Hyperbaric oxygen therapy suppresses hypoxia and reoxygenation injury to retinal pigment epithelial cells through activating peroxisome proliferator activator receptor-alpha signalling.

Retinal ischemia followed by reperfusion (IR) is a common cause of many ocular disorders, such as age-related macular degeneration (AMD), which leads to blindness in the elderly population, and proper therapies remain unavailable. Retinal pigment epithelial (RPE) cell death is a hallmark of AMD. Hyperbaric oxygen (HBO) therapy can improve IR tissue survival by inducing ischemic preconditioning responses. We conducted an in vitro study to examine the effects of HBO preconditioning on oxygen-glucose deprivation (OGD)-induced IR-injured RPE cells. RPE cells were treated with HBO (100% O2 at 3 atmospheres absolute for 90 min) once a day for three consecutive days before retinal IR onset. Compared with normal cells, the IR-injured RPE cells had lower cell viability, lower peroxisome proliferator activator receptor-alpha (PPAR-α) expression, more severe oxidation status, higher blood-retinal barrier disruption and more elevated apoptosis and autophagy rates. HBO preconditioning increased PPAR-α expression, improved cell viability, decreased oxidative stress, blood-retinal barrier disruption and cellular apoptosis and autophagy. A specific PPAR-α antagonist, GW6471, antagonized all the protective effects of HBO preconditioning in IR-injured RPE cells. Combining these observations, HBO therapy can reverse OGD-induced RPE cell injury by activating PPAR-α signalling.

Comparing the similarity and differences in MeSH terms associated with spine-specific journals using the forest plot: A bibliometric analysis.

BACKGROUND: A common concern in the literature is the comparison of the similarities and differences between research journals, as well as the types of research they publish. At present, there are no clear methodologies that can be applied to a given article of interest. When authors use an effective and efficient method to locate journals in similar fields, they benefit greatly. By using the forest plot and major medical subject headings (MeSH terms) of Spine (Phila Pa 1976) compared to Spine J, this study: displays relatively similar journals to the target journal online and identifies the effect of the similarity odds ratio of Spine (Phila Pa 1976) compared to Spine J. METHODS: From the PubMed library, we downloaded 1000 of the most recent top 20 most similar articles related to Spine (Phila Pa 1976) and then plotted the clusters of related journals using social network analysis (SNA). The forest plot was used to compare the differences in MeSH terms for 2 journals (Spine (Phila Pa 1976) and Spine J) based on odds ratios. The heterogeneity of the data was evaluated using the Q statistic and the I-square (I2) index. RESULTS: This study shows that: the journals related to Spine (Phila Pa 1976) can easily be presented on a dashboard via Google Maps; 8 journal clusters were identified using SNA; the 3 most frequently searched MeSH terms are surgery, diagnostic imaging, and methods; and the odds ratios of MeSH terms only show significant differences with the keyword "surgery" between Spine (Phila Pa 1976) and Spine J with homogeneity at I2 = 17.7% (P = .27). CONCLUSIONS: The SNA and forest plot provide a detailed overview of the inter-journal relationships and the target journal using MeSH terms. Based on the findings of this research, readers are provided with knowledge and concept diagrams that can be used in future submissions to related journals.

Citation analysis of the 100 top-cited articles on discectomy via endoscopy since 2011 using alluvial diagrams: bibliometric analysis.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) is synonymous with percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). PEID has gained increasing recognition for its small incision, quick recovery, short hospital stay, and equivalent clinical outcome to open surgery. Numerous articles related to PEID have been published in the literature. However, which countries, journals, subject categories, and articles have ultimate influence remains unknown. The study aimed to (1) display influential entities in 100 top-cited PEID-related articles (T100PEID) on the alluvial diagram and (2) investigate whether medical subject headings (i.e., MeSH terms) can be used to predict article citations. METHODS: T100PEID data can be found since 2011 in the PubMed and Web of Science (WOS) databases. Using alluvial diagrams, citation analysis was conducted to compare the dominant entities. We used social network analysis (SNA) to classify MeSH terms and research areas extracted from PubMed and WOS. The difference in article citations across subject categories and the predictive power of MeSH terms on article citations in T100 PEID were examined using one-way analysis of variance (ANOVA) and regression analysis. RESULTS: A total of 81% of T100PEID is occupied by the top three countries (the US, China, and South Korea). There was an overall T100PEID impact factor of 41.3 (IF = citations/100). Articles were published in Spine (Phila Pa 1976) (23%; IF = 41.3). Six subject categories were classified using the SNA. The most cited article authored by D Scott Kreiner from Ahwatukee Sports and Spine in the US state of Phoenix had 123 citations in PubMed. The network characteristics of T100PEID are displayed on the alluvial diagram. No difference was found in article citations among subject categories (F = 0.813, p = 0.543). The most frequently occurring MeSH term was surgery. MeSH terms were evident in the prediction power of the number of article citations (F = 15.21; p < 0 .001). CONCLUSION: We achieved a breakthrough by displaying the T100PEID network characteristics on the alluvial plateau. The MeSH terms can be used to classify article subject categories and predict T100PEID citations. The alluvial diagram can be applied to bibliometrics on 100 top-cited articles in future studies.

Exercise Rehabilitation and/or Astragaloside Attenuate Amyloid-beta Pathology by Reversing BDNF/TrkB Signaling Deficits and Mitochondrial Dysfunction.

We aim to investigate the mechanisms underlying the beneficial effects of exercise rehabilitation (ER) and/or astragaloside (AST) in counteracting amyloid-beta (Aß) pathology. Aß oligomers were microinjected into the bilateral ventricles to induce Aß neuropathology in rats. Neurobehavioral functions were evaluated. Cortical and hippocampal expressions of both BDNF/TrkB and cathepsin D were determined by the western blotting method. The rat primary cultured cortical neurons were incubated with BDNF and/or AST and ANA12 followed by exposure to aggregated Aß for 24 h. In vivo results showed that ER and/or AST reversed neurobehavioral disorders, downregulation of cortical and hippocampal expression of both BDNF/TrkB and cathepsin D, neural pathology, Aß accumulation, and altered microglial polarization caused by Aß. In vitro studies also confirmed that topical application of BDNF and/or AST reversed the Aß-induced cytotoxicity, apoptosis, mitochondrial distress, and synaptotoxicity and decreased expression of p-TrkB, p-Akt, p-GSK3ß, and ß-catenin in rat cortical neurons. The beneficial effects of combined ER (or BDNF) and AST therapy in vivo and in vitro were superior to ER (or BDNF) or AST alone. Furthermore, we observed that any gains from ER (or BDNF) and/or AST could be significantly eliminated by ANA-12, a potent BDNF/TrkB antagonist. These results indicate that whereas ER (or BDNF) and/or AST attenuate Aß pathology by reversing BDNF/TrkB signaling deficits and mitochondrial dysfunction, combining these two potentiates each other's therapeutic effects. In particular, AST can be an alternative therapy to replace ER.

Predicting Active NBA Players Most Likely to Be Inducted into the Basketball Hall of Famers Using Artificial Neural Networks in Microsoft Excel: Development and Usability Study.

The prediction of whether active NBA players can be inducted into the Hall of Fame (HOF) is interesting and important. However, no such research have been published in the literature, particularly using the artificial neural network (ANN) technique. The aim of this study is to build an ANN model with an app for automatic prediction and classification of HOF for NBA players. We downloaded 4728 NBA players' data of career stats and accolades from the website at basketball-reference.com. The training sample was collected from 85 HOF members and 113 retired Non-HOF players based on completed data and a longer career length (≥15 years). Featured variables were taken from the higher correlation coefficients (<0.1) with HOF and significant deviations apart from the two HOF/Non-HOF groups using logistical regression. Two models (i.e., ANN and convolutional neural network, CNN) were compared in model accuracy (e.g., sensitivity, specificity, area under the receiver operating characteristic curve, AUC). An app predicting HOF was then developed involving the model's parameters. We observed that (1) 20 feature variables in the ANN model yielded a higher AUC of 0.93 (95% CI 0.93-0.97) based on the 198-case training sample, (2) the ANN performed better than CNN on the accuracy of AUC (= 0.91, 95% CI 0.87-0.95), and (3) an ready and available app for predicting HOF was successfully developed. The 20-variable ANN model with the 53 parameters estimated by the ANN for improving the accuracy of HOF has been developed. The app can help NBA fans to predict their players likely to be inducted into the HOF and is not just limited to the active NBA players.

Mesenchymal stem cell-conditioned medium attenuates the retinal pathology in amyloid-ß-induced rat model of Alzheimer's disease: Underlying mechanisms.

Amyloid-beta (Aß) oligomer is known to contribute to the pathophysiology of age-related macular degeneration. Herein, we aimed to elucidate the in vivo and in vitro effects of Aß1-42 application on retinal morphology in rats. Our in vivo studies revealed that intracerebroventricular administration of Aß1-42 oligomer caused dysmorphological changes in both retinal ganglion cells and retinal pigment epithelium. In addition, in vitro studies revealed that ARPE-19 cells following Aß1-42 oligomer application had decreased viability along with apoptosis and decreased expression of the tight junction proteins, increased expression of both phosphor-AKT and phosphor-GSK3ß and decreased expression of both SIRT1 and ß-catenin. Application of conditioned medium (CM) obtained from mesenchymal stem cells (MSC) protected against Aß1-42 oligomer-induced retinal pathology in both rats and ARPE-19 cells. In order to explore the potential role of peptides secreted from the MSCs, we applied mass spectrometry to compare the peptidomics profiles of the MSC-CM. Gene ontology enrichment analysis and String analysis were performed to explore the differentially expressed peptides by predicting the functions of their precursor proteins. Bioinformatics analysis showed that 3-8 out of 155-163 proteins in the MSC-CM maybe associated with SIRT1/pAKT/pGSK3ß/ß-catenin, tight junction proteins, and apoptosis pathway. In particular, the secretomes information on the MSC-CM may be helpful for the prevention and treatment of retinal pathology in age-related macular degeneration.

Baicalein Decreases Hydrogen Peroxide-Induced Damage to NG108-15 Cells via Upregulation of Nrf2.

Baicalein is a flavonoid inhibitor of 12-lipoxygenase. Here, we investigated its effect on hydrogen peroxide-induced damage to NG108-15 cells. Hydrogen peroxide activated the mitochondrial apoptotic pathway, decreased Nrf2 expression, increased reactive oxygen species (ROS) levels, reduced viability, and increased cell death after 2-24 h treatment of NG108-15 cells. Co-treatment with hydrogen peroxide and baicalein completely suppressed the activation of mitochondrial apoptotic pathway by upregulating Nrf2 expression and reducing ROS stress and partially inhibited the effects on cell viability and cell death. Silencing of 12-lipoxygenase had a similar protective effect to baicalein on hydrogen peroxide-induced damage by blocking the hydrogen peroxide-induced decrease in Nrf2 expression and increase in ROS levels. Neither protective effect was altered by addition of 12-hydroxyeicosatetraenoic acid, the product of 12-lipoxygenase, suggesting that hydrogen peroxide induced damage via 12-lipoxygenase by another, as yet unknown, mechanism, rather than activating it. Co-treatment of cells with hydrogen peroxide and N-acetylcysteine or the Nrf2 inducer sulforaphane reduced hydrogen peroxide-induced damage in a similar fashion to baicalein, while the Nrf2 inhibitor retinoic acid blocked the protective effect of baicalein. Silencing Nrf2 also inhibited the protective effects of baicalein, sulforaphane, and N-acetylcysteine and resulted in high ROS levels, suggesting ROS elimination was mediated by Nrf2. Taken together our results suggest that baicalein protects cells from hydrogen peroxide-induced activation of the mitochondrial apoptotic pathway by upregulating Nrf2 and inhibiting 12-lipoxygenase to block the increase in ROS levels. Hydrogen peroxide also activates a second mitochondrial dysfunction independent death pathway which is resistant to baicalein.

Body cooling ameliorating spinal cord injury may be neurogenesis-, anti-inflammation- and angiogenesis-associated in rats.

BACKGROUND: Body cooling (BC) or mild hypothermia therapy (about 33°C) is reportedly effective for spinal cord injury (SCI). However, the mechanisms underlying the beneficial effects of BC remain unclear, so does BC ameliorating SCI via promoting neurogenesis, anti-inflammation, and angiogenesis. METHODS: The standard rat compression SCI model was tested hypothetically in two groups: one receiving BC (33°C) and the other, normothermia (37°C). Afterward, the effects of BC therapy on the hind limb locomotion, spinal cord infarction and apoptosis, angiogenesis, neurogenesis, and inflammation in these two groups of SCI were assessed. The other group of sham SCI was used as controls. RESULTS: Apoptosis (evidenced by higher numbers of terminal deoxynucleotidyl- transferase-mediated and duDP-biotin nick end-labeling-positive cells), infarct, activated inflammation (evidenced by higher levels of tumor necrosis factor-α, interleukin-1ß, and myeloperoxidase), and hind limb locomotor dysfunction were inspected in the untreated (37°C) SCI rats 4 days after SCI. When compared with those of untreated SCI rats, SCI rats receiving BC (33°C) displayed lower levels of apoptosis, infarct volume, activated inflammation, and hind limb locomotor dysfunction. In addition, that BC promoted both angiogenesis (evidenced by increased numbers of both vascular endothelial growth factors and bromodeoxyuridine-positive endothelial cells) and neurogenesis (evidenced by increased numbers of both glial cell line-derived neurotrophic growth factors and bromodeoxyuridine-neuronal-specific nuclear protein double positive cells) in the injured spinal cord was evaluated 4 days after SCI. CONCLUSION: BC (33°C) improved SCI outcomes by promoting angiogenesis, neurogenesis, and anti-inflammation in a rat SCI model.

Premarin improves outcomes of spinal cord injury in male rats through stimulating both angiogenesis and neurogenesis.

OBJECTIVE: To ascertain whether Premarin improves spinal cord injury outcomes in male rats by stimulating both angiogenesis and neurogenesis. DESIGN: Chi Mei Medical Center research laboratory. SUBJECTS: Male Sprague-Dawley rats 240-258 g. INTERVENTIONS: Anesthetized rats, after the onset of spinal cord injury, were divided into two groups and given the vehicle solution (1 mL/kg of body weight) or Premarin (1 mg/kg of body weight). Saline or Premarin solutions were administered intravenously and immediately after spinal cord injury. MEASUREMENTS AND MAIN RESULTS: Premarin (an estrogen sulfate) causes attenuation of spinal cord injury-induced spinal cord infarction and hind limb locomotor dysfunction. Spinal cord injury-induced apoptosis as well as activated inflammation was also significantly Premarin-reduced. In injured spinal cord, angiogenesis, neurogenesis, and production of an antiinflammatory cytokine were all Premarin therapy-promoted. CONCLUSIONS: Our results indicate that Premarin therapy may protect against spinal cord apoptosis after spinal cord injury through mechanisms stimulating both angiogenesis and neurogenesis in male rats.

Protection in rats with heatstroke: hyperbaric oxygen vs activated protein C therapy.

The present study was attempted to evaluate the therapeutic effects of activated protein C and/or hyperbaric oxygen in an animal model of heatstroke. Sixty-eight minutes heat stress (43 degrees C) initiated, the anesthetized rats were randomized to several groups and administered: 1) no resuscitation (vehicle solution plus normabaric air, 2) intravenous activated protein C (1mg in 1ml of normal saline per kg of body weight), 3) hyperbaric oxygen (100% oxygen at 202kpa for 17min), and 4) intravenous activated protein C plus hyperbaric oxygen. Another group of rats exposed to room temperature (26 degrees C) was used as normothermic controls. Blood sampling was 0min, 70min, and 85min after heat stress initiated. When the vehicle-treated rats underwent heat exposure, their survival time values found were to be 19-25min. Resuscitation with activated protein C or hyperbaric oxygen significantly and equally improved survival during heatstroke (134-159min). As compared with those of activated protein C or hyperbaric oxygen alone, combined activated protein C and hyperbaric oxygen significantly had higher survival time values (277-347min). All vehicle-treated heatstroke animals displayed systemic response, hypercoagulable state, and hepatic and renal dysfunction. Combined activated protein C and hyperbaric oxygen therapy reduced these heatstroke reactions better than activated protein C or hyperbaric oxygen alone. The results indicate consequently, combined activated protein C and hyperbaric oxygen therapy heightens benefit in combating heatstroke reactions.

Pituitary macroadenoma co-existent with supraclinoid internal carotid artery cerebral aneurysm: a case report and review of the literature.

With improved angiographic techniques and magnetic resonance angiography available today, an increasing number of incidental aneurysms are being detected. Occurrence of an intracranial aneurysm together with a pituitary adenoma presents tremendous risk to the patient, particularly when the aneurysm lies near the operative field.A 61-year-old woman presented with a progressive visual field defect. Neurological examination revealed bi-temporal haemianopia. Cerebral magnetic resonance imaging and angiography revealed a pituitary macroadenoma co-existent with a cerebral aneurysm near the sellar region. The patient underwent an endovascular procedure for aneurysm embolisation and then underwent surgery for removal of the pituitary adenoma via a trans-sphenoidal approach.We report our experience and emphasize the need for critical evaluation of neuroradiological examinations for precise diagnosis for avoiding a possible life-threatening situation.

Quantification of SMN1 and SMN2 genes by capillary electrophoresis for diagnosis of spinal muscular atrophy.

We present the first CE method for the separation and quantification of SMN1 and SMN2 genes. Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder deleted or mutated in SMN1 gene and retained at least one copy of SMN2 gene. However, these two genes are highly homologous, differentiation and quantification of SMN1 and SMN2 are therefore required in diagnosis to identify SMA patients and carriers. We developed a fluorescence-labeled conformation-sensitive CE method to quantitatively analyze PCR products covering the variable position in the SMN1/SMN2 genes using a copolymer solution composed of hydroxyethylcellulose and hydroxypropylcellulose. The DNA samples included 24 SMA patients, 52 parents of SMA patients (obligatory carriers), and 255 controls. Those 331 samples were blind analyzed to evaluate the method, and the results compared with those obtained using denaturing HPLC (DHPLC). Validation of accuracy was performed by comparing the results with those of DHPLC. Nine of total samples showed different results. Diagnosis of one fetus DNA among them was related to abortion or not, which was further confirmed by gel electrophoresis and DNA sequencing. Our method showed good coincidence with them, and proved the misdiagnosis of DHPLC. This simple and reliable CE method is a powerful tool for clinical genotyping of large populations to detect carriers and SMA patients.

Acute symptomatic hydrocephalus in Listeria monocytogenes meningitis.

Listeria monocytogenes meningitis appears to have increased in incidence. Although most reported cases of listeriosis involve the central nervous system, brain computed tomography is usually normal. Hydrocephalus is a common complication of tuberculous meningitis, which has a high prevalence in Taiwan. However, patients with L. monocytogenes meningitis rarely develop the complication of symptomatic hydrocephalus. We report a patient with L. monocytogenes meningitis who presented with persistent alteration of consciousness after appropriate antimicrobial therapy. Follow-up brain computed tomography revealed acute hydrocephalus. An Ommaya reservoir was implanted, and daily drainage of the cerebrospinal fluid was performed. The patient improved gradually and his mental status recovered completely 4 days later. This case should remind physicians to be aware of the possible occurrence of hydrocephalus in L. monocytogenes meningitis and that prompt cerebrospinal fluid drainage may achieve a good outcome.

Early post-operative seizures after burr-hole drainage for chronic subdural hematoma: correlation with brain CT findings.

The incidence of seizures in patients undergoing burr-hole crainiostomy with closed-system drainage for chronic subdural hematoma (CSDH) is low. The post-operative use of anticonvulsants is, thus, controversial. In this study, we tried to correlate pre-operative computed tomographic (CT) appearance of the CSDH with the need for post-operative seizure prophylaxis. From April 1998 to November 2001, 128 cases of CSDH surgically treated at our hospital were studied. All patients underwent burr-hole craniostomy with closed system drainage. All CSDHs were classified as low-density, isodense, and mixed-density lesions according to CT findings. The incidence of early post-operative seizures (within 3 weeks of surgery) among all patients was 5.4% (7/128). In the subgroups by lesion density, the incidences were 6.2% (1/16) in the low-density group, 2.4% (2/83) in the isodense group, and 13.7% (4/29) in the mixed-density group (all p < 0.05). The mean age among the seven patients (five males and two females) who had seizures was 71 years. The locations of the CSDHs among the 128 patients were the left side of the brain in 53 (41.4%) patients, right side in 45 (35.2%), and bilateral in 30 (23.4%) patients. Among the seven patients who suffered from post-operative seizures, five (71.4%) had left side CSDHs, one (14.2%) had a right side CSDH, and one (14.2%) had bilateral CSDHs. We concluded that the post-operative seizure rate appeared high in the group with mixed-density type lesions on CT, and in those with left unilateral CSDH. We suggest the use of prophylactic anticonvulsants for patients with mixed-density lesions on pre-operative CT.