Functionalized nanowires for miRNA-mediated therapeutic programming of naïve T cells.

Cellular programming of naïve T cells can improve the efficacy of adoptive T-cell therapy. However, the current ex vivo engineering of T cells requires the pre-activation of T cells, which causes them to lose their naïve state. In this study, cationic-polymer-functionalized nanowires were used to pre-program the fate of primary naïve CD8+ T cells to achieve a therapeutic response in vivo. This was done by delivering single or multiple microRNAs to primary naïve mouse and human CD8+ T cells without pre-activation. The use of nanowires further allowed for the delivery of large, whole lentiviral particles with potential for long-term integration. The combination of deletion and overexpression of miR-29 and miR-130 impacted the ex vivo T-cell differentiation fate from the naïve state. The programming of CD8+ T cells using nanowire-delivered co-delivery of microRNAs resulted in the modulation of T-cell fitness by altering the T-cell proliferation, phenotypic and transcriptional regulation, and secretion of effector molecules. Moreover, the in vivo adoptive transfer of murine CD8+ T cells programmed through the nanowire-mediated dual delivery of microRNAs provided enhanced immune protection against different types of intracellular pathogen (influenza and Listeria monocytogenes). In vivo analyses demonstrated that the simultaneous alteration of miR-29 and miR-130 levels in naïve CD8+ T cells reduces the persistence of canonical memory T cells whereas increases the population of short-lived effector T cells. Nanowires could potentially be used to modulate CD8+ T-cell differentiation and achieve a therapeutic response in vivo without the need for pre-activation.

Modality-Specific Feature Selection, Data Augmentation and Temporal Context for Improved Performance in Sleep Staging.

This work attempts to design an effective sleep staging system, making the best use of the available signals, strategies, and features in the literature. It must not only perform well on different datasets comprising healthy and clinical populations but also achieve good accuracy in cross-dataset experiments. Toward this end, we propose a model comprising multiple binary classifiers in a hierarchical fashion, where, at each level, one or more of EEG, EOG, and EMG are selected to best differentiate between two sleep stages. The best set of 100 features is chosen out of all the features derived from selected signals. The class imbalance in data is addressed by random undersampling and boosting techniques with decision trees as weak learners. Temporal context and data augmentation are used to improve the performance. We also evaluate the performance of our model by training and testing on different datasets. We compare the results of five approaches: using only EEG, EEG+EOG, EEG+EMG+EOG, EEG+EMG, and selective modality with a specific combination of EEG, EMG, and/or EOG at each level. The best results are obtained by considering features from EEG+EMG+EOG at each hierarchical level. The proposed model achieves average accuracies of 83.1%, 90.0%, 84.4%, 82.1%, 81.5%, 79.9%, and 73.7% on Sleep-EDF, Exp Sleep-EDF, ISRUC-S1, S2 and S3, DRMS-SUB, and DRMS-PAT datasets, respectively. For all the datasets except DRMS-SUB, the proposed method outperforms all the state-of-the-art approaches. Cross-dataset performance exceeds 80% for all datasets except DRMS-PAT; independent of whether the test data is from normal subjects or patients.

Cost-effectiveness of ticagrelor plus aspirin versus aspirin in acute ischaemic stroke or transient ischaemic attack: an economic evaluation of the THALES trial.

Objective: THALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS) or high-risk transient ischaemic attack (TIA). There are no cost-effectiveness analyses supporting this combination in Europe. To address this, a cost-effectiveness analysis was performed. Methods: Cost-effectiveness was evaluated using a decision tree and Markov model with a short-term and long-term (30-year) horizon. Stroke, mortality, bleeding and EuroQol-5 Dimension (EQ-5D) data from THALES were used to estimate short-term outcomes. Model transitions were based on stroke severity (disabling stroke was defined as modified Rankin Scale >2). Healthcare resource utilisation and EQ-5D data beyond 30 days were based on SOCRATES, another trial in AIS/TIA that compared ticagrelor with aspirin. Long-term costs, survival and disutilities were based on published literature. Unit costs were derived from national databases and discounted at 3% annually from a Swedish healthcare perspective. Results: One-month treatment with ticagrelor plus aspirin resulted in 12 fewer strokes, 4 additional major bleeds and cost savings of €95 000 per 1000 patients versus aspirin from a Swedish healthcare perspective. This translated into increased quality-adjusted life-years (0.04) and reduced societal costs (-€1358) per patient over a lifetime horizon. Key drivers of cost-effectiveness were number of patients experiencing subsequent disabling stroke and degree of disability. Findings were robust over a range of input assumptions. Conclusion: One month of treatment with ticagrelor plus aspirin is likely to improve outcomes and reduce costs versus aspirin in mild-to-moderate AIS or high-risk TIA. Trial registration number: NCT03354429.

Vitamin D Deficiency and Gingival Enlargement: A Case Report.

The occurrence of vitamin D insufficiency is rising constantly, and most pediatric patients are below the required levels. Individuals with vitamin D deficiency are more susceptible to inflammatory diseases because it reduces their immunity. The role of vitamin D deficiency in gingival enlargement has been reported in the literature. In this case report, we are describing a case in which a vitamin D supplement has resolved the gingival enlargement significantly without any invasive procedure. A 12-year-old boy reported a chief complaint of swollen gums in the upper and lower front teeth region. On clinical examination, there was minor surface plaque and calculus along with the formation of pseudopockets, but there was no clinical attachment loss. The patient has been advised to undergo laboratory tests for a complete blood profile, including a vitamin assessment. The patient reported after two and a half months with a gingivectomy on the first quadrant at a private clinic. They reported back to us because they didn't want the same trauma from surgery again and wanted a more conservative treatment option. So, on the basis of the reassessment of reports, vitamin D deficiency was confirmed, and treatment was started with 60,000 thousand I/U of vitamin D supplement weekly and advised for sunlight exposure with minimal clothing. There was a significant decrease in enlargement observed after the six-month follow-up period. Vitamin D supplements can be a more conservative treatment option for gingival enlargement of unknown etiology.

A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice.

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, which are essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters could overcome the shortcomings of parenteral vaccines and enhance pre- existing systemic immunity. Here we present a new protein subunit nanovaccine using multiadjuvanted (e.g. RIG-I: PUUC, TLR9: CpG) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL- NPs, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lung, and showed robust systemic humoral immunity. Interestingly, as a purely intranasal vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. Our data suggest that PUUC+CpG PAL-NP subunit vaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

Skin Prick Test in Educating Population of Rural Part of Eastern India and Promoting Health in Allergic Rhinitis: An Epidemiological Study.

Skin prick testing (SPT) is one of the most extensively used screening and diagnostic tool in contemporary allergy practice. It plays a vital role in diagnosis of type 1 hypersensitivity reaction in patients with rhinoconjunctivitis, asthma, urticaria, anapylaxis, atopic eczema and suspected food and drug allergy. The present study was undertaken to evaluate the pattern of allergenicity of aero-allergens and mites in the rural part of Eastern India using SPT. A total of 50 subjects (25 males and 25 females) were selected for the present study. Complete history and clinical symptoms were recorded according to ARIA guidelines. All the patients were subjected to SPT using 35 allergens. Positive sensitization was recorded in terms of frequency and measured in terms of maximum wheal diameter. The most common allergens observed were Gynandropsis gynandra (positive sensitization in 33 cases with wheal of 4.18 mm diameter) followed by Dermatophagoides farinae (25 cases, 6.12 mm diameter), Ageratum conyzoides (19 cases, 3.36 mm diameter), Cannabis sativa (17 cases, 3.52 mm diameter) and Cassia occidentalis (17 cases, 3.58 mm diameter). When the sensitivity was being compared between the most common allergens, statistical significance was obtained for Ageratum conyzoides and Cannabis sativa with Dermatophagoides farina (p value-0.0001). SPT is a reliable, minimally invasive procedure with immediate results useful in detection and promoting health of patients suffering from allergic rhinitis.

Single EOG channel performs well in distinguishing sleep from wake state for both healthy individuals and patients.

Using a single EOG channel, sleep-wake states of patients with different sleep disorders are accurately classified. We used polysomnography data of 27 patients (mixed apnea, periodic limb movement syndrome, sleep apnea-hypopnea syndrome, and dyssomnia) from DRMS-PAT and 20 healthy subjects from DRMS-SUB databases. We extracted a 67-dimensional feature vector, involving statistical features derived from ensemble empirical mode decomposition, approximate entropy, and relative powers in different frequency bands. Of these, the most relevant features are selected by exploiting mutual information between the features and corresponding labels. RUSBoost classifier is deployed to take care of the unbalanced data distribution. We achieved a high sensitivity of 97.5% and 95.3% as well as high specificity of 96.4% and 93.3% for sleep state in healthy and patients' groups, respectively. Ten-fold crossvalidation accuracies of 91.6% and 95% are achieved for patients and healthy individuals, respectively, using a single EOG channel. Clinical relevance-Accurate detection of sleep-wake states is crucial for the diagnosis of various sleep disorders including apnea-hypopnea syndrome and insomnia. Automated sleep-wake classification using EOG facilitates easy and convenient long-term sleep monitoring of patients without disturbing their sleep, thereby assisting the clinicians to analyze their sleeping patterns.

Assessment of submentalis muscle activity for sleep-wake classification of healthy individuals and patients with sleep disorders.

This work proposes a method utilizing only the submentalis EMG channel for the classification of sleep and wake states among the healthy individuals and patients with various sleep disorders such as sleep apnea hypopnea syndrome, dyssomnia, etc. We extracted autoregressive model parameters, discrete wavelet transform coefficients, Hjorth's complexity and mobility, relative bandpowers, Poincaré plot descriptors and statistical features from the EMG signal. We also used the energy of each epoch as a feature to distinguish between the sleep and wake states. Mutual information based feature selection approach was considered to obtain the top 25 features which provided maximum accuracy. For classification, we employed an ensemble of decision trees with random undersampling and boosting technique to deal with the class-imbalance problem in the sleep data. We achieved an overall accuracy of about 85% for the healthy population and about 70% on an average across different pathological groups. This work shows the potential of EMG chin activity for sleep analysis. Clinical Relevance- Automatic and reliable sleep-wake classification can reduce the burden of sleep experts in analyzing overnight sleep data (~ 8 hours) and also assist them to diagnose various neurological disorders at an early stage. Utilizing EMG channel provides an easier and convenient long-term recording of data without causing much disturbance in sleepunlike EEG which is inconvenient and hampers the natural sleep.

Lipid Membrane-Based Antigen Presentation to B Cells Using a Fully Synthetic Ex Vivo Germinal Center Model.

High-affinity antigen-specific B cells are generated within specialized structures, germinal centers (GCs), inside lymphoid organs. In GCs, follicular dendritic cells (FDCs) present antigens on their membrane surface to cognate B cells, inducing rapid proliferation and differentiation of the B cells toward antibody-secreting cells. The FDC's fluid membrane surface allows B cells to "pull" the antigens into clusters and internalize them, a process that frequently involves tearing off and internalizing FDC membrane fragments. To study this process ex vivo, liposomal membranes are used as the antigen-presenting FDC-like fluid lipid surface to activate B cells. In a fully synthetic in vitro GC model (sGC), which uses the microbead-based presentation of the CD40 Ligand and a cytokine cocktail to mimic T follicular helper cell signals to B cells, liposomes presenting a model antigen mimic effectively engage B cell receptors (BCRs) and induce greater BCR clustering compared to soluble antigens, resulting in rapid antigen internalization and proliferation of the B cells. B cells showed GC-like reactions and undergo efficient IgG1 class-switching. Taken together, the results suggest that fluid membrane-bound antigen induces a strong GC response and provides a novel synthetic in vitro system for studying GC biology in health and diseases, and for expanding therapeutic B cells ex vivo.

Effect of testing and social distancing measures on COVID-19 deaths in India: Role of pre-existing socio-economic factors.

We examine the effect of testing and social distancing measures on the severity of COVID19 across Indian states during the 68th day nationwide lockdown period. We also explore whether pre-existing socio-economic factors such as quality of health care and the ability to practice social distancing influences the effect of these policy measures across states. Using daily level data between April 1 and May 31 for 18 of the major states, we find that both testing and social distancing have a negative effect on COVID-19 fatalities in India. Further, testing is more helpful in reducing CFR for states with lower per capita health expenditure and weaker medical infrastructure. This highlights how ramping up testing can aid states that have a weak health care system through the detection of infection, contact tracing and isolation. In contrast, social distancing measures are more effective in states that are less populous and have lesser people dwelling in single-room houses. Our results confirm the role of pre-existing institutional factors in shaping the effect of policy actions on health outcomes.

Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine.

Despite success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability remain. Molecular adjuvants targeting pattern recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulates various PRRs, including toll-like receptors (TLRs) and retinoic acid-inducible gene I (RIG-I)-like receptors. We hypothesized that targeting PRRs using molecular adjuvants on nanoparticles (NPs) along with a stabilized spike protein antigen could stimulate broad and efficient immune responses. Adjuvants targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer NPs were combined with the S1 subunit of spike protein and assessed in vitro with isogeneic mixed lymphocyte reactions (isoMLRs). For in vivo studies, the adjuvant-NPs were combined with stabilized spike protein or spike-conjugated NPs and assessed using a two-dose intranasal or intramuscular vaccination model in mice. Combination adjuvant-NPs simultaneously targeting TLR and RIG-I receptors (MPLA+PUUC, CpG+PUUC, and R848+PUUC) differentially induced T cell proliferation and increased proinflammatory cytokine secretion by APCs in vitro. When delivered intranasally, MPLA+PUUC NPs enhanced CD4+CD44+ activated memory T cell responses against spike protein in the lungs while MPLA NPs increased anti-spike IgA in the bronchoalveolar (BAL) fluid and IgG in the blood. Following intramuscular delivery, PUUC NPs induced strong humoral immune responses, characterized by increases in anti-spike IgG in the blood and germinal center B cell populations (GL7+ and BCL6+ B cells) in the draining lymph nodes (dLNs). MPLA+PUUC NPs further boosted spike protein-neutralizing antibody titers and T follicular helper cell populations in the dLNs. These results suggest that protein subunit vaccines with particle-delivered molecular adjuvants targeting TLR4 and RIG-I could lead to robust and unique route-specific adaptive immune responses against SARS-CoV-2.

Nanoparticle-delivered TLR4 and RIG-I agonists enhance immune response to SARS-CoV-2 subunit vaccine.

Despite recent success in vaccinating populations against SARS-CoV-2, concerns about immunity duration, continued efficacy against emerging variants, protection from infection and transmission, and worldwide vaccine availability, remain. Although mRNA, pDNA, and viral-vector based vaccines are being administered, no protein subunit-based SARS-CoV-2 vaccine is approved. Molecular adjuvants targeting pathogen-recognition receptors (PRRs) on antigen-presenting cells (APCs) could improve and broaden the efficacy and durability of vaccine responses. Native SARS-CoV-2 infection stimulate various PRRs, including toll-like receptors (TLRs) and retinoic-acid-inducible gene I-like receptors (RIG-I). We hypothesized that targeting the same PRRs using adjuvants on nanoparticles along with a stabilized spike (S) protein antigen could provide broad and efficient immune responses. Formulations targeting TLR4 (MPLA), TLR7/8 (R848), TLR9 (CpG), and RIG-I (PUUC) delivered on degradable polymer-nanoparticles (NPs) were combined with the S1 subunit of S protein and assessed in vitro with isogeneic mixed lymphocyte reactions (iso-MLRs). For in vivo studies, the adjuvanted nanoparticles were combined with stabilized S protein and assessed using intranasal and intramuscular prime-boost vaccination models in mice. Combination NP-adjuvants targeting both TLR and RIG-I (MPLA+PUUC, CpG+PUUC, or R848+PUUC) differentially increased proinflammatory cytokine secretion (IL-1ß, IL-12p70, IL-27, IFN-ß) by APCs cultured in vitro, and induced differential T cell proliferation. When delivered intranasally, MPLA+PUUC NPs enhanced local CD4+CD44+ activated memory T cell responses while MPLA NPs increased anti-S-protein-specific IgG and IgA in the lung. Following intramuscular delivery, PUUC-carrying NPs induced strong humoral immune responses, characterized by increases in anti-S-protein IgG and neutralizing antibody titers and germinal center B cell populations (GL7+ and BCL6+ B cells). MPLA+PUUC NPs further boosted S-protein-neutralizing antibody titers and T follicular helper cell populations in draining lymph nodes. These results suggest that SARS-CoV-2-mimicking adjuvants and subunit vaccines could lead to robust and unique route-specific adaptive immune responses and may provide additional tools against the pandemic.

An Efficient Sleep Scoring Method using Visibility Graph and Temporal Features of Single-Channel EEG.

This work proposes a method utilizing the fusion of graph-based and temporal features for sleep stage identification. EEG epochs are transformed into visibility graphs from which mean degrees and degree distributions are obtained. In addition, autoregressive model parameters, Higuchi fractal dimension, multi-scale entropy, and Hjorth's parameters are calculated. All these features extracted from a single EEG channel (Pz-Oz) are fed to an ensemble classifier called random undersampling with boosting technique. Two different approaches i.e. 10-fold crossvalidation and 50%-holdout are utilized to evaluate the performance of the model. Cross-validation accuracies of 91.0% and 97.3%, and kappa coefficients of 0.82 and 0.94 are achieved for 6- and 2-state classifications, respectively, which are higher than those of existing studies.Clinical relevance- Automatic and reliable sleep stage classification can reduce the burden of sleep experts in analyzing overnight sleep data (~ 8 hours). It can also assist them to find specific traits of interest such as spindle density, by providing annotated sleep data (hypnogram), thereby eliminating the need for tedious and expensive manual scoring. An accurate 2-state (wake/sleep) classification is also crucial for the patients with disorders of consciousness, where stimulation during wake state is considered more effective than that in sleep state.

Understanding and improving cellular immunotherapies against cancer: From cell-manufacturing to tumor-immune models.

The tumor microenvironment (TME) is shaped by dynamic metabolic and immune interactions between precancerous and cancerous tumor cells and stromal cells like epithelial cells, fibroblasts, endothelial cells, and hematopoietically-derived immune cells. The metabolic states of the TME, including the hypoxic and acidic niches, influence the immunosuppressive phenotypes of the stromal and immune cells, which confers resistance to both host-mediated tumor killing and therapeutics. Numerous in vitro TME platforms for studying immunotherapies, including cell therapies, are being developed. However, we do not yet understand which immune and stromal components are most critical and how much model complexity is needed to answer specific questions. In addition, scalable sourcing and quality-control of appropriate TME cells for reproducibly manufacturing these platforms remain challenging. In this regard, lessons from the manufacturing of immunomodulatory cell therapies could provide helpful guidance. Although immune cell therapies have shown unprecedented results in hematological cancers and hold promise in solid tumors, their manufacture poses significant scale, cost, and quality control challenges. This review first provides an overview of the in vivo TME, discussing the most influential cell populations in the tumor-immune landscape. Next, we summarize current approaches for cell therapies against cancers and the relevant manufacturing platforms. We then evaluate current immune-tumor models of the TME and immunotherapies, highlighting the complexity, architecture, function, and cell sources. Finally, we present the technical and fundamental knowledge gaps in both cell manufacturing systems and immune-TME models that must be addressed to elucidate the interactions between endogenous tumor immunity and exogenous engineered immunity.

MTOR Signaling and Metabolism in Early T Cell Development.

The mechanistic target of rapamycin (mTOR) controls cell fate and responses via its functions in regulating metabolism. Its role in controlling immunity was unraveled by early studies on the immunosuppressive properties of rapamycin. Recent studies have provided insights on how metabolic reprogramming and mTOR signaling impact peripheral T cell activation and fate. The contribution of mTOR and metabolism during early T-cell development in the thymus is also emerging and is the subject of this review. Two major T lineages with distinct immune functions and peripheral homing organs diverge during early thymic development; the αß- and γδ-T cells, which are defined by their respective TCR subunits. Thymic T-regulatory cells, which have immunosuppressive functions, also develop in the thymus from positively selected αß-T cells. Here, we review recent findings on how the two mTOR protein complexes, mTORC1 and mTORC2, and the signaling molecules involved in the mTOR pathway are involved in thymocyte differentiation. We discuss emerging views on how metabolic remodeling impacts early T cell development and how this can be mediated via mTOR signaling.

Electrophysiological and Neuroimaging Studies - During Resting State and Sensory Stimulation in Disorders of Consciousness: A Review.

A severe brain injury may lead to a disorder of consciousness (DOC) such as coma, vegetative state (VS), minimally conscious state (MCS) or locked-in syndrome (LIS). Till date, the diagnosis of DOC relies only on clinical evaluation or subjective scoring systems such as Glasgow coma scale, which fails to detect subtle changes and thereby results in diagnostic errors. The high rate of misdiagnosis and inability to predict the recovery of consciousness for DOC patients have created a huge research interest in the assessment of consciousness. Researchers have explored the use of various stimulation and neuroimaging techniques to improve the diagnosis. In this article, we present the important findings of resting-state as well as sensory stimulation methods and highlight the stimuli proven to be successful in the assessment of consciousness. Primarily, we review the literature based on (a) application/non-use of stimuli (i.e., sensory stimulation/resting state-based), (b) type of stimulation used (i.e., auditory, visual, tactile, olfactory, or mental-imagery), (c) electrophysiological signal used (EEG/ERP, fMRI, PET, EMG, SCL, or ECG). Among the sensory stimulation methods, auditory stimulation has been extensively used, since it is easier to conduct for these patients. Olfactory and tactile stimulation have been less explored and need further research. Emotionally charged stimuli such as subject's own name or narratives in a familiar voice or subject's own face/family pictures or music result in stronger responses than neutral stimuli. Studies based on resting state analysis have employed measures like complexity, power spectral features, entropy and functional connectivity patterns to distinguish between the VS and MCS patients. Resting-state EEG and fMRI are the state-of-the-art techniques and have a huge potential in predicting the recovery of coma patients. Further, EMG and mental-imagery based studies attempt to obtain volitional responses from the VS patients and thus could detect their command-following capability. This may provide an effective means to communicate with these patients. Recent studies have employed fMRI and PET to understand the brain-activation patterns corresponding to the mental imagery. This review promotes our knowledge about the techniques used for the diagnosis of patients with DOC and attempts to provide ideas for future research.

Determination of Serum IgE and Eosinophils as a Diagnostic Indicator in Allergic Rhinitis.

Allergic Rhinitis is a chronic, inflammatory disease induced by an IgE-mediated reaction and identified clinically by the presence of symptoms of nasal discharge, itching, sneezing and nasal congestion. The aim and objectives of the study was to determine serum IgE and eosinophil levels in patients with allergic rhinitis and healthy controls, men and women, different age groups and to establish a correlation between serum IgE and eosinophil. A retrospective study was conducted in the outpatient department of ENT in ICARE institute of medical sciences and research, Haldia during the time span of March 2016 to February 2017. A total of 155 subjects (113 cases and 42 controls, 74 men and 81 women) of age 1 month-75 years were selected for the study. Blood samples obtained were analyzed to determine serum IgE and eosinophil levels and the results were subjected to statistical analysis using STATA 12 software. The mean values and standard deviation of the serum log IgE and eosinophil levels in cases and healthy controls, men and women, various age groups were obtained and tabulated using paired t test and MV test. Pearson's correlation was performed to establish a relationship between serum log IgE and eosinophil levels. The mean values of serum log IgE and eosinophil levels were found to be higher in cases (log IgE-5.65, IgE-814.36 IU/ml, eosinophil-4.49%) when compared to controls (log IgE-4.43, IgE-96.62 IU/ml, eosinophil-2.36%). Men predominance was seen in mean serum log IgE levels (IgE-1018.5 IU/ml, log IgE-5.92) whereas women predominance in mean eosinophil counts (4.96%) in allergic rhinitis. A weakly positive correlation of 0.194 was established between serum log IgE and eosinophil levels. Estimation of serum IgE and eosinophil can serve as a simple, non-invasive and reliable investigative tool in the diagnosis of allergic rhinitis.

Optimized nonviral gene delivery for primary urinary renal progenitor cells to enhance cell migration.

Progressive loss of glomerular podocytes during kidney disease leads to irreversible kidney failure, and is exacerbated by the fact that podocytes are terminally differentiated epithelial cells and unable to proliferate. Regeneration of lost podocytes must therefore derive from nonpodocyte sources. Human urine-derived renal progenitor cells (uRPCs) are attractive podocyte progenitors for cell therapy applications due to their availability from patient urine and ability to migrate to injured glomeruli and differentiate into de novo podocytes after intravenous administration. Because gene delivery has emerged as an important strategy to augment the functionality and survival of cell therapies prior to injection, in this work we optimized nonviral gene delivery conditions (cell density, DNA dose, % FBS, and transfection material composition) to primary uRPCs. Using the cationic polymer-peptide conjugate VIPER for gene delivery and the Sleeping Beauty transposon/transposase constructs for gene integration, we optimized transfection parameters to achieve efficient transgene expression (up to 55% transfected cells) and stable transgene expression (>65% integration efficiency) lasting up to 10 days. With these methods, we transfected uRPCs to overexpress CXCR4, an important chemokine receptor that mediates uRPC migration to the kidneys after intravenous injection, and demonstrate that CXCR4-uRPCs exhibit enhanced migration compared to mock-transfected cells.

A Randomized Proof-of-Principle Bite Force Study of Two Experimental Denture Adhesives and a Commercially Available Adhesive.

PURPOSE: To assess the efficacy of two experimental denture adhesive gels (adhesives 1 and 2) compared to a commercially available denture adhesive cream (positive control) and no adhesive (negative control). MATERIALS AND METHODS: This was a single-center, randomized, four-treatment, examiner-blind, crossover study in participants with well-made and at least moderately well-fitting maxillary complete dentures. Incisal bite force until denture dislodgment was measured before application (baseline) and over the following 12 hours for each of the treatments. Between-treatment differences in the area over baseline (AOB) for the bite force at each time point were analyzed using an analysis of covariance model. RESULTS: The efficacy and safety analyses were based on results from 48 participants. Compared to the negative control, adhesive 1 showed a statistically significantly higher bite force AOB over 12 hours (AOB0-12h; primary endpoint), as well as for AOB0-6h and AOB0-9h (all P < .05), but not for AOB0-1h or AOB0-3h. Adhesive 2 was not significantly different from the negative control or from adhesive 1 for any measure of AOB. The positive control was associated with a significantly higher bite force AOB than either of the experimental adhesives for all time points (P < .05). Although the positive control was well tolerated, both experimental adhesives were associated with a larger number of oral adverse events. CONCLUSION: Only adhesive 1 was significantly better than the negative control, and its performance did not match that of the positive control. Adhesives 1 and 2 showed the largest number of oral adverse events.

Randomized Clinical Study Comparing Three Experimental Denture Adhesives and Fixodent® versus No Adhesive.

OBJECTIVES: Denture adhesives can improve function, retention, stability, and bite force in well-fitting dentures. This single-center, randomized, five-arm, examiner-blind, crossover clinical study aimed to compare three experimental adhesives ("Adhesive 1," "Adhesive 2," "Adhesive 3") with slightly different formulations and a commercially marketed "Positive control" with a "No Adhesive" arm using incisal bite force measurements over 12 hours in subjects with a moderately well- to well-fitting maxillary denture. METHODS: Institutional review and informed consent were obtained and qualified subjects were randomly assigned to a treatment sequence. Prior to adhesive application, subjects were asked to bite on a transducer with increasing force until their maxillary denture dislodged (bite force measurement). This procedure was repeated at 0.5, 1, 3, 6, 9, and 12 hours after adhesive application, with results recorded electronically. Treatment differences in the area over baseline (AOB) were analyzed using an ANCOVA model. RESULTS: A total of 48 subjects completed the study. All experimental formulations showed statistically significantly higher bite force measurements compared to the No Adhesive arm at all time points (p < 0.0001 for Adhesive 1 and Adhesive 2 at all times; p < 0.003 for Adhesive 3 at all times). While numerical values for bite force favored the Positive control for the duration of the study, there were no significant statistical differences at any time point between Adhesive 2 and the Positive control, and only over three and six hours compared to Adhesive 1. However, differences favored the Positive control compared to Adhesive 3 at all time points. CONCLUSIONS: All denture adhesives gave statistically significantly better bite force AOB in moderately well- to well-fitting dentures compared to no adhesive. All denture adhesives tested were generally well tolerated.