Characterization of diamond and organic scintillation detectors utilizing radiation sources for continuous plasma operation.

This paper provides a comprehensive study of neutron calibration methodologies, specifically highlighting the capabilities for n-γ discrimination in diamond and EJ-309, and stilbene scintillation detectors. The calibration process detailed in this study includes pulse height analysis and pulse shape discrimination, relying on the analysis of charge deposition resulting from both γ and neutron interactions. Utilizing 60Co and 252Cf radiation sources, the energy spectra of these sources are obtained. The characterized detectors were used in ST40 experiments and allowed acquiring neutron signal during a plasma shot with good agreement among diamond and scintillation detectors. Then, the diamond detector was cross-calibrated against indium activation foils placed at the same location in proximity to the ST40 during plasma shots: both detectors measured a neutron flux of ≈106 cm-2 s-1 at ≈1 m distance from the tokamak center, and the discrepancy between the diamond detector and the activation foils is ≈25%.

Correlation between SDF-1α, CD34 positive hematopoietic stem cells and CXCR4 expression with liver fibrosis in CCl4 rat model.

BACKGROUND: One of the most frequent disorders is liver fibrosis. An improved understanding of the different events during the process of liver fibrosis & its reversibility could be helpful in its staging and in finding potential therapeutic agents. AIM: The goal of this research was to evaluate the relationship among CD34 + HPSCs, SDF-1α, and CXCR4 receptor expression with the percentage of the area of hepatic fibrosis. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were separated into the control group, liver injury group & spontaneous reversion group. The liver injury was induced by using 2 ml/kg CCl4 twice a week. Flow cytometric examination of CD34 + cells in the blood & liver was performed. Bone marrow & liver samples were taken for evaluation of the SDF-1α mRNA by PCR. Liver specimens were stained for histopathological and CXCR4 immuno-expression evaluation. RESULTS: In the liver injury group, the hepatic enzymes, fibrosis area percentage, CXCR4 receptor expression in the liver, CD34 + cells in the blood and bone marrow & the level SDF-1α in the liver and its concentration gradient were statistically significantly elevated with the progression of the liver fibrosis. On the contrary, SDF-1α in the bone marrow was statistically significantly reduced with the development of liver fibrosis. During the spontaneous reversion group, all the studied parameters apart from SDF-1α in the bone marrow were statistically substantially decreased compared with the liver injury group. We found a statistically substantial positive correlation between fibrosis area and all of the following: liver enzymes, CXCR4 receptor expression in the liver, CD34 + cells in the blood and liver, and SDF- 1α in the liver and its concentration gradient. In conclusion, in CCl4 rat model, the fibrosis area is significantly correlated with many parameters in the blood, bone marrow, and liver, which can be used during the process of follow-up during the therapeutic interventions.

Otological symptoms in patients with rheumatoid arthritis of the temporomandibular joint.

OBJECTIVE: The aim of the current study was to describe the pattern of otological symptoms in patients with rheumatoid arthritis (RA), having clinical temporomandibular joint (TMJ) involvement. This issue had not been previously addressed. METHODS: A questionnaire and examination findings protocol was applied for 141 patients with RA and 141 control subjects. RESULTS: Otological symptoms (otalgia, hearing loss, tinnitus, and vertigo), all had a significantly higher incidence in RA patients, compared to control subjects (P = .001). CONCLUSION: The onset and maintenance of otological symptoms in patients with TMJ involvement by RA probably result from peripheral, as well as central nervous system alterations in sensory stimuli programming.

Disposable platform for bacterial lysis and nucleic acid amplification based on a single USB-powered printed circuit board.

Recent advances in electronics and microfluidics have enabled several research groups to develop fully integrated, sample-to-result isothermal nucleic acid amplification test (NAAT) platforms for the point of care. However, high component counts and costs have limited translation of these platforms beyond the clinic to low-resource settings-including homes. Many NAATs include complex, multi-component heater electronics based on flex circuits or multiple printed circuit boards (PCBs) to support essential NAAT steps such as lysis, sample deactivation, and nucleic acid amplification. In contrast, current commercial assays for home use, such as those for pregnancy or ovulation that include electronics, typically have just one onboard PCB. This work describes a generalizable strategy to integrate all heaters and the electronics needed to control them onto a single low-cost, USB-powered PCB. We built a multiplexable disposable NAAT ("MD NAAT") platform that applies these principles, integrating small-area heaters that heat small regions to near-boiling (for pathogen lysis and deactivation) and large-area heaters (for amplification) on the same PCB. We show that both classes of heaters have high intra-board and inter-device reproducibility despite only heating a NAAT cartridge from below. We validated the small-area heaters by lysing methicillin-resistant Staphylococcus aureus (MRSA) cells and the large-area heaters by performing two types of isothermal NAATs (isothermal strand displacement amplification (iSDA) and loop-mediated isothermal amplification (LAMP)). These results demonstrate the merit of integrating NAAT heaters and control electronics onto a single printed circuit board and are a step toward translating NAATs to the home.

Temporomandibular disorder: A previously unreported complication of chronic suppurative otitis media.

OBJECTIVE: The aim of the current clinical study was to test the hypothesis that chronic suppurative otitis media (CSOM) might be significantly associated with signs of temporomandibular joint (TMJ) internal derangement. METHODS: The study involved 79 patients with CSOM and 79 control subjects. The TMJ was clinically examined in both groups. RESULTS: Signs of internal derangement of the TMJ(s) were found in 67.1% of CSOM patients versus 26.6% of control subjects (p = .001). CONCLUSION: CSOM may be associated with the extension of the inflammatory process into the TMJ, thereby predisposing to internal derangement of the joint.

Chronic craniomandibular pain after craniotomy: A long-term clinical study.

OBJECTIVE: Chronic craniomandibular/cervical pain and temporomandibular disorders have not been studied in patients who had a craniotomy several years previously. The aim of the current clinical work was to address these issues. METHODS: A total group of 150 ambulant patients who had a previous craniotomy was subclassified according to whether or not the temporalis muscle was manipulated. RESULTS: The average incidence of multiple subsite regional head and neck pain was 69.3% a number of years after a craniotomy. Evidence of internal derangement of the temporomandibular joint was significantly higher in the group that required manipulation of the temporalis muscle during the procedure. CONCLUSION: The pattern of chronic craniomandibular/cervical pain experienced years after a craniotomy supports the brain neuromatrix theory of pain.

Near-digital amplification in paper improves sensitivity and speed in biplexed reactions.

The simplest point-of-care assays are usually paper and plastic devices that detect proteins or nucleic acids at low cost and minimal user steps, albeit with poor limits of detection. Digital assays improve limits of detection and analyte quantification by splitting a sample across many wells (or droplets), preventing diffusion, and performing analyte amplification and detection in multiple small wells. However, truly digital nucleic acid amplification tests (NAATs) require costly consumable cartridges that are precisely manufactured, aligned, and operated to enable low detection limits. In this study, we demonstrate how to implement near-digital NAATs in low-cost porous media while approaching the low limits of detection of digital assays. The near-digital NAAT was enabled by a paper membrane containing lyophilized amplification reagents that automatically, passively meters and distributes a sample over a wide area. Performing a NAAT in the paper membrane while allowing diffusion captures many of the benefits of digital NAATs if the pad is imaged at a high spatial resolution during amplification. We show that the near-digital NAAT is compatible with a low-cost paper and plastic disposable cartridge coupled to a 2-layer rigid printed circuit board heater (the MD NAAT platform). We also demonstrate compatibility with biplexing and imaging with mobile phones with different camera sensors. We show that the near-digital NAAT increased signal-to-noise ratios by ~ 10×, improved limits of detection from above 103 copies of methicillin-resistant Staphylococcus aureus genomic DNA to between 100 and 316 copies in a biplexed reaction containing 105 copies of co-amplifying internal amplification control DNA, and reduced time-to-result from 45 min of amplification to 15-20 min for the positive samples.

A clinical study on the incidence of internal derangement of the temporomandibular joint following harvesting of temporalis fascia.

OBJECTIVE: The aim of the current clinical study was to reveal whether harvesting of a temporalis fascia graft would be associated with a higher incidence of temporomandibular joint (TMJ) internal derangement. METHODS: The study group involved 104 patients who had middle-ear operations, 67 of which involved harvesting of temporalis fascia and 37 that did not. The TMJs were clinically examined in each group. RESULTS: The total incidence of internal derangement of the TMJ was significantly higher in the group that had temporalis fascia harvesting (79.1%), compared to the group that did not have temporalis fascia harvesting (29.7%), (p= 0.001). CONCLUSION: Harvesting of temporalis fascia probably alters mandibular kinematics and predisposes to internal derangement of the TMJs.

Isothermal Amplification with a Target-Mimicking Internal Control and Quantitative Lateral Flow Readout for Rapid HIV Viral Load Testing in Low-Resource Settings.

Point-of-care diagnostics often use isothermal nucleic acid amplification for qualitative detection of pathogens in low-resource healthcare settings but lack sufficient precision for quantitative applications such as HIV viral load monitoring. Although viral load (VL) monitoring is an essential component of HIV treatment, commercially available tests rely on relatively high-resource chemistries like real-time polymerase chain reaction and are thus used on an infrequent basis for millions of people living with HIV in low-income countries. To address the constraints of low-resource settings on nucleic acid quantification, we describe a recombinase polymerase amplification and lateral flow detection approach that quantifies HIV-1 DNA or RNA by comparison to a competitive internal amplification control (IAC) of a known copy number, which may be set to any useful threshold (in our case, a clinically relevant threshold for HIV treatment failure). The IAC is designed to amplify alongside the HIV target with a similar efficiency, allowing for normalization of the assay to variation or inhibition and enabling an endpoint readout that is compatible with commercially available kits for nucleic acid lateral flow detection and interpretable with minimal instrumentation or by the naked eye. We find that this approach can reliably differentiate ≤600 or ≥1400 copies of HIV DNA from a 1000-copy threshold when lateral flow strips are imaged with a conventional office scanner and analyzed with free densitometry software. We further demonstrate a user-friendly adaptation of this analysis to process cell phone photographs with an automated script. Alternatively, we show via a survey that 21 minimally trained volunteers could reliably resolve ≥10-fold (log10) differences of HIV DNA or RNA by naked eye interpretation of lateral flow results. This amplification and detection workflow requires minimal instrumentation, takes just 30 min to complete, and when combined with a suitable sample preparation method, may enable HIV VL testing while the patient waits or a self-test, which has the potential to improve care. This approach may be adapted for other applications that require quantitative analysis of a nucleic acid target in low-resource settings.

A minireview of the anatomical and pathological factors pertaining to Costen's syndrome symptoms.

Objective: Interest in the symptoms pertaining to Costen's syndrome has revived in recent years. The aim of this work is to address the symptoms of Costen's syndrome from the basic science perspectiveMethods: A minireview of the literature related to Costen's syndrome symptoms was performed by retrieving relevant articles from the PubMed database from 1980 until 2021.Results: The validity of Costen's syndrome symptoms has been confirmed by a multitude of articles. Conclusion: Maladaptive plasticity in the central nervous system pathways probably accounts for the incidence and severity of Costen's syndrome symptoms.

A comparative clinical and radiographic study on patients with chronic facial pain with and without temporomandibular disorder presenting to an otolaryngology clinic.

Objective: Facial pain associated with temporomandibular disorder (TMD) is considered a component of Costen's syndrome. However, prior to the current study, no previous clinical and radiographic studies have addressed facial pain in patients with TMD. Methods: The study included 212 patients with chronic facial pain examined in an otolaryngology clinic. These were stratified into 132 patients with TMD and 80 patients without TMD. Clinical and radiographic findings were documented in both groups. Results: Forty-eight patients in the TMD group had normal endoscopic findings and clear CT scans and had their facial pain directly attributable to TMD. Conclusion: In patients presenting with facial pain, where nasal endoscopy reveals no abnormality, TMD should be specifically addressed, especially if CT scans of the paranasal sinuses are clear.

A comparative clinical study of arthrogenous versus myogenous temporomandibular disorder in patients presenting with Costen's syndrome.

Objective: Costen's syndrome involves otoneurological and sinonasal symptoms associated with temporomandibular disorder (TMD). The current study compared the symptoms related to Costen's syndrome in patients with arthrogenous versus myogenous TMD.Methods: The study involved 294 consecutive patients with TMD, prospectively examined over a period of 6 months. These were stratified into 180 patients with arthrogenous TMD and 114 patients with myogenous TMD. A questionnaire and examination protocol was applied for each patient.Results: Sinonasal symptoms were more common in the arthrogenous group (p = .001), whereas, hearing loss and vertigo were more common in the myogenous group (p = .001).Conclusion: The current study provides support for central nervous system neuroplastic changes in the genesis of Costen's syndrome symptoms.

Two-Fluorophore Mobile Phone Imaging of Biplexed Real-Time NAATs Overcomes Optical Artifacts in Highly Scattering Porous Media.

Nucleic acid amplification tests (NAATs) are common in laboratory and clinical settings because of their low time to result and exquisite sensitivity and specificity. Laboratory NAATs include onboard positive controls to reduce false negatives and specialized hardware to enable real-time fluorescence detection. Recent efforts to translate NAATs into at-home tests sacrifice one or more of the benefits of laboratory NAATs, such as sensitivity, internal amplification controls (IACs), or time to result. In this manuscript, we describe a mobile-phone-based strategy for real-time imaging of biplexed NAATs in paper. The strategy consisted of: (1) using mobile phones with multipass excitation and emission filters on the flash and camera to image the signal from distinct fluorophore-labeled probe types in a biplexed NAAT in a glass fiber membrane; and (2) analyzing the differential fluorescence signal between the red and green color channels of phone images to overcome a strong evaporation-induced optical artifact in heated glass fiber pads due to changes in the refractive index. We demonstrated that differential fluorescence imaging enabled low limits of detection (316 copies of methicillin-resistant Staphylococcus aureus DNA) in our lab's "MD NAAT" platform, even in biplexed isothermal strand displacement amplification reactions containing 100k copies of coamplifying IAC DNA templates. These results suggest that two-fluorophore mobile phone imaging may enable translating the benefits of extant laboratory-based, real-time NAATs to the point of care.

A comparative clinical study of temporomandibular disorder patients in the otolaryngology clinic versus a rheumatology clinic.

Objective Temporomandibular disorders (TMD) may be associated with local or widespread symptoms, including pain. The aim of this study was to compare clinical features of TMD patients presenting to an otolaryngology clinic with TMD patients presenting to a rheumatology clinic. Methods The study included 107 patients in the otolaryngology setting and 103 patients in the rheumatology setting. A comparison between both groups was made regarding the clinical data. Results Patients in the otolaryngology setting featured more otological symptoms, compared with those in the rheumatology setting. Otological symptoms were affirmed in 70 patients (65.4%) in the otolaryngology setting but in only 18 patients (17.5%) in the rheumatology setting (p = 0.001). Patients in the rheumatology setting showed more structural TMJ changes, compared with those in the otolaryngology setting (p < 0.01). Conclusion Patients presenting to the otolaryngologist may clinically and pathologically represent a different cohort from those presenting to the rheumatologist.

Mobile Phone Ratiometric Imaging Enables Highly Sensitive Fluorescence Lateral Flow Immunoassays without External Optical Filters.

Paper-based diagnostic tests based on the lateral flow immunoassay concept promise low-cost, point-of-care detection of infectious diseases, but such assays suffer from poor limits of detection. One factor that contributes to poor analytical performance is a reliance on low-contrast chromophoric optical labels such as gold nanoparticles. Previous attempts to improve the sensitivity of paper-based diagnostics include replacing chromophoric labels with enzymes, fluorophores, or phosphors at the expense of increased fluidic complexity or the need for device readers with costly optoelectronics. Several groups, including our own, have proposed mobile phones as suitable point-of-care readers due to their low cost, ease of use, and ubiquity. However, extant mobile phone fluorescence readers require costly optical filters and were typically validated with only one camera sensor module, which is inappropriate for potential point-of-care use. In response, we propose to couple low-cost ultraviolet light-emitting diodes with long Stokes-shift quantum dots to enable ratiometric mobile phone fluorescence measurements without optical filters. Ratiometric imaging with unmodified smartphone cameras improves the contrast and attenuates the impact of excitation intensity variability by 15×. Practical application was shown with a lateral flow immunoassay for influenza A with nucleoproteins spiked into simulated nasal matrix. Limits of detection of 1.5 and 2.6 fmol were attained on two mobile phones, which are comparable to a gel imager (1.9 fmol), 10× better than imaging gold nanoparticles on a scanner (18 fmol), and >2 orders of magnitude better than gold nanoparticle-labeled assays imaged with mobile phones. Use of the proposed filter-free mobile phone imaging scheme is a first step toward enabling a new generation of highly sensitive, point-of-care fluorescence assays.

Effect of human umbilical cord blood derived CD34+ hematopoietic stem cell on the expression of Wnt4 and P53 genes in a rat model of hepatocellular carcinoma.

BACKGROUND AND AIM OF THE WORK: Hepatocellular carcinoma (HCC) is the most frequent primary liver malignancy. Chronic liver injuries as chronic hepatitis C and hepatitis B viruses, aflatoxins consumption and nonalcoholic fatty liver disease are well-established causes of HCC. HCC is associated with a series of molecular changes, as alternation in glypican-3, P53 expression and Wnt/ß-catenin pathway. Hepatic cancer progenitor cells could contribute to HCC development. This research aimed to study the effectiveness of human CD34+ hematopoietic stem cell on Wnt4 and P53 genes expression, histopathological grading and hepatic progenitor cells percentage in HCC rat model. MATERIALS AND METHODS: HCC was induced in the experimental group of outbred Sprague Dawley rats by administration of 50 mg/L N-nitroso-Di-Ethylamine (DEN) in drinking water for 15 weeks. Forty-six animals were used in total, they were initially subdivided into two groups; control (n = 6) and experimental (n = 40), the latter consisting of 4 DEN-unaffected, 6 DEN-lethalities and 30 surviving DEN-animals with elevated AFP. These 30 animals with elevated AFP were then subdivided into a new HCC control group (n = 15) and the stem cell treated group (n = 15). The latter group was injected with CD34+ human hematopoietic stem cell (1 × 106 cells/rat) in the rat's tail vein. Cyclosporine A (10 mg/kg) was injected intraperitoneal, starting 24 h before human stem cell transplantation. After 20 weeks passing since the beginning of the experiment, all rats were sacrificed and liver specimens were subjected to histopathological examination, RT-PCR in order to examine Wnt4 and P53 gene expression and flow cytometry to measure hepatic progenitor OV6 positive cells percentage. RESULTS: The saline-treated HCC group (with prior 15 week DEN exposure) showed higher levels of wnt4 and p53 gene expression (1.59 and 1.36 fold, respectively) and increased percentage in OV6+ progenitor cells (+4.9% in absolute terms) compared to saline-treated controls (p < 0.01, ANOVA). Compared with the saline HCC-group, transplantation with CD34+ human hematopoietic stem cells produced a further increase in the levels of wnt4 (+19.4%) and p53 gene expression (+53%), a 2-fold increase in the percentage of cancer progenitor cells and increased HCC pathology grading (all p < 0.01). The positive correlation between p53 and HCC grade (Spearman rho +0.73, p < 0.05) and negative correlation between wnt and OV6+% levels (rho -0.65, p < 0.05) in the saline-HCC group were not observed in the CD34+ HCC group. CONCLUSIONS: Human CD34+ cells transplantation has a deteriorating effect on HCC.

Effect of human umbilical cord blood stem cell transplantation on oval cell response in 2-AAF/CCL4 liver injury model: experimental immunohistochemical study.

BACKGROUND: Oval cells, specific liver progenitors, are activated in response to injury. The human umbilical cord blood (hUCB) is a possible source of transplantable hepatic progenitors and can be used in cases of severe liver injury. We detected the effect of hUCB stem cell transplantation on natural response of oval cells to injury. METHODS: Twenty-four female albino rats were randomly divided into three groups: (A) control, (B) liver injury with hepatocyte block, and (C) hUCB transplanted group. Hepatocyte block was performed by administration of 2-acetylaminofluorene (2-AAF) for 12 days. CCL4 was administrated at day 5 from experiment start. Animals were sacrificed at 9 days post CCL4 administration, and samples were collected for biochemical and histopathological analysis. Oval cell response to injury was evaluated by the percentage of oval cells in the liver tissue and frequency of cells incorporated into new ducts. RESULTS: Immunohistochemical analysis of oval cell response to injury was performed. There was significant deviation in the hUCB-transplanted (4.9 ± 1.4) and liver injury groups (2.4 ± 0.9) as compared to control (0.89 ± 0.4) 9 days post injury. Detection of oval cell response was dependant on OV-6 immunoreactivity. For mere localization of cells with human origin, CD34 antihuman immunoreactivity was performed. There was no significant difference in endogenous OV-6 immunoreactivity following stem cell transplantation as compared to the liver injury group. CONCLUSIONS: In vivo transplantation of cord blood stem cells (hUCB) does not interfere with natural oval cell response to liver injury.

Wavelengths and Lifetimes of Paper Autofluorescence: A Simple Substrate Screening Process to Enhance the Sensitivity of Fluorescence-Based Assays in Paper.

Porous media made of nitrocellulose and glass fiber are common "paper" substrates for lateral flow assays, microfluidic paper analytical devices and other point-of-care diagnostic assays. Such assays commonly use optical labels such as gold nanoparticles, latex beads, or fluorescent nanoparticles to visualize the presence of analytes. Fluorescent labels are commonly used in bioassays to enhance sensitivity, but autoluminescence of the paper substrate worsens signal-to-noise ratios of fluorescence-based assays. To date, there exists no systematic investigation of autoluminescence wavelengths or lifetimes of porous membranes used in lateral flow assays. In response, we quantified the autoluminescence of commonly used porous materials across the visible spectrum via excitation-emission spectroscopy and time-resolved fluorescence spectroscopy, and demonstrate that autoluminescence is solely due to autofluorescence with lifetimes of about 5 ns in the visible spectrum. Counterintuitively, we found that spectroscopy alone does not provide sufficient information to select candidate paper substrates for fluorophore-labeled assays. Therefore, we developed a simple quantitative framework to select a low-fluorescence substrate that minimizes both the overlap of paper and fluorophore emission spectra and the fluorescence intensity on an imaging system of interest (such as a gel imager). Use of this framework was shown to lower the limit of detection of an influenza A nucleoprotein immunoassay by over 50%. The tools developed in this manuscript enable assay developers to screen appropriate, low-fluorescence porous substrates and enhance the sensitivity of membrane-based fluorescence assays.

Sensitive Protein Detection and Quantification in Paper-Based Microfluidics for the Point of Care.

The design of appropriate diagnostic assays for the point of care requires development of suitable biosensors, detection methods, and diagnostic platforms for sensitive, quantitative detection of biological analytes. Protein targets in particular are especially challenging to detect quantitatively and sensitively due to the lack of amplification strategies akin to nucleic acid amplification. However, recent advances in transducer and biosensor design, new detection labels, and paper-based microfluidics may realize the goal of sensitive, fast, portable, and low-cost protein detection. In this review, we discuss the biochemistry, optics, and engineering advances that may be leveraged to design such a sensitive protein diagnostic assay. The binding kinetics, mechanisms of binding in porous networks, and potential transducers are explained in detail. We discuss the relative merits of various optical detection strategies, potential detection labels, optical readout approaches, and image-processing techniques that are amenable to point-of-care use. To conclude, we present a systematic analysis of potential approaches to enhance the sensitivity of paper-based assays. The assay development framework presented here provides bioassay developers a strategy to methodically enhance the sensitivity and point-of-care suitability of protein diagnostics.