Detecting abnormal seismic activity areas of Anatolian plate and deformation directions using Python Geospatial libraries.

Various inaccurate traditional models have resulted in major ambiguities and gaps in the interpretation of Anatolian plate deformation directions. To address this issue, a GIS-based spatial statistical analysis method was used for the first time to detect the directional distribution of deformation along the Anatolian Plate in Turkey. Two strategies were used in this study: firstly, identifying the abnormally active seismic areas by detecting significant hotspot and cold spot clusters and confirming this detection using optimized hotspot analysis for earthquake events that occurred from 1900 to the end of 2019. Secondly, detecting the directional distribution of deformation using a Standard Deviational Ellipse (SDE) by calculating the standard deviation of the x and y coordinates from the mean center for each set of earthquake events in the Anaconda Python Platform and ArcGIS 10.8 software. Our improved geostatistical analysis results confirmed the existence of abnormal seismic hazard zones within the study area and three deformation directions: the east-west trend, the southeast-northwest trend, and the south-north trend.

Association of Kaiso and partner proteins in oral squamous cell carcinoma.

Objectives: 1. Identification of protein expression and subcellular localization of E-cadherin (E-cad), p120 catenin (P120ctn), and Kaiso in oral cancer (OC). 2. To study the protein expression of cyclin D1 and c-Myc (Kaiso targets) and determine their relationship with the expression and localization of Kaiso. Methods: Histological grading was performed in accordance with Broder's criteria. Expression and localization data for E-cad, p120ctn, Kaiso, cyclin D1, and c-Myc were acquired using immunohistochemistry. Data were analyzed using SPSS version 21. The chi-square test was used to measure the statistical significance of associations, with p < 0.05 as statistically significant. Results: Of 47 OC cases, 36% showed low E-cad expression and 34% showed low p120ctn. Low Kaiso expression was recognized in 78% of tumor specimens. Aberrant cytoplasmic localization of p120ctn was seen in 80.8% cases. Cytoplasmic Kaiso localization was appreciated in 87% of tumor tissues, whereas 29.7% lacked any nuclear Kaiso. Kaiso expression was significantly associated with the expression of cyclin D1 but not with c-Myc. Conclusion: The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools.

Jugular Vein Phlebectasia (IJP): Surgically Manageable But Ignored Entity.

IJP is a rare, congenital, benign, isolated, sporadically occurring fusiform or saccular dilatation of Internal Jugular Vein (IJV) of unknown aetiology usually presenting as a unilateral neck mass. It is mostly seen in children and young adults. We report a 4 year old male presented to Expert ENT & Diagnostic Centre presenting with history of painless right neck swelling in the right carotid triangle first observed on crying with no history of trauma, facial congestion, chronic cough, difficulty in swallowing or breathing, non febrile, venous humps, heaviness or cessation of normal voice. Diagnosis of right IJP was made. Exploration and wrapping the dilated segment in polytetrafluoroethylene tube graft was done. Because of its rarity, this entity is frequently ignored or misdiagnosed. This case report intends to stress the importance of keeping IJP as differential diagnosis while dealing with such a swelling to avoid invasive investigations and inappropriate treatment.

Spindle Cell Carcinoma of Nasal Septum: A Rare Case Report with Review of Literature.

Spindle Cell Carcinoma (SpCC) is a rare neoplasm that occurs mainly in the upper aero-digestive tract, mostly in larynx. We present a case of SpCC arising from nasal septum. Surgical excision was done with postoperative chemo-radiotherapy and the patient is in follow-up and is asymptomatic from the last 24 months.

Relation of salivary MMP-8 with oral submucous fibrosis and oral squamous cell carcinoma: a cross sectional analytical study.

OBJECTIVES: We aim to evaluate salivary matrix metalloproteinases (MMP-8) levels in oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) for the purpose of diagnosis at the early stage via non-invasive method. SETTING: The study was multicentre, carried out at a tertiary care hospital in Karachi, Pakistan. PARTICIPANTS: A total 60 participants of any age, sex and ethnicity were randomly selected for the purpose of this study. Patients demonstrating clinical evidence of OSF and biopsy-proven cases of OSCC were included. Patients with indeterminate histopathological report, immunodeficiency, autoimmune disorder, chronic medical and periodontal disease (periodontal depth greater than 5 mm) and individuals with interincisal mouth opening greater than 35 mm were excluded from the study. INTERVENTIONS: Salivary MMP-8 levels were observed in OSF, healthy and OSCC groups by using ELISA. One way analysis of variance was applied to establish whether MMP-8 levels of disease-free individuals and patients suffering from OSF and OSCC differed from each other. RESULTS: Statistically significant difference in salivary MMP-8 expression in diseased and control group was observed. MMP-8 levels in OSCC (0.64 ng/mL) and OSF (0.66 ng/mL) were underexpressed as compared with healthy participants (7.9 ng/mL). CONCLUSION: MMP-8 levels were underexpressed in OSCC and OSF patients as compared with controls, which imply that MMP-8 level has an inverse relation with OSCC and OSF.

Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC.

BACKGROUND: A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC). METHODS: Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis. RESULTS: Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa. CONCLUSION: Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.

A comparative evaluation of cardiac and neurological safety status of two commonly used oral hypoglycaemic agents in T2-DM Swiss albino mice model.

Background: Diabetes mellitus (DM), along with its associated complications, including diabetic neuropathy and hyperlipidemia, has become a global concern in the last few decades. The main objective of our study is to evaluate the comparative neuro-safety status, serum plasma glucose, and lipid-lowering potential of two widely recognized antidiabetic drugs named metformin and glimepiride. Methods: The neurological evaluation was done by open field test, hole board test, forced swimming test, dark and lighthouse test, and elevated plus maze test by employing diazepam as standard. Serum blood glucose level of streptozotocin (STZ)-induced diabetic mice was determined by glucose oxidizing method using a glucometer. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C) levels were estimated by using the reference method where atorvastatin was used as standard. Results: In neurological evaluation, both drugs produce almost the same anxiolytic activity in the open field test, hole board test, light and dark house test, and elevated plus maze test. However, in the forced swimming test, glimepiride produced more antidepressant activity than metformin. Glimepiride was found to remarkably reduce serum glucose and VLDL-C levels more than metformin, whereas, for other parameters, metformin takes over glimepiride sometimes took over the standard atorvastatin. Conclusions: The results of our study indicate that both oral hypoglycaemic drugs alter the lipid index while producing some anxiolytic effects on the central nervous system. Thus, recommended to be carefully administered to patients with low BMI and might be beneficial to patients suffering from peripheral nerve function and anxiety.

Analytical Study Of Salivary Mmp-12 Expression In Oral Submucous Fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is majorly a pathology pertaining to Asian population, reported most in Pakistan, India, Nepal, Bangladesh, and Taiwan. Equilibrium existing between Matrix metalloproteinases (MMP) & tissue inhibitors of matrix metalloproteinases is imperative for the normal integrity of connective tissues. However, this mechanism is disturbed in the presence of OSF, resulting in an increase in the extracellular matrix. METHODS: It is an analytical study including two groups with a total of 60 participants. The first group consists of 30 healthy participants and the other group consists of 30 patients presenting with oral submucous fibrosis. Collected samples of saliva were stored at -80 °C after centrifugation. For ELISA investigation, the procedure was performed as per manufacturer's instruction. Salivary matrix metalloproteinases- 12 concentration was estimated with the help of a standard curve. Data was analysed using SPSS 23. Mann Whitney test was applied to determine the difference existing in Matrix metalloproteinases- 12 levels between healthy and oral submucous fibrosis participants. p-value <0.05 was contemplated as significant. RESULTS: Statistical investigation indicated significant difference in Matrix metalloproteinases- 12 levels between Oral submucous fibrosis and healthy group (p<0.05). Saliva samples obtained from oral submucous fibrosis patients demonstrated raised concentrations of Matrix metalloproteinases- 12 as compared to healthy participants. CONCLUSIONS: Our study demonstrates significant upsurge in Matrix metalloproteinases- 12 expression in samples of saliva obtained from oral submucous fibrosis patients as compared to healthy individuals. Therefore, salivary Matrix metalloproteinases- 12 could serve as a useful diagnostic marker for OSF.

Association of salivary Cathepsin B in different histological grades among patients presenting with oral squamous cell carcinoma.

BACKGROUND: Oral cancer is considered a major public health problem due to its high mortality and morbidity rates. Survival rate of OSCC can be significantly improved by using non-invasive tool such as salivary biomarkers for detection of OSCC which is considered a promising approach. Cathepsin B is a lysosomal cysteine protease, present in abundant quantities in lysosome of cells, tissues and different biological fluids. Increased expression of Cathepsin B was observed in many malignancies including oral cancer. The present study was designed to determine the salivary levels of Cathepsin B in different histological grades of OSCC. METHOD: In this study, total no. of 80 research participants were enrolled which were divided into four groups. Each group comprised 20 participants, group 1 comprised 20 patients of OSCC (well differentiated), group 2 comprised 20 patients of OSCC (moderately differentiated), group 3 comprised 20 patients of OSCC (poorly differentiated) and group 4 comprised 20 healthy controls. Saliva sample was collected from all the four study groups and salivary Cathepsin B levels were analyzed by ELISA sandwich technique in duplicate. RESULTS: Salivary levels of Cathepsin B were significantly increased with p value (< 0.001) in patients of OSCC as compared to control group according to both histological grades and tumor size. Highest mean Cathepsin B levels in well differentiated OSCC followed by poorly differentiated OSCC and moderately differentiated OSCC were observed. CONCLUSION: Results of the present study suggests that Cathepsin B has a great value as a salivary biomarker for diagnosis and monitoring of OSCC in different histological grades. This will further lead to increase survival rate and improve the prognosis of OSCC.

Unusual Presentation of a Giant Schwannoma of Left Lateral Border of Tongue: A Rare Case Report.

Schwannoma is a benign, encapsulated, slow-growing and generally solitary tumour that arise from Schwann cells of the peripheral nerve sheath. Approximately 1-12% occur intraorally with the tongue being one of the site. We report a case of schwannoma of the tongue in a 33-year-old male patient. It presented as a slow growing mass of the tongue. We did the surgical excision of the tumour with the help of CO2 laser, and the patient is in follow-up and is asymptomatic from the last 7 months.

Prevalence of Gastroesophageal Reflux Disease and Associated Risk Factors in the Eastern Region, Saudi Arabia.

Background Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder characterized by heartburn and acid regurgitation. A higher incidence is found in Arab countries. Untreated GERD has a negative impact on individuals that interfere with daily activities and impaired quality of life. This study aims to estimate the prevalence of GERD and associated risk factors in the Eastern region, Saudi Arabia. Material & Methodology A descriptive cross-sectional study was carried out among 1517 healthy participants from the Eastern province of Saudi Arabia from May to August 2021. The sample was randomly collected through a structured self-administered questionnaire. The questionnaire was composed of questions related to sociodemographic and lifestyle characteristics as risk factors for GERD. The existence of GERD was assessed by using GERD Questionnaire (GerdQ) for diagnosing GERD, when the score is 8 or more. Results A total of 1517 participants were included in the study: 58.8% male, 41.2% female; 9% of whom were pregnant. The age of participants ranged from 18 to 58 with a mean age of 27.5 ± 11.4 years old. The existence of GERD was 20.6% among the total participants, in which their GerdQ scores were 3-7 (68.9%), 8-10 (22.1%), and 8-11 (8.5%). The higher risk groups of having GERD were pregnant women, smoker, being male, regular usage of analgesia, soft drinks, and having a family history of GERD. Conclusion This study showed the prevalence of GERD among the general population of the Eastern region, Saudi Arabia was 20.6%. Several sociodemographic and lifestyle characteristics were associated with the disease. Further studies are needed to explore the role of psychological factors in developing GERD.

The retromandibular transparotid approach vs. retromandibular retroparotid approach for the mandibular condyle: our clinical experience

Aim: The mandible is regarded as a frequently fractured bone in patients who present with maxillofacial trauma accounting for almost 15.5% to 59% of all facial fractures. Managing condylar trauma has remained to be a point of contention amongst experts, regardless of the advances in surgical modalities and methodologies, and the treatment plan is often determined by the preference and the experience of the surgeon. There exist various approaches in the literature, each with its own specific benefits and drawbacks. With this study, we aimed to evaluate the prevalence of post-operative complications in patients who experienced ORIF by means of the retromandibular approach, by comparing the outcomes of one group having undergone transparotid surgery, with another that underwent retroparotid surgery. Methods: An experimental trial was undertaken. Convenience sampling was done from among the cases of condylar neck and base fracture visiting the department of OMFS, Dow University of Health Sciences from January 2017 to December 2019. An overall 26 patients were divided into 2 groups of 13 members each; one was managed using Open Reduction Internal Fixation (ORIF) by means of a retromandibular transparotid approach while the other group was treated with ORIF by means of a retromandibular retroparotid approach. A 6 month follow-up was done to assess range of active motion, occlusion, and complications such as deviation/deflection, neural injury, infections, sialocele, salivary fistulae and Frey's syndrome in both groups. Results: There was no statistically significant difference between the two groups in terms of inter-incisal opening, right and left lateral movements, or protrusion. One patient in the retroparotid group had deviation on mouth opening (7.69%), while one in the transparotid group reported with infection (7.69%), and 2 developed post operative seromas (15.38%). None had persisting facial nerve palsy at 6 months. Conclusion: We find no significant disparity between the 2 approaches at a follow-up of 6 months; therefore, the primary determining factor for selection of either technique is surgeon preference and appropriate case selection

Novel Presentation of Terminal Ileitis Associated with Secukinumab Therapy.

Inflammatory bowel disease (IBD) and psoriasis are chronic inflammatory immune-mediated diseases. The interleukin-23- (IL23-) T helper (Th)17 pathway has been implicated in their pathogenesis, with multiple biologic therapies targeting this pathway. IL-17, the main proinflammatory cytokine produced by (TH)17, has been targeted by antibodies and IL-17 receptor blockers with favorable outcomes in treating psoriasis and psoriatic arthritis. However, their role in IBD is unpredictable as studies reported worsening of IBD with agents targeting IL-17 and rare case reports with new-onset IBD. We present a case of Crohn's-like severe terminal ileitis and worsening diverticulitis complicated by intestinal perforation requiring total parenteral nutrition shortly after being started on secukinumab.

A study on the severity and prevention measures of COVID-19 among dental professionals in clinical practice management.

BACKGROUND: Medical professionals, especially dental professionals, have been adversely affected by the pandemic of COVID-19 due to an increased chance of exposure to patients because of close contact during treatments. OBJECTIVES: This study aimed to evaluate knowledge about the disease and assess ways of precautions to be taken during the pandemic. METHODS: A questionnaire was developed and registered at Google Forms. The study population included dental practitioners, working in hospitals and clinics. A total of 495 dental practitioners from 14 different countries across the world responded. Most dentists were aware of the required modifications in the management of patients. The points allotted for each correct/best answer by participants for a group of questions regarding each component (Knowledge, Perceptions, and Practices) were added/summed to generate an overall score for each of the three components. RESULTS: Both univariate and multivariate analysis employed for the evaluation of results. Moreover, the total practice score was significantly associated with gender and sector of practice. Multivariable analysis model using multiple linear regressions was formulated by including those variables which were significant at the univariate stage. Hence, the practice sector was the only variable found to be significantly associated with the total knowledge score (p-value < 0.05). CONCLUSION: This study, based on our experience and relevant guidelines and research, introduces essential knowledge about COVID-19 and infection in dental settings.

Androgen Receptor, Although Not a Specific Marker For, Is a Novel Target to Suppress Glioma Stem Cells as a Therapeutic Strategy for Glioblastoma.

Targeting androgen receptor (AR) has been shown to be promising in treating glioblastoma (GBM) in cell culture and flank implant models but the mechanisms remain unclear. AR antagonists including enzalutamide are available for treating prostate cancer patients in clinic and can pass the blood-brain barrier, thus are potentially good candidates for GBM treatment but have not been tested in GBM orthotopically. Our current studies confirmed that in patients, a majority of GBM tumors overexpress AR in both genders. Enzalutamide inhibited the proliferation of GBM cells both in vitro and in vivo. Although confocal microscopy demonstrated that AR is expressed but not specifically in glioma cancer stem cells (CSCs) (CD133+), enzalutamide treatment significantly decreased CSC population in cultured monolayer cells and spheroids, suppressed tumor sphere-forming capacity of GBM cells, and downregulated CSC gene expression at mRNA and protein levels in a dose- and time-dependent manner. We have, for the first time, demonstrated that enzalutamide treatment decreased the density of CSCs in vivo and improved survival in an orthotopic GBM mouse model. We conclude that AR antagonists potently target glioma CSCs in addition to suppressing the overall proliferation of GBM cells as a mechanism supporting their repurposing for clinical applications treating GBM.

Structural correlates of the audiological and emotional components of chronic tinnitus.

The objective is to investigate white matter tracts, more specifically the arcuate fasciculus and acoustic radiation, in tinnitus and assess their relationship with distress, loudness and hearing loss. DTI images were acquired for 58 tinnitus patients and 65 control subjects. Deterministic tractography was first performed to visualize the arcuate fasciculus and acoustic radiation tracts bilaterally and to calculate tract density, fractional anisotropy, radial diffusivity, and axial diffusivity for tinnitus and control subjects. Tinnitus patients had a significantly reduced tract density compared to controls in both tracts of interest. They also exhibited increased axial diffusivity in the left acoustic radiation, as well as increased radial diffusivity in the left arcuate fasciculus, and both the left and right acoustic radiation. Furthermore, they exhibited decreased fractional anisotropy in the left arcuate fasciculus, as well as the left and right acoustic radiation tracts. Partial correlation analysis showed: (1) a negative correlation between arcuate fasciculus tract density and tinnitus distress, (2) a negative correlation between acoustic radiation tract density and hearing loss, (3) a negative correlation between acoustic radiation tract density and loudness, (4) a positive correlation between left arcuate fasciculus and tinnitus distress for radial diffusivity, (5) a negative correlation between left arcuate fasciculus and tinnitus distress for fractional anisotropy, (6) a positive correlation between left and right acoustic radiation and hearing loss for radial diffusivity, (7) No correlation between any of the white matter characteristics and tinnitus loudness. Structural alterations in the acoustic radiation and arcuate fasciculus correlate with hearing loss and distress in tinnitus but not tinnitus loudness showing that loudness is a more functional correlate of the disorder which does not manifest structurally.

Estimation of salivary matrix metalloproteinases- 12 (MMP- 12) levels among patients presenting with oral submucous fibrosis and oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma is a global threat and accounts for approximately 90% of malignant oral lesions. The emergence of oral carcinoma is linked to precancerous lesions, which act as precursors of the disease. Matrix metalloproteinases appear to play a significant role in the pathogenesis of both precancerous conditions and oral malignancies due to their participation in remodeling of the extracellular matrix. METHODOLOGY: This is an analytical study conducted at Dow University of Health Sciences, Pakistan. Unstimulated saliva samples were collected from healthy, oral submucous fibrosis and oral squamous cell carcinoma patients. The level of MMP-12 was estimated using enzyme-linked immunosorbent assay. One-way Analysis of variance was run to determine if MMP-12 levels differ between the three groups, which was preceded by post hoc Tuckey test. MMP-12 cut off values were determined using Receiver operating characteristic curve. RESULTS: A significant difference in salivary MMP-12 expression was observed in OSF and OSCC (p < 0.001). The expression of salivary MMP-12 was higher in OSF and OSCC patients as compared to the healthy group (p < 0.001). The mean MMP-12 expression in OSCC appeared higher than in OSF cases (p < 0.05). MMP-12 value of [Formula: see text] 4.05 ng/ml and [Formula: see text] 4.20 ng/ml is predictive of OSF and OSCC respectively, with 100% sensitivity and specificity (p < 0.001). CONCLUSION: Increased expression of MMP-12 appears as the healthy patient advances to OSF and OSCC. The study results also demonstrate higher MMP-12 expression in OSCC patients as compared to OSF. Therefore, the estimation of salivary MMP-12 serves as a valuable non-invasive early diagnostic tool in diagnosing oral submucous fibrosis and oral squamous cell carcinoma.

The effect of occipital nerve field stimulation on the descending pain pathway in patients with fibromyalgia: a water PET and EEG imaging study.

BACKGROUND: Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory, and mood problems. Recently, occipital nerve field stimulation (ONS) has been proposed as an effective potential treatment for fibromyalgia-related pain. The aim of this study is to unravel the neural mechanism behind occipital nerve stimulation's ability to suppress pain in fibromyalgia patients. MATERIALS AND METHODS: Seven patients implanted with subcutaneous electrodes in the C2 dermatoma were enrolled for a Positron Emission Tomography (PET) H215O activation study. These seven patients were selected from a cohort of 40 patients who were part of a double blind, placebo-controlled study followed by an open label follow up at six months. The H215O PET scans were taken during both the "ON" (active stimulation) and "OFF" (stimulating device turned off) conditions. Electroencephalogram (EEG) data were also recorded for the implanted fibromyalgia patients during both the "ON" and "OFF" conditions. RESULTS: Relative to the "OFF" condition, ONS stimulation resulted in activation in the dorsal lateral prefrontal cortex, comprising the medial pain pathway, the ventral medial prefrontal cortex, and the bilateral anterior cingulate cortex as well as parahippocampal area, the latter two of which comprise the descending pain pathway. Relative deactivation was observed in the left somatosensory cortex, constituting the lateral pain pathway as well as other sensory areas such as the visual and auditory cortex. The EEG results also showed increased activity in the descending pain pathway. The pregenual anterior cingulate cortex extending into the ventral medial prefrontal cortex displayed this increase in the theta, alpha1, alpha2, beta1, and beta2 frequency bands. CONCLUSION: PET shows that ONS exerts its effect via activation of the descending pain inhibitory pathway and the lateral pain pathway in fibromyalgia, while EEG shows activation of those cortical areas that could be responsible for descending inhibition system recruitment. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov , number NCT00917176 (June 10, 2009).

Establishment of a Human iPSC- and Nanofiber-Based Microphysiological Blood-Brain Barrier System.

The blood-brain barrier (BBB) is an active and complex diffusion barrier that separates the circulating blood from the brain and extracellular fluid, regulates nutrient transportation, and provides protection against various toxic compounds and pathogens. Creating an in vitro microphysiological BBB system, particularly with relevant human cell types, will significantly facilitate the research of neuropharmaceutical drug delivery, screening, and transport, as well as improve our understanding of pathologies that are due to BBB damage. Currently, most of the in vitro BBB models are generated by culturing rodent astrocytes and endothelial cells, using commercially available transwell membranes. Those membranes are made of plastic biopolymers that are nonbiodegradable, porous, and stiff. In addition, distinct from rodent astrocytes, human astrocytes possess unique cell complexity and physiology, which are among the few characteristics that differentiate human brains from rodent brains. In this study, we established a novel human BBB microphysiologocal system, consisting of a three-dimensionally printed holder with a electrospun poly(lactic- co-glycolic) acid (PLGA) nanofibrous mesh, a bilayer coculture of human astrocytes, and endothelial cells, derived from human induced pluripotent stem cells (hiPSCs), on the electrospun PLGA mesh. This human BBB model achieved significant barrier integrity with tight junction protein expression, an effective permeability to sodium fluorescein, and higher transendothelial electrical resistance (TEER) comparing to electrospun mesh-based counterparts. Moreover, the coculture of hiPSC-derived astrocytes and endothielial cells promoted the tight junction protein expression and the TEER value. We further verified the barrier functions of our BBB model with antibrain tumor drugs (paclitaxel and bortezomib) and a neurotoxic peptide (amyloid ß 1-42). The human microphysiological system generated in this study will potentially provide a new, powerful tool for research on human BBB physiology and pathology.

Improvement of Reliability of Diffusion Tensor Metrics in Thigh Skeletal Muscles.

OBJECTIVE: Quantitative diffusion tensor imaging (DTI) of skeletal muscles is challenging due to the bias in DTI metrics, such as fractional anisotropy (FA) and mean diffusivity (MD), related to insufficient signal-to-noise ratio (SNR). This study compares the bias of DTI metrics in skeletal muscles via pixel-based and region-of-interest (ROI)-based analysis. METHODS: DTI of the thigh muscles was conducted on a 3.0-T system in N = 11 volunteers using a fat-suppressed single-shot spin-echo echo planar imaging (SS SE-EPI) sequence with eight repetitions (number of signal averages (NSA) = 4 or 8 for each repeat). The SNR was calculated for different NSAs and estimated for the composite images combining all data (effective NSA = 48) as standard reference. The bias of MD and FA derived by pixel-based and ROI-based quantification were compared at different NSAs. An "intra-ROI diffusion direction dispersion angle (IRDDDA)" was calculated to assess the uniformity of diffusion within the ROI. RESULTS: Using our standard reference image with NSA = 48, the ROI-based and pixel-based measurements agreed for FA and MD. Larger disagreements were observed for the pixel-based quantification at NSA = 4. MD was less sensitive than FA to the noise level. The IRDDDA decreased with higher NSA. At NSA = 4, ROI-based FA showed a lower average bias (0.9% vs. 37.4%) and narrower 95% limits of agreement compared to the pixel-based method. CONCLUSION: The ROI-based estimation of FA is less prone to bias than the pixel-based estimations when SNR is low. The IRDDDA can be applied as a quantitative quality measure to assess reliability of ROI-based DTI metrics.