Highly emissive blue graphene quantum dots with excitation-independent emission via ultrafast liquid-phase photoreduction.

Graphene oxide quantum dots (GOQDs) are promising candidates for biomedical applications since they have lower toxicity and higher biocompatibility than traditional semiconductor quantum dots. However, oxygen functional groups such as epoxy and hydroxyl groups usually induce nonradiative relaxation, which leads to GOQDs exhibiting nonemissive properties. For the enhancement of the emission efficiency of GOQDs, the number of nonradiative relaxation sites should be reduced. This paper reports the synthesis of highly luminescent reduced GOQDs prepared by liquid-phase photoreduction (LPP-rGOQDs). First, GOQDs was fabricated from single-walled carbon nanotubes through chlorate-based oxidation and separation after acoustic cavitation. Subsequently, LPP-rGOQDs were obtained by liquid-phase photoreduction of the GOQD suspension under intense pulsed light irradiation. Liquid-phase photoreduction selectively reduced epoxy groups present on the basal plane of GOQDs, and hydrogenated the basal plane without removal of carbonyl and carboxyl groups at the edges of the GOQDs. Such selective removal of oxidative functional groups was used to control the reduction degree of GOQDs, closely related to their optical properties. The optimized LPP-rGOQDs were bright blue in color and showed quantum yields up to about 19.7%, which was 10 times the quantum yield of GOQDs. Furthermore, the LPP-rGOQDs were utilized to image a human embryonic kidney (HEK293A), and a low cytotoxicity level and satisfactory cell imaging performance were observed.

Fine-needle aspiration cytology for neck lesions in patients with antithrombotic/anticoagulant medications: systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to determine the true risk of bleeding and nondiagnostic (ND) specimens associated with fine-needle aspiration cytology (FNAC) for neck lesions in patients taking antithrombotic/anticoagulation (AT/AC) medications. METHODS: Using the Population Intervention Comparison and Outcome modeling, we searched PubMed and Google Scholar databases to identify studies published between January 2000 and March 2023 reporting the safety and sample adequacy of FNAC for neck lesions in patients taking AT/AC medications. The pooled incidences of bleeding and ND specimens and pooled risk ratio (RR) with 95% confidence intervals (CIs) obtained using a fixed-effects model were compared for patients continuing AT/AC (AT/AC group) and patients not receiving AT/AC therapy (no-AT/AC group). RESULTS: We included six original articles involving a total of 3014 patients. The pooled incidence of bleeding was 0.9% (95% CI, 0.344-2.026) and 0.7% (95% CI, 0.390-1.146) in the AT/AC and no-AT/AC groups, respectively. The pooled RR under the fixed-effects model was 1.39 (95% CI, 0.56-3.44) with no evidence of between-study heterogeneity (I2 = 0.0%; p = 0.92). The pooled incidence of ND specimens was 7.6% (95% CI, 5.617-10.073) and 7.6% (95% CI, 6.511-8.752) in the AT/AC and no-AT/AC groups, respectively. The pooled RR under the fixed-effects model was 1.33 (95% CI, 0.98-1.81) with moderate between-study heterogeneity (I2 = 60.0%; p = 0.06). CONCLUSIONS: The AT/AC medication is not associated with increased risk of bleeding or ND specimens in FNAC for neck lesions. Therefore, interruption of the AT/AC medication is not recommended before FNAC even in patients taking AT/AC medications. CLINICAL RELEVANCE STATEMENT: This study is the first meta-analysis evaluating risk of bleeding and nondiagnostic specimens associated with fine-needle cytology for neck lesions in patients taking antithrombotic/anticoagulation (AT/AC) medications. This suggests withholding AT/AC medications is not mandatory for safe and diagnostic FNACs. KEY POINTS: • True risk of fine-needle aspiration cytology (FNAC) for neck lesions in patients taking antithrombotic/anticoagulation (AT/AC) medications is still controversial. • This meta-analysis demonstrated that maintaining AT/AC medication was not associated with increased risk in terms of both bleeding and nondiagnostic samples. • Interruption of the AT/AC medication is not needed for safe and diagnostic FNAC for neck lesions even in patients taking AT/AC medications.

Ultrasound-guided ethanol ablation versus the Sistrunk operation as a primary treatment for thyroglossal duct cysts.

PURPOSE: This study compared ethanol ablation (EA) with the Sistrunk operation (SO) with regard to feasibility, treatment efficacy, and cost-effectiveness. The goal was to evaluate whether EA could replace SO as a primary treatment modality for thyroglossal duct cysts (TGDCs). METHODS: This retrospective case-control study included patients with TGDCs who were treated with either EA or SO between 2016 and 2022. The primary outcome variables evaluated were treatment efficacy (as measured by the volume reduction rate [VRR] and treatment success rate), complications, and cost-effectiveness. RESULTS: A total of 72 patients were enrolled, with 33 in the EA group and 39 in the SO group. The procedure or operation times for the EA and SO groups were 9 and 82 minutes, respectively (P<0.001). At the final follow-up appointment, the VRR was 94.1% for the EA group and 100.0% for the SO group (P<0.001). Treatment success was achieved for 32 patients (97.0%) in the EA group and for all 39 patients (100.0%) in the SO group (P=0.458). The overall complication rates were 0.0% and 17.9% in the EA and SO groups, respectively (P=0.013). The total costs, including all treatment procedures and follow-up ultrasound examinations, were $485 and $1,081.7 for the EA and SO groups, respectively (P<0.001). CONCLUSION: EA demonstrates superiority over SO in terms of feasibility, safety, and costeffectiveness, while maintaining comparable treatment efficacy. Despite the need for multiple treatment sessions in approximately one-quarter of patients, EA can serve as a primary treatment modality for selected patients with TGDCs, supplanting SO.

Ultrasound-Guided Ethanol Ablation as a Primary Treatment for Thyroglossal Duct Cyst: Feasibility, Characteristics, and Outcomes.

OBJECTIVES: To evaluate the feasibility, characteristics, and outcomes of ultrasound-guided ethanol ablation (US-EA) as a primary treatment for thyroglossal duct cysts (TGDCs). STUDY DESIGN: Prospective case series. SETTING: Single center study. METHODS: The inclusion criteria were as follows: (i) patients with TGDC aged ≥18 years, (ii) benign TGDC in imaging and cytological examinations, and (iii) patients' need for nonsurgical scarless treatment. US-EA was used as the primary treatment strategy. The primary outcome variables were the volume reduction rate (VRR) and cosmetic score at the last follow-up. RESULTS: We enrolled 28 patients with TGDC. The median TGDC volume at baseline was 6.7 mL. The median procedure time of the US-EA was 6.5 minutes. The median volumes of the cyst aspirate and injected ethanol were 4.0 and 2.0 mL, respectively. Overall, 18, 8, and 2 patients underwent 1, 2, and 3 treatment sessions, respectively. There were no complications. The median VRR was 96.2%, and the treatment success rate was 96.4%. The World Health Organization cosmetic score decreased from 4 (baseline) to 1 (after treatment) in all patients. The subjective grade for cosmetic satisfaction was satisfactory or highly satisfactory in all patients. The VRR, treatment success rate, and the number of treatment sessions did not differ as functions of the characteristics of the TGDC, including the initial volume, septation, debris, or viscosity of the cyst fluid. CONCLUSION: US-EA was feasible, safe, and effective in patients with TGDC. Therefore, US-EA can be used as a primary treatment for TGDC, evading general anesthesia and surgical scar.

Prevalence and Characteristics of Human Papillomavirus Infection in Oropharyngeal Squamous Cell Papilloma.

Studies on human papillomavirus (HPV) infection in oropharyngeal squamous papilloma (OPSP) are lacking, although HPV infection has been recognized as the primary cause of oropharyngeal cancer for several decades. This study aimed to evaluate the prevalence and characteristics of HPV infections in patients with OPSP. We retrospectively enrolled patients with histologically confirmed OPSP in whom the presence of HPV infections and p16 expression were evaluated. The results of HPV infection in OPSP were analyzed according to the clinicodemographic profiles. Of the 83 patients included in this study, HPV test results were positive in 12 patients, with an overall prevalence of 14.5%. HPV genotypes involved low-risk and high-risk HPV types in three (3.6%) and nine (10.8%) patients, respectively. The most prevalent genotype was HPV16, accounting for 58.3% of all HPV infections. None of the OPSPs showed p16 IHC positivity. There were trends toward a higher prevalence of high-risk HPV infection in patients with OPSP aged ≤45 years, never-smokers, and those with multifocal diseases. These findings could enhance our understanding of HPV infection in OPSP and be used as valuable epidemiological data for the management of HPV-associated OPSP and regarding the possible efficacy of HPV vaccinations in OPSP.

Parathyroidectomy for primary hyperparathyroidism: A retrospective analysis of localization, surgical characteristics, and treatment outcomes.

OBJECTIVE: To evaluate parathyroidectomy for primary hyperparathyroidism (PHPT) regarding localization, surgical characteristics, and treatment outcomes. METHODS: Seventy-eight patients who underwent parathyroidectomy for PHPT were retrospectively reviewed. The results were analyzed according to intraoperative localization technique (IOLT), intraoperative parathyroid hormone (IOPTH) monitoring, and intraoperative nerve monitoring (IONM). The localization accuracy of ultrasonography (US), computed tomography (CT), and single-photon emission computed tomography (SPECT)-CT with sestamibi Tc99m was evaluated. RESULTS: Parathyroidectomy was successfully completed in all 78 patients, achieving 100% surgical cure. For 60 patients with IOPTH monitoring, 10-min IOPTH decreased >50% from baseline in 57 (95.0%), and they achieved surgical cure. In the remaining three (5.0%) patients with ≤50% decrease in 10-min IOPTH, 20-min IOPTH decreased >50% from baseline in two (3.3%) patients, achieving surgical cure without additional neck exploration. There were no differences in surgical cure and complications as a function of IOLT use or IOPTH monitoring. Operating time was significantly shorter with IOLT and IOPTH monitoring than without (IOLT: 70.9 min vs. 88.0 min, p = 0.013; IOPTH: 74.9 min vs. 91.9 min, p = 0.037). All 78 patients had adenoma including one patient with a double adenoma. Vocal cord paralysis was not observed in our series, regardless of IONM. US, CT, and SPECT-CT localized the pathological parathyroid gland accurately in 88.1%, 85.5%, and 86.8% of patients, respectively (p = 0.894). CONCLUSION: The surgical outcomes of parathyroidectomy for PHPT were excellent regardless of IOLT and IOPTH monitoring. However, these techniques can maximize the performance of parathyroid surgery by reducing operating time and rescuing challenging cases.

Primary concurrent chemoradiation therapy with triweekly cisplatin as a standard protocol in patients aged ≥65 years with head and neck squamous cell carcinoma.

AIM: To evaluate the results of primary concurrent chemoradiation therapy (CCRT) with triweekly cisplatin in patients with head and neck squamous cell carcinoma (HNSCC) aged ≥65 years by comparing these patients to those aged < 65 years. METHODS: This prospective, single-center study enrolled patients with HNSCC for whom CCRT was indicated as the primary treatment. The major endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 169 patients were enrolled; 75 (44.4%) and 94 (55.6%) patients were aged ≥65 and < 65 years, respectively. The mean cumulative cisplatin doses were 192.8 mg/m2 and 212.3 mg/m2 in patients ≥65 and < 65, respectively (p < .001). The incidence rates of any grade 3-4 toxicities were 37.3% and 51.1% in the age ≥65 and < 65 groups, respectively (p = .085). The 5-year locoregional control, distant control, PFS, ultimate PFS, and disease-specific survival were comparable between both groups. The 5-year OS was significantly lower in the ≥65 group than the < 65 group (65.5% vs. 86.4%, p = .010) due to a lower salvage rate and higher incidence of non-HNSCC-related death. In a Cox regression analysis, age ≥65 years was not associated with increased risk of treatment failure but was associated with higher overall death rate (hazard ratio, 2.590; 95% confidence interval, 1.219-5.502; p = .013). CONCLUSION: CCRT with a triweekly cisplatin regimen could act as the standard of ca for HNSCC in elderly patients. However, the relatively lower OS compared to younger patients should be acknowledged, despite a favorable disease control rates.

Ultrasonography for masses of the pharynx and larynx and assessment of laryngeal squamous cell carcinoma.

OBJECTIVE: To evaluate the ultrasonography (US) characteristics of pharyngeal/laryngeal masses and the role of US in the assessment of laryngeal squamous cell carcinoma (LSCC). METHODS: This study enrolled patients who underwent US for evaluation of pharyngeal/laryngeal masses between 2018 and 2021. Characteristics of pharyngeal/laryngeal masses and subsite invasion in cases of LSCC were evaluated using US. RESULTS: Forty-six patients with pharyngeal (n = 22) /laryngeal (n = 24) masses were enrolled. The pathological results were benign and malignant in 7 (15.2%) and 39 (84.8%) patients, respectively. Malignant masses were significantly associated with US characteristics of heterogeneity (P = 0.002), irregular/speculated margin (P < 0.001), and increased internal vascularity (P = 0.014) compared with benign masses. In patients with LSCC, the detection rate of US for subsites invasion, including that of the anterior commissure, paraglottic space, outer cortex of the thyroid cartilage, cricoid cartilage, and extralaryngeal soft tissue, was similar to that of computed tomography (CT). Although the difference was not statistically significant, US more frequently demonstrated invasion of the inner cortex of the thyroid cartilage than CT (40.9% vs. 22.7%; P = 0.195). US and CT had a concordance rate of 81% (18 of 22 patients) in determining the tumour stage of the lesions. CONCLUSION: US could facilitate differentiation between benign and malignant masses of the pharynx and larynx in selective patients and has a possible role in the assessment of LSCC.

Evaluation of Carotid Space Schwannoma Using Ultrasonography: Characteristics and Role in Defining the Nerve of Origin.

OBJECTIVES: We aimed to evaluate the ultrasonography (US) characteristics of carotid space schwannoma and their role in identifying the nerve of origin. METHODS: This prospective study enrolled patients with cervical carotid space schwannoma accessible by US. The US characteristics of vagus nerve schwannomas (VNSs) and sympathetic nerve schwannomas (SNSs) were assessed; a carotid space schwannoma was defined as a VNS if the tumor originated in the mid-vagal region and an SNS if it arose posterior to the intact vagus nerve, displacing the vagus nerve anteriorly. RESULTS: Twenty patients with carotid space schwannoma were enrolled. The vagus and sympathetic nerves were identified as the nerve of origin in 12 and 8 patients, respectively. VNSs were centered at levels II, III, and IV in 5, 3, and 4 patients, respectively, while SNSs were centered at levels II (7 patients) and IV (1 patient) (P = .105). The maximal diameters were 3.2 and 4.8 cm for VNSs and SNSs, respectively (P = .011). Internal vascularity was absent and low in 9 and 3 VNSs, respectively, and low and intermediate in 4 SNSs each (P = .002). Twelve patients with VNSs underwent active surveillance without immediate surgery; no adverse events occurred during the 55.2-month follow-up period. Eight patients with potential SNSs underwent surgery, confirming the sympathetic nerve as the nerve of origin. CONCLUSIONS: US facilitates identification of the nerve of origin in cervical carotid space schwannoma. VNSs are more frequent in infrahyoid locations and tend to be smaller in size with lower vascularity compared with SNSs on US.

Dysfunction of NMDA receptors in neuronal models of an autism spectrum disorder patient with a DSCAM mutation and in Dscam-knockout mice.

Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.

Autophagy activity contributes to the impairment of social recognition in Epac2-/- mice.

Autophagy is a lysosomal degradation pathway that regulates cellular homeostasis. It is constitutively active in neurons and controls the essential steps of neuronal development, leading to its dysfunction in neurodevelopmental disorders. Although mTOR-associated impaired autophagy has previously been reported in neurodevelopmental disorders, there is lack of information about the dysregulation of mTOR-independent autophagy in neurodevelopmental disorders. In this study, we investigated whether the loss of Epac2, involved in the mTOR-independent pathway, affects autophagy activity and whether the activity of autophagy is associated with social-behavioral phenotypes in mice with Epac2 deficiencies. We observed an accumulation of autophagosomes and a significant increase in autophagic flux in Epac2-deficient neurons, which had no effect on mTOR activity. Next, we examined whether an increase in autophagic activity contributed to the social behavior exhibited in Epac2-/- mice. The social recognition deficit observed in Epac2-/- mice recovered in double transgenic Epac2-/-: Atg5+/- mice. Our study suggests that excessive autophagy due to Epac2 deficiencies may contribute to social recognition defects through an mTOR-independent pathway.

Forebrain glutamatergic neuron-specific Ctcf deletion induces reactive microgliosis and astrogliosis with neuronal loss in adult mouse hippocampus.

CCCTC-binding factor (CTCF), a zinc finger protein, is a transcription factor and regulator of chromatin structure. Forebrain excitatory neuron-specific CTCF deficiency contributes to inflammation via enhanced transcription of inflammation-related genes in the cortex and hippocampus. However, little is known about the long-term effect of CTCF deficiency on postnatal neurons, astrocytes, or microglia in the hippocampus of adult mice. To address this, we knocked out the Ctcf gene in forebrain glutamatergic neurons (Ctcf cKO) by crossing Ctcf-floxed mice with Camk2a-Cre mice and examined the hippocampi of 7.5-10-month-old male mice using immunofluorescence microscopy. We found obvious neuronal cell death and reactive gliosis in the hippocampal cornu ammonis (CA)1 in 7.5-10-month-old cKO mice. Prominent rod-shaped microglia that participate in immune surveillance were observed in the stratum pyramidale and radiatum layer, indicating a potential increase in inflammatory mediators released by hippocampal neurons. Although neuronal loss was not observed in CA3, and dentate gyrus (DG) CTCF depletion induced a significant increase in the number of microglia in the stratum oriens of CA3 and reactive microgliosis and astrogliosis in the molecular layer and hilus of the DG in 7.5-10-month-old cKO mice. These results suggest that long-term Ctcf deletion from forebrain excitatory neurons may contribute to reactive gliosis induced by neuronal damage and consequent neuronal loss in the hippocampal CA1, DG, and CA3 in sequence over 7 months of age. [BMB Reports 2021; 54(6): 317-322].

Loss of the neuronal genome organizer and transcription factor CTCF induces neuronal death and reactive gliosis in the anterior cingulate cortex.

CCCTC-binding factor (CTCF) is a genome organizer that regulates gene expression through transcription and chromatin structure regulation. CTCF also plays an important role during the developmental and adult stages. Cell-specific CTCF deletion studies have shown that a reduction in CTCF expression leads to the development of distinct clinical features and cognitive disorders. Therefore, we knocked out Ctcf (CTCF cKO) in the excitatory neurons of the forebrain in a Camk2a-Cre mouse strain to examine the role of CTCF in cell death and gliosis in the cortex. CTCF cKO mice were viable, but they demonstrated an age-dependent increase in reactive gliosis of astrocytes and microglia in the anterior cingulate cortex (ACC) from 16 weeks of age prior to neuronal loss observed at over 20 weeks of age. Consistent with these data, qRT-PCR analysis of the CTCF cKO ACC revealed changes in the expression of inflammation-related genes (Hspa1a, Prokr2 and Itga8) linked to gliosis and neuronal death. Our results suggest that prolonged Ctcf gene deficiency in excitatory neurons results in neuronal cell death and gliosis, possibly through functional changes in inflammation-related genes.

Perseverative stereotypic behavior of Epac2 KO mice in a reward-based decision making task.

Successfully navigating dynamic environments requires balancing the decision to stay at an optimal choice with that to switch to an alternative to acquire new knowledge. However, the genetic factors and cellular activity shaping this "stay or switch" action decision remains largely unidentified. Here we find that mice carrying a deletion of the exchange protein directly activated by cAMP 2 (Epac2) gene, a putative autism locus, exhibit perseverative "stay" behavior in a dynamic foraging task. Anatomical analysis found that the loss of Epac2 resulted in a significant decrease in the density of PV-expressing interneurons in the ventrolateral orbitofrontal cortex (OFC) and dorsal striatum (dSTR). Further, in vitro whole cell patch clamp recordings of PV+ GABAergic interneurons in the dSTR revealed altered neural activity in Epac2 KO mice in response to dopamine. Our findings highlight a potential role of Epac2 in structural changes and neural responses of PV-expressing GABAergic interneurons in the ventrolateral OFC and dSTR during value-based reinforcement learning and link Epac2 function to abnormal decision-making processes and perseverative behaviors seen in autism.

Cohen Syndrome Patient iPSC-Derived Neurospheres and Forebrain-Like Glutamatergic Neurons Reveal Reduced Proliferation of Neural Progenitor Cells and Altered Expression of Synapse Genes.

Cohen syndrome (CS), a rare autosomal recessive disorder, has been associated with genetic mutations in the VPS13B gene, which regulates vesicle-mediated protein sorting and transport. However, the cellular mechanism underlying CS pathogenesis in patient-derived human neurons remains unknown. We identified a novel compound heterozygous mutation, due to homozygous variation of biparental origin and heterozygous variation inherited from the father, in the VPS13B gene in a 20-month-old female patient. To understand the cellular pathogenic mechanisms, we generated induced pluripotent stem cells (iPSCs) from the fibroblasts of the CS patient. The iPSCs were differentiated into forebrain-like functional glutamatergic neurons or neurospheres. Functional annotation from transcriptomic analysis using CS iPSC-derived neurons revealed that synapse-related functions were enriched among the upregulated and downregulated genes in the CS neurons, whereas processes associated with neurodevelopment were enriched in the downregulated genes. The developing CS neurospheres were small in size compared to control neurospheres, likely due to the reduced proliferation of SOX2-positive neural stem cells. Moreover, the number of SV2B-positive puncta and spine-like structures was significantly reduced in the CS neurons, suggesting synaptic dysfunction. Taking these findings together, for the first time, we report a potential cellular pathogenic mechanism which reveals the alteration of neurodevelopment-related genes and the dysregulation of synaptic function in the human induced neurons differentiated from iPSCs and neurospheres of a CS patient.

Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations.

Significant clinical symptoms of Cohen syndrome (CS), a rare autosomal recessive disorder, include intellectual disability, facial dysmorphism, postnatal microcephaly, retinal dystrophy, and intermittent neutropenia. CS has been associated with mutations in the VPS13B (vacuolar protein sorting 13 homolog B) gene, which regulates vesicle-mediated protein sorting and transport; however, the cellular mechanism underlying CS pathogenesis in patient-derived neurons remains uncertain. This report states that autophagic vacuoles accumulate in CS fibroblasts and the axonal terminals of CS patient-specific induced pluripotent stem cells (CS iPSC)-derived neurons; additionally, autophagic flux was significantly increased in CS-derived neurons compared to control neurons. VPS13B knockout HeLa cell lines generated using the CRISPR/Cas9 genome editing system showed significant upregulation of autophagic flux, indicating that VSP13B may be associated with autophagy in CS. Transcriptomic analysis focusing on the autophagy pathway revealed that genes associated with autophagosome organization were dysregulated in CS-derived neurons. ATG4C is a mammalian ATG4 paralog and a crucial regulatory component of the autophagosome biogenesis/recycling pathway. ATG4C was significantly upregulated in CS-derived neurons, indicating that autophagy is upregulated in CS neurons. The autophagy pathway in CS neurons may be associated with the pathophysiology exhibited in the neural network of CS patients.

HIF2α/EFEMP1 cascade mediates hypoxic effects on breast cancer stem cell hierarchy.

Breast cancer stem cells (BCSCs) have been shown to contribute to tumor growth, metastasis, and recurrence. They are also markedly resistant to conventional cancer treatments, such as chemotherapy and radiation. Recent studies have suggested that hypoxia is one of the prominent micro-environmental factors that increase the self-renewal ability of BCSCs, partially by enhancing CSC phenotypes. Thus, the identification and development of new therapeutic approaches based on targeting the hypoxia-dependent responses in BCSCs is urgent. Through various in vitro studies, we found that hypoxia specifically up-regulates BCSC sphere formation and a subset of CD44+/CD24-/low CSCs. Hypoxia inducible factors 2α (HIF2α) depletion suppressed CSC-like phenotypes and CSC-mediated drug resistance in breast cancer. Furthermore, the stimulatory effects of hypoxia-induced HIF2α on BCSC sphere formation were successfully attenuated by epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) knockdown. Taken together, these data suggest that HIF2α mediates hypoxia-induced cancer growth/metastasis and that EFEMP1 is a downstream effector of hypoxia-induced HIF2α during breast tumorigenesis.

Pneumoretroperitoneum, Pneumomediastinum, Subcutaneous Emphysema After a Rectal Endoscopic Mucosal Resection.

An endoscopic mucosal resection (EMR) is an effective and safe therapeutic technique for treating a patient with a laterally-spreading tumor (LST). Colonoscopic-procedure-related complications are noted to be about 2.8% worldwide, and a perforation is the most common. Most colon perforations cause pneumoperitoneum. However, a perforation within the retroperitoneal portion of the colon (rectum and some of sigmoid colon) may cause an extraperitoneal perforation, and the leaking free air may induce pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema, depending on the amount of discharged air. Herein, we present the case of a patient with an extraperitoneal colon microperforation which manifested as pneumoretroperitoneum, pneumomediastinum, and subcutaneous emphysema after an EMR for a sigmoid LST, which was successfully treated with medical treatment and endoscopic clipping.

Involvement of cAMP-guanine nucleotide exchange factor II in hippocampal long-term depression and behavioral flexibility.

BACKGROUND: Guanine nucleotide exchange factors (GEFs) activate small GTPases that are involved in several cellular functions. cAMP-guanine nucleotide exchange factor II (cAMP-GEF II) acts as a target for cAMP independently of protein kinase A (PKA) and functions as a GEF for Rap1 and Rap2. Although cAMP-GEF II is expressed abundantly in several brain areas including the cortex, striatum, and hippocampus, its specific function and possible role in hippocampal synaptic plasticity and cognitive processes remain elusive. Here, we investigated how cAMP-GEF II affects synaptic function and animal behavior using cAMP-GEF II knockout mice. RESULTS: We found that deletion of cAMP-GEF II induced moderate decrease in long-term potentiation, although this decrease was not statistically significant. On the other hand, it produced a significant and clear impairment in NMDA receptor-dependent long-term depression at the Schaffer collateral-CA1 synapses of hippocampus, while microscopic morphology, basal synaptic transmission, and depotentiation were normal. Behavioral testing using the Morris water maze and automated IntelliCage system showed that cAMP-GEF II deficient mice had moderately reduced behavioral flexibility in spatial learning and memory. CONCLUSIONS: We concluded that cAMP-GEF II plays a key role in hippocampal functions including behavioral flexibility in reversal learning and in mechanisms underlying induction of long-term depression.

Comparative measurement of aortic root by transthoracic echocardiography in normal Korean population based on two different guidelines.

BACKGROUND: Aortic root size is an important parameter in vascular diseases and can be easily assessed by transthoracic echocardiography. However, measurements values may vary according to cardiac cycle and the definition used for edge. This study aimed to define normal values according to the measurement method specified by two different guidelines to determine the influence of the different methods on echocardiographic measurements. METHODS: Healthy Korean adults were enrolled. The aortic root diameters were measured twice at four levels (aortic annulus, sinuses of Valsalva, sinotubular junction, and ascending aorta) by the 2005 American Society of Echocardiography (ASE) guidelines (measured from leading edge to leading edge during diastole) and the 2010 ASE pediatric guidelines (measured from inner edge to inner edge during systole). RESULTS: One hundred twelve subjects aged 20-69 years were enrolled. The aortic diameters (cm) determine by the aforementioned two guidelines showed significant difference. Measurements were larger in 2005 ASE guideline at aortic annuls, sinuses of Valsalva, and sinotubular junction level, but smaller at ascending aortic level with 2-3mm of differences. Intraobserver variability was similarly good, but interobserver variability was slightly higher than intraobserver variability in both measurement methods. BSA and age was most important determinant for aortic root size. CONCLUSIONS: The measurement method of aortic root can affect the echocardiographic result. The measurement method should be noted when assessing clinical significance of aortic root measurement.