Predicting intracranial involvement: Unveiling perineural spread in COVID-19-associated mucormycosis, a novel phenomenon.

This study aimed to investigate the risk factors associated with intracranial involvement in COVID-19-associated mucormycosis (CAM) and to develop a nomogram model for predicting the risk of intracranial involvement, with a specific focus on perineural spread. An ambispective analysis was conducted on 275 CAM patients who received comprehensive treatment. Univariable and multivariable logistic regression analyses were performed to identify independent risk factors, and a nomogram was created based on the results of the multivariable analysis. The performance of the nomogram was evaluated using a receiver operating characteristic (ROC) curve, and the discriminatory capacity was assessed using the area under the curve (AUC). The model's calibration was assessed through a calibration curve and the Hosmer Lemeshow test. In the results, the multivariable logistic regression analysis revealed that age (OR: 1.23, 95% CI 1.06-3.79), HbA1c (OR: 7.168, 95% CI 1.724-25.788), perineural spread (OR: 6.3, 95% CI 1.281-19.874), and the disease stage were independent risk factors for intracranial involvement in CAM. The developed nomogram demonstrated good discriminative capacity with an AUC of 0.821 (95% CI 0.713-0.909) as indicated by the ROC curve. The calibration curve showed that the nomogram was well-calibrated, and the Hosmer Lemeshow test yielded a P-value of 0.992, indicating a good fit for the model. In conclusion, this study found that CAM particularly exhibits perineural spread, which is a predictive factor for intracranial involvement. A nomogram model incorporating age, HbA1c, disease stage, and perineural spread was successfully developed for predicting intracranial involvement in CAM patients in both in-patient and out-patient settings.

Discovery of perineural spread in COVID-19-associated mucormycosis reveals a new predictive model for intracranial complications which is crucial for early intervention.

Efficacy of oral folinic acid supplementation in children with autism spectrum disorder: a randomized double-blind, placebo-controlled trial.

Oral folinic acid has shown potential to improve symptoms in children with autism spectrum disorder (ASD). However, randomized controlled trials (RCTs) are limited. This double-blind, placebo-controlled RCT aimed to compare changes in Childhood Autism Rating Scale (CARS) scores in children with ASD aged 2-10 years, among folinic acid (2 mg/kg/day, maximum of 50 mg/day) and placebo groups at 24 weeks, in comparison with baseline. Both the groups received standard care (ABA and sensory integration therapy). Secondary objectives included changes in behavioral problems measured by the Child Behavior Checklist (CBCL) and serum levels of anti-folate receptor autoantibodies and folic acid, correlated with changes in autism symptom severity. Out of the 40 participants recruited in each group, 39 and 38 participants completed the 24-week follow-up in the folinic acid and placebo groups, respectively. The change in CARS score was higher in the folinic acid group (3.6 ± 0.8) compared to the placebo group (2.4 ± 0.7, p < 0.001). Changes in CBCL total score and CBCL internalizing score were also better in the folinic acid group (19.7 ± 9.5 vs. 12.6 ± 8.4 and 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001 for both). High-titer anti-folate receptor autoantibodies were positive in 32/40 and 33/40 cases in the folinic acid and placebo groups, respectively (p = 0.78). In the placebo group, improvement in CARS score was comparable regardless of autoantibody status (p = 0.11), but in the folinic acid group, improvement was more pronounced in the high-titer autoantibody group (p = 0.03). No adverse reactions were reported in either group. CONCLUSIONS: Oral folinic acid supplementation is effective and safe in improving ASD symptoms, with more pronounced benefits in children with high titers of folate receptor autoantibodies. TRIAL REGISTRATION:  CTRI/2021/07/034901, dated 15-07-2021. WHAT IS KNOWN: • Folate receptor autoantibodies are more prevalent in children with autism spectrum disorder (ASD) compared to typically developing children. • Folate receptor autoantibodies play a significant role in the neuropathogenesis of autism spectrum disorder. WHAT IS NEW: • Add-on oral folinic acid supplementation is safe and effective in reducing the severity of symptoms in children with ASD. • The clinical benefits are more pronounced in children with high titers of folate receptor autoantibodies.

Impact of Drug Conjugation on Thermal and Metabolic Stabilities of Aglycosylated and N-Glycosylated Antibodies.

N-linked glycosylation is one of the most common and complex posttranslational modifications that govern the biological functions and physicochemical properties of therapeutic antibodies. We evaluated thermal and metabolic stabilities of antibody-drug conjugates (ADCs) with payloads attached to the C'E loop in the immunoglobulin G (IgG) Fc CH2 domain, comparing the glycosylated and aglycosylated Fc ADC variants. Our study revealed that introduction of small-molecule drugs into an aglycosylated antibody can compensate for thermal destabilization originating from structural distortions caused by elimination of N-linked glycans. Depending on the conjugation site, glycans had both positive and negative effects on plasma stability of ADCs. The findings highlight the importance of consideration for selection of conjugation site to achieve desirable physicochemical properties and plasma stability.

Enhanced apoptosis, survivin down-regulation and assisted immunochemotherapy by curcumin loaded amphiphilic mixed micelles for subjugating endometrial cancer.

Survivin is up-regulated in 83% of endometrial cancer leading to resistance development. As endometrial tumor advances, it also elicits chronic inflammation characterized by increased cytokine secretion and immune cells infiltration. The present study was designed to engineer mixed micellar curcumin loaded formulation for investigating survivin down-regulation, its anti-cancer and cytokine modulatory potential against endometrial cancer Ishikawa cells. Flory-Huggins interaction parameter (χpd) was applied to predict the compatibility between curcumin and surfactant mixture. The developed and characterized formulations were used to comparatively assess hemolysis, cellular uptake, cell-viability, apoptosis, mitochondrial membrane potential loss, rhodamine accumulation and bioavailability. In-vitro cytotoxicity in Vero cells demonstrated no deleterious effects on cell population. We saw better bioavailability, significant rhodamine accumulation, changes in protein expression and modulation in TNF-α, IL-6 and IL-10 levels. In conclusion, developed formulation warrants exploring the therapeutic interventions for overcoming resistance development in endometrial cancer.

Finite element solution of unsteady mixed convection flow of micropolar fluid over a porous shrinking sheet.

The objective of this investigation is to analyze the effect of unsteadiness on the mixed convection boundary layer flow of micropolar fluid over a permeable shrinking sheet in the presence of viscous dissipation. At the sheet a variable distribution of suction is assumed. The unsteadiness in the flow and temperature fields is caused by the time dependence of the shrinking velocity and surface temperature. With the aid of similarity transformations, the governing partial differential equations are transformed into a set of nonlinear ordinary differential equations, which are solved numerically, using variational finite element method. The influence of important physical parameters, namely, suction parameter, unsteadiness parameter, buoyancy parameter and Eckert number on the velocity, microrotation, and temperature functions is investigated and analyzed with the help of their graphical representations. Additionally skin friction and the rate of heat transfer have also been computed. Under special conditions, an exact solution for the flow velocity is compared with the numerical results obtained by finite element method. An excellent agreement is observed for the two sets of solutions. Furthermore, to verify the convergence of numerical results, calculations are conducted with increasing number of elements.

Trial-history biases in evidence accumulation can give rise to apparent lapses in decision-making.

Trial history biases and lapses are two of the most common suboptimalities observed during perceptual decision-making. These suboptimalities are routinely assumed to arise from distinct processes. However, previous work has suggested that they covary in their prevalence and that their proposed neural substrates overlap. Here we demonstrate that during decision-making, history biases and apparent lapses can both arise from a common cognitive process that is optimal under mistaken beliefs that the world is changing i.e. nonstationary. This corresponds to an accumulation-to-bound model with history-dependent updates to the initial state of the accumulator. We test our model's predictions about the relative prevalence of history biases and lapses, and show that they are robustly borne out in two distinct decision-making datasets of male rats, including data from a novel reaction time task. Our model improves the ability to precisely predict decision-making dynamics within and across trials, by positing a process through which agents can generate quasi-stochastic choices.

Dependability and Prognostic Value of Biomarkers in COVID-19 Associated Rhino-Orbito- Cerebral Mucormycosis- A Long Term Ambispective Study.

COVID-19 pandemic, which has exhibited a wide clinical spectrum and an unexpected surge in mucormycosis cases, understanding various biomarkers' roles becomes pivotal. As mucormycosis leads to clinical morbidity and mortality through angioinvasion and thromboembolism, unveiling the correlation between these markers and disease progression can shed light on the reasons behind mucormycosis's emergence as an epidemic, especially following the second wave of COVID-19. This long term ambispective observational study, conducted from May 2020 to July 2023, aimed to assess specific biomarkers as predictors of severity in COVID-19-associated mucormycosis (CAM). Biomarkers measured included ESR, CRP, D-dimer, IL-8, PCT, serum ferritin, and neutrophil-lymphocyte ratio (NLR) at different time points. Data analysis employed descriptive statistics, repeated measure ANOVA, Spearman correlations, ROC curve analysis, and logistic regression. Of 290 patients, 198 completed the 2-year follow-up. Elevated baseline biomarker levels significantly decreased with treatment initiation. CRP and NLR emerged as significant predictors of severe CAM, with odds ratio 2.926 (95% CI 1.466-4.360) and 2.203 (95% CI 0.863-1.040) respectively. Factors influencing CAM progression included age, CRP, and NLR, while all biomarkers independently predicted mortality. A death prediction model using CRP, PCT, D-dimer, NLR, and IL-8 demonstrated exceptional performance, with a sensitivity of 83.1% and specificity of 100%. Elevated inflammatory markers in CAM patients showed a decline with treatment, with NLR and CRP proving crucial for predicting severity. Serial monitoring of IL-8, CRP, PCT, NLR, D-dimer, and ferritin provides insights into disease progression and prognosis. The study underscores the importance of biomarker assessment in managing CAM, especially in the context of the unpredictable clinical spectrum of COVID-19 and the subsequent mucormycosis surge. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04921-3.

A multi-region recurrent circuit for evidence accumulation in rats.

Decision-making based on noisy evidence requires accumulating evidence and categorizing it to form a choice. Here we evaluate a proposed feedforward and modular mapping of this process in rats: evidence accumulated in anterodorsal striatum (ADS) is categorized in prefrontal cortex (frontal orienting fields, FOF). Contrary to this, we show that both regions appear to be indistinguishable in their encoding/decoding of accumulator value and communicate this information bidirectionally. Consistent with a role for FOF in accumulation, silencing FOF to ADS projections impacted behavior throughout the accumulation period, even while nonselective FOF silencing did not. We synthesize these findings into a multi-region recurrent neural network trained with a novel approach. In-silico experiments reveal that multiple scales of recurrence in the cortico-striatal circuit rescue computation upon nonselective FOF perturbations. These results suggest that ADS and FOF accumulate evidence in a recurrent and distributed manner, yielding redundant representations and robustness to certain perturbations.

Association Between Clinical Severity, Neuroimaging, and Electroencephalographic Findings in Children with Subacute Sclerosing Panencephalitis.

BACKGROUND: Children diagnosed with subacute sclerosing panencephalitis (SSPE) display a range of neuroimaging abnormalities during different stages of the disease, but their exact clinical significance remains unclear. METHODS: In this retrospective cohort study, our objective was to examine magnetic resonance imaging (MRI) abnormalities in the brains of patients aged 18 years or younger with subacute sclerosing panencephalitis. We aimed to correlate these MRI abnormalities with clinical severity, sociodemographic variables, electroencephalographic (EEG) abnormalities, and cerebrospinal anti-measles antibody titers. RESULTS: The study included 112 cases of subacute sclerosing panencephalitis (mean age at onset: 8.9 ± 2.6 years). MRI analysis at the time of presentation revealed the following abnormalities: subcortical white matter signal changes (n = 95), periventricular white matter signal changes (n = 76), splenium of corpus callosum involvement (n = 39), diffuse corpus callosum involvement (n = 27), cerebral atrophy (n = 35), basal ganglia involvement (n = 10), and brain stem involvement (n = 2). Notably, subcortical white matter involvement, periventricular white matter involvement, diffuse corpus callosum involvement, and basal ganglia involvement were more prevalent in patients with stage III and IV subacute sclerosing panencephalitis (P < .05 for all). Cerebral atrophy was also significantly more common in patients with stage III compared to those with stage IV subacute sclerosing panencephalitis (P < .0001). However, no substantial positive or negative associations were found between MRI findings and EEG abnormalities, other sociodemographic/clinical variables, and cerebrospinal fluid measles-specific antibody titers (P > .05). CONCLUSION: Early in the disease progression of subacute sclerosing panencephalitis, the temporoparietal and parietooccipital regions of the subcortical white matter are affected. Neuroimaging abnormalities exhibit a stronger association with Jabbour's clinical staging, but do not show significant associations with other clinical, sociodemographic, and EEG features.

Effectiveness of IMPUTE ADT-1 mobile application in children with autism spectrum disorder: An interim analysis of an ongoing randomized controlled trial.

Objectives: IMPUTE Inc., a software firm dedicated to healthcare technology, has developed a mobile medical application known as IMPUTE ADT-1 for children with autism spectrum disorder (ASD) based on the principle of applied behavior analysis. Materials and Methods: The primary objective of this trial was to compare the efficacy of add-on treatment with IMPUTE ADT-1 in children with ASD aged two to six years as compared to standard care alone for 12 weeks (in terms of change in Autism Diagnostic Observation Schedule [ADOS-2] scores). The secondary objective of the study was to assess the compliance with IMPUTE ADT-1 among participants and also to evaluate the feedback of parents regarding IMPUTE ADT-1 at the end of 12 weeks. The application provides personalized programs tailored to each user's needs, and the program evolves based on the user's progress. It also utilizes face tracking, eye tracking, and body tracking to gather behavior-related information for each child and apply it in reinforcement learning employing artificial intelligence-based algorithms. Results: Till the time of interim analysis, 37 and 33 children had completed 12-week follow-up in IMPUTE ADT-1 and control arm. At 12 weeks, as compared to baseline, change in social affect domain, repetitive ritualistic behavior domain, total ADOS-2 score, and ADOS-2 comparison score was better in the intervention group as compared to the control group (P < 0.001 for all). A total of 30 (81%), 28 (75%), and 29 (78%) caregivers in the IMPUTE ADT-1 group believed that the ADT-1 app improved their child's verbal skills, social skills, and reduced repetitive behavior, respectively. Conclusion: IMPUTE ADT-1 mobile application has the efficacy to improve the severity of autism symptoms in children. Parents of these children also feel that the application is beneficial for improving the socialization and verbal communication of their children.

Trial-history biases in evidence accumulation can give rise to apparent lapses.

Trial history biases and lapses are two of the most common suboptimalities observed during perceptual decision-making. These suboptimalities are routinely assumed to arise from distinct processes. However, several hints in the literature suggest that they covary in their prevalence and that their proposed neural substrates overlap - what could underlie these links? Here we demonstrate that history biases and apparent lapses can both arise from a common cognitive process that is normative under misbeliefs about non-stationarity in the world. This corresponds to an accumulation-to-bound model with history-dependent updates to the initial state of the accumulator. We test our model's predictions about the relative prevalence of history biases and lapses, and show that they are robustly borne out in two distinct rat decision-making datasets, including data from a novel reaction time task. Our model improves the ability to precisely predict decision-making dynamics within and across trials, by positing a process through which agents can generate quasi-stochastic choices.

Development and validation of a predictive model assessing the risk of seizure recurrence in children with neurocysticercosis.

INTRODUCTION: Neurocysticercosis (NCC) is a significant factor contributing to the incidence of seizures in developing countries. While numerous studies have investigated the recurrence of seizures in NCC, their reliability is often limited. METHODS: We assessed the socio-demographic, clinical, and neuroimaging details of 161 children with seizures caused by NCC. We monitored them for seizure recurrence over a 6-month follow-up period. We divided the children into two groups: those with seizure recurrence and those without. Subsequently, we identified predictive factors associated with seizure recurrence through univariate analysis, followed by multivariate binary logistic regression. We evaluated the prognostic model for discrimination and calibration and then internally validated it using the bootstrap method. RESULTS: A total of 23 children experienced breakthrough seizures. In multivariate analysis, the presence of epileptiform abnormalities in electroencephalogram (EEG), more than 5 NCC lesions, the presence of perilesional edema greater than 2 cm in maximum dimension, and a cluster of seizures before presentation were significantly associated with seizure recurrence (p < 0.05). These factors were included in the final NEPC (Number of NCC lesions, Epileptiform EEG abnormality, Perilesional edema, and Cluster of seizures) score. The final model exhibited good discrimination (AUC = 89.1 %; 95 % CI=80.5-95.3 %, p < 0.001) and calibration (p = 0.54). A score of 4 appeared to be the optimal threshold for discriminating between individuals with and without seizure recurrence, with sensitivity and specificity values of 85 % and 87 %, respectively. Interrater reliability was very strong between two pediatric neurologists and strong between a pediatric neurologist and a pediatric neurology trainee resident (k = 0.92 and 0.86, respectively). CONCLUSION: The NEPC score demonstrates good sensitivity and specificity in predicting seizure recurrence in pediatric children with NCC.

Transitions in dynamical regime and neural mode underlie perceptual decision-making.

Perceptual decision-making is the process by which an animal uses sensory stimuli to choose an action or mental proposition. This process is thought to be mediated by neurons organized as attractor networks 1,2 . However, whether attractor dynamics underlie decision behavior and the complex neuronal responses remains unclear. Here we use an unsupervised, deep learning-based method to discover decision-related dynamics from the simultaneous activity of neurons in frontal cortex and striatum of rats while they accumulate pulsatile auditory evidence. We show that contrary to prevailing hypotheses, attractors play a role only after a transition from a regime in the dynamics that is strongly driven by inputs to one dominated by the intrinsic dynamics. The initial regime mediates evidence accumulation, and the subsequent intrinsic-dominant regime subserves decision commitment. This regime transition is coupled to a rapid reorganization in the representation of the decision process in the neural population (a change in the "neural mode" along which the process develops). A simplified model approximating the coupled transition in the dynamics and neural mode allows inferring, from each trial's neural activity, the internal decision commitment time in that trial, and captures diverse and complex single-neuron temporal profiles, such as ramping and stepping 3-5 . It also captures trial-averaged curved trajectories 6-8 , and reveals distinctions between brain regions. Our results show that the formation of a perceptual choice involves a rapid, coordinated transition in both the dynamical regime and the neural mode of the decision process, and suggest pairing deep learning and parsimonious models as a promising approach for understanding complex data.

Unveiling the Silent Struggle: A Teen's Battle With Heart Failure Masking Takayasu Arteritis.

We hereby report a 17-year-old adolescent who presented with heart failure with an underlying diagnosis of Takayasu arteritis. Her clinical complaints were intermittent fever, claudication pain in the left upper limb, New York Heart Association (NYHA) grade III dyspnea, and episodes of dizziness for the past two years. On examination, she was unconscious, had absent peripheral pulses, and had severe hypotension. Diagnostic investigations revealed anemia, deranged renal and liver functions, cardiomegaly on chest X-rays, and severe coarctation of the aorta on echocardiography. Further imaging with CT aortography highlighted extensive arterial wall thickening. Laboratory findings included elevated inflammatory markers and negative autoimmune and infectious markers, confirming the diagnosis of large vessel vasculitis (Takayasu arteritis) with heart failure with reduced ejection fraction (LVEF 20-25%) in NYHA class III. The patient was managed with a combination of antihypertensive medications, diuretics, and immunosuppressive therapy. Subsequent follow-up demonstrated improvement in heart failure symptoms and inflammatory markers. This case emphasizes the challenging diagnostic and therapeutic considerations in managing Takayasu arteritis with concurrent cardiovascular complications in the adolescent population.

Epley's Manoeuvre: A Single Line Treatment for Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo.

Benign Paroxysmal Positional Vertigo (BPPV) is the commonest cause of peripheral vertigo. Displaced free floating otoconia in the semicircular canals are responsible for brief attacks of vertigo and nystagmus. Epley's manoeuvre relocates these particles into the utricle. Here we studied the efficacy of Epley's manoeuvre in posterior semicircular canal BPPV without labyrinthine sedatives. 120 patients presented with positional vertigo were included in the study based on positive Dix- hallpike test from August 2018 to July 2019. These patients were treated with only the Epley's manoeuvre and followed up for 6 months. Patients who were previously on labyrinthine sedatives were advised to stop them and treated with only the Epley's manoeuvre. In our study of 120 patients, mean age was 43.5 yrs. Females (52.5%) were commonly affected. Left side posterior semicircular involvement was more than the right side. Epley's manoeuvre had 90% efficacy at 1st week and 100% efficacy at 4th week. Duration of vertigo had significant association (p < 0.01) with the number of sessions required. There was significant improvement in the duration of vertigo attack (p < 0.0001) and frequency of attack (p < 0.0001) before and after the manoeuvre. Epley's manoeuvre lead to significant (p < 0.001) improvement in the quality of life of affected patients measured by DHI scoring. In our 6 months follow up, 10 recurrences occurred having significant (p < 0.01) association with the duration of vertigo attack. Only Epley's manoeuvre without any labyrinthine sedatives is an effective treatment for posterior semicircular canal BPPV patients. It also improves the quality of life of affected patients.

A Clinico-Pathological Study of Allergic Fungal Rhinosinusitis at a Tertiary Care Center of Western Rajasthan.

Allergic fungal rhinosinusitis (AFRS) is a non-invasive fungal sinusitis resulting from an immunologic response to the presence of extra mucosal fungal hyphae in the sinuses. Here we studied clinicopathological characteristics of AFRS among patients of chronic rhinosinusitis with nasal polyposis who underwent Functional Endoscopic Sinus Surgery (FESS) at a tertiary care in western Rajasthan. Standard ethical protocol was followed for the present study. We did a prospective study on admitted patients of chronic rhinosinusitis with nasal polyposis in the department of Otorhinolaryngology and Head & neck surgery, Dr. S. N. Medical College, Jodhpur from January 2018 to August 2019, who underwent FESS. The patient's history, clinical and endoscopic findings with radiological features were recorded. Biopsy specimens were sent for fungal staining, culture, and histopathology. As per Bent and Kuhn criteria, 25 cases out of 100 were diagnosed as AFRS, mean age was 27.46 ± 13.36. Nasal obstruction and nasal discharge were the most common symptoms. On histopathological examination fungal hyphae found in 18 cases (72%), allergic mucin in 25 cases (100%) and eosinophilic infiltrate in 20 cases (80%). Fungal culture positive in 15 cases (60%) of AFRS. In which aspergillus flavus present in 12 (80%). Allergic fungal rhinosinusitis should be considered as an important differential diagnosis in patients with chronic rhinosinusitis with nasal polyposis and for this surgery should be the treatment of choice.

Multiple network properties overcome random connectivity to enable stereotypic sensory responses.

Connections between neuronal populations may be genetically hardwired or random. In the insect olfactory system, projection neurons of the antennal lobe connect randomly to Kenyon cells of the mushroom body. Consequently, while the odor responses of the projection neurons are stereotyped across individuals, the responses of the Kenyon cells are variable. Surprisingly, downstream of Kenyon cells, mushroom body output neurons show stereotypy in their responses. We found that the stereotypy is enabled by the convergence of inputs from many Kenyon cells onto an output neuron, and does not require learning. The stereotypy emerges in the total response of the Kenyon cell population using multiple odor-specific features of the projection neuron responses, benefits from the nonlinearity in the transfer function, depends on the convergence:randomness ratio, and is constrained by sparseness. Together, our results reveal the fundamental mechanisms and constraints with which convergence enables stereotypy in sensory responses despite random connectivity.

An approach for long-term, multi-probe Neuropixels recordings in unrestrained rats.

The use of Neuropixels probes for chronic neural recordings is in its infancy and initial studies leave questions about long-term stability and probe reusability unaddressed. Here, we demonstrate a new approach for chronic Neuropixels recordings over a period of months in freely moving rats. Our approach allows multiple probes per rat and multiple cycles of probe reuse. We found that hundreds of units could be recorded for multiple months, but that yields depended systematically on anatomical position. Explanted probes displayed a small increase in noise compared to unimplanted probes, but this was insufficient to impair future single-unit recordings. We conclude that cost-effective, multi-region, and multi-probe Neuropixels recordings can be carried out with high yields over multiple months in rats or other similarly sized animals. Our methods and observations may facilitate the standardization of chronic recording from Neuropixels probes in freely moving animals.

Self healing hydrogels: A new paradigm immunoadjuvant for delivering peptide vaccine.

Immunoadjuvants are added to the vaccines in order to enhance and prolong the antigen specific immune responses when used in consolidation with specific vaccine antigens. This permits the use of antigen in lower quantity and allows immunization protocols practicing the vaccine with smaller doses. Self-healing hydrogels have the ability to heal the damages instinctively and reinstate its framework to ordinariness in absence of external stimuli. Moreover, self-healing hydrogel having various properties such as shear-thinning and reversible sol-gel transformation properties allow it to be readily delivered via injection. Therefore, in the present review, self- healing hydrogel is projected to be used as a carrier for sustained release of peptide and as an analogous to immunoadjuvant. The sustained release property of self-healing hydrogel may be credited to the changes in the structure in response to internal or external stimuli. In addition to the huge potential of stimuli-responsive self-healing hydrogels, they also exhibit good mechanical properties. These properties make self-healing hydrogel as a smart material in delivering the vaccines. Moreover, we have also summarized diverse range of physical and chemical reactions reported for the scale-up of self-healing hydrogels in this review.