Exploring educational transformations through the Innovative Flipped Learning Instruction Project Symposium.

The flipped classroom is an innovative pedagogy that shifts content delivery outside the classroom, utilizing in-class time for interactive learning. The preclass and in-class activities in this framework encourage individualized learning and collaborative problem-solving among students, fostering engagement. The Innovative Flipped Learning Instruction Project (IFLIP) conducted faculty development workshops over 4 years, guiding science, technology, engineering, and mathematics (STEM) faculty in integrating flipped teaching (FT) into their courses. The research aimed to assess its impact on pedagogical practices, explore its effectiveness, and provide a framework to implement FT across multiple institutions. It sought to evaluate the experiences of these educators throughout the transitional period of instructional change. In the fourth year of this project, a symposium was organized for IFLIP participants to share their experiences and findings concerning FT. This symposium helped promote collaboration among IFLIP participants and faculty interested in FT to disseminate participants' knowledge and experiences in implementing FT strategies. A survey conducted at the end of the symposium indicated that faculty participants with FT experience continued to embrace this pedagogy, and the new adopters expressed intentions to incorporate it into their courses. The survey revealed positive responses: 93% of respondents plan to integrate FT methods in future classes, 90% gained new information from the symposium and intend to implement it, and 91% are likely to recommend FT to colleagues. Ultimately, the symposium underscored the transformative impact of FT in empowering educators to deepen students' conceptual understanding, emphasizing the significance of this pedagogical approach in advancing the quality of education.NEW & NOTEWORTHY Flipped pedagogy shifts content delivery outside the classroom, emphasizing interactive learning during in-class time. The Innovative Flipped Learning Instruction Project (IFLIP) guided science, technology, engineering, and mathematics (STEM) faculty in integrating flipped teaching (FT), tracked experiences during this transition, and provided a framework for FT implementation. A fourth-year symposium fostered collaboration, revealing sustained enthusiasm for FT. The symposium underscored its transformative impact on deepening students' understanding, highlighting its significance in enhancing education quality.

Carbachol increases locus coeruleus activation by targeting noradrenergic neurons, inhibitory interneurons and inhibitory synaptic transmission.

The locus coeruleus (LC) consists of noradrenergic (NA) neurons and plays an important role in controlling behaviours. Although much of the knowledge regarding LC functions comes from studying behavioural outcomes upon administration of muscarinic acetylcholine receptor (mAChR) agonists into the nucleus, the exact mechanisms remain unclear. Here, we report that the application of carbachol (CCh), an mAChR agonist, increased the spontaneous action potentials (sAPs) of both LC-NA neurons and local inhibitory interneurons (LC I-INs) in acute brain slices by activating M1/M3 mAChRs (m1/3 AChRs). Optogenetic activation of LC I-INs evoked inhibitory postsynaptic currents (IPSCs) in LC-NA neurons that were mediated by γ-aminobutyric acid type A (GABAA ) and glycine receptors, and CCh application decreased the IPSC amplitude through a presynaptic mechanism by activating M4 mAChRs (m4 AChRs). LC-NA neurons also exhibited spontaneous phasic-like activity (sPLA); CCh application increased the incidence of this activity. This effect of CCh application was not observed with blockade of GABAA and glycine receptors, suggesting that the sPLA enhancement occurred likely because of the decreased synaptic transmission of LC I-INs onto LC-NA neurons by the m4 AChR activation and/or increased spiking rate of LC I-INs by the m1/3 AChR activation, which could lead to fatigue of the synaptic transmission. In conclusion, we report that CCh application, while inhibiting their synaptic transmission, increases sAP rates of LC-NA neurons and LC I-INs. Collectively, these effects provide insight into the cellular mechanisms underlying the behaviour modulations following the administration of muscarinic receptor agonists into the LC reported by the previous studies.

Subacute two stage metatarsal lengthening with gradual distraction for brachymetatarsia: A consecutive case series and literature review.

BACKGROUND: This study examined the functional and clinical outcomes of subacute two stage metatarsal lengthening with gradual distraction for brachymetatarsia. This technique was developed to overcome the disadvantages of one-stage metatarsal lengthening and gradual distraction. METHODS: Four feet of three patients with congenital brachymetatarsia underwent subacute two stage metatarsal lengthening with gradual distraction. Pain, function, and alignment were assessed preoperatively and at follow-ups using the American Orthopaedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal-interphalangeal scale, and any complications were recorded. RESULTS: The patients were followed up for a mean of 18.1 ± 6.9 (range, 12.6-28.1) months. The mean metatarsal length gain was 15.2 ± 3.2 (range, 12.1-18.5) mm, and the corresponding percent increase was 32.5 % ± 7.0 % (range, 25.7-41.1 %). The mean AOFAS score (0-100) was 97.5 ± 5.0 at the final follow-up. The external fixator index was 10.2 ± 1.5 (range, 8.1-11.6) days/cm. None of the patients experienced metatarsophalangeal stiffness, subluxation or dislocation of the metatarsophalangeal joint, loss of correction, pin tract infection, delayed union, nonunion, or angular deformities. CONCLUSION: Subacute two stage metatarsal lengthening with gradual distraction is a reliable alternative treatment for brachymetatarsia.

Arthroscopic-assisted radiocarpal ligaments tensioning for dynamic radiocarpal instability.

BACKGROUND: Dynamic radiocarpal instability is one of the causes of post-trauma radial-sided wrist pain. It is not easy to diagnose and may possibly be overlooked. The key ligaments responsible for dynamic radiocarpal instability are the radioscaphocapitate (RSC) and long radiolunate (LRL) ligaments. Tensioning of these 2 ligaments could be a method of treatment for dynamic carpal instability. We proposed a method for arthroscopic thermal shrinkage of these 2 ligaments, and for setting a landmark arthroscopically to facilitate identification of these 2 ligaments during the combined open suture tensioning procedure. METHODS: Between January 2016 and May 2020, 12 patients treated with this method were enrolled. The mean age was 33.3 years (range, 18-57 years), and the mean duration from injury to operation was 7.8 months (range, 3-25 months). The diagnosis was mainly depended on the physical examinations and confirmed under arthroscopy. The mean follow-up was 17.7 months (range, 12-26 months). RESULTS: All the patients had marked improvement of pain, grip strength, the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), and the radiocarpal stability. The wrist range of motion showed significant decrease around 5o in both flexion and extension and around 4o in the ulnar deviation at the final follow-ups. All patients were able to return to their previous full level of work and activities. CONCLUSIONS: We conclude that arthroscopic thermal shrinkage combined with open suture tensioning can be effective in treating dynamic carpal instability, while the arthroscopic-assisted landmark setting can help identify the accurate location of the RSC and LRL ligaments without dissecting too much soft tissue.

Transosseous Suturing for the Correction of Juvenile Hallux Valgus: A Preliminary Case Series Study.

Background and Objectives: Many treatment modalities are available for juvenile hallux valgus. However, all of them have some disadvantages. Therefore, we developed a transosseous suturing procedure. Materials and Methods: Six patients (seven feet) with juvenile hallux valgus received transosseous suturing procedure. Clinical and radiological examinations were performed preoperatively and postoperatively. All patients underwent the soft tissue release procedure, followed by transosseous suturing with Fiberwire (in which sutures are anchored with mini plates). Results: The mean IMA and HVA decreased from 15.6° ± 2.6° to 7.3° ± 1.1° and 39.2° ± 3.3° to 12.5° ± 3.1°, respectively. Corrections achieved in the IMA and HVA of all patients were maintained through the last follow-up. The mean American Orthopedic Foot & Ankle Society score improved from 53.3 ± 3.5 to 86.9 ± 4.7 points. Conclusions: Based on these preliminary data, the transosseous suturing technique demonstrated satisfactory results and apparent improvements in the IMA and HVA without early complications.

Sudden deafness: a comparison between age groups.

OBJECTIVES: This study compared sudden deafness (SD) cases in 20-year age bands to investigate their causes and treatment outcome. DESIGN: Retrospective study. STUDY SAMPLES: 178 unilateral SD patients were divided into four 20-year age-groups, namely Groups I (aged 0-19 years, n = 6), II (aged 20-39 years, n = 33), III (aged 40-59 years, n = 63), and IV (aged 60-79 years, n = 76). METHODS: An inner ear test battery and/or serology assay were performed. RESULTS: Incidence of SD in relation to overall neurotological cases did not significantly differ among the four groups. Groups I and II showed two or three audiographic patterns, while Groups III and IV had six audiographic patterns indicating that the aetiology of Groups I and II may be of the same origin, while Groups III and IV had multiple aetiologies. The hearing improvement rate was significantly higher in Groups III (62%) and IV (62%) than in Groups I (16%) and II (33%). CONCLUSION: SD inevitably affects individuals of all ages. Significant differences in the audiographic patterns and speculative causes may account for various outcomes of treatment in each 20-year age band. Those SD patients aged 40-59 and 60-79 years showed significantly better treatment outcomes than those aged 0-19 and 20-39 years.

Leptin -2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population.

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The current case-control study aimed to examine the effects of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) single-nucleotide polymorphisms (SNPs) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP -2548 have a significant low risk for the development of clinical stage (A/G: adjusted odds ratio [AOR] = 0.670, 95% confidence interval [CI] = 0.454-0.988, P < 0.05; A/G + G/G: AOR = 0.676, 95% CI = 0.467-0.978, P < 0.05) compared to patients with ancestral homozygous A/A genotype. In addition, an interesting result was found that the impact of LEP -2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP -2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP -2548 G/A showed a poor clinicopathological development of oral cancer; population without tobacco consumption and with polymorphic LEP -2548 G/A gene may significantly increase the risk to have oral cancer.

Functional variant of CHI3L1 gene is associated with neck metastasis in oral cancer.

OBJECTIVES: Oral cancer is the most common head and neck malignancy, and it is associated with a high recurrence rate and lymph node metastasis potential. YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein that serves as a biomarker in several diseases. It also plays a crucial role in regulating many characteristics of cancer, such as cell growth, migration, anti-apoptosis, and angiogenesis. Accumulating evidence supports the link between single-nucleotide polymorphisms (SNPs) and oral cancer, but no report on the association between CHI3L1 polymorphisms and oral cancer is available. Thus, the present study evaluated the contribution of CHI3L1 SNPs to oral cancer susceptibility and clinicopathology. MATERIALS AND METHODS: This study recruited a total of 2362 subjects, comprising 1190 healthy male controls and 1172 male patients with oral cancer. Allelic discrimination of the CHI3L1 polymorphisms - 1371 G>A (rs6691378), - 247 G>A (rs10399805), - 131 C>G (rs4950928), and + 2950 T>C (rs880633) was assessed through real-time polymerase chain reaction. RESULTS: We detected a significant association of rs10399805 and rs6691378 with the risk of oral cancer (AOR, 1.537; 95% CI, 1.089-2.168; p = 0.014; AOR, 1.561; 95% CI, 1.131-2.156; p = 0.007, respectively) after adjustment for three potential confounders, smoking, betel nut chewing, and alcohol consumption. Moreover, we found that oral cancer patients carrying the homozygous A/A genotype of the rs10399805 (p = 0.035) or rs6691378 polymorphism (p = 0.023) showed a significantly lower risk of lymph node metastasis. Moreover, according to the Genotype-Tissue Expression database, the rs10399805 and rs6691378 polymorphisms in the promoter region were associated with decreased levels of CHI3L1 mRNA. CONCLUSIONS: In conclusion, we found that the homozygous mutant allele of rs10399805 and rs6691378 appeared to have significantly lower risk of lymph node metastasis and associated with its mRNA levels in oral cancer. CLINICAL RELEVANCE: The CHI3L1 polymorphisms rs10399805 and rs6691378 may act as biomarkers for predicting lymph node metastasis in oral cancer patients.

The Role of Gastrodin on Hippocampal Neurons after N-Methyl-D-Aspartate Excitotoxicity and Experimental Temporal Lobe Seizures.

Tian ma (Gastrodia elata, GE) is an ancient Chinese herbal medicine that has been suggested to be effective as an anticonvulsant and analgesic, and to have sedative effects against vertigo, general paralysis, epilepsy and tetanus. The primary active ingredient isolated from GE is termed gastrodin, which is the glucoside of 4-hydroxybenzyl alcohol (4-HBA). Gastrodin can abolish hypoxia-, glutamate- and N-methyl-D-aspartate (NMDA) receptor-induced toxicity in primary culture of rat cortical neurons, and reduces seizure severity in seizure-sensitive gerbils. We evaluated the effect of gastrodin on NMDA excitotoxicity in hippocampal slice cultures (HSCs) with propidium iodide (PI) fluorescence measurement. We also evaluated the effects of gastrodin for treating active in vivo temporal lobe seizures induced by lithium/pilocarpine. Seizure severity, time span to seizure onset, mortality rate and hippocampal histology for survivors were compared. The effect of gastrodin was evaluated for treating in vitro seizures induced by Mg²âº-free medium in hippocampal slices. Frequencies and amplitudes of epileptiform discharges were compared. The effect of gastrodin on synaptic transmission was evaluated on hippocampal CA1 Schaffer collaterals. Application of 25 µM gastrodin significantly suppressed NMDA excitotoxicity in CA3 but not in CA1 hippocampus and dentate gyrus. Intraventricular gastrodin accelerated seizure onset for 12 min after intraperitoneal pilocarpine injection (P = 0.051). Three of five rats (60%) in the gastrodin group, and three of four (75%) in the dimethyl sulfoxide (DMSO) group died within 3 days after status epilepticus (SE). Gastrodin also failed to inhibit epileptiform discharges in hippocampal slices induced by Mg²âº-free medium, believed to be NMDA receptor-mediated spontaneous activity. The frequencies of the spontaneous epileptiform discharges were similar under treatments with 25 µM gastrodin, 200 µM gastrodin and DMSO. For the evaluation of gastrodin on synaptic transmission, application of DMSO, 25 µM or 200 µM gastrodin had no significant effect on excitatory postsynaptic potential (EPSP) slopes. Gastrodin at 200 µM decreased paired-pulse facilitation (PPF) from 1.23 ± 0.04 to 1.12 ± 0.04 (P = 0.002). In conclusion, gastrodin failed to suppress in vivo and in vitro seizures in our study. Gastrodin showed no effect on hippocampal Schaffer collateral EPSP. These findings suggest that gastrodin does not interact with ionotropic glutamate receptors to inhibit NMDA receptor-facilitated seizures. However, gastrodin showed protective effects against NMDA toxicity on cultured hippocampal slices. Nevertheless, gastrodin is still a potential neuroprotective agent against NMDA excitotoxicity, with potential benefits for stroke and patients with epilepsy.

Lateral Approach for Scaphoid Excision and Capitolunate Arthrodesis in the Treatment of Scapholunate Advanced Collapse and Scaphoid Nonunion Advanced Collapse Wrists: A Case Series.

OBJECTIVE: The dorsal approach is commonly used in open wrist arthrodesis. However, the extensor compartments and the dorsal wrist capsule need to be opened. We propose and evaluate a lateral approach using a small incision over the scaphoid anatomical snuffbox, which could be more straightforward for performing scaphoid excision and capitolunate arthrodesis in the treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC). METHODS: Between 2016 and 2021, 10 patients were enrolled retrospectively and underwent the lateral approach for scaphoid excision and capitolunate arthrodesis. We presented the radiographic outcomes, including fusion status, capitolunate angle, and carpal height ratio. The functional outcomes of wrist range of motion, grip strength, visual analog scale (VAS) score for pain, Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, and Mayo wrist score were evaluated. The data obtained were analyzed and presented as the mean and standard deviation (SD). RESULTS: All 10 patients achieved solid bone fusion, and the mean follow-up period was 20.4 (range 12-38; SD 10.1) months. Postoperatively, the mean capitolunate angle and carpal height ratio improved from 18.1° (range 8-34°; SD 8.6°) to 2.9° (range 0-5°; SD 1.9°) and 0.45 (range 0.40-0.49; SD 0.03)% to 0.50 (range 0.46-0.54; SD 0.02)%, respectively. The average preoperative and final follow-up functional results were as follows: flexion-extension arc of 76.5° (range 50-110°; SD 20.0°) and 74.0° (range 65-90°; SD 9.1°); VAS pain score of 5.8 (range 4-7; SD 1.0) and 0.9 (range 0-2; SD 0.6); QuickDASH score of 55.9 (range 40.9-79.5; SD 11.4) and 26.1 (range 18.2-36.4; SD 6.0); and Mayo wrist score of 46.5 (range 25-60; SD 13.8) and 72.5 (range 70-80; SD 3.5), respectively. CONCLUSIONS: The lateral approach for scaphoid excision and capitolunate arthrodesis in treating SLAC and SNAC can provide a straightforward way for performance. This approach does not require disruption of the dorsal wrist capsule and extensor retinaculum. Bony healing can be achieved, and functional outcomes can be improved.

Outcomes of Percutaneous Pinning for Interfragmentary Fixation in Treating Bennett Fractures With Tiny Avulsion Fragments.

For Bennett fractures with tiny avulsion fragments, healing may be jeopardized owing to limited fracture contact surface if displacement of reduced fracture junctions occurs. This study aimed to assess the efficacy of treating Bennett fractures with tiny avulsion fragments using percutaneous small-diameter K-wires for tiny fragment fixation and thumb carpometacarpal (CMC) joint transfixation. From 2011 to 2019, we retrospectively enrolled patients with Gedda type 3 Bennett fractures who underwent operation with K-wire percutaneous pinning for the tiny fragment and CMC joint. We enrolled a total of 13 patients (13 fractures) with a mean age of 26.9 years (range, 18-42 years) at operation and a mean follow-up time of 17.9 months (range, 12-34 months). At the final follow-up, the shortened Disabilities of the Arm, Shoulder and Hand Questionnaire mean score was 4.7, and the visual analog scale score for pain during activity was 0.7. Mean grip strength was 34.7 kg (97.7% of the value on the unaffected side). Mean pinch strength was 5.4 kg (90.5% of the value on the unaffected side). Mean first web opening angle was 66.2° (96.6% of the value on the unaffected side). There were no changes in gap and step-off during the healing process and no osteoarthritic changes in the thumb CMC joint at the final follow-up. For Bennett fractures with tiny avulsion fragment, percutaneous treatment with small-diameter K-wires for fragment fixation and thumb CMC joint transfixation provides a viable alternative with fracture healing and good functional outcomes. [Orthopedics. 2023;46(2):103-107.].

The role of family intimacy in playing collaborative e-sports with a Switch device to predict the experience of flow and anxiety during COVID-19 lockdown.

During the COVID-19 pandemic, most people have more time to stay at home and play games together. In particular, so as to maintain social distancing, most people play with their family members. To understand how people's family intimacy affects their game experience and perceived value of playing, the present study applied a boating game, River Survival, played collaboratively via Swtich. People with experience of playing the game with family members were targeted in this study. They were notified via Facebook and Line special interest groups and responded to the questionnaire through a website. Data of 301 respondents were validated, and were subjected to structural equation modeling. The results of this study indicated that family intimacy positively predicted flow experience, but there was no significant relation to gameplay anxiety. Flow experience positively predicted perceived value, but gameplay anxiety did not significantly predict perceived value. The implication of this study is that without intimacy among team members, players cannot experience flow state or perceived game values.

Longitudinal Voice Outcomes Following Serial Potassium Titanyl Phosphate Laser Procedures for Recurrent Respiratory Papillomatosis.

OBJECTIVE: Repeated surgical interventions are usually required to control recurrent respiratory papillomatosis (RRP), but at considerable risk of worsened postoperative voice quality. Potassium titanyl phosphate (KTP) laser has been reported to effectively manage RRP; however, voice quality after repeated procedures has not been investigated. METHODS: This study recruited 16 patients with RRP treated using KTP laser between 2013 and 2019. KTP laser procedures were performed under general anesthesia via direct suspension laryngoscope or under local anesthesia via flexible endoscope, depending on the need for pathological proof, patient tolerance, and lesion size and location. Disease control was investigated by videolaryngostroboscopy. Voice outcome was evaluated using a 10-item voice handicap index (VHI-10), acoustic and perceptual analyzes. RESULTS: We reviewed the medical records of 11 male and 5 female patients with RRP (age range: 23-73 years). Five patients received KTP laser once, six patients received it 2 to 5 times, and five patients received 6 to 15 procedures. Median VHI-10 decreased from 28.3 to 12.0 points after the initial procedure and were maintained at 10.1 to 11.0 points following subsequent procedures (P < .01, generalized estimating equation). Acoustic and perceptual analysis of voice quality also revealed significant improvements (P < .01), which remained stable even after 6 to 10 KTP laser procedures. Minor adverse events included slight fibrotic change of vocal folds and glottic web, but these did not significantly alter postoperative voice quality. CONCLUSION: This longitudinal follow-up study revealed that serial KTP laser procedures can effectively control RRP while preserving phonatory function and maintaining adequate voice quality. LEVEL OF EVIDENCE: 4.

Problem solving strategies used by RN-to-BSN students in an online problem-based learning course.

It is essential that nursing students develop the problem solving and critical thinking skills required in the current health care environment. Problem-based learning has been promoted as a way to help students acquire those skills; however, gaps exist in the knowledge base of the strategies used by learners. The purpose of this case study was to gain insight into the problem solving experience of a group of six RN-to-BSN students in an online problem-based learning course. Data, including discussion transcripts, reflective papers, and interview transcripts, were analyzed using a qualitative approach. Students expanded their use of resources and resolved the cases, identifying relevant facts and clinical applications. They had difficulty communicating their findings, establishing the credibility of sources, and offering challenging feedback. Increased support and direction are needed to facilitate the development of problem solving abilities of students in the problem-based learning environment.

Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. METHODS: Heterozygous necdin-deficient mice (B6.Cg-Ndntm1ky) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/-p) animals, which were examined of LC-NE neuronal activity, developmental reflexes, and plethysmography. RESULTS: On slice electrophysiology, LC-NE neurons of Ndntm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndntm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. CONCLUSIONS: LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.

GABAB receptor-mediated tonic inhibition of locus coeruleus neurons plays a role in deep anesthesia induced by isoflurane.

Noradrenergic neurons in the locus coeruleus referred to as locus coeruleus neurons, provide the major supply of norepinephrine to the forebrain and play important roles in behavior through regulation of wakefulness and arousal. In a previous study using brain slice preparations, we reported that locus coeruleus neurons are subject to tonic inhibition mediated by γ-aminobutyric acid B receptors (GABABRs) and that the extent of tonic inhibition varies with ambient GABA levels. Since ambient GABA in the locus coeruleus was reported to fluctuate during the sleep-wakefulness cycle, here we tested whether GABABR-mediated tonic inhibition of locus coeruleus neurons could be a mechanism underlying changes in brain arousal. We first demonstrated that GABABR-mediated tonic inhibition of locus coeruleus neurons also exists in vivo by showing that local infusion of CGP35348, a GABABR antagonist, into the locus coeruleus increased the firing rate of locus coeruleus neurons in anesthetized rats. We then showed that this manipulation accelerated the behavioral emergence of rats from deep anesthesia induced by isoflurane. Together, these observations show that GABABR-mediated tonic inhibition of locus coeruleus neurons occurs in vivo and support the idea that this effect may be important in regulating the functional state of the brain.

Involvement of endothelial nitric oxide synthase gene variants in the aggressiveness of uterine cervical cancer.

To date, few studies explore the involvement of endothelial nitric oxide synthase (eNOS) gene variants in uterine cervical cancer. Therefore, we conducted this study to assess the clinical implication of eNOS in cervical carcinogenesis, clinicopathological characteristics and patient survival. One hundred and seventeen patients with cervical invasive cancer and 95 with preinvasive lesions and 330 control women were consecutively enrolled. Real time polymerase chain reaction was used to examine the genotypic distributions of eNOS single nucleotide polymorphisms (SNPs) rs1799983 (894G>T) at the exon 7 region and rs2070744 (-786T>C) at the promoter region. Our results indicated no significant associations among genotypic distributions of eNOS SNPs and patients with cervical invasive cancer and those with preinvasive lesions as well as normal controls. However, cervical cancer patients with genotypes TC/CC in eNOS SNP rs2070744 carried less risk of advanced stage [odds ratios (OR) = 0.30, 95% confidence interval (CI)=0.09-0.97, p=0.036], parametrium invasion (OR=0.16, 95% CI=0.02-0.75, p=0.009) and pelvic lymph node metastasis (OR=0.12, 95% CI=0.01-0.89, p=0.016). In conclusion, although eNOS SNPs rs2070744 and rs1799983 do not display significant associations with cervical carcinogenesis and patient survival, cervical cancer patients with genotypes TC/CC in rs2070744 carry less risk of advanced stage, parametrium invasion and pelvic lymph node metastasis in Taiwan.

Bioinspired Diatomite Membrane with Selective Superwettability for Oil/Water Separation.

Membranes with selective superwettability for oil/water separation have received significant attention during the past decades. Hierarchical structures and surface roughness are believed to improve the oil repellency and the stability of Cassie-Baxter state. Diatoms, unicellular photosynthetic algae, possess sophisticated skeletal shells (called frustules) which are made of hydrated silica. Motivated by the hierarchical micro- and nanoscale features of diatom, we fabricate a hierarchical diatomite membrane which consists of aligned micro-sized channels by the freeze casting process. The fine nano-porous structures of frustules are well preserved after the post sintering process. The bioinspired diatomite membrane performs both underwater superoleophobicity and superhydrophobicity under various oils. Additionally, we demonstrate the highly efficient oil/water separation capabililty of the membranes in various harsh environments. The water flux can be further adjusted by tuning the cooling rates. The eco-friendly and robust bioinspired membranes produced by the simple, cost-effective freeze casting method can be potentially applied for large scale and efficient oil/water separation.

Cholinergic and glutamatergic transmission at synapses between pedunculopotine tegmental nucleus axonal terminals and A7 catecholamine cell group noradrenergic neurons in the rat.

We characterized transmission from the pedunculopotine tegmental nucleus (PPTg), which contains cholinergic and glutamatergic neurons, at synapses with noradrenergic (NAergic) A7 neurons. Injection of an anterograde neuronal tracer, biotinylated-dextran amine, into the PPTg resulted in labeling of axonal terminals making synaptic connection with NAergic A7 neurons. Consistent with this, extracellular stimulation using a train of 10 pulses at 100 Hz evoked both fast and slow excitatory synaptic currents (EPSCs) that were blocked, respectively, by DNQX, a non-N-methyl-d-aspartate receptor blocker, or atropine, a cholinergic muscarinic receptor (mAChR) blocker. Interestingly, many spontaneous-like, but stimulation-dependent, EPSCs, were seen for up to one second after the end of stimulation and were blocked by DNQX and decreased by EGTA-AM, a membrane permeable form of EGTA, showing they are glutamatergic EPSCs causing by asynchronous release of vesicular quanta. Moreover, application of atropine or carbachol, an mAChR agonist, caused, respectively, an increase in the number of asynchronous EPSCs or a decrease in the frequency of miniature EPSCs, showing that mAChRs mediated presynaptic inhibition of glutamatergic transmission of the PPTg onto NAergic A7 neurons. In conclusion, our data show direct synaptic transmission of PPTg afferents onto pontine NAergic neurons that involves cooperation of cholinergic and glutamatergic transmission. This dual-transmitter transmission drives the firing rate of NAergic neurons, which may correlate with axonal and somatic/dendritic release of NA.

Rosiglitazone Suppresses In Vitro Seizures in Hippocampal Slice by Inhibiting Presynaptic Glutamate Release in a Model of Temporal Lobe Epilepsy.

Peroxisomal proliferator-activated receptor gamma (PPARγ) is a nuclear hormone receptor whose agonist, rosiglitazone has a neuroprotective effect to hippocampal neurons in pilocarpine-induced seizures. Hippocampal slice preparations treated in Mg2+ free medium can induce ictal and interictal-like epileptiform discharges, which is regarded as an in vitro model of N-methyl-D-aspartate (NMDA) receptor-mediated temporal lobe epilepsy (TLE). We applied rosiglitazone in hippocampal slices treated in Mg2+ free medium. The effects of rosiglitazone on hippocampal CA1-Schaffer collateral synaptic transmission were tested. We also examined the neuroprotective effect of rosiglitazone toward NMDA excitotoxicity on cultured hippocampal slices. Application of 10 µM rosiglitazone significantly suppressed amplitude and frequency of epileptiform discharges in CA1 neurons. Pretreatment with the PPARγ antagonist GW9662 did not block the effect of rosiglitazone on suppressing discharge frequency, but reverse the effect on suppressing discharge amplitude. Application of rosiglitazone suppressed synaptic transmission in the CA1-Schaffer collateral pathway. By miniature excitatory-potential synaptic current (mEPSC) analysis, rosiglitazone significantly suppressed presynaptic neurotransmitter release. This phenomenon can be reversed by pretreating PPARγ antagonist GW9662. Also, rosiglitazone protected cultured hippocampal slices from NMDA-induced excitotoxicity. The protective effect of 10 µM rosiglitazone was partially antagonized by concomitant high dose GW9662 treatment, indicating that this effect is partially mediated by PPARγ receptors. In conclusion, rosiglitazone suppressed NMDA receptor-mediated epileptiform discharges by inhibition of presynaptic neurotransmitter release. Rosiglitazone protected hippocampal slice from NMDA excitotoxicity partially by PPARγ activation. We suggest that rosiglitazone could be a potential agent to treat patients with TLE.