A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria.

Background: Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. Objective: To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. Methods: This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response. Results: C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders. Conclusions: IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.

Automated Shoulder Implant Manufacturer Detection using Encoder Decoder based Classifier from X-ray Images.

Total shoulder arthroplasty is the process of replacing the damaged ball and socket joint in the shoulder with a prosthesis made with polyethylene and metal components. The prosthesis helps to restore the normal range of motion and reduce pain, enabling the patient to return to their daily activities. These implants may need to be replaced over the years due to damage or wear and tear. It is a tedious and time-consuming process to identify the type of implant if medical records are not properly maintained. Artificial intelligence systems can speed up the treatment process by classifying the manufacturer and model of the prosthesis. We have proposed an encoder-decoder based classifier along with the supervised contrastive loss function that can identify the implant manufacturer effectively with increased accuracy of 92% from X-ray images overcoming the class imbalance problem.

Neuroscience Engagement and Outreach on Neurodevelopmental Disorders: A Report from India.

The current project was funded by the Global Engagement Seed Grant from the International Brain Research Organisation (IBRO) as part of the IBRO-led Global Engagement Initiative. The project was focused on public awareness about neurodevelopmental disorders (NDDs) as well as neuroscience engagement. Thus, the project had two specific aims: (a) public awareness about epidemiology, diagnosis, risk factors, prevention of NDDs and relevant government guidelines and available policies (b) public engagement in neuroscience. Therefore, the current project report with an emphasis on the requirement of neuroscience engagement and outreach at the societal level, highlights several activities such as population-based workshops and webinars, carried out as part of the project in both rural and urban areas to enhance the public engagement in neuroscience and awareness on several NDDs. Key message: India is an extremely diverse country with significant variations in cultural, educational, financial, socioeconomic status and linguistic aspects. With about 27% of its population living below the poverty line, India accounts for about 23 million children suffering from a disability, most of whom do not seek medical help. These data highlight the gravity of the situation which calls for urgent actions from governments, healthcare professionals, researchers and policymakers to design adequate public awareness programs regarding several prevalent NDDs. Therefore, the current project was an effort to bring public awareness about brain health and the epidemiology, diagnosis and prevention of NDDs and relevant government guidelines and available policies.

Moderate intrinsic phenotypic alterations in C9orf72 ALS/FTD iPSC-microglia despite the presence of C9orf72 pathological features.

While motor and cortical neurons are affected in C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), it remains largely unknown if and how non-neuronal cells induce or exacerbate neuronal damage. We differentiated C9orf72 ALS/FTD patient-derived induced pluripotent stem cells into microglia (iPSC-MG) and examined their intrinsic phenotypes. Similar to iPSC motor neurons, C9orf72 ALS/FTD iPSC-MG mono-cultures form G4C2 repeat RNA foci, exhibit reduced C9orf72 protein levels, and generate dipeptide repeat proteins. Healthy control and C9orf72 ALS/FTD iPSC-MG equally express microglial specific genes and perform microglial functions, including inflammatory cytokine release and phagocytosis of extracellular cargos, such as synthetic amyloid beta peptides and healthy human brain synaptoneurosomes. RNA sequencing analysis revealed select transcriptional changes of genes associated with neuroinflammation or neurodegeneration in diseased microglia yet no significant differentially expressed microglial-enriched genes. Moderate molecular and functional differences were observed in C9orf72 iPSC-MG mono-cultures despite the presence of C9orf72 pathological features suggesting that a diseased microenvironment may be required to induce phenotypic changes in microglial cells and the associated neuronal dysfunction seen in C9orf72 ALS/FTD neurodegeneration.

Autophagy and mitophagy: physiological implications in kidney inflammation and diseases.

Autophagy is a ubiquitous intracellular cytoprotective quality control program that maintains cellular homeostasis by recycling superfluous cytoplasmic components (lipid droplets, protein, or glycogen aggregates) and invading pathogens. Mitophagy is a selective form of autophagy that by recycling damaged mitochondrial material, which can extracellularly act as damage-associated molecular patterns, prevents their release. Autophagy and mitophagy are indispensable for the maintenance of kidney homeostasis and exert crucial functions during both physiological and disease conditions. Impaired autophagy and mitophagy can negatively impact the pathophysiological state and promote its progression. Autophagy helps in maintaining structural integrity of the kidney. Mitophagy-mediated mitochondrial quality control is explicitly critical for regulating cellular homeostasis in the kidney. Both autophagy and mitophagy attenuate inflammatory responses in the kidney. An accumulating body of evidence highlights that persistent kidney injury-induced oxidative stress can contribute to dysregulated autophagic and mitophagic responses and cell death. Autophagy and mitophagy also communicate with programmed cell death pathways (apoptosis and necroptosis) and play important roles in cell survival by preventing nutrient deprivation and regulating oxidative stress. Autophagy and mitophagy are activated in the kidney after acute injury. However, their aberrant hyperactivation can be deleterious and cause tissue damage. The findings on the functions of autophagy and mitophagy in various models of chronic kidney disease are heterogeneous and cell type- and context-specific dependent. In this review, we discuss the roles of autophagy and mitophagy in the kidney in regulating inflammatory responses and during various pathological manifestations.

Iron therapy mitigates chronic kidney disease progression by regulating intracellular iron status of kidney macrophages.

Systemic iron metabolism is disrupted in chronic kidney disease (CKD). However, little is known about local kidney iron homeostasis and its role in kidney fibrosis. Kidney-specific effects of iron therapy in CKD also remain elusive. Here, we elucidate the role of macrophage iron status in kidney fibrosis and demonstrate that it is a potential therapeutic target. In CKD, kidney macrophages exhibited depletion of labile iron pool (LIP) and induction of transferrin receptor 1, indicating intracellular iron deficiency. Low LIP in kidney macrophages was associated with their defective antioxidant response and proinflammatory polarization. Repletion of LIP in kidney macrophages through knockout of ferritin heavy chain (Fth1) reduced oxidative stress and mitigated fibrosis. Similar to Fth1 knockout, iron dextran therapy, through replenishing macrophage LIP, reduced oxidative stress, decreased the production of proinflammatory cytokines, and alleviated kidney fibrosis. Interestingly, iron markedly decreased TGF-ß expression and suppressed TGF-ß-driven fibrotic response of macrophages. Iron dextran therapy and FtH suppression had an additive protective effect against fibrosis. Adoptive transfer of iron-loaded macrophages alleviated kidney fibrosis, validating the protective effect of iron-replete macrophages in CKD. Thus, targeting intracellular iron deficiency of kidney macrophages in CKD can serve as a therapeutic opportunity to mitigate disease progression.

Cardiac Anomaly Detection from Cine MRI Images using Physiological Features and Random Forest Classifier.

Computer-aided diagnosis (CAD) with cine MRI is a foremost research topic to enable improved, faster, and more accurate diagnosis of cardiovascular diseases (CVD). However, current approaches that use manual visualization or conventional clinical indices can lack accuracy for borderline cases. Also, manual visualization of 3D/4D MR data is time-consuming and expert-dependent. We try to simplify this process by creating an end-to-end automated CAD system that segments the critical substructures of the heart. The new domain-related physiological features are then calculated from the segmented regions. These features are fed to a random forest classifier that identifies the anomaly. We have obtained a very high accuracy when testing this end-to-end approach on the Automated Cardiac Diagnosis challenge (ACDC) dataset (4 pathologies, 1 normal). To prove the generalizability of the method we have blind-tested this approach on M&Ms-2 dataset which is a multi-center, multi-vendor, and multi-disease dataset with better than 90% accuracy.

3D Cardiac Substructures Segmentation from CMRI using Generative Adversarial Network (GAN).

Cardiac magnetic resonance imaging (CMRI) improves the diagnosis of cardiovascular diseases by providing images at high spatio-temporal resolution helping physicians in providing correct treatment plans. Segmentation and identification of various substructures of the heart at different cardiac phases of end-systole and end-diastole helps in the extraction of ventricular function information such as stroke volume, ejection fraction, myocardium thickness, etc. Manual delineation of the substructures is tedious, time-consuming, and error-prone. We have implemented a 3D GAN that includes 3D contextual information capable of segmenting and identifying the substructures at different cardiac phases with improved accuracy. Our method is evaluated on the ACDC dataset (4 pathologies, 1 healthy group) to show that the proposed out-performs other methods in literature with less amount of data. Also, the proposed provided a better Dice score in segmentation surpassing other methods on a blind-tested M&Ms dataset.

Conditional deletion of myeloid-specific mitofusin 2 but not mitofusin 1 promotes kidney fibrosis.

Macrophages exert critical functions during kidney injury, inflammation, and tissue repair or fibrosis. Mitochondrial structural and functional aberrations due to an imbalance in mitochondrial fusion/fission processes are implicated in the pathogenesis of chronic kidney disease. Therefore, we investigated macrophage-specific functions of mitochondrial fusion proteins, mitofusin (MFN)1 and MFN2, in modulating macrophage mitochondrial dynamics, biogenesis, oxidative stress, polarization, and fibrotic response. MFN1 and MFN2 were found to be suppressed in mice after adenine diet-induced chronic kidney disease, in transforming growth factor-beta 1-treated bone marrow-derived macrophages, and in THP-1-derived human macrophages (a human leukemic cell line). However, abrogating Mfn2 but not Mfn1 in myeloid-lineage cells resulted in greater macrophage recruitment into the kidney during fibrosis and the macrophage-derived fibrotic response associated with collagen deposition culminating in worsening kidney function. Myeloid-specific Mfn1 /Mfn2 double knockout mice also showed increased adenine-induced fibrosis. Mfn2-deficient bone marrow-derived macrophages displayed enhanced polarization towards the profibrotic/M2 phenotype and impaired mitochondrial biogenesis. Macrophages in the kidney of Mfn2-deficient and double knockout but not Mfn1-deficient mice exhibited greater mitochondrial mass, size, oxidative stress and lower mitophagy under fibrotic conditions than the macrophages in the kidney of wild-type mice. Thus, downregulation of MFN2 but not MFN1 lead to macrophage polarization towards a profibrotic phenotype to promote kidney fibrosis through a mechanism involving suppression of macrophage mitophagy and dysfunctional mitochondrial dynamics.

Effects of pointing movements on visuospatial working memory in a joint-action condition: Evidence from eye movements.

Previous studies showed that (a) performing pointing movements towards to-be-remembered locations enhanced their later recognition, and (b) in a joint-action condition, experimenter-performed pointing movements benefited memory to the same extent as self-performed movements. The present study replicated these findings and additionally recorded participants' fixations towards studied arrays. Each trial involved the presentation of two consecutive spatial arrays, where each item occupied a different spatial location. The item locations of one array were encoded by mere visual observation (the no-move array), whereas the locations of the other array were encoded by observation plus pointing movements (the move array). Critically, in Experiment 1, participants took turns with the experimenter in pointing towards the move arrays (joint-action condition), while in Experiment 2 pointing was performed only by the experimenter (passive condition). The results showed that the locations of move arrays were recognized better than the locations of no-move arrays in Experiment 1, but not in Experiment 2. The pattern of eye-fixations was in line with behavioral findings, indicating that in Experiment 1, fixations to the locations of move arrays were higher in number and longer in duration than fixations to the locations of no-move arrays, irrespective of the agent who performed the movements. In contrast, no differences emerged in Experiment 2. We propose that, in the joint-action condition, self- and other-performed pointing movements are coded at the same representational level and their functional equivalency is reflected in a similar pattern of eye-fixations.

Heart Region Segmentation using Dense VNet from Multimodality Images.

Cardiovascular diseases (CVD) have been identified as one of the most common causes of death in the world. Advanced development of imaging techniques is allowing timely detection of CVD and helping physicians in providing correct treatment plans in saving lives. Segmentation and Identification of various substructures of the heart are very important in modeling a digital twin of the patient-specific heart. Manual delineation of various substructures of the heart is tedious and time-consuming. Here we have implemented Dense VNet for detecting substructures of the heart from both CT and MRI multimodality data. Due to the limited availability of data we have implemented an on-the-fly elastic deformation data augmentation technique. The result of the proposed has been shown to outperform other methods reported in the literature on both CT and MRI datasets.

Bringing high spatial resolution to the far-infrared: A giant leap for astrophysics.

The far-infrared (FIR) regime is one of the wavelength ranges where no astronomical data with sub-arcsecond spatial resolution exist. None of the medium-term satellite projects like SPICA, Millimetron, or the Origins Space Telescope will resolve this malady. For many research areas, however, information at high spatial and spectral resolution in the FIR, taken from atomic fine-structure lines, from highly excited carbon monoxide (CO), light hydrides, and especially from water lines would open the door for transformative science. A main theme will be to trace the role of water in proto-planetary discs, to observationally advance our understanding of the planet formation process and, intimately related to that, the pathways to habitable planets and the emergence of life. Furthermore, key observations will zoom into the physics and chemistry of the star-formation process in our own Galaxy, as well as in external galaxies. The FIR provides unique tools to investigate in particular the energetics of heating, cooling, and shocks. The velocity-resolved data in these tracers will reveal the detailed dynamics engrained in these processes in a spatially resolved fashion, and will deliver the perfect synergy with ground-based molecular line data for the colder dense gas.

Antimicrobial potential and in vitro cytotoxicity study of polyvinyl pyrollidone-stabilised silver nanoparticles synthesised from Lysinibacillus boronitolerans.

The main emphasis herein is on the eco-friendly synthesis and assessment of the antimicrobial potential of silver nanoparticles (AgNPs) and a cytotoxicity study. Silver nanoparticles were synthesised by an extracellular method using bacterial supernatant. Biosynthesised silver nanoparticles were characterised by UV-vis spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised silver nanoparticles exhibited a characteristic peak at 420 nm. TEM analysis depicted the spherical shape and approximately 20 nm size of nanoparticles. Silver nanoparticles carry a charge of -33.75 mV, which confirms their stability. Biogenic polyvinyl pyrrolidone-coated AgNPs exhibited significant antimicrobial effects against all opportunistic pathogens (Gram-positive and Gram-negative bacteria, and fungi). Silver nanoparticles equally affect the growth of both Gram-positive and Gram-negative bacteria, with a maximum inhibition zone observed at 22 mm and a minimum at 13 mm against Pseudomonas aeruginosa and Fusarium graminearum, respectively. The minimum inhibitory concentration (MIC) of AgNPs against P. aeruginosa and Staphylococcus aureus was recorded at between 15 and 20 µg/ml. Synthesised nanoparticles exhibited a significant synergistic effect in combination with conventional antibiotics. Cytotoxicity estimates using C2C12 skeletal muscle cell line via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test and lactate dehydrogenase assay were directly related to the concentration of AgNPs and length of exposure. On the basis of the MTT test, the IC50 of AgNPs for the C2C12 cell line was approximately 5.45 µg/ml concentration after 4 h exposure.

Prevalence of non-alcoholic fatty liver disease and factors associated with it in Indian women with a history of gestational diabetes mellitus.

AIMS/INTRODUCTION: This study aims to evaluate the prevalence of and factors associated with non-alcoholic fatty liver disease (NAFLD) in Indian women with prior gestational diabetes mellitus (GDM) diagnosed using International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIALS AND METHODS: This cross-sectional study (2018-2019) enrolled women with and without prior GDM. Study participants underwent detailed assessments, including relevant medical, obstetric and demographic details; 75-g oral glucose tolerance test with glucose and insulin estimation at 0, 30 and 120 min; and other relevant biochemical and anthropometric measurements. NAFLD status was defined by ultrasonography. RESULTS: We evaluated a total of 309 women (201 and 108 with and without prior GDM, respectively) at a mean age of 31.9 ± 5.0 years and median of 16 months (interquartile range 9-38 months) following the index delivery. The prevalence of NAFLD was significantly higher in women with prior GDM (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%). On logistic regression analysis (fully adjusted model), the odds of NAFLD were 2.11-fold higher in women with prior GDM (95% confidence interval 1.16-3.85, P = 0.014). Overweight/obesity, metabolic syndrome, prediabetes and homeostasis model of assessment of insulin resistance (a measure of insulin resistance) were positively associated with NAFLD, whereas the Matsuda index (a measure of insulin sensitivity) showed a negative association with NAFLD. CONCLUSIONS: The prevalence of NAFLD is high in women with prior GDM. Such women also have a high burden of cardiometabolic risk factors. Future studies should evaluate the intermediate and long-term hepatic and cardiovascular risk, and the impact of lifestyle interventions in reducing morbidity in such women.

Mitochondrial dysfunction in kidney injury, inflammation, and disease: Potential therapeutic approaches.

Mitochondria are energy-producing organelles that not only satisfy the high metabolic demands of the kidney but sense and respond to kidney injury-induced oxidative stress and inflammation. Kidneys are rich in mitochondria. Mitochondrial dysfunction plays a critical role in the progression of acute kidney injury and chronic kidney disease. Mitochondrial responses to specific stimuli are highly regulated and synergistically modulated by tightly interconnected processes, including mitochondrial dynamics (fission, fusion) and mitophagy. The counterbalance between these processes is essential in maintaining a healthy network of mitochondria. Recent literature suggests that alterations in mitochondrial dynamics are implicated in kidney injury and the progression of kidney diseases. A decrease in mitochondrial fusion promotes fission-induced mitochondrial fragmentation, but a reduction in mitochondrial fission produces excessive mitochondrial elongation. The removal of dysfunctional mitochondria by mitophagy is crucial for their quality control. Defective mitochondrial function disrupts cellular redox potential and can cause cell death. Mitochondrial DNA derived from damaged cells also act as damage-associated molecular patterns to recruit immune cells and the inflammatory response can further exaggerate kidney injury. This review provides a comprehensive overview of the role of mitochondrial dysfunction in acute kidney injury and chronic kidney disease. We discuss the processes that control mitochondrial stress responses to kidney injury and review recent advances in understanding the role of mitochondrial dysfunction in inflammation and tissue damage through the use of different experimental models of kidney disease. We also describe potential mitochondria-targeted therapeutic approaches.

Peak Alpha Frequency in Relation to Cognitive Performance.

Objective Peak alpha frequency (PAF) is reported to be a nervous system property which is genetically endowed and reflected in individual's cognitive functioning. Cognitive performance denotes the mental processes for effective changes in response to situations in general and mental task in particular. None of the study has till now used reading comprehension as a measure of cognitive functioning, which is considered to be a measure of higher cognitive processes. The reading comprehension task used in the study implies certain cognitive processes such as reading ability, comprehension, memory performance involving information maintenance, and retrieval. Therefore, the study was conducted to test the hypothesis of differences in cognitive reading comprehension performance between high- and low-peak alpha subjects. Materials and Methods A group of 300 healthy participants were selected on the basis of incidental-cum-probabilistic sampling from seven districts of Indian state of Haryana. In the present study, reading comprehension task (Hindi-English; bilingual format) was used to assess the cognitive performance and multichannel electroencephalography alpha frequencies were recorded to measure PAF through power spectrum density analysis of each subject. Results The findings revealed that individuals with high-peak alpha frequency had significantly higher score ( p < 0.05) on reading comprehension task as compared with individuals with low PAF. Conclusion The present study concluded that the reading comprehension task is effected by peak alpha frequency of an individual. PAF can be considered to be a correlate of cognitive performance.

Autophagy in kidney disease: Advances and therapeutic potential.

Autophagy is a highly conserved intracellular catabolic process for the degradation of cytoplasmic components that has recently gained increasing attention for its importance in kidney diseases. It is indispensable for the maintenance of kidney homeostasis both in physiological and pathological conditions. Investigations utilizing various kidney cell-specific conditional autophagy-related gene knockouts have facilitated the advancement in understanding of the role of autophagy in the kidney. Recent findings are raising the possibility that defective autophagy exerts a critical role in different pathological conditions of the kidney. An emerging body of evidence reveals that autophagy exhibits cytoprotective functions in both glomerular and tubular compartments of the kidney, suggesting the upregulation of autophagy as an attractive therapeutic strategy. However, there is also accumulating evidence that autophagy could be deleterious, which presents a formidable challenge in developing therapeutic strategies targeting autophagy. Here, we review the recent advances in research on the role of autophagy during different pathological conditions, including acute kidney injury (AKI), focusing on sepsis, ischemia-reperfusion injury, cisplatin, and heavy metal-induced AKI. We also discuss the role of autophagy in chronic kidney disease (CKD) focusing on the pathogenesis of tubulointerstitial fibrosis, podocytopathies including focal segmental glomerulosclerosis, diabetic nephropathy, IgA nephropathy, membranous nephropathy, HIV-associated nephropathy, and polycystic kidney disease.

Carbonyl iron and iron dextran therapies cause adverse effects on bone health in juveniles with chronic kidney disease.

Anemia is a frequent complication of chronic kidney disease (CKD), related in part to the disruption of iron metabolism. Iron therapy is very common in children with CKD and excess iron has been shown to induce bone loss in non-CKD settings, but the impact of iron on bone health in CKD remains poorly understood. Here, we evaluated the effect of oral and parenteral iron therapy on bone transcriptome, bone histology and morphometry in two mouse models of juvenile CKD (adenine-induced and 5/6-nephrectomy). Both modalities of iron therapy effectively improved anemia in the mice with CKD, and lowered bone Fgf23 expression. At the same time, iron therapy suppressed genes implicated in bone formation and resulted in the loss of cortical and trabecular bone in the mice with CKD. Bone resorption was activated in untreated CKD, but iron therapy had no additional effect on this. Furthermore, we assessed the relationship between biomarkers of bone turnover and iron status in a cohort of children with CKD. Children treated with iron had lower levels of circulating biomarkers of bone formation (bone-specific alkaline phosphatase and the amino-terminal propeptide of type 1 procollagen), as well as fewer circulating osteoblast precursors, compared to children not treated with iron. These differences were independent of age, sex, and glomerular filtration rate. Thus, iron therapy adversely affected bone health in juvenile mice with CKD and was associated with low levels of bone formation biomarkers in children with CKD.