Ultrasound Assessment of the Gastrocnemius Muscle as a Potential Tool for Identifying Sarcopenia in Patients with Type 2 Diabetes.

Objective: This study aims to examine the clinical significance of ultrasound evaluation of the gastrocnemius muscle (GM) in identifying sarcopenia in patients with type 2 diabetes (T2D). Methods: One hundred and fifty-three patients with T2D were included in this study. We measured the appendicular skeletal muscle mass index (ASMI), handgrip strength, and 6-meter walking speed. The US-derived muscle thickness (MT), cross-sectional area (CSA), and shear wave ultrasound elastography (SWE) of GM were also measured. We assessed the correlations between clinical indicators and US features. The model for screening sarcopenia was established using stepwise logistic regression. Stepwise linear regression was used to identify a set of variables that jointly estimated ASMI. The model's ability to identify sarcopenia and low muscle mass was assessed by receiver operating characteristic (ROC) curve analysis. Results: The prevalence of sarcopenia in this study was 24.2%. The CSA, MT and SWE values of the patients with sarcopenia were lower than those of patients without sarcopenia (all p < 0.05). ASMI was positively correlated with CSA (r = 0.56, p < 0.001) and MT (r = 0.39, p < 0.001). Handgrip strength was positively correlated with CSA (r = 0.45, p < 0.001), MT (r = 0.25, p < 0.001), and SWE (r = 0.26, p = 0.002). A diagnostic model for sarcopenia was established with a sensitivity of 81.1%, specificity of 75.0%, and an area under the curve (AUC) of 0.800. The estimated ASMI equation was developed and found to have a positive correlation with actual ASMI (r = 0.70, p < 0.001). It was also effective in diagnosing low muscle mass, with an AUC of 0.787 for males and 0.783 for females. Conclusion: Ultrasonographic assessment of the gastrocnemius muscle was found to be a useful and convenient method for detecting sarcopenia in patients with T2D.

Malnutrition Is Associated with Diabetic Retinopathy in Patients with Type 2 Diabetes.

Background: The relationship between malnutrition and diabetic retinopathy (DR) is still unclear. The purpose of this study is to investigate the relationship between malnutrition and DR in type 2 diabetic patients. Methods: A cross-sectional study was conducted on 612 patients with type 2 diabetes mellitus. Four malnutrition assessment tools: Global Leadership Initiative on Malnutrition (GLIM) criteria, controlling nutritional status (CONUT), nutritional risk index (NRI), and prognostic nutritional index (PNI), were applied to assess the nutritional status of the study population. The association between malnutrition and DR was examined using multivariable logistic regression and ordered logistic regression. Results: The proportion of malnutrition varied from 10.0% to 34.3% in total patients and from 16.3% to 45.1% in DR patients across the assessment tools. DR patients were more likely to be malnourished than patients without DR. The adjusted odds ratios (aOR) and 95% confidence interval (CI) for DR of malnutrition defined by different tools were 1.86 (1.01-3.14) for GLIM criteria, 1.67 (1.04-2.70) for NRI, and 2.24 (1.07-4.69) for PNI. The aOR and 95% CI for the severity of DR of malnutrition defined by different tools were 1.99 (1.12-3.51) for GLIM criteria, 1.65 (1.06-2.58) for NRI, and 2.51 (1.31-4.79) for PNI. Conclusions: Malnutrition was common in DR patients, and it was closely linked to the presence and severity of DR. Diabetic patients with DR should undergo nutritional assessment and early treatment of malnutrition to prevent the onset or progression of DR.

Wearable Biosensor with Molecularly Imprinted Conductive Polymer Structure to Detect Lentivirus in Aerosol.

The coronavirus disease (COVID-19) pandemic has increased pressure to develop low-cost, compact, user-friendly, and ubiquitous virus sensors for monitoring infection outbreaks in communities and preventing economic damage resulting from city lockdowns. As proof of concept, we developed a wearable paper-based virus sensor based on a molecular imprinting technique, using a conductive polyaniline (PANI) polymer to detect the lentivirus as a test sample. This sensor detected the lentivirus with a 4181 TU/mL detection limit in liquid and 0.33% to 2.90% detection efficiency in aerosols at distances ranging from 30 cm to 60 cm. For fabrication, a mixture of a PANI monomer solution and virus were polymerized together to form a conductive PANI sensing element on a polyethylene terephthalate (PET) paper substrate. The sensing element exhibited formation of virus recognition sites after the removal of the virus via ultrasound sonication. A dry measurement technique was established that showed aerosol virus detection by the molecularly imprinted sensors within 1.5 h of virus spraying. This was based on the mechanism via which dispensing virus droplets on the PANI sensing element induced hybridization of the virus and molecularly imprinted virus recognition templates in PANI, influencing the conductivity of the PANI film upon drying. Interestingly, the paper-based virus sensor was easily integrated with a wearable face mask for the detection of viruses in aerosols. Since the paper sensor with molecular imprinting of virus recognition sites showed excellent stability in dry conditions for long periods of time, unlike biological reagents, this wearable biosensor will offer an alternative approach to monitoring virus infections in communities.

CD8+ T Cells Trigger Auricular Dermatitis and Blepharitis in Mice after Zika Virus Infection in the Absence of CD4+ T Cells.

Zika virus (ZIKV) became a public health concern when it re-emerged in 2015 owing to its ability to cause congenital deformities in the fetus and neurological complications in adults. Despite extensive data on protection, the interplay of protective and pathogenic adaptive immune responses toward ZIKV infection remains poorly understood. In this study, using a T-cell‒deficient mouse model that retains persistent ZIKV viral titers in the blood and organs, we show that the adoptive transfer of CD8+ T cells led to a significant reduction in viral load. This mouse model reveals that ZIKV can induce grossly visible auricular dermatitis and blepharitis, mediated by ZIKV-specific CD8+ T cells. Single-cell RNA sequencing of these causative CD8+ T cells from the ears shows an overactivated and elevated cytotoxic signature in mice with severe symptoms. Our results strongly suggest a role for CD8+ T-cell‒associated pathologies after ZIKV infection in CD4+ T-cell‒immunodeficient patients.

Perfluorooctanesulfonic Acid Detection Using Molecularly Imprinted Polyaniline on a Paper Substrate.

Perfluorinated compounds like perfluorooctanesulfonic acid (PFOS) are synthetic water pollutants and have accumulated in environments for decades, causing a serious global health issue. Conventional assays rely on liquid chromatography and mass spectroscopy that are very expensive and complicated and thus limit the large-scale monitoring of PFOS in wastewater. To achieve low-cost and accurate detection of PFOS, we designed a paper-based sensor with molecularly imprinted polyaniline electrodes that have recognition sites specific to PFOS. The calibration curve of resistivity ratios as a function of PFOS concentrations has a linear range from 1 to 100 ppt with a coefficient of determination of 0.995. The estimated limit of detection is 1.02 ppt. We also investigated attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS) spectra of the surface of the polyaniline (PANI) electrodes to propose the potential recognition sites in polyaniline matrix and the detection mechanism. This electrical paper sensor with low cost and excellent sensitivity and selectivity provides the potential for large-scale monitoring of wastewater.

A Gel-Based Separation-Free Point-of-Care Device for Whole Blood Glucose Detection.

This article introduces a gel-based separation-free point-of-care (POC) device for whole blood glucose colorimetric detection. Enzymes and a chromogenic substrate needed for colorimetric detection of glucose were entrapped in a photopolymerized poly(ethylene) glycol diacrylate (PEG-DA) hydrogel that was cast-molded into a circular shape. Our method enables colorimetric detection without the need for preseparation of blood plasma as the nanometer-scale three-dimensional porous structure of the hydrogel allows the diffusion of small analytes such as glucose while blocking the much larger blood cells. Our method requires less enzymatic concentration and, hence, offers a cost-saving benefit. In addition, PEG-DA also acts as an enzyme stabilizer, and the shelf-life testing result shows that enzyme activity can be maintained in PEG-DA over a long period of time. The concept of this simple, cost-effective method was demonstrated by the colorimetric detection of blood glucose directly from human whole bloodthout any sample preparation steps. The results were compared with those of a spectrophotometry method and showed relative error ranging from 5 to 19%, and less than 9% when compared with a commercial glucose meter. The presented method has the potential to be broadly utilized for other whole blood biomolecule analyses in POC testing applications.

A Low-cost and Enzyme-free Glucose Paper Sensor.

A low-cost and enzyme-free glucose paper sensor is presented as a promising alternative to glucose test strips. This paper-based glucose sensor is prepared with molecularly imprinted (MIP) polyaniline (PANI) electrode. The determination of glucose concentrations was studied by the impedance change of the paper sensor before and after the blood samples dispensing at a low frequency. A comparison of the linear and polynomial regression was applied to analyze the impedance ratio as a function of glucose concentrations. The proposed glucose paper sensor showed a limit of detection (LoD) of 1.135 mM. This novel and non-enzymatic paper sensor suggests a low-cost glucose test assay and can improve the quality of routine testing for diabetic patients.

Hierarchical Representation for Chromatic Processing across Macaque V1, V2, and V4.

The perception of color is an internal label for the inferred spectral reflectance of visible surfaces. To study how spectral representation is transformed through modular subsystems of successive cortical areas, we undertook simultaneous optical imaging of intrinsic signals in macaque V1, V2, and V4, supplemented by higher-resolution electrophysiology and two-photon imaging in awake macaques. We find a progressive evolution in the scale and precision of chromotopic maps, expressed by a uniform blob-like architecture of hue responses within each area. Two-photon imaging reveals enhanced hue-specific cell clustering in V2 compared with V1. A phenomenon of endspectral (red and blue) responses that is clear in V1, recedes in V2, and is virtually absent in V4. The increase in mid- and extra-spectral hue representations through V2 and V4 reflects the nature of hierarchical processing as higher areas read out locations in chromatic space from progressive integration of signals relayed by V1.

Isolation of cancer-derived extracellular vesicle subpopulations by a size-selective microfluidic platform.

Extracellular vesicles (EVs) play an important role in intercellular communication. Recently, there has been increasing interest in EVs as potential diagnostic biomarkers and therapeutic vehicles. However, the molecular properties and cargo information of EV subpopulations have not yet been fully investigated due to lack of reliable and reproducible EV separation technology. Current approaches have faced difficulties with efficiently isolating EVs from biofluids, especially subpopulations of small EVs. Here, we report an EV isolation method based on a size-selective microfluidic platform (ExoSMP) via nanomembrane filtration and electrophoretic force. This unique platform offers an enhanced approach to sorting a heterogeneous population of EVs based on size, with the additional advantages of being label-free and low-cost, and featuring a short processing time (<1 h), and convenient integration with downstream analysis. In this research, we used ExoSMP to demonstrate the isolation of cancer-derived small EVs (30-120 nm) with high recovery (94.2%) and reproducibility at an optimum sample flow rate. Furthermore, we investigated isolation of EV subpopulations by altering nanomembrane combinations with different pore size combinations (50 and 100 nm, 30 and 100 nm, 30 and 200 nm, and 30 and 50 nm). This ExoSMP technique can serve as a standardized EV isolation/separation tool, facilitating the clinical prospects of EVs and opening up a new avenue for future point-of-care applications in liquid biopsies.

Type I interferon shapes the quantity and quality of the anti-Zika virus antibody response.

OBJECTIVES: Zika virus (ZIKV) is a mosquito-borne flavivirus that re-emerged in 2015. The association between ZIKV and neurological complications initiated the development of relevant animal models to understand the mechanisms underlying ZIKV-induced pathologies. Transient inhibition of the type I interferon (IFN) pathway through the use of an IFNAR1-blocking antibody, MAR1-5A3, could efficiently permit active virus replication in immunocompetent animals. Type I IFN signalling is involved in the regulation of humoral responses, and thus, it is crucial to investigate the potential effects of type I IFN blockade towards B-cell responses. METHODS: In this study, comparative analysis was conducted using serum samples collected from ZIKV-infected wild-type (WT) animals either administered with or without MAR1-5A3. RESULTS: Serological assays revealed a more robust ZIKV-specific IgG response and subtype switching upon inhibition of type I IFN due to the abundance of antigen availability. This observation was corroborated by an increase in germinal centres, plasma cells and germinal centre B cells. Interestingly, although both groups of animals recognised different B-cell linear epitopes in the E and NS1 regions, there was no difference in neutralising capacity. Further characterisation of these epitopes in the E protein revealed a detrimental role of antibodies that were generated in the absence of type I IFN. CONCLUSION: This study highlights the role of type I IFN in shaping the anti-ZIKV antibody response to generate beneficial antibodies and will help guide development of better vaccine candidates triggering efficient neutralising antibodies and avoiding detrimental ones.

A Low-Cost Paper Glucose Sensor with Molecularly Imprinted Polyaniline Electrode.

For the hundreds of millions of worldwide diabetic patients, glucose test strips are the most important and commonly used tool for monitoring blood glucose levels. Commercial test strips use glucose oxidases as recognition agents, which increases the cost and reduces the durability of test strips. To lower the cost of glucose sensors, we developed a paper-based electrical sensor with molecularly imprinted glucose recognition sites and demonstrated the determination of various glucose concentrations in bovine blood solutions. The sensing electrode is integrated with molecular recognition sites in the conductive polymer. A calibration graph as a function of glucose concentration in aqueous solution was acquired and matched with a correlation coefficient of 0.989. We also demonstrated the determination of the added glucose concentrations ranging from 2.2 to 11.1 mM in bovine blood samples with a linear correlation coefficient of 0.984. This non-enzymatic glucose sensor has the potential to reduce the health care cost of test strips as well as make glucose sensor test strips more accessible to underserved communities.

The Serpentine Illusion: A Visual Motion Illusion Induced by Phase-Shifted Line Gratings.

In a pattern of horizontal lines containing ± 45° zigzagging phase-shifted strips, vivid illusory motion is perceived when the pattern is translated up or down at a moderate speed. Two forms of illusory motion are seen: [i] a motion "racing" along the diagonal interface between the strips and [ii] lateral (sideways) motion of the strip sections. We found the relative salience of these two illusory motions to be strongly influenced by the vertical spacing and length of the line gratings, and the period length of the zigzag strips. Both illusory motions are abolished when the abutting strips are interleaved, separated by a gap or when a real line is superimposed at the interface. Illusory motion is also severely weakened when equiluminant colored grating lines are used. Illusory motion perception is fully restored at < 20% luminance contrast. Using adaptation, we find that line-ends alone are insufficient for illusory motion perception, and that both physical carrier motion and line orientation are required. We finally test a classical spatiotemporal energy model of V1 cells that exhibit direction tuning changes that are consistent with the direction of illusory motion. Taking this data together, we constructed a new visual illusion and surmise its origin to interactions of spatial and temporal energy of the lines and line-ends preferentially driving the magnocellular pathway.

Going with the Flow: The Neural Mechanisms Underlying Illusions of Complex-Flow Motion.

Studying the mismatch between perception and reality helps us better understand the constructive nature of the visual brain. The Pinna-Brelstaff motion illusion is a compelling example illustrating how a complex moving pattern can generate an illusory motion perception. When an observer moves toward (expansion) or away (contraction) from the Pinna-Brelstaff figure, the figure appears to rotate. The neural mechanisms underlying the illusory complex-flow motion of rotation, expansion, and contraction remain unknown. We studied this question at both perceptual and neuronal levels in behaving male macaques by using carefully parametrized Pinna-Brelstaff figures that induce the above motion illusions. We first demonstrate that macaques perceive illusory motion in a manner similar to that of human observers. Neurophysiological recordings were subsequently performed in the middle temporal area (MT) and the dorsal portion of the medial superior temporal area (MSTd). We find that subgroups of MSTd neurons encoding a particular global pattern of real complex-flow motion (rotation, expansion, contraction) also represent illusory motion patterns of the same class. They require an extra 15 ms to reliably discriminate the illusion. In contrast, MT neurons encode both real and illusory local motions with similar temporal delays. These findings reveal that illusory complex-flow motion is first represented in MSTd by the same neurons that normally encode real complex-flow motion. However, the extraction of global illusory motion in MSTd from other classes of real complex-flow motion requires extra processing time. Our study illustrates a cascaded integration mechanism from MT to MSTd underlying the transformation from external physical to internal nonveridical flow-motion perception.SIGNIFICANCE STATEMENT The neural basis of the transformation from objective reality to illusory percepts of rotation, expansion, and contraction remains unknown. We demonstrate psychophysically that macaques perceive these illusory complex-flow motions in a manner similar to that of human observers. At the neural level, we show that medial superior temporal (MSTd) neurons represent illusory flow motions as if they were real by globally integrating middle temporal area (MT) local motion signals. Furthermore, while MT neurons reliably encode real and illusory local motions with similar temporal delays, MSTd neurons take a significantly longer time to process the signals associated with illusory percepts. Our work extends previous complex-flow motion studies by providing the first detailed analysis of the neuron-specific mechanisms underlying complex forms of illusory motion integration from MT to MSTd.