groups: (1) the control group receiving only water,;(2) the 1X group (49.2 mg/kg/day); (3) the 2X group (98.4 g/kg/day); and (4) the 5X group (246 g/kg/day). All groups were orally administered the supplements for four consecutive weeks. The evaluation included grip strength, swimming endurance, an exhaustion test, and serum biochemistry analysis. Additionally, the study examined the bioactive peptides through matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and conducted bacterial reverse mutation and acute oral toxicity tests for safety assessment. The findings indicated that Chlorich®EnergyBoost supplementation led to a significant reduction in serum lactate levels by 14.08% to 22.54% and blood urea nitrogen levels by 12.23% to 16.76%, an increase in the lactate clearance rate by 0.28 to 0.35, an enhancement of muscle glycogen storage by 1.10 to 1.44-fold, and hepatic glycogen storage by 1.41 to 1.47-fold. These results demonstrated dose-dependent effects. MALDI-TOF analysis revealed the expression of dihydrolipoamide dehydrogenase and superoxide dismutase. Both the bacterial reverse mutation and acute oral toxicity tests showed no adverse effects. [ABSTRACT FROM AUTHOR]

Anterior nasal septum abscess is not a rare clinical disease entity. In terms of the etiologies of the disease, bacteria are obviously more common than fungi. Fungal culture and pathological examination are essential for diagnosis of a fungal abscess of the anterior nasal septum and the basis of prescription of antifungal agents. We report a 57-year-old male patient who came to our outpatient clinic due to refractory nasal congestion for 3 weeks despite receiving treatments by a local medical doctor. Radical surgery with postoperative adjuvant radiotherapy for the right buccal cancer was carried out 14 years ago. The patient has diabetes mellitus and the blood sugar level has been well controlled by oral hypoglycemic agents over the past several years. Computed tomography revealed an abscess in the anterior septum along with rhinosinusitis. Incision and drainage of the nasal septum abscess and functional endoscopic sinus surgery were carried out. Fungal culture and pathological examination confirmed a fungal abscess in the anterior nasal septum and fungal ball rhinosinusitis. Antibiotics and an antifungal agent were given, and the postoperative course was uneventful. A dialectical argument was made regarding the causal relationship between the fungal abscess of the anterior nasal septum and maxillary fungal ball sinusitis. A literature review of the previous case reports was carried out to elucidate the immune status of patients of this disease. In order to reach a rapid establishment of a fungal abscess of the anterior nasal septum, clinicians should keep this disease in mind and remain vigilant. An immuno-compromised status is more commonly found in patients with fungal abscess of the anterior nasal septum and is another important characteristic of this disease. Prompt diagnosis and effective treatment are equally important in patients with lower immune status of this kind, and the latter is based on the former. [ABSTRACT FROM AUTHOR]