A comparison of skeletal and dental changes in patients with a Class II relationship treated with clear aligner mandibular advancement and Herbst appliance followed by comprehensive orthodontic treatment.

INTRODUCTION: The objective of this study was to compare the skeletal and dental changes of patients with a Class II relationship treated with clear aligner mandibular advancement (MA) and Herbst appliances followed by comprehensive orthodontic treatment. METHODS: The participants included 20 patients treated with MA and 20 with the Herbst appliance. Orthodontic records were taken before treatment, after the functional appliance, and completion of phase II treatment. The skeletal and dental changes across the 3-time periods were evaluated using a matched paired t test for each treatment. A 2-sample t test was used to examine the changes across periods between 2 treatment groups (P <0.05). RESULTS: Significant reduction in overjet, overbite, and change in molar relationship were obtained by both appliances with similar skeletal and dental contributions. This was contributed by a forward movement of the mandible and mandibular molars, backward movement of the maxillary molars, and retraction of the maxillary incisors. After phase II treatment, both appliances could maintain the skeletal and dental changes achieved during the advancement phase. Greater change in overbite (2.4 mm vs 1.4 mm), an eruption of maxillary incisors (0.9 mm vs 0.1 mm), and proclination of mandibular incisors were found with the Herbst group (3.9° vs -2.1°). The average total treatment time was similar with the 2 appliances. CONCLUSIONS: Both functional appliances were equally effective in reducing the overjet and overbite and achieving a Class I molar relationship with a similar length of treatment time. The Herbst design lacked control of the mandibular incisor proclination, and clear aligners offered better vertical control and management of the mandibular incisor inclination.

Prediction of whole-cell transcriptional response with machine learning.

MOTIVATION: Applications in synthetic and systems biology can benefit from measuring whole-cell response to biochemical perturbations. Execution of experiments to cover all possible combinations of perturbations is infeasible. In this paper, we present the host response model (HRM), a machine learning approach that maps response of single perturbations to transcriptional response of the combination of perturbations. RESULTS: The HRM combines high-throughput sequencing with machine learning to infer links between experimental context, prior knowledge of cell regulatory networks, and RNASeq data to predict a gene's dysregulation. We find that the HRM can predict the directionality of dysregulation to a combination of inducers with an accuracy of >90% using data from single inducers. We further find that the use of prior, known cell regulatory networks doubles the predictive performance of the HRM (an R2 from 0.3 to 0.65). The model was validated in two organisms, Escherichia coli and Bacillus subtilis, using new experiments conducted after training. Finally, while the HRM is trained with gene expression data, the direct prediction of differential expression makes it possible to also conduct enrichment analyses using its predictions. We show that the HRM can accurately classify >95% of the pathway regulations. The HRM reduces the number of RNASeq experiments needed as responses can be tested in silico prior to the experiment. AVAILABILITY AND IMPLEMENTATION: The HRM software and tutorial are available at https://github.com/sd2e/CDM and the configurable differential expression analysis tools and tutorials are available at https://github.com/SD2E/omics_tools. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hybrid CNN-SVR Blood Pressure Estimation Model Using ECG and PPG Signals.

Continuous blood pressure (BP) measurement is vital in monitoring patients' health with a high risk of cardiovascular disease. The complex and dynamic nature of the cardiovascular system can influence BP through many factors, such as cardiac output, blood vessel wall elasticity, circulated blood volume, peripheral resistance, respiration, and emotional behavior. Yet, traditional BP measurement methods in continuously estimating the BP are cumbersome and inefficient. This paper presents a novel hybrid model by integrating a convolutional neural network (CNN) as a trainable feature extractor and support vector regression (SVR) as a regression model. This model can automatically extract features from the electrocardiogram (ECG) and photoplethysmography (PPG) signals and continuously estimates the systolic blood pressure (SBP) and diastolic blood pressure (DBP). The CNN takes the correct topology of input data and establishes the relationship between ECG and PPG features and BP. A total of 120 patients with available ECG, PPG, SBP, and DBP data are selected from the MIMIC III database to evaluate the performance of the proposed model. This novel model achieves an overall Mean Absolute Error (MAE) of 1.23 ± 2.45 mmHg (MAE ± STD) for SBP and 3.08 ± 5.67 for DBP, all of which comply with the accuracy requirements of the AAMI SP10 standard.

Clinical characteristics and visual outcomes of non-resolving subretinal fluid in neovascular AMD despite continuous monthly anti-VEGF injections: a long-term follow-up.

PURPOSE: To describe the clinical characteristics and visual outcomes of neovascular age-related macular degeneration (NV-AMD) patients with irregular pigment epithelium detachment (PED) and non-resolving subretinal fluid (SRF) despite continuous monthly injections of anti-vascular endothelial growth factor (VEGF). METHODS: This is a retrospective case series, including NV-AMD patients treated in a tertiary academic practice. Inclusion criteria were NV-AMD diagnosis, with irregular PED, and non-resolving SRF treated with continuous monthly anti-VEGF intravitreal injections. Data collection included best corrected visual acuity (BCVA), central macular thickness (CMT), sub-foveal choroidal thickness (SFCT), and type and location of PED as seen on optical coherence tomography (OCT). RESULTS: A total of 738 patients with NV-AMD underwent anti-VEGF injections during the follow-up period and 20 eyes of 19 patients (14 females and 5 males) met the inclusion criteria. Average age was 81.7 ± 6.6 years, mean follow-up time was 32.1 ± 23.5 months, and mean number of injections was 31.3 ± 24.2. Mean VA was 0.26 ± 0.21 logMAR (Snellen 20/36) at baseline versus 0.20 ± 0.23 logMAR (Snellen 20/32) at the end of the follow-up (P = 0.28). All eyes presented with sub-foveal, type 1 macular neovascularization (MNV). Average sub-foveal choroidal thickness changed from 189.70 ± 68.46 µm at baseline to 169.00 ± 63.06 µm (P < 0.001) at last follow-up. CONCLUSION: Patients with type 1 NV-AMD, irregular PED, and non-resolving SRF and under continuous treatment of monthly anti-VEGF injections may maintain good visual acuity after long period of time.

PIGMENT EPITHELIAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION: Long-Term Visual Acuity May Improve With Higher Injection Index.

PURPOSE: To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. METHODS: Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: <9). RESULTS: Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. CONCLUSION: Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

Mixed oxide nanotubes in nanomedicine: A dead-end or a bridge to the future?

Nanomedicine has seen a significant rise in the development of new research tools and clinically functional devices. In this regard, significant advances and new commercial applications are expected in the pharmaceutical and orthopedic industries. For advanced orthopedic implant technologies, appropriate nanoscale surface modifications are highly effective strategies and are widely studied in the literature for improving implant performance. It is well-established that implants with nanotubular surfaces show a drastic improvement in new bone creation and gene expression compared to implants without nanotopography. Nevertheless, the scientific and clinical understanding of mixed oxide nanotubes (MONs) and their potential applications, especially in biomedical applications are still in the early stages of development. This review aims to establish a credible platform for the current and future roles of MONs in nanomedicine, particularly in advanced orthopedic implants. We first introduce the concept of MONs and then discuss the preparation strategies. This is followed by a review of the recent advancement of MONs in biomedical applications, including mineralization abilities, biocompatibility, antibacterial activity, cell culture, and animal testing, as well as clinical possibilities. To conclude, we propose that the combination of nanotubular surface modification with incorporating sensor allows clinicians to precisely record patient data as a critical contributor to evidence-based medicine.

Evaluating the preventive and curative effects of Toxocara canis larva in Freund's complete adjuvant-induced arthritis.

Helminthic infection and the parallel host immune reactions are the results of a protracted dynamic co-interaction between the host and worms. An assessment of the effect of Toxocara canis infection on arthritis in rats stimulated by Freund's complete adjuvant (FCA) was the main purpose of the investigation. An arthritis model was established by the administration of 0.1 mL FCA in the palmar surface. Cytokine assessment, evaluating oedema and the use of a rheumatoid arthritis (RA) score provided evidence of the protective effects of T canis against adjuvant-induced arthritis (AIA). The cytokines TGF-ß, IFN-É£, IL-10 and IL-17 were measured to assess the anti-inflammatory effect of T canis infection. Besides, arthritis swelling findings were evaluated in rat paws. The data showed that T canis infection significantly modulated the immune response by alleviating inflammatory cytokines and increasing TGF-ß as an anti-inflammatory cytokine. Evaluations of arthritis swelling showed low severity and faster recuperation. These findings suggest that the products derived from T canis eggs might be a potential therapeutic candidate to treat autoimmune diseases like the arthritis.

Prevalence of Toxocara and Toxascaris infection among human and animals in Iran with meta-analysis approach.

BACKGROUND: Toxocariasis is a worldwide zoonotic parasitic disease caused by species of Toxocara and Toxascaris, common in dogs and cats. Herein, a meta-analysis was contrived to assess the prevalence of Toxocara/Toxascaris in carnivore and human hosts in different regions of Iran from April 1969 to June 2019. METHODS: The available online articles of English (PubMed, Science Direct, Scopus, and Ovid) and Persian (SID, Iran Medex, Magiran, and Iran Doc) databases and also the articles that presented in held parasitology congresses of Iran were involved. RESULTS: The weighted prevalence of Toxocara/Toxascaris in dogs (Canis familiaris) and cats (Felis catus) was 24.2% (95% CI: 18.0-31.0%) and 32.6% (95% CI: 22.6-43.4%), respectively. Also, pooled prevalence in jackal (Canis aureus) and red fox (Vulpes vulpes) was 23.3% (95% CI: 7.7-43.2%) and 69.4% (95% CI: 60.3-77.8%), correspondingly. Weighted mean prevalence of human cases with overall 28 records was 9.3% (95% CI: 6.3-13.1%). The weighted prevalence of Toxocara canis, Toxocara cati, and Toxascaris leonina was represented as 13.8% (95% CI: 9.8-18.3%), 28.5% (95% CI: 20-37.7%) and 14.3% (95% CI: 8.1-22.0%), respectively. CONCLUSION: Our meta-analysis results illustrate a considerable prevalence rate of Toxocara/Toxascaris, particularly in cats and dogs of northern parts of Iran. The presence of suitable animal hosts, optimum climate and close contact of humans and animals would have been the reason for higher seroprevalence rates of human cases in our region. Given the significance clinical outcomes of human Toxocara/Toxascaris, necessary measures should be taken.

DETECTION OF NEUROSENSORY RETINAL DETACHMENT COMPLICATING DEGENERATIVE RETINOSCHISIS BY ULTRA-WIDEFIELD FUNDUS AUTOFLUORESCENCE IMAGING.

PURPOSE: To determine whether neurosensory retinal detachment complicating degenerative retinoschisis (RS) can be reliably detected with ultra-widefield fundus autofluorescence evaluation. METHODS: Consecutive patients diagnosed with RS who had ultra-widefield fundus autofluorescence imaging were included in this retrospective case series. According to the fundus autofluorescence patterns, we divided the eyes into two groups: 1) eyes with RS and a hyperautofluorescent leading edge and 2) eyes with RS and without hyperautofluorescence. Peripheral spectral domain optical coherence tomography images at the level of RS were obtained. RESULTS: Thirty-eight eyes that met eligibility criteria were identified. Review of ultra-widefield fundus autofluorescence demonstrated 21/39 (55%) eyes with distinctive hyperautofluorescence over the area of RS (Group A) and 17/38 (45%) eyes without any form of hyperautofluorescence (Group B). Spectral domain optical coherence tomography images confirmed the presence of full-thickness neurosensory retina separation from the underlying retinal pigment epithelium in the areas of hyperautofluorescence in 10/10 eyes (100%) from Group A. None (0/11; 0%) of the eyes from Group B showed full-thickness neurosensory retina separation on the spectral domain optical coherence tomography imaging of the retina-RS interface. CONCLUSION: Hyperautofluorescent findings suggest the presence of a neurosensory retinal detachment. Retinal detachment associated with RS can be reliably detected on ultra-widefield fundus autofluorescence and may be a useful diagnostic imaging modality.

Follicular B Cells Promote Atherosclerosis via T Cell-Mediated Differentiation Into Plasma Cells and Secreting Pathogenic Immunoglobulin G.

OBJECTIVE: B cells promote or protect development of atherosclerosis. In this study, we examined the role of MHCII (major histocompatibility II), CD40 (cluster of differentiation 40), and Blimp-1 (B-lymphocyte-induced maturation protein) expression by follicular B (FO B) cells in development of atherosclerosis together with the effects of IgG purified from atherosclerotic mice. APPROACH AND RESULTS: Using mixed chimeric Ldlr-/- mice whose B cells are deficient in MHCII or CD40, we demonstrate that these molecules are critical for the proatherogenic actions of FO B cells. During development of atherosclerosis, these deficiencies affected T-B cell interactions, germinal center B cells, plasma cells, and IgG. As FO B cells differentiating into plasma cells require Blimp-1, we also assessed its role in the development of atherosclerosis. Blimp-1-deficient B cells greatly attenuated atherosclerosis and immunoglobulin-including IgG production, preventing IgG accumulation in atherosclerotic lesions; Blimp-1 deletion also attenuated lesion proinflammatory cytokines, apoptotic cell numbers, and necrotic core. To determine the importance of IgG for atherosclerosis, we purified IgG from atherosclerotic mice. Their transfer but not IgG from nonatherosclerotic mice into Ldlr-/- mice whose B cells are Blimp-1-deficient increased atherosclerosis; transfer was associated with IgG accumulating in atherosclerotic lesions, increased lesion inflammatory cytokines, apoptotic cell numbers, and necrotic core size. CONCLUSIONS: The mechanism by which FO B cells promote atherosclerosis is highly dependent on their expression of MHCII, CD40, and Blimp-1. FO B cell differentiation into IgG-producing plasma cells also is critical for their proatherogenic actions. Targeting B-T cell interactions and pathogenic IgG may provide novel therapeutic strategies to prevent atherosclerosis and its adverse cardiovascular complications.

Polyethylene glycol-coated porous magnetic nanoparticles for targeted delivery of chemotherapeutics under magnetic hyperthermia condition.

PURPOSE: Although magnetite nanoparticles (MNPs) are promising agents for hyperthermia therapy, insufficient drug encapsulation efficacies inhibit their application as nanocarriers in the targeted drug delivery systems. In this study, porous magnetite nanoparticles (PMNPs) were synthesized and coated with a thermosensitive polymeric shell to obtain a synergistic effect of hyperthermia and chemotherapy. MATERIALS AND METHODS: PMNPs were produced using cetyltrimethyl ammonium bromide template and then coated by a polyethylene glycol layer with molecular weight of 1500 Da (PEG1500) and phase transition temperature of 48 ± 2 °C to endow a thermosensitive behavior. The profile of drug release from the nanostructure was studied at various hyperthermia conditions generated by waterbath, magnetic resonance-guided focused ultrasound (MRgFUS), and alternating magnetic field (AMF). The in vitro cytotoxicity and hyperthermia efficacy of the doxorubicin-loaded nanoparticles (DOX-PEG1500-PMNPs) were assessed using human lung adenocarcinoma (A549) cells. RESULTS: Heat treatment of DOX-PEG1500-PMNPs containing 235 ± 26 mg·g-1 DOX at 48 °C by waterbath, MRgFUS, and AMF, respectively led to 71 ± 4%, 48 ± 3%, and 74 ± 5% drug release. Hyperthermia treatment of the A549 cells using DOX-PEG1500-PMNPs led to 77% decrease in the cell viability due to the synergistic effects of magnetic hyperthermia and chemotherapy. CONCLUSION: The large pores generated in the PMNPs structure could provide a sufficient space for encapsulation of the chemotherapeutics as well as fast drug encapsulation and release kinetics, which together with thermosensitive characteristics of the PEG1500 shell, make DOX-PEG1500-PMNPs promising adjuvants to the magnetic hyperthermia modality.

Discrimination of Two Cultivars of Alpinia Officinarum Hance Using an Electronic Nose and Gas Chromatography-Mass Spectrometry Coupled with Chemometrics.

Background: Alpinia officinarum Hance is both an herbal medicine and a condiment, and generally has different cultivars such as Zhutou galangal and Fengwo galangal. The appearance of these A. officinarum cultivars is similar, but their chemical composition and quality are different. It is therefore important to discriminate between different A. officinarum plants to ensure the consistency of the efficacy of the medicine. Therefore, we used an electronic nose (E-nose) to explore the differences in odor information between the two cultivars for fast and robust discrimination. Methods: Odor and volatile components of all A. officinarum samples were detected by the E-nose and gas chromatography-mass spectrometry (GC-MS), respectively. The E-nose sensors and GC-MS data were analyzed respectively by principal component analysis (PCA), the correlation between E-nose sensors and GC-MS data were analyzed by partial least squares (PLS). Results: It was found that Zhutou galangal and Fengwo galangal can be discriminated by combining the E-nose with PCA, and the E-nose sensors S2, S6, S7, S9 were important sensors for distinguishing different cultivars of A. officinarum. A total of 56 volatile components of A. officinarum were identified by the GC-MS analysis, and the composition and content of the volatile components from the two different A. officinarum cultivars were different, in particular the relative contents of 1,8-cineole and α-farnesene. The classification result by PCA analysis based on GC-MS data was consistent with the E-nose results. The PLS analysis demonstrated that the volatile terpene, alcohol and ester components primarily interacted with the sensors S2 and S7, indicating that particular E-nose sensors were highly correlated with some aroma constituents. Conclusions: Combined with advanced chemometrics, the E-nose detection technology can discriminate two cultivars of A. officinarum, with GC-MS providing support to determine the material basis of the E-nose sensors' response.

ULTRAWIDEFIELD AUTOFLUORESENCE IN ABCA4 STARGARDT DISEASE.

PURPOSE: To report the ultrawidefield fundus autofluorescence (UWF-FAF) patterns in ABC4A Stargardt disease. METHODS: A retrospective cohort study of patients with a clinical diagnosis of Stargardt disease, confirmed ABCA4 genotype, and ultrawidefield fundus autofluorescence imaging using an Optos P200Tx. Four independent graders evaluated the images. Ultrawidefield fundus autofluorescence images were evaluated for the presence of posterior pole and peripheral findings, and were classified into one of three types (Type I: lesions confined to the macula with no peripheral findings; Type II: macular atrophy with flecks only in the periphery; Type III: macular atrophy and varying degrees of peripheral atrophy). RESULTS: Ultrawidefield fundus autofluorescence was performed on 58 eyes of 29 patients. Reviews of images revealed the presence of peripheral (outside the 55° view of standard nonwidefield FAF imaging) alterations on UWF-FAF in 76% of eyes. Overall, the UWF-FAF pattern was classified as Type I in 24% eyes (14/58), Type II in 24% (14/58), and Type III in 52% (30/58). The most common genetic mutations were c.2588G>C (6/29 patients, 20.7%), and c.5882G>A (5/29 patients, 17.2%). CONCLUSION: Ultrawidefield fundus autofluorescence reveals peripheral changes in the majority of patients with Stargardt disease. Peripheral FAF changes may have implications for diagnosis, prognosis, and management of individual patients with Stargardt disease.

EARLY DETECTION OF RETINAL HEMANGIOBLASTOMAS IN VON HIPPEL-LINDAU DISEASE USING ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY.

PURPOSE: To study the use of ultra-widefield fluorescein angiography (UWF FA) in the detection and management of retinal capillary hemangioblastomas in patients with von Hippel-Lindau disease. METHODS: This is a retrospective study of patients with von Hippel-Lindau disease who underwent UWF FA using the Optos camera at a single center from June 2009 to May 2015. The clinical use of UWF FA was reviewed, and the number of hemangioblastomas identified on UWF FA was compared with ophthalmoscopy and a simulated seven standard field (7SF) FA montage. RESULTS: Twenty eyes of 10 patients were identified. Only 33% of lesions seen on UWF FA were also found on ophthalmoscopy, and 88% of lesions visualized on UWF FA were located outside the 7SF overlay. In 5 eyes that had gaze steering, 18% of lesions could be visualized only on gaze-steered images. For the 14 eyes with data available, 6 had procedures recommended and 8 eyes observed based on data from UWF FA. One of 20 eyes had a lesion on ophthalmoscopy that was missed by imaging. CONCLUSION: Ultra-widefield FA using the Optos camera is helpful for the evaluation and management of patients with von Hippel-Lindau disease. The UWF FA with gaze steering appears to detect more hemangioblastomas than ophthalmoscopy and conventional angiography.

CD4+ natural killer T cells potently augment aortic root atherosclerosis by perforin- and granzyme B-dependent cytotoxicity.

RATIONALE: CD4(+) natural killer T (NKT) cells augment atherosclerosis in apolipoprotein E-deficient (ApoE)(-/-) mice but their mechanisms of action are unknown. OBJECTIVES: We investigated the roles of bystander T, B, and NK cells; NKT cell-derived interferon-γ, interleukin (IL)-4, and IL-21 cytokines; and NKT cell-derived perforin and granzyme B cytotoxins in promoting CD4(+) NKT cell atherogenicity. METHODS AND RESULTS: Transfer of CD4(+) NKT cells into T- and B-cell-deficient ApoE(-/-)Rag2(-/-) mice augmented aortic root atherosclerosis by ≈75% that was ≈30% of lesions in ApoE(-/-) mice; macrophage accumulation similarly increased. Transferred NKT cells were identified in the liver and atherosclerotic lesions of recipient mice. Transfer of CD4(+) NKT cells into T-, B-cell-deficient, and NK cell-deficient ApoE(-/-)Rag2(-/-)γC(-/-) mice also augmented atherosclerosis. These data indicate that CD4(+) NKT cells can exert proatherogenic effects independent of other lymphocytes. To investigate the role of NKT cell-derived interferon-γ, IL-4, and IL-21 cytokines and perforin and granzyme B cytotoxins, CD4(+) NKT cells from mice deficient in these molecules were transferred into NKT cell-deficient ApoE(-/-)Jα18(-/-) mice. CD4(+) NKT cells deficient in IL-4, interferon-γ, or IL-21 augmented atherosclerosis in ApoE(-/-)Jα18(-/-) mice by ≈95%, ≈80%, and ≈70%, respectively. Transfer of CD4(+) NKT cells deficient in perforin or granzyme B failed to augment atherosclerosis. Apoptotic cells, necrotic cores, and proinflammatory VCAM-1 (vascular cell adhesion molecule) and MCP-1 (monocyte chemotactic protein) were reduced in mice receiving perforin-deficient NKT cells. CD4(+) NKT cells are twice as potent as CD4(+) T cells in promoting atherosclerosis. CONCLUSIONS: CD4(+) NKT cells potently promote atherosclerosis by perforin and granzyme B-dependent apoptosis that increases postapoptotic necrosis and inflammation.

A miniature shock wave driven micro-jet injector for needle-free vaccine/drug delivery.

This article presents a miniature shock wave driven micro-jet generator to deliver liquid drugs into human skin, to a controlled depth, with minimal invasion. The device can release the vaccine/drug to the depth of dermal blood vessels, without breaching much of the microcirculation system of dermis. The drug delivery technique is needle-free, which can reduce pain, trauma, and contamination besides minimal dosage and systemic exposure. The device can also be used to deliver liquid or colloidal drugs into soft tissues in human. The mechanical analyses of the device were carried out by analyzing the strength of the impulse of the shock wave, measuring the velocity of the generated jet and capturing the pressure exerted by the jet on the target. The penetrating ability of the jet was investigated by delivering it into sample of human skin and gelatin slabs. Theoretical analyses were carried out on the physics of the delivery and the predicted results had a close agreement with the experimental observations. The development can offer an important cost-effective solution to needle-free health care worldwide. Biotechnol. Bioeng. 2016;113: 2507-2512. © 2016 Wiley Periodicals, Inc.

Synthesizing and staining manganese oxide nanoparticles for cytotoxicity and cellular uptake investigation.

BACKGROUND: For decades, contrast agents have been used to reduce longitudinal (T1) or transverse (T2) relaxation times. High toxicity of gadolinium-based contrast agents leads researchers to new T1 contrast agents. Manganese oxide (MnO) nanoparticle (NP) with the lower peril and good enough signal change ability has been offered as a new possibility for magnetic resonance imaging (MRI). METHODS: The synthesized NPs were investigated for physicochemical and biological properties by X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscope, dynamic light scattering (DLS), inductively coupled plasma, enzyme-linked immunosorbent assay, and 3T magnetic resonance imaging. RESULTS: Due to physical contact importance of T1 contrast agents with tissues' protons, extremely thin layer of the surfactant, less than 2nm, was coated on NPs for aqueous stabilizing. The hydrophilic gentisic acid with low Dalton, around 154, did that role truly. Moreover, decreasing NP size to 5nm which increases available surface for the proton relaxation is another important parameter to reach an appropriate longitudinal relaxation rate. The NPs didn't reveal any side effects on the cells, and cellular uptake was considerable. CONCLUSIONS: The synthesized NPs represented a promising result in comparison to clinical gadolinium chelates, due to higher r1 relaxivity and lower toxicity. GENERAL SIGNIFICANCE: In addition to considerable signal change and cellular uptake, Prussian blue was tried on MnO NPs for the initial time, which can be observed within cells by pale blue color.

The role of ergonomic training interventions on decreasing neck and shoulders pain among workers of an Iranian automobile factory: a randomized trial study.

BACKGROUND: Ergonomic training had been implemented for prevention or reduction of neck and shoulder complaints among workers. The purpose of the present study was to assess the role of ergonomic training intervention on decreasing the prevalence of neck and shoulder complaints among workers of an automobile factory. METHODS: Within the present randomized clinical trial, the role of three ergonomic training methods on the prevalence of neck and shoulders pain among 503 workers of an automobile factory (Response rate: 94.23%) was assessed. The eligible workers were randomly allocated into the following three interventional (pamphlet, lecture, workshop) groups and one control group. The Nordic questionnaire was used to assess the prevalence of neck and shoulder complaints. We followed and assessed the prevalence of neck and shoulders complaints among the study employees before and one year after the intervention. We used chi-square and Mann-Whitney tests to compare the prevalence of neck and shoulder complaints between the trial and control groups. A two-tailed P-value less than or equal to 0.05 was considered statistically significant. RESULTS: The prevalence of neck and shoulders complaints among the study employees at the recent week (p= 0.002) and year (p= 0.02) had been significantly decreased in the study employees after participating in the study workshop. The prevalence of neck and shoulders complaints at the recent week and year did not significantly changed in the study employees after receiving the pamphlet and lecture as ergonomic trainings. CONCLUSION: Workshop as an ergonomic training method had an effective and powerful role on decreasing the prevalence of neck and shoulders complaints among workers.

Cytotoxic and proinflammatory CD8+ T lymphocytes promote development of vulnerable atherosclerotic plaques in apoE-deficient mice.

BACKGROUND: Heart attacks and strokes, leading causes of deaths globally, arise from thrombotic occlusion of ruptured vulnerable atherosclerotic plaques characterized by abundant apoptosis, large necrotic cores derived from inefficient apoptotic cell clearance, thin fibrous caps, and focal inflammation. The genesis of apoptosis and necrotic cores in these vulnerable atherosclerotic plaques remains unknown. Cytotoxic CD8(+) T lymphocytes represent up to 50% of leukocytes in advanced human plaques and dominate early immune responses in mouse lesions, yet their role in atherosclerosis also remains unresolved. METHODS AND RESULTS: CD8(+) T-lymphocyte depletion by CD8α or CD8ß monoclonal antibody in apolipoprotein E-deficient mice fed a high-fat diet ameliorated atherosclerosis by reducing lipid and macrophage accumulation, apoptosis, necrotic cores, and monocyte chemoattractant protein 1, interleukin 1ß, interferon γ, and vascular cell adhesion molecule 1. Transfer of CD8(+) T cells into lymphocyte-deficient, apolipoprotein E-deficient mice partially reconstituted CD8(+) T cells in lymphoid compartments and was associated with CD8(+) T-cell infiltration in lesions, increased lipid and macrophage accumulation, apoptotic cells, necrotic cores, and interleukin 1ß in atherosclerotic lesions. Transfer of CD8(+) T cells deficient in perforin, granzyme B, or tumor necrosis factor α but not interferon γ failed to increase atherosclerotic lesions despite partial reconstitution in the lymphoid system and the presence in atherosclerotic lesions. Macrophages, smooth muscle cells, and endothelial cells were identified as apoptotic targets. CONCLUSIONS: We conclude that CD8(+) T lymphocytes promote the development of vulnerable atherosclerotic plaques by perforin- and granzyme B-mediated apoptosis of macrophages, smooth muscle cells, and endothelial cells that, in turn, leads to necrotic core formation and further augments inflammation by tumor necrosis factor α secretion.

Potently immunosuppressive 5-fluorouracil-resistant mesenchymal stromal cells completely remit an experimental autoimmune disease.

We treated mice with 5-fluorouracil (5-FU) to isolate a quiescent and undifferentiated mesenchymal stromal cell (MSC) population from the bone marrow. We examined these 5-FU-resistant MSCs (5-FU-MSCs) free from hematopoietic components for CFU fibroblasts (CFU-Fs) and assessed their immunosuppressive potential in vitro and in vivo. We differentiated fibroblastic CFU-Fs (Fibro-CFU-Fs) from mixed CFU-Fs, based on the absence of in situ expression of CD11b and CD45 hematopoietic markers, as well as on their differentiation capacity. Fibro-CFU-Fs were associated with increased numbers of large-sized Fibro-CFU-Fs (≥9 mm(2)) that displayed enhanced capacity for differentiation into adipogenic and osteogenic mesenchymal lineages. Administration of these 5-FU-resistant CD11b(-)CD45(-) MSCs 6 d after myelin oligodendrocyte glycoprotein (MOG) immunization completely remitted MOG-induced experimental autoimmune encephalomyelitis after initial development of mild disease. The remission was accompanied by reduced CNS cellular infiltration and demyelination, as well as a significant reduction in anti-MOG Ab and splenocyte proliferation to MOG. MOG-stimulated splenocytes from these mice showed elevated levels of Th2 cytokines (IL-4, IL-5, and IL-6) and decreased IL-17. Compared with untreated MSCs, 5-FU-MSCs demonstrated potent immunosuppression of Con A-stimulated splenocytes in vitro, even at a 1:320 MSC/splenocyte ratio. Immunosuppression was accompanied by elevated IL-1ra, IL-10, and PGE(2). Blocking IL-1ra, IL-10, and PGE(2), but not IL-6, heme oxygenase-1, and NO, attenuated 5-FU-MSC-induced immunosuppression. Together, our findings suggested that immunosuppression by 5-FU-MSC is mediated by a combination of elevated IL-1ra, IL-10, and PGE(2), anti-inflammatory Th2 cytokines, and decreased IL-17. Our findings suggested that 5-FU treatment identifies a population of potently immunosuppressive 5-FU-MSCs that have the potential to be exploited to remit autoimmune diseases.