BiZact-Assisted Endoscopic Resection of a Sinonasal Tumor.

The BiZact device, a bipolar electrosurgical scissor designed for tonsillectomy, minimizes thermal tissue damage and seals blood vessels <3 mm in diameter while dividing the soft tissue. This study describes the authors' experience with sinonasal tumor surgery using a BiZact and discusses its clinical utility and advantages. The authors analyzed BiZact-assisted endoscopic sinonasal tumor surgery cases between January 2021 and May 2023. Data were collected on patients' demographics, histopathology, extent of tumor involvement, surgical records, and postoperative medical records. Clinical utility was assessed using the success rate of complete tumor excision, estimated blood loss during surgery, device-related complications, and operation time. A survey of the surgeons' BiZact experience was also conducted. The diagnoses of the 20 patients in this study included squamous cell carcinoma (n = 2), malignant melanoma (n = 1), sarcoma (n = 1), natural killer cell lymphoma (n = 1), inverted papilloma (n = 12), angiofibroma (n = 2), and schwannoma (n = 1). This pilot study demonstrated a shortened operative time, with a median of 0.8 hours and <100 mL of intraoperative blood loss. In addition, no BiZact-related complications were observed. The BiZact device allows efficient sinonasal surgery because it has the unique advantage of one-step sealing and cutting. BiZact-assisted endoscopic sinonasal tumor surgery is a beneficial and safe procedure that reduces blood loss during surgery, shortens the operative time, and minimizes postoperative complications.

Platelet-rich plasma injection for empty nose syndrome: A case report.

Empty nose syndrome (ENS) is a relatively rare disease found in patients who have undergone sinonasal surgery, characterized by excessive reduction of the turbinate, causing intranasal turbulence and loss of receptors within the nasal mucosa. Patients diagnosed with the disease usually experience symptoms including dryness of the nose, nasal pain, paradoxical nasal obstruction, and crusts in the nasal cavity. ENS can be treated with conservative care such as nasal irrigation or nasal moisturizers. Accurate efficacy of surgical treatment of ENS is often difficult to predict and is accompanied by operational obstacles and complications. Platelet-rich plasma (PRP) has recently gained attention as a regenerative therapy in several medical fields. We present two cases of ENS treated by injection of PRP as a simple and less invasive method, and describe its efficacy with nasal endoscopy and subjective questionnaires.

Design, Implementation, and Evolution of the Medicaid Outcomes Distributed Research Network (MODRN).

BACKGROUND: In the US, Medicaid covers over 80 million Americans. Comparing access, quality, and costs across Medicaid programs can provide policymakers with much-needed information. As each Medicaid agency collects its member data, multiple barriers prevent sharing Medicaid data between states. To address this gap, the Medicaid Outcomes Distributed Research Network (MODRN) developed a research network of states to conduct rapid multi-state analyses without sharing individual-level data across states. OBJECTIVE: To describe goals, design, implementation, and evolution of MODRN to inform other research networks. METHODS: MODRN implemented a distributed research network using a common data model, with each state analyzing its own data; developed standardized measure specifications and statistical software code to conduct analyses; and disseminated findings to state and federal Medicaid policymakers. Based on feedback on Medicaid agency priorities, MODRN first sought to inform Medicaid policy to improve opioid use disorder treatment, particularly medication treatment. RESULTS: Since its 2017 inception, MODRN created 21 opioid use disorder quality measures in 13 states. MODRN modified its common data model over time to include additional elements. Initial barriers included harmonizing utilization data from Medicaid billing codes across states and adapting statistical methods to combine state-level results. The network demonstrated its utility and addressed barriers to conducting multi-state analyses of Medicaid administrative data. CONCLUSIONS: MODRN created a new, scalable, successful model for conducting policy research while complying with federal and state regulations to protect beneficiary health information. Platforms like MODRN may prove useful for emerging health challenges to facilitate evidence-based policymaking in Medicaid programs.

Palatopharyngeal muscle suspension suture technique for patients with obstructive sleep apnea.

PURPOSE: Palatal surgery remains a major option for patients with obstructive sleep apnea (OSA). We sought to evaluate the therapeutic outcomes of the palatopharyngeal muscle suspension suture technique (PSST) as a novel palatal surgery for patients with OSA. MATERIALS AND METHODS: Of the 816 patients who underwent polysomnography (PSG) from February 1, 2017, to June 30, 2020, 30 patients with OSA who underwent PSST were retrospectively reviewed. The medical records of the patients were also recorded. Among the 30 patients with OSA, nine who underwent preoperative and postoperative PSG were analyzed. RESULTS: Of the 30 patients with OSA, 28 (93.3 %) were male. The mean (SD, standard deviation) age was 43.3 (12.7) years, and the mean (SD) body mass index was 27.3 (3.2). As objective parameters, the mean (SD) apnea-hypopnea index was significantly decreased from 45.9 (21.20) to 29.03 (21.62) (p < 0.05) and the mean (SD) lowest oxygen saturation improved significantly from 77.6 % (7.14 %) to 84.6 (5.17 %) (p < 0.05). As a subjective parameter, the mean (SD) Epworth Sleepiness Scale score decreased significantly from 10 (4.95) to 6.9 (4.57) (p < 0.05), and the mean (SD) visual analog scale score for snoring decreased significantly from 6.3 (1.8) to 3.1 (1.9) (p < 0.001). No complications, such as upper airway obstruction, intractable postoperative bleeding, or velopharyngeal insufficiency, were observed in any of the patients postoperatively. CONCLUSIONS: A novel palatal surgery, PSST, has numerous advantages as a useful surgical option for patients with OSA. It is minimally invasive, easy, time-saving, and relatively reversible.

The role of right temporo-parietal junction in stimulus evaluation.

A predominant model of the temporo-parietal junction (TPJ) claims that this region is critical for attentional orienting/reorienting toward an unexpected, but behaviorally significant stimulus. However, recent studies have suggested that the TPJ is also involved in the process of evaluating stimulus, especially matching between external sensory inputs and internal representations. While some studies provide evidence for the involvement of the TPJ in stimulus evaluation, the nature of the evaluative process mediated by the TPJ remains unclear. To address this issue, we tested whether the TPJ activation amplitude and its peak latency is proportional to the demand of the evaluative process. We found that when the amount of sensory evidence for the matching process was abundant, the TPJ was transiently activated. Importantly, the TPJ activation showed a greater and more sustained pattern while the sensory evidence was accumulating for a longer period of time. These findings suggest that the TPJ function is associated with the evaluative process of matching sensory inputs with internal representations, as well as attentional reorienting.

Use of Medications for Treatment of Opioid Use Disorder Among US Medicaid Enrollees in 11 States, 2014-2018.

Importance: There is limited information about trends in the treatment of opioid use disorder (OUD) among Medicaid enrollees. Objective: To examine the use of medications for OUD and potential indicators of quality of care in multiple states. Design, Setting, and Participants: Exploratory serial cross-sectional study of 1 024 301 Medicaid enrollees in 11 states aged 12 through 64 years (not eligible for Medicare) with International Classification of Diseases, Ninth Revision (ICD-9 or ICD-10) codes for OUD from 2014 through 2018. Each state used generalized estimating equations to estimate associations between enrollee characteristics and outcome measure prevalence, subsequently pooled to generate global estimates using random effects meta-analyses. Exposures: Calendar year, demographic characteristics, eligibility groups, and comorbidities. Main Outcomes and Measures: Use of medications for OUD (buprenorphine, methadone, or naltrexone); potential indicators of good quality (OUD medication continuity for 180 days, behavioral health counseling, urine drug tests); potential indicators of poor quality (prescribing of opioid analgesics and benzodiazepines). Results: In 2018, 41.7% of Medicaid enrollees with OUD were aged 21 through 34 years, 51.2% were female, 76.1% were non-Hispanic White, 50.7% were eligible through Medicaid expansion, and 50.6% had other substance use disorders. Prevalence of OUD increased in these 11 states from 3.3% (290 628 of 8 737 082) in 2014 to 5.0% (527 983 of 10 585 790) in 2018. The pooled prevalence of enrollees with OUD receiving medication treatment increased from 47.8% in 2014 (range across states, 35.3% to 74.5%) to 57.1% in 2018 (range, 45.7% to 71.7%). The overall prevalence of enrollees receiving 180 days of continuous medications for OUD did not significantly change from the 2014-2015 to 2017-2018 periods (-0.01 prevalence difference, 95% CI, -0.03 to 0.02) with state variability in trend (90% prediction interval, -0.08 to 0.06). Non-Hispanic Black enrollees had lower OUD medication use than White enrollees (prevalence ratio [PR], 0.72; 95% CI, 0.64 to 0.81; P < .001; 90% prediction interval, 0.52 to 1.00). Pregnant women had higher use of OUD medications (PR, 1.18; 95% CI, 1.11-1.25; P < .001; 90% prediction interval, 1.01-1.38) and medication continuity (PR, 1.14; 95% CI, 1.10-1.17, P < .001; 90% prediction interval, 1.06-1.22) than did other eligibility groups. Conclusions and Relevance: Among US Medicaid enrollees in 11 states, the prevalence of medication use for treatment of opioid use disorder increased from 2014 through 2018. The pattern in other states requires further research.

The Role of Orthography in Lexical Processing of the Phonological Variants in Second Language.

There is evidence that orthographic knowledge can influence on-line spoken-word recognition. Interestingly, when graphic and phonetic codes are not congruent due to the application of phonological alternation processes, people report hearing sounds that are matched to graphic (underlying), not phonetic codes (Hallé et al. in J Mem Lang 43:618-639, 2000). It is, however, not known whether the same effect arises in the processing of a non-native language (L2). In the present study, advanced Mandarin learners of Korean as well as native Korean listeners performed a phoneme monitoring task using words undergoing obstruent nasalization in Korean. The results showed that orthographic information dominated the phonetic judgments of the native Korean listeners, while the Mandarin learners' judgments relied more on the phonetic input. These results suggest that even the lexical access of highly experienced L2 learners differs from that of native speakers and that advanced learners still have difficulty employing orthographic information to access the L2 lexicon.

Stoichiometry-Controlled Synthesis of Nanoparticulate Mixed-Metal Oxyhydroxide Oxygen Evolving Catalysts by Electrochemistry in Aqueous Nanodroplets.

Mixed-metal oxyhydroxides-especially those of Ni and Fe-are one of the most active classes of materials known for catalyzing the oxygen evolution reaction (OER). Here, nanoparticulate mixed metal oxyhydroxides (of Ni, Fe, and Co) were prepared on an electrode surface by electrochemical reaction of a precursor solution encapsulated in aqueous nanodroplets (AnDs), with each of the droplets containing 10 s of attoliters of fluid. Electrode reactions and synthesis can be monitored in situ by electrochemistry as single AnD stochastically lands and interacts with the working electrode. Resultant metal oxyhydroxide nanoparticles can be size and composition controlled precisely by modulating the precursor solution stored in the AnD. Nanoparticulate metal oxyhydroxides were implemented as catalysts for the OER and exhibited superior catalysis compared to their thin-film counterparts, demonstrating a hundred-thousand-fold enhancement in atom efficiency at comparable turnover rates.

Intravitreal aflibercept for submacular hemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the efficacy of intravitreal aflibercept monotherapy for submacular hemorrhage secondary to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This prospective, phase 4 clinical trial included 29 patients diagnosed with fovea-involving submacular hemorrhage secondary to neovascular AMD (7 patients) or PCV (22 patients). Patients were initially administered 3 monthly aflibercept injections, followed by 1 injection every 2 months. The primary outcome measure was changes in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) during the 56-week study period. Other key outcome measures were the proportion of patients who exhibited changes in BCVA of ≥ 15 ETDRS letters from baseline and changes in central retinal thickness (CRT). RESULTS: The mean size of hemorrhage was 6.2 ± 4.8-disc-diameter area. The mean BCVA significantly improved from 52.9 ± 17.8 ETDRS letters at week 0 (baseline) to 71.8 ± 16.1 letters at week 56 (P < 0.001). At week 56, improvement in BCVA of ≥ 15 letters was noted in 16 patients (55.2%), whereas none of the patients experienced a loss of ≥ 15 letters. The mean CRT significantly decreased from 498.9 ± 194.2 µm at week 0 to 248.3 ± 45.0 µm at week 56 (P < 0.001). During the study period, retinal break developed in one patient. CONCLUSIONS: Intravitreal aflibercept administered every 2 months after the 3 initial monthly doses was found to be an effective and safe treatment method for submacular hemorrhage secondary to neovascular AMD.

Protective effect of Lactobacillus casei HY2782 against particulate matter toxicity in human intestinal CCD-18Co cells and Caenorhabditis elegans.

OBJECTIVES: To investigate the preventive effect of Lactobacillus casei HY2782 on toxicity induced by particulate matter (PM, inhalable particles less than 10 µm in diameter) in human intestinal CCD-18Co cells and a model animal Caenorhabditis elegans. RESULTS: L. casei HY2782 treatment prevented PM-induced intestinal cell death via cellular reactive oxygen species production and membrane disruption attenuation. PM significantly decreased the total number of eggs laid and the body bending activity of C. elegans, demonstrating PM toxicity. L. casei HY2782 treatment restored the reproductive toxicity and decline in locomotion activity induced by PM in C. elegans. Overall, L. casei HY2782 attenuated PM toxicity in vitro in cultured intestinal cells and in vivo in the model nematode. CONCLUSION: Our study provides a potential clue for developing L. casei HY2782 probiotics that attenuate PM-induced cellular and physiological toxicity; however, further in-depth preclinical trials using mammalian animal models and clinical trials are required.

Stress Estimation through Deep Rock Core Diametrical Deformation and Joint Roughness Assessment Using X-ray CT Imaging.

In-situ stress estimation plays an important role on the success of an underground project. However, no method is error-free, and therefore a combination of methods is desirable. In this study, the in-situ stresses for a geothermal project have been assessed through the analysis of a deep rock core taken at 4.2 km, using the diametrical core deformation analysis (DCDA) method that relates the diametrical core expansion after stress relief with the stresses assuming elastic deformation. The extracted granodiorite core sample of 100 mm of diameter was intersected with a closed joint at a dip angle of 80.8° with respect to the vertical coring direction. The core sample was scanned using an industrial X-ray computed tomography (CT), and the diametrical deformation measurements were computed with CT slices. Results from using the DCDA method indicated an average horizontal stress difference of 13.3 MPa, similar to that reported for a nearby exploration well. Furthermore, the stress orientations were compared with the orientation of maximum roughness values. The results indicated a correlation between the orientation of the maximum horizontal stress and the orientation of the minimum joint roughness coefficient, implying a possible tracking of stress orientation using joint roughness anisotropy.

The Role of Primary Care in Improving Access to Medication-Assisted Treatment for Rural Medicaid Enrollees with Opioid Use Disorder.

BACKGROUND: The opioid epidemic has disproportionately affected rural areas, where a limited number of health care providers offer medication-assisted treatment (MAT), the mainstay of treatment for opioid use disorder (OUD). Rural residents with OUD may face multiple barriers to engagement in MAT including long travel distances. OBJECTIVE: To examine the degree to which rural residents with OUD are engaged with primary care providers (PCPs), describe the role of rural PCPs in MAT delivery, and estimate the association between enrollee distance to MAT prescribers and MAT utilization. DESIGN: Retrospective cohort study. PARTICIPANTS: Medicaid-enrolled adults diagnosed with OUD in 23 rural Pennsylvania counties. MAIN MEASURES: Primary care utilization, MAT utilization, distance to nearest possible MAT prescriber, mean distance traveled to actual MAT prescribers, and continuity of pharmacotherapy. KEY RESULTS: Of the 7930 Medicaid enrollees with a diagnosis of OUD, a minority (18.6%) received their diagnosis during a PCP visit even though enrollees with OUD had 4.1 visits to PCPs per person-year in 2015. Among enrollees with an OUD diagnosis recorded during a PCP visit, about half (751, 50.8%) received MAT, most of whom (508, 67.6%) received MAT from a PCP. Enrollees with OUD with at least one PCP visit were more likely than those without a PCP visit to receive MAT (32.7% vs. 25%; p < 0.001), and filled more buprenorphine and naltrexone prescriptions (mean = 11.1 vs. 9.3; p < 0.001). The median of the distances traveled to actual MAT prescribers was 48.8 miles, compared to a median of 4.2 miles to the nearest available MAT prescriber. Enrollees traveling a mean distance greater than 45 miles to MAT prescribers were less likely to receive continuity of pharmacotherapy (OR = 0.71, 95% CI = 0.56-0.91, p = 0.007). CONCLUSIONS: PCP utilization among rural Medicaid enrollees diagnosed with OUD is high, presenting a potential intervention point to treat OUD, particularly if the enrollee's PCP is located nearer than their MAT prescriber.

Differences in immune contextures among different molecular subtypes of gastric cancer and their prognostic impact.

BACKGROUND: Gastric cancers have been recently classified in accordance with their molecular characteristics, thus demonstrating the complex nature of cancers and an association with the immune contexture within the tumor microenvironment. This study aimed to investigate the correlation between the molecular subtype and immune contexture of gastric cancers. METHODS: The immune contexture, including the type, density, and location of tumor-infiltrating lymphocytes (TILs), of gastric cancer patients was examined and immune subtypes were classified based on it. In particular, PD-L1 expression on tumor cells and TILs and Foxp3+ TILs was assessed in accordance with molecular subtypes. RESULTS: High levels of visual TIL estimates and Foxp3+ TILs were markedly associated with increased overall survival (P = 0.001, P < 0.001, separately). Immune subtypes were associated with tumor size, gross type, depth of invasion, lymph node metastatic status, lymphovascular invasion, perineural invasion, and microsatellite instability status. EBV-positive (C1) and MSI (C2) gastric cancers, considered subtypes with better prognosis, were significantly associated with high TIL levels (P < 0.05). In contrast, epithelial-mesenchymal transition (EMT, C3) gastric cancers with poor overall survival displayed low levels of Foxp3+ TILs. Type II tumors (low level of TILs/low PD-L1 expression) displayed a significant correlation with poor overall survival (P = 0.004) and accounted for the highest proportion in the aberrant p53-expressing (C4) gastric cancers. CONCLUSION: The molecular subtype of gastric cancers is correlated with the immune subtype, including immune contexture and PD-L1 expression, within the tumor microenvironment.

Adherence trajectories of buprenorphine therapy among pregnant women in a large state Medicaid program in the United States.

PURPOSE: Little is known about the longitudinal patterns of buprenorphine adherence among pregnant women with opioid use disorder, especially when late initiation, nonadherence, or early discontinuation of buprenorphine during pregnancy may increase the risk of adverse outcomes. We aimed to identify distinct trajectories of buprenorphine use during pregnancy, and factors associated with these trajectories in Medicaid-enrolled pregnant women. METHODS: A retrospective cohort study included 2361 Pennsylvania Medicaid enrollees aged 15 to 46 having buprenorphine therapy during pregnancy and a live birth between 2008 and 2015. We used group-based trajectory models to identify buprenorphine use patterns in the 40 weeks prior to delivery and 12 weeks postdelivery. Multivariable multinomial logistic regression models were used to identify factors associated with specific trajectories. RESULTS: Six distinct trajectories were identified. Four groups initiated buprenorphine during the first trimester of the pregnancy (early initiators): 31.6% with persistently high adherence, 15.1% with moderate-to-high adherence, 10.5% with declining adherence, and 16.7% with early discontinuation. Two groups did not initiate buprenorphine until midsecond or third trimester (late initiators): 13.5% had moderate-to-high adherence and 12.6% had low-to-moderate adherence. Factors significantly associated with late initiation and discontinuation were younger age, non-white race, residents of rural counties, fewer outpatient visits, more frequent emergency department visits and hospitalizations, and lower buprenorphine daily dose. CONCLUSIONS: Six buprenorphine treatment trajectories during pregnancy were identified in this population-based Medicaid cohort, with 25% of women initiating buprenorphine late during pregnancy. Understanding trajectories of buprenorphine use and factors associated with discontinuation/nonadherence may guide integration of behavioral treatment with obstetrical/gynecological care to improve buprenorphine treatment during pregnancy.

The impact of Medicaid expansion on postpartum health care utilization among pregnant women with opioid use disorder.

Background: Opioid use disorder (OUD) during pregnancy has increased dramatically over the past decade, as have associated adverse maternal health outcomes. Although Medicaid has long been the largest payer for deliveries in the United States, states' decisions to expand Medicaid eligibility to low-income adults has the potential to increase access to care for women in the postpartum period. This study aimed to determine the impact of the 2015 Pennsylvania Medicaid expansion on postpartum insurance coverage and preventive care utilization among pregnant women with opioid use disorder (OUD). Methods: In 2017, we conducted a retrospective cohort study using 2013-2015 administrative Medicaid data provided by the Pennsylvania Department of Human Services. We identified 1562 women with opioid use disorder who had a live birth delivery in a pre-Medicaid expansion or post-expansion study period. We compared length of continuous enrollment in Medicaid following delivery, postpartum visit attendance, and contraception initiation between groups. Results: More women in the post-expansion group remained enrolled in Medicaid at 300 days postpartum, relative to the pre-expansion group (87% vs. 81%). Medicaid expansion was not associated with differences in postpartum visit attendance or contraceptive use. However, women who remained enrolled in Medicaid for at least 300 days post delivery had an increased odds of postpartum visit attendance (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.04, 2.4). Conclusion: The rate of continuous Medicaid enrollment among postpartum women with OUD was significantly higher after expansion, whereas rates of preventive care utilization were unaffected. Although improving insurance coverage for women with OUD is an important step to improve access to recommended preventive care, additional efforts are needed to ensure utilization of such care.

A Comparison of Endoscopic Reduction for Medial Blowout Fractures Using a Bioresorbable Panel and Silastic Sheet.

BACKGROUND: The aim of the study was to compare the effectiveness of endoscopic endonasal reduction using a bioresorbable panel and silastic sheet packed with Merocel for blowout fractures of the medial orbital wall. DESIGN: Retrospective study. METHODS: The study group consisted of 147 patients who underwent endoscopic endonasal reduction of a blowout fracture of the medial orbital wall between January 2005 and December 2016. Fifty-seven fractures were repaired using a splint formed by a silastic sheet and Merocel (splint group), whereas 90 fractures were repaired using a bioresorbable panel for interposition (interposition group). Postoperative complications and surgical outcomes of the 2 groups were compared. RESULTS: Preoperative diplopia in both groups (n = 30) was resolved except 1 in interposition group after the reduction. Enophthalmos was resolved in 10 cases in the splint group and in 6 cases in the interposition group. In postoperative CT scans, 20 of the 57 cases in the splint group exhibited under- or overcorrection, compared with 9 of the 90 cases in the interposition group (P < 0.05). There were no sinus infections or implant-related side effects in the interposition group except for implant extrusion in 4 cases, whereas 7 cases developed sinusitis in the splint group (P < 0.05). CONCLUSIONS: Endonasal endoscopic reduction using a bioresorbable panel may be considered as a surgical alternative for the treatment of medial orbital blowout fractures.

Varicella zoster virus-associated Chorioretinitis: a case report.

BACKGROUND: Chorioretinitis is an unusual form of varicella zoster virus (VZV)-associated uveitis, and no report has described VZV-associated chorioretinitis using serial optical coherence tomography (OCT) images obtained during the course of resolution. CASE PRESENTATION: A 61-year-old woman presented with acute, unilateral vision loss in her right eye. Her visual acuity was count fingers in the right eye and 16/20 in the left eye, and she exhibited skin vesicles on her right forehead. Slit lamp biomicroscopy, funduscopy, OCT, and intraocular fluid analysis were performed. The right eye exhibited multiple inflammatory lesions at the posterior pole, macular edema, and disc swelling on the fundus examination. OCT revealed predominant involvement of the choroid and the retinal pigment epithelium (RPE). Intraocular fluid analysis showed positivity for VZV. The patient was admitted and treated with intravenous acyclovir. Additional oral prednisolone was used to reduce the inflammatory reaction. After 2 weeks of treatment with acyclovir, the lesion resolved, with undulation of the RPE. Her final visual acuity was 20/20. CONCLUSIONS: VZV-associated posterior uveitis may present as multifocal chorioretinitis. Intraocular fluid analysis is important to detect an infectious origin.

High-throughput and direct measurement of androgen levels using turbulent flow chromatography liquid chromatography-triple quadrupole mass spectrometry (TFC-LC-TQMS) to discover chemicals that modulate dihydrotestosterone production in human prostate cancer cells.

OBJECTIVES: To develop a high-throughput screening system to measure the conversion of testosterone to dihydrotestosterone (DHT) in cultured human prostate cancer cells using turbulent flow chromatography liquid chromatography-triple quadrupole mass spectrometry (TFC-LC-TQMS). RESULTS: After optimizing the cell reaction system, this method demonstrated a screening capability of 103 samples, including 78 single compounds and 25 extracts, in less than 12 h without manual sample preparation. Consequently, fucoxanthin, phenethyl caffeate, and Curcuma longa L. extract were validated as bioactive chemicals that inhibited DHT production in cultured DU145 cells. In addition, naringenin boosted DHT production in DU145 cells. CONCLUSION: The method can facilitate the discovery of bioactive chemicals that modulate the DHT production, and four phytochemicals are potential candidates of nutraceuticals to adjust DHT levels in male hormonal dysfunction.

Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy.

Positive feedback loop between Sox2 and Sox6 inhibits neuronal differentiation in the developing central nervous system.

How a pool of undifferentiated neural progenitor cells is maintained in the developing nervous system is an issue that remains unresolved. One of the key transcription factors for self-renewal of these cells is Sox2, the forced expression of which has been shown to inhibit neuronal differentiation in vivo. To dissect the molecular mechanisms of Sox2 activity, a ChIP-on-chip assay has been carried out for Sox2, and multiple candidate direct target genes have been isolated. In this report, we provide evidence indicating that Sox6, which like Sox2 belongs to the SRY-related HMG box transcription factor family, is a bona-fide direct regulatory target of Sox2. In vivo, Sox6 expression is seen with a temporal lag in Sox2-positive neural precursor cells in the ventricular zone, and Sox2 promotes expression of Sox6 as a transcriptional activator. Interestingly, gain- and loss-of-function assays indicate that Sox6 in turn is required for the maintenance of Sox2 expression, suggesting that a positive feedback loop, which functions to inhibit premature neuronal differentiation, exists between the two transcription factors.