Role of prazosin in patients with Guillain-Barré syndrome with sympathetic overactivity: A cohort study.

INTRODUCTION/AIMS: In Guillain-Barré syndrome (GBS), patients with dysautonomia demonstrate sympathetic overactivity (SO). This study assessed the role of prazosin (α1-blocker) in the management of SO. METHODS: This cohort study was conducted from January 2022 to September 2023. Thirty-two GBS patients with SO received prazosin (2.5-10 mg three times a day) (prazosin group). For comparison, we included historical controls that included 33 GBS patients having SO with similar baseline characteristics, including median age and disability, who did not receive prazosin, from a GBS registry of patients admitted during February 2018-December 2021. The primary endpoint was days to resolution of SO. Secondary endpoints were daily fluctuations in the systolic (SBP) and diastolic blood pressure (DBP), duration of hospital stay, in-hospital mortality, and disability at 3 months. RESULTS: The median ages of both the treatment and the control groups were 36 (IQR 25-49) years and 43 (66.2%) were males. The demographic and clinical parameters were comparable. Prazosin resulted in significantly earlier normalization of SO compared to the control group (median 15 vs. 20 days; p = .01). The mean fluctuations in the SBP and DBP at 15 days were significantly lower in the prazosin group. However, the duration of hospital stay and good recovery at 3 months were comparable. Three patients developed hypotension, while two patients died (ventilator-associated pneumonia) in the prazosin group. DISCUSSION: This study provides new evidence supporting the role of prazosin in SO, and needs randomized trials to confirm our findings.

An Outbreak of Acute Hemorrhagic Conjunctivitis Caused by Coxsackievirus A24 in Eastern Uttar Pradesh, India 2023.

INTRODUCTION: Acute hemorrhagic conjunctivitis (AHC) outbreaks are caused mostly by viruses. During July-August 2023, there was a sudden spike in acute hemorrhage conjunctivitis cases in Eastern Uttar Pradesh, India. To identify the etiological and gain molecular epidemiology of the agent, the study was conducted. METHODOLOGY: Conjunctival swabs were collected from patients (n = 128) with presumed acute hemorrhage conjunctivitis visiting two tertiary care hospitals. RESULTS: Enteroviruses infection was identified in 96 (75%) patients. In these patients, coxsackievirus A24 (CV-A24) infection was further confirmed by targeting the genetic regions of 3C protease and VP1. Furthermore, the study established the outbreak was caused by the genotype IV of CV-A24 with the highest genetic similarity with CV-A24 reported from Northeast India, China, and Pakistan circulating during the same period. The comparison of our study sequences with earlier Indian outbreak strains (2007) revealed four amino acid substitutions at the 3C region ("S21N," "V30I," "S66I," and "V75I") and three non-synonymous mutations at the VP1 region ("L16I," "P21S," and "N301D"). CONCLUSION: The study findings revealed that the AHC outbreak was caused by genotype IV of CV-A24 in this region. Molecular identification accompanied by phylogenetic analysis will be useful in studying the enterovirus epidemiology associated with AHC outbreaks.

Role of T2 relaxometry in localization of mesial temporal sclerosis and the degree of hippocampal atrophy in patients with intractable temporal lobe epilepsy: A cross sectional study.

Mesial temporal lobe epilepsy is one of the most common causes of refractory epilepsy worldwide. A good percentage of patients do not have detectable hippocampal atrophy on magnetic resonance imaging (MRI). The objective of this study is to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable temporal lobe epilepsy (TLE). T2 relaxometry can also be used to correlate the clinical severity of the disease with the relaxometry readings in those who have hippocampal atrophy as well as those who do not. Thirty two patients having clinical and electrophysiological features of TLE were enrolled and a MRI brain with T2 relaxometry was done. Hippocampal T2 relaxometry values were calculated in the head, body, and tail of the hippocampus and average T2 relaxometry values were calculated, and a comparison was done with the controls. For patients with unilateral involvement, the contralateral side was taken as control and in cases of bilateral involvement, controls were identified from normal subjects. T2 relaxometry is found to be superior to MR visual analysis in the early detection of cases of hippocampal sclerosis where there is no atrophy on visual analysis. Nine out of 32 patients (28%) were normal on MR visual analysis; however, showed increased values on T2 relaxometry, correlating with clinical and electrophysiological diagnosis. The rest of the patients with hippocampal atrophy showed a correlation of T2 relaxometry values with the degree of atrophy. The hippocampal T2 measurement is thus more sensitive and specific. The study was clinically significant (p < .0001). There was a mild female predilection of the disease and there was no significant correlation with comorbidities. There was a strong positive correlation with patients having a history of febrile seizures in childhood. T2 relaxometry may accurately lateralize the majority of patients with persistent TLE and offers evidence of hippocampus injury in those patients who do not show evidence of atrophy on MRI and also the T2 relaxometry values correlated with the degree of atrophy. Early identification of hippocampal sclerosis is crucial for prompt management which offers better outcomes.

Inspection of Enamel Removal Using Infrared Thermal Imaging and Machine Learning Techniques.

Within aerospace and automotive manufacturing, the majority of quality assurance is through inspection or tests at various steps during manufacturing and assembly. Such tests do not tend to capture or make use of process data for in-process inspection and certification at the point of manufacture. Inspection of the product during manufacturing can potentially detect defects, thus allowing consistent product quality and reducing scrappage. However, a review of the literature has revealed a lack of any significant research in the area of inspection during the manufacturing of terminations. This work utilises infrared thermal imaging and machine learning techniques for inspection of the enamel removal process on Litz wire, typically used for aerospace and automotive applications. Infrared thermal imaging was utilised to inspect bundles of Litz wire containing those with and without enamel. The temperature profiles of the wires with or without enamel were recorded and then machine learning techniques were utilised for automated inspection of enamel removal. The feasibility of various classifier models for identifying the remaining enamel on a set of enamelled copper wires was evaluated. A comparison of the performance of classifier models in terms of classification accuracy is presented. The best model for enamel classification accuracy was the Gaussian Mixture Model with expectation maximisation; it achieved a training accuracy of 85% and enamel classification accuracy of 100% with the fastest evaluation time of 1.05 s. The support vector classification model achieved both the training and enamel classification accuracy of more than 82%; however, it suffered the drawback of a higher evaluation time of 134 s.

A Spectroscopic Reflectance-Based Low-Cost Thickness Measurement System for Thin Films: Development and Testing.

The requirement for alternatives in roll-to-roll (R2R) processing to expand thin film inspection in wider substrates at lower costs and reduced dimensions, and the need to enable newer control feedback options for these types of processes, represents an opportunity to explore the applicability of newer reduced-size spectrometers sensors. This paper presents the hardware and software development of a novel low-cost spectroscopic reflectance system using two state-of-the-art sensors for thin film thickness measurements. The parameters to enable the thin film measurements using the proposed system are the light intensity for two LEDs, the microprocessor integration time for both sensors and the distance from the thin film standard to the device light channel slit for reflectance calculations. The proposed system can deliver better-fit errors compared with a HAL/DEUT light source using two methods: curve fitting and interference interval. By enabling the curve fitting method, the lowest root mean squared error (RMSE) obtained for the best combination of components was 0.022 and the lowest normalised mean squared error (MSE) was 0.054. The interference interval method showed an error of 0.09 when comparing the measured with the expected modelled value. The proof of concept in this research work enables the expansion of multi-sensor arrays for thin film thickness measurements and the potential application in moving environments.

Investigating the Effect of Real-Time Center of Pressure Feedback Training on the Swing Phase of Lower Limb Kinematics in Transfemoral Prostheses With SACH Foot.

Transfemoral amputee often encounters reduced toe clearance resulting in trip-related falls. Swing-phase joint angles have been shown to influence the toe clearance; therefore, training intervention that targets shaping the swing phase joint angles can potentially enhance toe clearance. The focus of this study was to investigate the effect of the shift in the location of the center of pressure (CoP) during heel strike on modulation of the swing-phase joint angles in able-bodied participants (n = 6) and transfemoral amputees (n = 3). We first developed a real-time CoP-based visual feedback system such that participants could shift the CoP during treadmill walking. Next, the kinematic data were collected during two different walking sessions-baseline (without feedback) and feedback (shifting the CoP anteriorly/posteriorly at heel strike to match the target CoP location). Primary swing-phase joint angle adaptations were observed with feedback such that during the midswing phase, posterior CoP shift feedback significantly increases (p < 0.05) the average hip and knee flexion angle by 11.55 deg and 11.86 deg, respectively, in amputees, whereas a significant increase (p < 0.05) in ankle dorsiflexion, hip and knee flexion angle by 3.60 deg, 3.22 deg, and 1.27 deg, respectively, compared to baseline was observed in able-bodied participants. Moreover, an opposite kinematic adaptation was seen during anterior CoP shift feedback. Overall, results confirm a direct correlation between the CoP shift and the modulation in the swing-phase lower limb joint angles.

Mobile Robots for In-Process Monitoring of Aircraft Systems Assemblies.

Currently, systems installed on large-scale aerospace structures are manually equipped by trained operators. To improve current methods, an automated system that ensures quality control and process adherence could be used. This work presents a mobile robot capable of autonomously inspecting aircraft systems and providing feedback to workers. The mobile robot can follow operators and localise the position of the inspection using a thermal camera and 2D lidars. While moving, a depth camera collects 3D data about the system being installed. The in-process monitoring algorithm uses this information to check if the system has been correctly installed. Finally, based on these measurements, indications are shown on a screen to provide feedback to the workers. The performance of this solution has been validated in a laboratory environment, replicating a trailing edge equipping task. During testing, the tracking and localisation systems have proven to be reliable. The in-process monitoring system was also found to provide accurate feedback to the operators. Overall, the results show that the solution is promising for industrial applications.

Loss of HIF1A From Pancreatic Cancer Cells Increases Expression of PPP1R1B and Degradation of p53 to Promote Invasion and Metastasis.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinomas (PDACs) are hypovascular, resulting in the up-regulation of hypoxia inducible factor 1 alpha (HIF1A), which promotes the survival of cells under low-oxygen conditions. We studied the roles of HIF1A in the development of pancreatic tumors in mice. METHODS: We performed studies with KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx1-Cre (KPC) mice, KPC mice with labeled pancreatic epithelial cells (EKPC), and EKPC mice with pancreas-specific depletion of HIF1A. Pancreatic and other tissues were collected and analyzed by histology and immunohistochemistry. Cancer cells were cultured from PDACs from mice and analyzed in cell migration and invasion assays and by immunoblots, real-time polymerase chain reaction, and liquid chromatography-mass spectrometry. We performed studies with the human pancreatic cancer cell lines PATU-8988T, BxPC-3, PANC-1, and MiaPACA-2, which have no or low metastatic activity, and PATU-8988S, AsPC-1, SUIT-2 and Capan-1, which have high metastatic activity. Expression of genes was knocked down in primary cancer cells and pancreatic cancer cell lines by using small hairpin RNAs; cells were injected intravenously into immune-competent and NOD/SCID mice, and lung metastases were quantified. We compared levels of messenger RNAs in pancreatic tumors and normal pancreas in The Cancer Genome Atlas. RESULTS: EKPC mice with pancreas-specific deletion of HIF1A developed more advanced pancreatic neoplasias and PDACs with more invasion and metastasis, and had significantly shorter survival times, than EKPC mice. Pancreatic cancer cells from these tumors had higher invasive and metastatic activity in culture than cells from tumors of EKPC mice. HIF1A-knockout pancreatic cancer cells had increased expression of protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B). There was an inverse correlation between levels of HIF1A and PPP1R1B in human PDAC tumors; higher expression of PPP1R1B correlated with shorter survival times of patients. Metastatic human pancreatic cancer cell lines had increased levels of PPP1R1B and lower levels of HIF1A compared with nonmetastatic cancer cell lines; knockdown of PPP1R1B significantly reduced the ability of pancreatic cancer cells to form lung metastases in mice. PPP1R1B promoted degradation of p53 by stabilizing phosphorylation of MDM2 at Ser166. CONCLUSIONS: HIF1A can act a tumor suppressor by preventing the expression of PPP1R1B and subsequent degradation of the p53 protein in pancreatic cancer cells. Loss of HIF1A from pancreatic cancer cells increases their invasive and metastatic activity.

Neurological manifestations of coronavirus disease 2019: exploring past to understand present.

SARS-CoV-2 infection, resulting in Coronavirus disease 2019 (COVID-19), has significantly affected the entire world. It was labelled a pandemic by World Health Organization. Although it commonly produces respiratory symptoms, neurological features have been described. Neurological manifestations may vary from non-specific symptoms such as headache, dizziness, myalgia and/or fatigue, olfactory or taste dysfunction to specific syndromes including meningitis, stroke, acute transverse myelitis and Guillain-Barre syndrome. This review describes potential pathogenetic mechanisms and neurological manifestations of COVID-19 along with its management. Considering structural and pathogenetic similarity of SARS-CoV-2 with SARS-CoV and MERS viruses, we compared their neurological manifestations and mentioned few features expected in COVID-19 in future. Interestingly, many COVID-19 cases may present with pure neurological manifestations at onset with non-neurological features manifesting few days later and we propose the term "Neuro-COVID syndrome" for such cases. Awareness of neurological manifestations may facilitate its management and improve outcome in such patients.

A Knowledge-Based Cognitive Architecture Supported by Machine Learning Algorithms for Interpretable Monitoring of Large-Scale Satellite Networks.

Cyber-physical systems such as satellite telecommunications networks generate vast amounts of data and currently, very crude data processing is used to extract salient information. Only a small subset of data is used reactively by operators for troubleshooting and finding problems. Sometimes, problematic events in the network may go undetected for weeks before they are reported. This becomes even more challenging as the size of the network grows due to the continuous proliferation of Internet of Things type devices. To overcome these challenges, this research proposes a knowledge-based cognitive architecture supported by machine learning algorithms for monitoring satellite network traffic. The architecture is capable of supporting and augmenting infrastructure engineers in finding and understanding the causes of faults in network through the fusion of the results of machine learning models and rules derived from human domain experience. The system is characterised by (1) the flexibility to add new or extend existing machine learning algorithms to meet the user needs, (2) an enhanced pattern recognition and prediction through the support of machine learning algorithms and the expert knowledge on satellite infrastructure, (3) the ability to adapt to changing conditions of the satellite network, and (4) the ability to augment satellite engineers through interpretable results. An industrial real-life satellite case study is provided to demonstrate how the architecture could be used. A single blind experimental methodology was used to validate the results generated by our approach.

Fluorescent probes with high pKa values based on traditional, near-infrared rhodamine, and hemicyanine fluorophores for sensitive detection of lysosomal pH variations.

Sterically hindered fluorescent probes (A-C) have been developed by introducing 2-aminophenylboronic acid pinacol ester to a traditional, A, a near-infrared rhodamine dye, B, and a near-infrared hemicyanine dye, C, forming closed spirolactam ring structures. Probe A was non-fluorescent under basic pH conditions whereas probes B and C were moderately fluorescent with fluorescence quantum yields of 9% and 5% in pH 7.4 PBS buffer containing 1% ethanol, respectively. With all probes increasing acidity leads to significant increases in fluorescence at 580 nm, 644 and 744 nm for probes A, B and C with fluorescence quantum yields of 26%, 21% and 10% in pH 4.5 PBS buffer containing 1% ethanol, respectively. Probes A, B and C were calculated to have pKa values of 5.81, 5.45 and 6.97. The difference in fluorescence under basic conditions is ascribed to easier opening of the closed spirolactam ring configurations due to significant steric hindrance between the 2-aminophenylboronic acid pinacol ester residue and an adjacent H atom in the xanthene derivative moiety in probe B or C. The probes show fast, reversible, selective and sensitive fluorescence responses to pH changes, and are capable of sensing lysosomal pH variations in living cells.

PVT1 dependence in cancer with MYC copy-number increase.

'Gain' of supernumerary copies of the 8q24.21 chromosomal region has been shown to be common in many human cancers and is associated with poor prognosis. The well-characterized myelocytomatosis (MYC) oncogene resides in the 8q24.21 region and is consistently co-gained with an adjacent 'gene desert' of approximately 2 megabases that contains the long non-coding RNA gene PVT1, the CCDC26 gene candidate and the GSDMC gene. Whether low copy-number gain of one or more of these genes drives neoplasia is not known. Here we use chromosome engineering in mice to show that a single extra copy of either the Myc gene or the region encompassing Pvt1, Ccdc26 and Gsdmc fails to advance cancer measurably, whereas a single supernumerary segment encompassing all four genes successfully promotes cancer. Gain of PVT1 long non-coding RNA expression was required for high MYC protein levels in 8q24-amplified human cancer cells. PVT1 RNA and MYC protein expression correlated in primary human tumours, and copy number of PVT1 was co-increased in more than 98% of MYC-copy-increase cancers. Ablation of PVT1 from MYC-driven colon cancer line HCT116 diminished its tumorigenic potency. As MYC protein has been refractory to small-molecule inhibition, the dependence of high MYC protein levels on PVT1 long non-coding RNA provides a much needed therapeutic target.

Design, synthesis, in silico and in vitro evaluation of novel diphenyl ether derivatives as potential antitubercular agents.

Diphenyl ether derivatives inhibit mycobacterial cell wall synthesis by inhibiting an enzyme, enoyl-acyl carrier protein reductase (InhA), which catalyses the last step in the fatty acid synthesis cycle of genus Mycobacterium. To select and validate a protein crystal structure of enoyl-acyl carrier protein reductase of Mycobacterium tuberculosis for designing inhibitors using molecular modelling, a cross-docking and correlation study was performed. A series of novel 1-(3-(3-hydroxy-4-phenoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) ethan-1-ones were synthesized from this model and screened for their antitubercular activity against M. tuberculosis H37Rv. Compound PYN-8 showed good antitubercular activity on M. tuberculosis H37Rv (MIC = 4-7 µM) and Mycobacterium bovis (% inhibition at 10 µM = 95.91%). Cytotoxicity of all the synthesized derivatives was assessed using various cell lines, and they were found to be safe. Structure of PYN-8 was also confirmed by single-crystal X-ray diffraction. The molecular modelling studies also corroborated the biological activity of the compounds. Further, in silico findings revealed that all these tested compounds exhibited good ADME properties and drug likeness and thus may be considered as potential candidates for further drug development.

Applying a 6 DoF Robotic Arm and Digital Twin to Automate Fan-Blade Reconditioning for Aerospace Maintenance, Repair, and Overhaul.

The UK is home to several major air commercial and transport hubs. As a result, there is a high demand for Maintenance, Repair, and Overhaul (MRO) services to ensure that fleets of aircraft are in airworthy conditions. MRO services currently involve heavy manual labor. This creates bottlenecks, low repeatability, and low productivity. Presented in this paper is an investigation to create an automation cell for the fan-blade reconditioning component of MRO. The design and prototype of the automation cell is presented. Furthermore, a digital twin of the grinding process is developed and used as a tool to explore the required grinding force parameters needed to effectively remove surface material. An integration of a 6-DoF industrial robot with an end-effector grinder and a computer vision system was undertaken. The computer vision system was used for the digitization of the fan-blade surface as well as tracking and guidance of material removal. Our findings reveal that our proposed system can perform material removal, track the state of the fan blade during the reconditioning process and do so within a closed-loop automated robotic work cell.

Effect of Composition and Thickness on the Perpendicular Magnetic Anisotropy of (Co/Pd) Multilayers.

Magnetic materials with perpendicular magnetic anisotropy (PMA) have wide-ranging applications in magnetic recording and sensing devices. Multilayers comprised of ferromagnetic and non-magnetic metals (FM-NM) are interesting materials, as their magnetic anisotropy depends strongly on composition and growth parameters. In this context, (Co/Pd) multilayers have gained huge interest recently due to their robustness and tunable PMA. Here, we report a systematic study of the effect of composition on the magnetic anisotropy of (Co/Pd) multilayers grown by Direct Current (DC) magnetron sputtering. Four different series of (Co/Pd)×10 multilayers with different thicknesses of Co and Pd were examined. Vibrating sample magnetometery was used to determine the magnetic anisotropy of these films. X-ray diffraction and transmission electron microscopy experiments were performed to understand the structural morphology of the films. Our results showed that (Co/Pd)×10 multilayers exhibit PMA when the Co to Pd ratio is less than or equal to 1 and the thickness of Co layers is not more than 5 Å. Maximum effective anisotropy energy is shown by the films with a Co to Pd ratio of 1/3.

Functionalized Gold Nanoparticles: Synthesis, Properties and Applications--A Review.

The past few decades have witnessed significant advances in the development of functionalized gold nanoparticles for applications in various fields such as chemistry, biology, pharmacy and physics. Although it has been more than 150 years since they were first synthesized, extensive research has recently been undertaken to improve or modify gold nanoparticles, thereby opening up opportunities to enhance and optimize their potential and breadth of their applicability. Recently developed methods have allowed a precise control of gold nanoparticle size and the modification of gold nanoparticles with suitable protecting and functionalizing agents, facilitate their applications in different areas such as chemical and biological sensing, imaging and biomedical applications. This review focuses on the recent developments in various methods for the size and shape controlled synthesis of gold nanoparticles, understanding of different properties of gold nanoparticles and their applications in various fields. Particular attention is given to the chemical and biological sensing applications of gold nanoparticles and on the advances in the controlled ordering of gold nanoparticles for creating nanostructures for diverse applications.

Cholesterol Oxidase Functionalised Polyaniline/Carbon Nanotube Hybrids for an Amperometric Biosensor.

Functional carbon nanotubes (CNT) have attracted much attention for analytical and biomedical applications. This paper describes the fabrication of a cholesterol oxidase (ChOx) immobilised polyaniline (PANI)/CNT composite electrode for the amperometric detection of cholesterol. The prepared ChOx/PANI/CNT/Au bioelectrode bound ChOx via the available functionalties of PANI (-NH2) and CNT (-COOH). Moreover, the CNT creates a network inside the matrix that strengthens the mechanical property of the bioelectrode. The multifunctional matrix is presumed to provide a 3D-mesoporous surface, which substantially enhances enzyme activity. The linear range of the biosensor for cholesterol oleate was 30-280 µM with a response time of 10 sec.

Ultrasensitive detection of human liver hepatocellular carcinoma cells using a label-free aptasensor.

Liver cancer is one of the most common cancers in the world and has no effective cure, especially in later stages. The development of a tangible protocol for early diagnosis of this disease remains a major challenge. In the present manuscript, an aptamer-based, label-free electrochemical biosensor for the sensitive detection of HepG2, a hepatocellular carcinoma cell line, is described. The target cells are captured in a sandwich architecture using TLS11a aptamer covalently attached to a gold surface and a secondary TLS11a aptamer. The application of TLS11a aptamer as a recognition layer resulted in a sensor with high affinity for HepG2 cancer cells in comparison with control cancer cells of human prostate, breast, and colon tumors. The aptasensor delivered a wide linear dynamic range over 1 × 10(2) to 1 × 10(6) cells/mL, with a detection limit of 2 cells/mL. This protocol provides a precise method for sensitive detection of liver cancer with significant advantages in terms of simplicity, low cost, and stability.