Biochemical and biological characterization of the venoms of Naja kaouthia and Naja mandalayensis from Myanmar and neutralization effects of BPI cobra antivenom.

Snakebite is a neglected public health issue, with many scientific and medical issues to be solved. Cobras are among the most common venomous snakes in Myanmar and are responsible for a considerable number of severe snakebite envenoming. There are three species of cobra (Naja kaouthia, Naja mandalayensis and Ophiophagus hannah) in Myanmar. The study aims to characterize the N. kaouthia and N. mandalayensis venoms and to investigate the efficacy of anti-cobra antivenom (BPI) against the two venoms. Protein components and fibrinogenolytic activity were determined by SDS-PAGE. Enzymatic activities for PLA2, protease and acetylcholinesterase were determined by spectrophotometric method. Anticoagulant activity was determined by recalcification time of citrated human plasma. Myotoxicity, necrotizing activity, median lethal dose (LD50) and median effective dose (ED50) were determined by WHO recommended methods. The SDS-PAGE displayed the proteins and enzymes containing in two venoms were different. N. kaouthia venom exhibited more in PLA2, acetylcholinesterase, anticoagulant, fibrinogenolytic and necrotizing activities than N. mandalayensis venom. N. mandalayensis venom had more protease activity and myotoxicity than N. kaouthia venom. The median lethal dose (LD50) of N. kaouthia and N. mandalayensis venom was 4.33 µg/mouse and 5.04 µg/mouse respectively. Both venoms induced fibrinogen Aα chain degradation in 30 min (N. kaouthia) and in 6 h (N. mandalayensis). The same median effective dose (ED50) (19.56 µg/mouse) showed that anti-NK antivenom can neutralize against lethal effect of N. mandalayensis venom. It can also neutralize the protease activity, anticoagulant activity and fibrinogenolytic activity of both venoms. Immunodiffusion and immunoblotting studies showed that the antivenom recognized its homologous venom (N. kaouthia) and cross-reacted against the heterologous venom (N. mandalayensis). The anti-NK antivenom is suitable to use for N. mandalayensis bite if monospecific antivenom is not available.

Anopheles diversity, biting behaviour and transmission potential in forest and farm environments of Gia Lai province, Vietnam.

BACKGROUND: Despite recent reductions in Vietnam, malaria transmission persists in some areas in forests and farmlands where a high density of Anopheles mosquitoes relative to other environments occurs. To inform effective malaria control measures, it is important to understand vector bionomics and the malaria transmission role of Anopheles spp. in the highland regions of Vietnam. This study was conducted to quantify the abundance, composition and biting behaviour of the Anopheles mosquito population, and the proportion of Plasmodium spp. infected mosquitoes collected from forest and agricultural farm sites in Gia Lai province, Vietnam. METHODS: Forest and agricultural farm sites in Gia Lai province were selected for mosquito collections (total eight sites). Mosquito collection was performed by Human-baited Double Net Trap (HDNT), animal-baited traps (ABT) using cattle, and CDC light traps. Captured mosquitoes were identified morphologically, and salivary glands of Anopheles mosquitoes were examined for sporozoites using microscopy. Plasmodium infection was determined by Polymerase Chain Reaction (PCR), and identification of blood meal type was determined by PCR and diffuse serum agglutination assay. RESULTS: A total of 1815 Anopheles mosquitoes belonging to 19 species were collected by ABT (n = 1169), HDNT (n = 471) and CDC light trap (n = 175). Anopheles abundance and diversity varied by district and environment. Capture by HDNT of Anopheles of vectorial concern was observed between early evening and early morning. Plasmodium vivax infection was determined by PCR in two Anopheles dirus specimens captured by HDNT in forest sites. Blood from a range of hosts could, including human blood, could be detected in species considered primary and secondary vectors An. dirus, and Anopheles aconitus, and Anopheles maculatus, respectively. CONCLUSIONS: A low number of Anopheles spp. considered primary vectors of concern and very low numbers of Plasmodium spp. infected Anopheles mosquitoes were captured at the end of the rainy season in the Central Highlands of Vietnam. However, capture species of vectorial concern by HDNT throughout the early to late evening demonstrates that use of additional personal protective measures could supplement current preventative measures, such as bed nets to prevent exposure to vectors of concern in this region.

Importance of Age and Noncontrast-Enhancing Tumor as Biomarkers for Isocitrate Dehydrogenase-Mutant Glioblastoma: A Multicenter Study.

PURPOSE: This study aimed to investigate the most useful clinical and magnetic resonance imaging (MRI) parameters for differentiating isocitrate dehydrogenase (IDH)-mutant and -wildtype glioblastomas in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. METHODS: This multicenter study included 327 patients with IDH-mutant or IDH-wildtype glioblastoma in the 2016 World Health Organization classification who preoperatively underwent MRI. Isocitrate dehydrogenase mutation status was determined by immunohistochemistry, high-resolution melting analysis, and/or IDH1/2 sequencing. Three radiologists independently reviewed the tumor location, tumor contrast enhancement, noncontrast-enhancing tumor (nCET), and peritumoral edema. Two radiologists independently measured the maximum tumor size and mean and minimum apparent diffusion coefficients of the tumor. Univariate and multivariate logistic regression analyses with an odds ratio (OR) were performed. RESULTS: The tumors were IDH-wildtype glioblastoma in 306 cases and IDH-mutant glioblastoma in 21. Interobserver agreement for both qualitative and quantitative evaluations was moderate to excellent. The univariate analyses revealed a significant difference in age, seizure, tumor contrast enhancement, and nCET ( P < 0.05). The multivariate analysis revealed significant difference in age for all 3 readers (reader 1, odds ratio [OR] = 0.960, P = 0.012; reader 2, OR = 0.966, P = 0.048; reader 3, OR = 0.964, P = 0.026) and nCET for 2 readers (reader 1, OR = 3.082, P = 0.080; reader 2, OR = 4.500, P = 0.003; reader 3, OR = 3.078, P = 0.022). CONCLUSIONS: Age and nCET are the most useful parameters among the clinical and MRI parameters for differentiating IDH-mutant and IDH-wildtype glioblastomas.

In vivo evaluation of compliance mismatch on intimal hyperplasia formation in small diameter vascular grafts.

Small diameter synthetic vascular grafts have high failure rate due to the thrombosis and intimal hyperplasia formation. Compliance mismatch between the synthetic graft and native artery has been speculated to be one of the main causes of intimal hyperplasia. However, changing the compliance of synthetic materials without altering material chemistry remains a challenge. Here, we used poly(vinyl alcohol) (PVA) hydrogel as a graft material due to its biocompatibility and tunable mechanical properties to investigate the role of graft compliance in the development of intimal hyperplasia and in vivo patency. Two groups of PVA small diameter grafts with low compliance and high compliance were fabricated by dip casting method and implanted in a rabbit carotid artery end-to-side anastomosis model for 4 weeks. We demonstrated that the grafts with compliance that more closely matched with rabbit carotid artery had lower anastomotic intimal hyperplasia formation and higher graft patency compared to low compliance grafts. Overall, this study suggested that reducing the compliance mismatch between the native artery and vascular grafts is beneficial for reducing intimal hyperplasia formation.

Fucoidan and topography modification improved in situ endothelialization on acellular synthetic vascular grafts.

Thrombogenesis remains the primary failure of synthetic vascular grafts. Endothelial coverage is crucial to provide an antithrombogenic surface. However, most synthetic materials do not support cell adhesion, and transanastomotic endothelial migration is limited. Here, a surface modification strategy using fucoidan and topography was developed to enable fast in situ endothelialization of polyvinyl alcohol, which is not endothelial cell-adhesive. Among three different immobilization approaches compared, conjugation of aminated-fucoidan promoted endothelial monolayer formation while minimizing thrombogenicity in both in vitro platelet rich plasma testing and ex vivo non-human primate shunt assay. Screening of six topographical patterns showed that 2 µm gratings increased endothelial cell migration without inducing inflammation responses of endothelial cells. Mechanistic studies demonstrated that fucoidan could attract fibronectin, enabling integrin binding and focal adhesion formation and activating focal adhesion kinase (FAK) signaling, and 2 µm gratings further enhanced FAK-mediated cell migration. In a clinically relevant rabbit carotid artery end-to-side anastomosis model, 60% in situ endothelialization was observed throughout the entire lumen of 1.7 mm inner diameter modified grafts, compared to 0% of unmodified graft, and the four-week graft patency also increased. This work presents a promising strategy to stimulate in situ endothelialization on synthetic materials for improving long-term performance.

Reducing malaria transmission in forest-going mobile and migrant populations in Lao PDR and Cambodia: protocol for stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Countries of the Greater Mekong Sub-region aim to achieve malaria elimination by 2030. In the region, malaria is concentrated in high-risk areas and populations such as forest-going mobile and migrant populations (MMPs). However, routine protective measures such as long-lasting insecticidal nets do not prevent all infectious bites in these high-risk populations. Evidence for the effectiveness of a personal protection package tailored to forest-going MMPs which is acceptable, feasible, and cost-effective for reducing malaria transmission is required to inform the malaria elimination toolkit in the region. METHODS: A personal protection package consisting of long-lasting insecticidal hammock net, insect repellent and health communication pamphlet was developed in consultation with relevant implementing partners from Cambodia and Lao PDR. An open stepped-wedge cluster-randomised controlled trial will be conducted over a period of 12 months in a minimum of 488 villages (~ 428 in Lao PDR and ~ 60 in Cambodia) to evaluate the effectiveness of the personal protection package. Villages will be randomised into 11 blocks, with blocks transitioned in random order from control to intervention states at monthly intervals, following a 1-month baseline period. The primary outcome of the trial is the prevalence of Plasmodium spp. infection diagnosed by rapid diagnostic test. Difference in prevalence of malaria infection will be estimated across intervention and control periods using generalized linear mixed modelling. Nested within the stepped-wedge cluster-randomised controlled trial is a mixed-methods study to explore the acceptability of the personal protection package, feasibility of implementing a personal protection package as a vector control intervention, and knowledge, attitude and practice of MMPs regarding malaria prevention; and cost-analysis to determine the cost-effectiveness of implementing a personal protection package. DISCUSSION: This study, using a rigorous design and mixed-methods methodology, will evaluate whether a personal protection package can reduce residual malaria transmission among forest-going MMPs in Cambodia and Lao PDR. It will also measure implementation research outcomes such as effectiveness of the intervention package, cost-effectiveness, acceptability, and feasibility, in order to inform potential national and regional policy. Trial registration This trial was prospectively registered on ClinicalTrials.gov (NCT05117567) on 11th November 2021.

Virtual Noncontrast Images Derived From Contrast-Enhanced Dual-Layer Spectral Abdominal Computed Tomography: A Pilot Study Between Pediatric and Adult Scans.

OBJECTIVE: We aimed to compare the accuracy of virtual noncontrast (VNC) images obtained from contrast-enhanced dual-layer spectral computed tomography (DLSCT) scans of the abdomen between pediatric and adult patients. METHODS: We retrospectively studied 10 pediatric and 40 adult patients who underwent unenhanced and contrast-enhanced DLSCT for nontraumatic acute abdomen or a follow-up of tumor or aneurysm. On true noncontrast (TNC) and VNC images, we placed a region-of-interest on 7 abdominal structures. The mean attenuation difference between VNC and TNC images was compared between these structures and between pediatric and adult scans. Data were analyzed by using the Wilcoxon signed-rank test, 1-way analysis of variance, Scheffe's test and independent t test. A P value less than 0.05 was considered statistically significant. RESULTS: In mean attenuation difference between VNC and TNC images, there was a significant interstructure difference in adult scans (P < 0.05), but not in pediatric scans. Mean attenuation difference between VNC and TNC images of the kidney was significantly higher on adult than pediatric scans (P = 0.0046). CONCLUSIONS: The VNC images obtained from contrast-enhanced DLSCT data may be more accurate on pediatric than adult scans. Patient age can be a factor influencing the accuracy of the VNC images.

Rabbit Surgery Protocol for End-to-End and End-to-Side Vascular Graft Anastomosis.

Preclinical testing in animal model is a required stage of vascular device development. Among small animal models, rabbits provide vasculature with relative larger caliber for anastomotic implantation of vascular grafts as preclinical testing before conducting large animal studies. Rabbits have similar hemostatic mechanism with human and can accommodate vascular grafts with various diameters at different locations, and thus provide a valid model to assess small-diameter vascular grafts. This chapter will describe the procedures and materials required to conduct survival surgery in rabbit carotid artery models for implantation of small-diameter tubular grafts with an end-to-side and end-to-end anastomotic technique.

Vascular Imaging in Small Animals Using Clinical Ultrasound Scanners.

Conventional ultrasound with frequency (2-15 MHz) has been a global diagnostic and therapeutic tool in clinical medicine, and high-frequency ultrasound (>30 MHz) has been a powerful investigative device for preclinical studies such as cardiovascular research. In this chapter, we describe the use of conventional ultrasound with a 2.5-10 MHz transducer as an investigative device for the measurement/detection of blood flow in rabbit model. The chapter will describe the procedures for the preparation of sonographer, imaging locations, and the details of the rabbits used as well as detailed imaging steps for the preoperative, immediately after operation, and postoperative follow-up ultrasound for vascular surgery, using a vascular graft implantation as an example. We also provide useful notes to avoid pitfalls for successful imaging. The overall goal of this chapter is to deliver the steps in using low-cost, non-invasive, and highly versatile clinical ultrasound imaging in preclinical small animal testing.

Characteristics and significance of "green snake" bites in Myanmar, especially by the pit vipers Trimeresurus albolabris and Trimeresurus erythrurus.

Snakebite is an important problem in Myanmar. Regionally, bites by Eastern Russell's vipers, Daboia siamensis (Viperidae, Viperinae), and monocled cobras, Naja kaouthia are considered medically important, but those categorised as "green snake" bites are not. However, these may include bites by green pit vipers, Trimeresurus spp. (Viperidae, Crotalinae) for which no antivenom is available in Myanmar. Elsewhere in Southeast Asia, these snakes are reported to cause local and systemic envenoming. As part of the Myanmar Snakebite Project, prospective case data were collected over 3 years from five hospitals in the Mandalay region. These included 3803 snakebite cases reported from Mandalay region. Of these, 355 were listed as bites by a witnessed green-coloured snake. In 22 cases, the snakes responsible were retained and preserved, then expertly identified; 21 were medically important white-lipped pit vipers (Trimeresurus albolabris), and one as an Asian vine snake, Ahaetulla prasina (Colubridae, Ahaetuliinae) which is not of medical importance. Among confirmed Trimeresurus albolabris bites, 15/21 developed swelling of the bitten limb, and 3/21 coagulopathy, defined as a positive 20-min whole blood clotting test (20WBCT). None developed necrosis, blistering, thrombocytopenia or acute kidney injury (AKI). Of the remaining 333 patients bitten by green snakes that were not specifically identified, 241 (72%) developed swelling of the bitten limb, and 62 (19%) coagulopathy. AKI occurred in 21/333 patients, but only one required dialysis. At least 10/21 of the cases with AKI in this study were more likely to represent bites from Trimeresurus spp. than D. siamensis because the snake responsible was brought into the hospital, examined and described by the treating physician as "green-coloured". This study describes a previously unpublished case of AKI from envenoming by T. erythrurus in Yangon, and reviews cases of AKI following bites by this species and T. albolabris in Myanmar. This confirms that, at least on rare occasions, Trimeresurus spp. envenoming can cause AKI. This has important implications for snakebite management in Myanmar as the finding of local swelling, coagulopathy and AKI is generally considered pathognomonic of D. siamensis envenoming. Further collection of confirmed Trimeresurus spp. bites is required in Myanmar in order better to define the syndrome of envenoming and to assess the possible need for antivenom against Trimeresurus spp. in this country.

Usefulness of Virtual Monochromatic Images and Iodine Maps Derived from Dual-Energy Computed Tomography for Diagnosing Deep Neck Abscesses.

OBJECTIVE: We aimed to determine whether dual-energy computed tomography (CT) is useful for evaluating deep neck abscesses. METHODS: This study included 22 consecutive patients who were clinically suspected of having a deep neck abscess and underwent dual-energy CT. Conventional 120-kVp images, 70- and 40-keV virtual monochromatic images (VMIs), and iodine maps were inspected to calculate the contrast ratio of the abscess rim (AR) to the abscess center (AC) or to the adjacent muscle (M). The diagnostic certainty of abscesses was assessed on these images. RESULTS: Twenty (91%) of 22 patients had a definitive diagnosis. The contrast ratio for AR/AC and AR/M was significantly higher on 40-keV VMIs and iodine maps than on 120-kVp images and 70-keV VMIs (P < 0.05). On both 40-keV VMIs and iodine maps, the diagnostic certainty of abscess improved in 3 (15%) cases compared with 120-kVp images and 70-keV VMIs. CONCLUSIONS: Dual-energy CT-based 40-keV VMIs and iodine maps are useful for evaluating deep neck abscesses and may improve diagnostic certainty.

Enhanced efficiency of nonviral direct neuronal reprogramming on topographical patterns.

Nonviral direct neuronal reprogramming holds significant potential in the fields of tissue engineering and regenerative medicine. However, the issue of low reprogramming efficiency poses a major barrier to its application. We propose that topographical cues, which have been applied successfully to enhance lineage-directed differentiation and multipotent stem cell transdifferentiation, could improve nonviral direct neuronal reprogramming efficiency. To investigate, we used a polymer-BAM (Brn2, Ascl1, Myt1l) factor transfection polypex to reprogram primary mouse embryonic fibroblasts. Using a multiarchitecture chip, we screened for patterns that may improve transfection and/or subsequent induced neuron reprogramming efficiency. Selected patterns were then investigated further by analyzing ß-tubulin III (TUJ1) and microtubule-associated protein 2 (MAP2) protein expression, cell morphology and electrophysiological function of induced neurons. Certain hierarchical topographies, with nanopatterns imprinted on micropatterns, significantly improved the percentage of TUJ1+ and MAP2+ cells. It is postulated that the microscale base pattern enhances initial BAM expression while the nanoscale sub-pattern promotes subsequent maturation. This is because the base pattern alone increased expression of TUJ1 and MAP2, while the nanoscale pattern was the only pattern yielding induced neurons capable of firing multiple action potentials. Nanoscale patterns also produced the highest fraction of cells showing spontaneous synaptic activity. Overall, reprogramming efficiency with one dose of polyplex on hierarchical patterns was comparable to that of five doses without topography. Thus, topography can enhance nonviral direct reprogramming of fibroblasts into induced neurons.

Evaluation of cervical ossification of the posterior longitudinal ligament with 3D broadband IR-prepared ultrashort echo-time imaging: a pilot study.

PURPOSE: We aimed to evaluate the feasibility of 3D broadband inversion-recovery-prepared ultrashort echo-time (3D IRP UTE) imaging for assessing ossification of the posterior longitudinal ligament (OPLL). MATERIALS AND METHODS: The study consisted of 25 consecutive patients with cervical OPLL [13 women, 12 men; mean age 66.3 (47-84) years] who underwent CT, 3T conventional MR, and 3D IRP UTE imaging studies. Two readers independently assessed the 3D IRP UTE images for the type (mixed, continuous, circumscribed, segmental) and distribution of OPLL. All readers consensually assessed the diagnostic certainty of OPLL on conventional MR and 3D IRP UTE images by using a 3-point scale system. Interobserver and intermodality agreement was assessed by κ statistics. A Wilcoxon signed-rank test was used to evaluate the difference of diagnostic certainty between conventional MR and 3D IRP UTE imaging. RESULTS: Interobserver and intermodality agreements were good (κ = 0.73) and excellent (κ = 0.81) for the OPLL type, and excellent (κ = 0.85) and good (κ = 0.76) for the assessment of the distribution of OPLL, respectively. The mean level of the diagnostic certainty of OPLL was significantly higher for 3D IRP UTE than conventional MR imaging (p = 0.002). CONCLUSION: 3D IRP UTE imaging may be useful for assessing OPLL.

Added Value of Contrast-enhanced 3D-FLAIR MR Imaging for Differentiating Cystic Pituitary Adenoma from Rathke's Cleft Cyst.

PURPOSE: Half of the surgically proven Rathke's cleft cysts (RCCs) can be preoperatively misdiagnosed as cystic pituitary adenoma (CPA). We aimed to evaluate the usefulness of contrast-enhanced (CE) 3D T2 fluid-attenuated inversion-recovery (3D T2-FLAIR) imaging for differentiating between CPA and RCC. METHODS: This retrospective study included six patients with RCC (all pathologically confirmed) and six patients with CPA (five pathologically confirmed, one clinically diagnosed). The 12 patients underwent pre- and post-contrast T1-weighted (T1W)- and 3D T2-FLAIR imaging at 3T. Based on the degree of enhancement of the lesion wall, two radiologists independently scored the images using a 3-point grading system. Interobserver agreement was calculated by using the κ coefficient. The statistical significance of grading differences was analyzed with the Mann-Whitney U-test. Another neuroradiologist first interpreted conventional MR images (1st session), and then the reader read images to which the 3D T2-FLAIR images had been added (2nd session). Sensitivity, specificity, and accuracy of the reader's interpretation were calculated. RESULTS: Interobserver agreement for post-contrast T1W- and 3D T2-FLAIR images was excellent (κ = 1.000 and 0.885, respectively). Although the mean enhancement grade on post-contrast T1W images of RCCs and CPAs was not significantly different, on post-contrast 3D T2-FLAIR images it was significantly higher for RCCs and CPAs (P < 0.05). Three CPAs (50%) showed remarkable, donut-like enhancement along the inner margin of the cyst on CE-3D T2-FLAIR images; this was not the case on CE-T1W images. The sensitivity, specificity, and accuracy of the 2nd session were 1.00, 0.83, and 0.92, respectively, which were improved compared to the 1st session (1.00, 0.50, and 0.75, respectively). CONCLUSION: CE-3D FLAIR imaging is useful for discriminating CPAs and RCCs.

Conditional unnecessity of head CT for whole-body CT of traffic accident victims: a pilot study.

PURPOSE: To investigate whether head CT should be included in whole-body CT in road traffic accident victims. METHODS: A review of electronic medical records identified 124 patients (81 males, 43 females; age 4 to 92 years, mean 47.7 years) involved in a road traffic accident in a 12-month period. All had undergone whole-body CT and physical and neurologic examinations. We recorded their age, sex, Glasgow Coma Scale (GCS), systolic blood pressure (SBP), the type of traffic accident, and the presence/absence of visible trauma above the clavicles (VTCs) and of acute traumatic brain injury (TBI) on CT. Statistical analyses were performed to evaluate predictors of acute TBI. RESULTS: Of 124 patients, 34 (27%) manifested acute TBI on CT. Univariate analysis identified their age, GCS, SBP, VTCs, and the accident type as statistically significant factors for acute TBI (p < 0.05). Multivariate analysis demonstrated VTCs, GCS score < 15, and SBP ≤ 90 mmHg were significant independent predictors of acute TBI (p = 0.001, p = 0.001, and p = 0.004, respectively); the odds ratio was 16.07 for VTCs, 14.85 for GCS score < 15, and 13.78 for SBP ≤ 90 mmHg. No patients without both decrease in GCS score and VTCs manifested acute TBI. CONCLUSION: Our pilot study showed that visible trauma above the clavicles and decrease in GCS score were highly associated with the presence of acute TBI in road traffic accident victims. In whole-body CT, a head CT may not be indicated in patients without these factors.

A National Survey on Safety Management at MR Imaging Facilities in Japan.

PURPOSE: To investigate safety management at Japanese facilities performing human MRI studies. METHODS: All Japanese facilities performing human MRI studies were invited to participate in a comprehensive survey that evaluated their MRI safety management. The survey used a questionnaire prepared with the cooperation of the Safety Committee of the Japanese Society for Magnetic Resonance in Medicine. The survey addressed items pertaining to the overall MRI safety management, questions on the occurrence of incidents, and questions specific to facility and MRI scanner or examination. The survey covered the period from October 2017 to September 2018. Automated machine learning was used to identify factors associated with major incidents. RESULTS: Of 5914 facilities, 2015 (34%) responded to the questionnaire. There was a wide variation in the rate of compliance with MRI safety management items among the participating facilities. Among the facilities responding to this questionnaire, 5% reported major incidents and 27% reported minor incidents related to MRI studies. Most major incidents involved the administration of contrast agents. The most influential factor in major incidents was the total number of MRI studies performed at the facility; this number was significantly correlated with the risk of major incidents (P < 0.0001). CONCLUSION: There were large variations in the safety standards applied at Japanese facilities performing clinical MRI studies. The total number of MRI studies performed at a facility affected the number of major incidents.

Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients.

Endothelial dysfunction has been implicated in atherosclerosis, ischemic heart disease, and stroke. Endothelial progenitor cells (EPCs), found in the bone marrow and peripheral blood as rare cell population, demonstrated a high proliferation and differentiation capacity. Understanding how such diseases influence the quantity and functionality of EPCs is essential for the development of novel therapies. This study aims to investigate the factors that affect the quantity and functionality of circulating EPCs in stroke patients and healthy controls. Blood samples were collected once from healthy donors (n = 30) and up to 3 times (within 7 days (baseline), 3 and 12 months post-stroke) from stroke patients (n = 207). EPC subpopulations were isolated with flow cytometry for characterization. The Matrigel tubular formation assay was performed as a measure of functionality. An increased amount of circulating EPCs was observed in stroke patients over 45 years when compared to age-matched healthy individuals. EPCs showed a rising trend in stroke patients over the 12-month post-stroke period, reaching statistical significance at 12 months post-stroke. Isolated CD34+KDR+ cells from stroke patients showed impairment in tubular formation capability when compared to cells from healthy donors. The quantity and vasculogenic function of circulating EPCs in peripheral blood have been effectively evaluated in stroke patients and healthy control donors in this study. Age and stroke are found to be 2 influencing factors on the angiogenic capacity. It is suggested that the increase in EPC number is triggered by the recovery response following ischemic stroke. Graphical abstract.

Assessment of Noise Exposure and Hearing Loss Among Workers in Textile Mill (Thamine), Myanmar: A Cross-Sectional Study.

BACKGROUND: In a wide range of industries, noise-induced hearing loss remains one of the most prevalent occupational problems. This study aimed to assess the noise exposure level and associated factors of hearing loss among textile workers in Yangon Region, Myanmar. METHODS: A cross-sectional study was conducted at a Textile mill (Thamine), Yangon Region, from April to December 2018. In total, 226 workers who were randomly selected from 3 weaving sections participated in face-to-face interviews using a structured questionnaire. A digital sound level meter and pure-tone audiometer were used for the assessment of noise exposure level and hearing loss, respectively. Logistic regression analysis was performed to assess the associated factors of hearing loss. RESULTS: In total workers, 66.4% were exposed to ≥85 dB(A) of noise exposure, and the prevalence of hearing loss was 25.7%. Age ≥35 years, below high school education, hearing difficulty, tinnitus, hypertension, > 9 years of service duration in a textile mill were positively associated with hearing loss. After adjusting confounding factors, age ≥35 years (adjusted odds ratio = 6.90, 95% confidence interval = 3.45-13.82) and tinnitus (adjusted odds ratio = 2.88, 95% confidence interval = 1.13-7.37) were persistently associated with hearing loss. CONCLUSION: Providing occupational hazard education and enforcement of occupational safety regulations should be taken to decrease the noise exposure level. The regular audiometry test should be conducted for assessment of hearing threshold shift. The employer needs to implement a hearing conservation program in workplace when noise exposure reaches or exceeds 85 dB(A) for 8 hours.

Fucoidan functionalization on poly(vinyl alcohol) hydrogels for improved endothelialization and hemocompatibility.

The performance of clinical synthetic small diameter vascular grafts remains disappointing due to the fast occlusion caused by thrombosis and intimal hyperplasia formation. Poly(vinyl alcohol) (PVA) hydrogels have tunable mechanical properties and a low thrombogenic surface, which suggests its potential value as a small diameter vascular graft material. However, PVA does not support cell adhesion and thus requires surface modification to encourage endothelialization. This study presents a modification of PVA with fucoidan. Fucoidan is a sulfated polysaccharide with anticoagulant and antithrombotic properties, which was shown to potentially increase endothelial cell adhesion and proliferation. By mixing fucoidan with PVA and co-crosslinked by sodium trimetaphosphate (STMP), the modification was achieved without sacrificing mechanical properties. Endothelial cell adhesion and monolayer function were significantly enhanced by the fucoidan modification. In vitro and ex-vivo studies showed low platelet adhesion and activation and decreased thrombin generation with fucoidan modified PVA. The modification proved to be compatible with gamma sterilization. In vivo evaluation of fucoidan modified PVA grafts in rabbits exhibited increased patency rate, endothelialization, and reduced intimal hyperplasia formation. The fucoidan modification presented here benefited the development of PVA vascular grafts and can be adapted to other blood contacting surfaces.

Effect of Ethylene Oxide Sterilization on Polyvinyl Alcohol Hydrogel Compared with Gamma Radiation.

This study investigated the effects of terminal sterilization of polyvinyl alcohol (PVA) biomaterials using clinically translatable techniques, specifically ethylene oxide (EtO) and gamma (γ) irradiation. While a few studies have reported the possibility of sterilizing PVA with γ-radiation, the use of EtO sterilization of PVA requires additional study. PVA solutions were chemically crosslinked with trisodium trimetaphosphate and sodium hydroxide. The three experimental groups included untreated control, EtO, and γ-irradiation, which were tested for the degree of swelling and water content, and mechanical properties such as radial compliance, longitudinal tensile, minimum bend radius, burst pressure, and suture retention strength. In addition, samples were characterized with scanning electron microscopy, differential scanning calorimetry, X-ray photoelectron spectroscopy, and water contact angle measurements. Cell attachment was assessed using the endothelial cell line EA.hy926, and the sterilized PVA cytotoxicity was studied with a live/dead stain. Platelet and fibrin accumulation was measured using an ex vivo shunt baboon model. Finally, the immune responses of PVA implants were analyzed after a 21-day subcutaneous implantation in rats and a 30-day implantation in baboon. EtO sterilization reduced the PVA graft wall thickness, its degree of swelling, and water content compared with both γ-irradiated and untreated PVA. Moreover, EtO sterilization significantly reduced the radial compliance and increased Young's modulus. EtO did not change PVA hydrophilicity, while γ-irradiation increased the water contact angle of the PVA. Consequently, endothelial cell attachment on the EtO-sterilized PVA showed similar results to the untreated PVA, while cell attachment significantly improved on the γ-irradiated PVA. When exposing the PVA grafts to circulating whole blood, fibrin accumulation of EtO-sterilized PVA was found to be significantly lower than γ-irradiated PVA. The immune responses of γ-irradiated PVA, EtO-treated PVA, and untreated PVA were compared. Implanted EtO-treated PVA showed the least MAC387 reaction. The terminal sterilization methods in this study changed PVA hydrogel properties; nevertheless, based on the characterizations performed, both sterilization methods were suitable for sterilizing PVA. We concluded that EtO can be used as an alternative method to sterilize PVA hydrogel material. Impact statement Polyvinyl alcohol (PVA) hydrogels have been used for a variety of tissue replacements, including neural, cardiac, meniscal, cartilage, muscle, pancreatic, and ocular applications. In addition, PVA can be made into a tubular shape and used as a small-diameter vascular graft. Ethylene oxide (EtO) is one of the Food and Drug Administration-approved methods for sterilization, but its effect on PVA has not been studied extensively. The outcome of this study provides the effects of EtO and γ-irradiation of PVA grafts on both the material properties and the in vivo responses, particularly for vascular applications. Knowledge of these effects may ultimately improve the success rate of PVA vascular grafts.