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Design and development of efficient drug delivery technologies that impart site-specificity is the need of the hour for the effective treatment of lung cancer. The emergence of materials science and nanotechnology partially helped drug delivery scientists to achieve this objective. Various stimuli-responsive materials that undergo degradation at the pathological tumor microenvironment (TME) have been developed and explored for drug delivery applications using nanotechnological approaches. Nanoparticles (NPs), owing to their small size and high surface area to volume ratio, demonstrated enhanced cellular internalization, permeation, and retention at the tumor site. Such passive accumulation of stimuli-responsive materials helped to achieve spatiotemporally controlled and targeted drug delivery within the tumors. In this review, we discussed various stimuli—physical (interstitial pressure, temperature, and stiffness), chemical (pH, hypoxia, oxidative stress, and redox state), and biological (receptor expression, efflux transporters, immune cells, and their receptors or ligands)—that are characteristic to the TME. We mentioned an array of biomaterials-based nanoparticulate delivery systems that respond to these stimuli and control drug release at the TME. Further, we discussed nanoparticle-based combinatorial drug delivery strategies. Finally, we presented our perspectives on challenges related to scale-up, clinical translation, and regulatory approvals. This article discusses about the role of biomaterials and nanoparticulate drug delivery systems to impart spatiotemporally controlled drug delivery in lung cancer therapy against physical, chemical, and biological stimuli of the tumor microenvironment. Further, this article presents the challenges associated with scale-up, regulatory approvals, and clinical translation of engineered nanomaterials-based therapeutics. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most commonly diagnosed cancer among women. Chemo-, immune- and photothermal therapies are employed to manage BC. However, the tumor microenvironment (TME) prevents free drugs and nanocarriers (NCs) from entering the tumor premises. Formulation scientists rely on enhanced permeation and retention (EPR) to extravasate NCs in the TME. However, recent research has demonstrated the inconsistent nature of EPR among different patients and tumor types. In addition, angiogenesis, high intra-tumor fluid pressure, desmoplasia, and high cell and extracellular matrix density resist the accumulation of NCs in the TME. In this review, we discuss TME normalization as an approach to improve the penetration of drugs and NCSs in the tumor premises. Strategies such as normalization of tumor vessels, reversal of hypoxia, alleviation of high intra-tumor pressure, and infiltration of lymphocytes for the reversal of therapy failure have been discussed in this manuscript. Strategies to promote the infiltration of anticancer immune cells in the TME after vascular normalization have been discussed. Studies strategizing time points to administer TME-normalizing agents are highlighted. Mechanistic pathways controlling the angiogenesis and normalization processes are discussed along with the studies. This review will provide greater tumor-targeting insights to the formulation scientists. [ABSTRACT FROM AUTHOR]

Artificial Intelligence (AI) and AI-driven technologies are transforming industries across the board, with the pharmaceutical sector emerging as a frontrunner beneficiary. This article explores the growing impact of AI and Machine Learning (ML) within pharmaceutical Regulatory Affairs, particularly in dossier preparation, compilation, documentation, submission, review, and regulatory compliance. By automating time-intensive tasks, these technologies streamline workflows, accelerate result generation, and shorten the product approval timeline. However, despite their immense potential, AI and ML also introduce new challenges. Issues such as AI software validation, data management security and privacy, potential biases, ethical concerns, and change management requirements must be addressed. This review highlights current AI-based tools actively used by regulatory professionals such as DocShifter, Veeva Vault, RiskWatch, Freyr SubmitPro, Litera Microsystems, cortical.io etc., examines both the benefits and obstacles of integrating these advanced systems into regulatory practices. Given the rapid pace of technological innovation, the article underscores the need for proactive collaboration with regulatory bodies to manage these developments. It also stresses the importance of adapting to evolving regulatory frameworks and embracing new technologies. Although regulatory agencies like the United Sates Food and Drug Administration (USFDA), European Medicines Agency (EMA), and Medicines and Healthcare products Regulatory Agency (MHRA) are working on guidelines for AI and ML adoption, clear, standardized protocols are still in the works. While the journey ahead may be complex, the integration of AI promises to fundamentally reshape regulatory processes and accelerate the approval of safe, effective pharmaceutical products. [ABSTRACT FROM AUTHOR]

The current advent explores the potential of itraconazole (ITR) in prostate cancer (PCa), by its incorporation into albumin nanoparticles (NP). ITR as a repurposed moiety has displayed tremendous potential in various cancers. However, poor aqueous solubility poses hurdles towards its clinical translation. Amorphisation of ITR was observed post-incorporation within NP matrix which could prevent its precipitation in aqueous media. ITR NP was developed using quality by design and multivariate analysis and evaluated for cellular uptake, cell proliferation inhibition and the mechanism of PCa cell inhibition. Time and concentration-dependent serum stability and hemolytic potential revealed safety of ITR NP. Morphological changes and nuclear staining studies revealed the efficacy of ITR and ITR NP in promoting growth inhibition of PC-3 cells. Superior qualitative and quantitative uptake, reactive oxygen species (ROS) and mitochondrial impairment for ITR NP in comparison with ITR and control group was observed. Cell cycle study revealed remarkable G2/M phase inhibition in PC-3 cells. ITR NP demonstrated superior anticancer potential in 3D tumoroids mimicking the micro-metastatic lesions compared to control and ITR. Hence, ITR NP can be a favorable alternative therapeutic alternative in PCa. [ABSTRACT FROM AUTHOR]

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180–230 nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel. [ABSTRACT FROM AUTHOR]

This study contributes to the overarching Indian Environmental Radiation Monitoring Network initiative, concentrating on the continual assessment of the gamma absorbed dose rate in outdoor air attributable to natural gamma radiation in Kolkata, West Bengal, India. Over a span of fourteen years (2011–2024), data were gathered from 32 monitoring sites within the city utilizing permanently installed Geiger-Mueller detector-based environmental radiation monitors. This paper offers an analysis of extensive findings from long-term monitoring efforts. The absorbed gamma dose rate in outdoor air varied among the monitoring sites, ranging from 78 ± 5 to 137 ± 4 nGy h− 1, with a mean value of 107 ± 12 nGy h− 1. The estimated mean annual effective dose due to outdoor natural gamma radiation ranged from 0.10 ± 0.01 to 0.17 ± 0.01 mSv y− 1, with an overall mean of 0.13 ± 0.01 mSv y−1. [ABSTRACT FROM AUTHOR]

Abiraterone acetate (ABA), a biopharmaceutical class IV drug suffers from solubility and permeability pitfalls resulting in limited oral bioavailability and positive food effect, i.e. multi-fold enhancement in drug absorption in the presence of food. This poses difficulties to physicians towards the estimation of dose and dosage regimen required for efficacious therapy of prostate cancer (PCa). Nanostructured lipid carriers (NLC) have demonstrated tremendous outcomes in enhancing the oral bioavailability of various entities along with food effect attenuation. In this study, Quality by design and multivariate analysis was employed for optimization of ABA loaded NLC (ABA NLC). The optimal size, PDI and zeta potential obtained using QbD were 134.6 nm, 0.163 and -15.7 mV respectively. Ex vivo qualitative and quantitative intestinal permeability studies demonstrated improved traversion of NLC through the intestinal segments. In vitro dissolution profile in biorelevant fast and fed gastric and intestinal media revealed minimal differences for ABA NLC compared to ABA. In vivo pharmacokinetics was performed to decipher the efficacy of ABA NLC in mitigating the food effect of ABA. The studies demonstrated 14.51-fold and 1.94-fold improvement in oral bioavailability during fasted and fed state respectively as compared to free ABA. The absorption mechanism of ABA NLC using chylomicron flow blocking approach conveyed lymphatic uptake as the major mechanism. Cmax fast/fed ratio was 0.9758 whereas, AUC fast/fed ratio was 0.9386, which being nearly equivalent, confirmed the food effect attenuation. Therefore, the results of the study demonstrate optimal pharmacokinetics of ABA NLC and its utility in circumventing the fast fed variability. [ABSTRACT FROM AUTHOR]

Purpose: Despite stringent regulations enforced by the United States Food and Drug Administration (USFDA), numerous drug products still enter the market without adequate assurance of safety and efficacy, resulting in frequent recalls. To explore the real picture of such recalls, this analysis focuses on the USFDA drug recalls with a glance at medical devices, food products, biological products, cosmetics, tobacco products, and veterinary products from 2019 to 2023. The research aims to quantify and categorize these drug recalls, examining various contributing factors to recommend strategies for minimizing future recalls. Additionally, it investigates the influence of global and national crises, such as the COVID-19 pandemic, on the USFDA’s drug recall process. Methods: Data from USFDA Enforcement reports were collected and sorted, and descriptive statistics were used to analyse drug recalls. Results: Between 2019 and 2023, the USFDA documented 31125 recalls, of which 6217 involved drug products from 593 different companies. These recalls are frequently initiated by the companies themselves, with primary causes including sterility assurance failures, contamination, and improper storage conditions. Conclusions: Drug recalls are a double-edged sword: while they are essential for protecting public health, they can also disrupt supply chains and lead to drug shortages, especially when there are no alternatives available. To prevent such disruptions, strict adherence to current Good Manufacturing Practices, along with comprehensive internal audits and rigorous USFDA inspections are vital for manufacturers to maintain quality standards and minimize the risk of recalls. [ABSTRACT FROM AUTHOR]

This study explores the comprehensive approach of utilizing physiographical and geophysical electrical resistivity tomography (ERT) investigation to evaluate and address the challenges associated with abandoned, unplanned water-filled galleries in Chasnala Colliery, located in Jharkhand, India. The integrated methodologies facilitate a thorough examination of subsurface conditions, encompassing factors such as geological stability, hydrological fluctuations, and environmental considerations. Utilizing physiographical analysis is of utmost importance in identifying locations with potential risks and developing appropriate site-specific reclamation procedures in the study area. The ERT analysis has successfully confirmed the findings of the physiographical study, revealing the presence of five distinct underground galleries, namely, GL1, GL2, GL3, GL4, and GL5, that are likely submerged in water. These galleries establish connections between the underground spaces and the groundwater, as indicated by their low resistivity values of ~50 Ωm or less. The resistivity measurements exhibit variations that can be attributed to fluctuations in the underground water content. The Wenner, Schlumberger, and dipole–dipole arrays have adeptly discerned the existence of water-filled underground galleries with commendable accuracy. However, the joint array configuration stands out as the pre-eminent choice among these standards due to its unparalleled technical robustness. The findings concurred with the notable correlation between water-filled galleries’ spatial arrangement and shallow groundwater level. The integration of physiographical and ERT data improves the precision of subsurface characterization, facilitating informed decision-making for efficient water management and site rehabilitation in the context of opencast mining. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to meticulously analyse the trends and recurrent challenges that emerge from Warning Letters (WLs) issued by the United States Food and Drug Administration (USFDA), focusing on current Good Manufacturing Practices (cGMP) voilations. By investigating the organizational, procedural, and systemic factors that precipitate these non-compliances, the research provides a comprehensive overview of the obstacles to cGMP adherence. Methods: The framework for this study involved a detailed statistical analysis of WLs issued from 2019 to 2024, accessible through the USFDA database. Each letter was categorized and analysed according to violation type, frequency, and underlying causes. This approach facilitated a nuanced understanding of the major and minor compliance issues affecting the pharmaceutical industry. Results: The analysis of total 186 WLs reveals a predominance of violations related to cGMP standards and adulteration of drug products, pinpointing these areas as significant compliance. The study further categorizes and discusses minor violations to offer a holistic view of the compliance landscape in pharmaceutical insdustries. Conclusion: The findings from the WLs suggests a critical need for enhanced regulatory vigilance and quality assurance processes within pharmaceutical companies. The recurrent nature of certain violations highlights potential systemic flaws in how cGMP guidelines are implemented and adhered to across the industry. This research advocates for a proactive regulatory strategy by forecasting regulatory trends and identifying cGMP enforcement challenges, aiming to strengthen quality, streamline inspections, reduce compliance discrepancies, and improve public health outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore genetic variations associated with DNA repair mechanisms to enhance the management of both oral cancer (OC) and oral precancer (OPC). Methods: A cohort of 380 patients diagnosed with OC and OPC, comprising 220 males and 160 females, was analyzed. Participants were categorized based on their tobacco-chewing habits, with corresponding control groups established. Key genetic markers investigated for polymorphisms included OGG1, APE1, and XRCC1. Results: The XRCC1 Arg280H variant demonstrated significant associations with the susceptibility to both OC and OPC across various models. Further analyses, incorporating factors such as tobacco and alcohol consumption, unveiled a correlation between the XRCC1 Arg194Trp variant and an elevated risk of developing head and neck cancer. Stratified analyses also revealed an increased risk of OC or OPC based on the specific site of the cancer. Conclusion: The study underscores the importance of XRCC1 polymorphisms, particularly XRCC1 Arg280H and XRCC1 Arg194Trp, within the genetic framework of OC and OPC. Understanding these genetic associations provides valuable insights for the potential development of targeted interventions aimed at individuals predisposed to these conditions. [ABSTRACT FROM AUTHOR]

The large-scale removal of trees from forests to make way for human activities is known as deforestation, given that it may result in soil erosion, natural habitat deterioration, biodiversity loss, and water cycle disturbance, this is a major environmental problem. As a source of food, clean water, oxygen, and medicines as well as an essential component of the hydrological cycle—they supply water to the atmosphere through transpiration—forests are a contributing factor to climate change and global warming. In addition to decreasing soil fertility and rainfall, deforestation increases the likelihood of floods and droughts and has a major effect on global warming. Deforestation monitoring is an important input for forest management that helps to prepare an action plan, but monitoring is still a challenging task. Hence, there is a need for an accurate deforestation mechanism to monitor those areas that have been converted from forest to non-forest areas. Therefore, in this paper a deep learning-based forest monitoring approach has been proposed, which is implemented in two steps: (i) a machine learning-based classification technique has been applied to the Sentinel-2 images to classify the forest and non-forest areas, and (ii) a deep learning-based change detection technique is proposed to detect the changes occurred during 2017–2022 of the Kukrail forest range situated in India. The performance of the proposed algorithm is assessed by estimating the error measuring parameters like Precision, Recall, and F1 Score, and it is observed that the proposed approach is quite suitable for forest area change monitoring. [ABSTRACT FROM AUTHOR]

The Jharia coalfield stands as a paramount asset within the Indian economy. However, many pressing issues, such as coal fires, land subsidence, unplanned mining, child labor, deforestation, and air pollution, demand immediate attention. Effective planning and comprehensive mitigation strategies are imperative to address these challenges. This research centers on evaluating an area near Bhuiyadih village subjected to rat hole mining using non-invasive geophysical methods. The evaluation includes a joint analysis of multiple geophysical techniques, such as gravity, magnetic, and seismic surface wave methods. The potential data has been evaluated by generating edge detection, upward continuation maps, and radial average power spectrum (RAPS) plots. Seismic surface wave velocity structure has been evaluated and used as a constraint to model the subsurface structures using potential field data. Evaluating subsurface layers from the RAPS, Seismic surface wave model, and 2D model generated from the potential data indicates a weathered layer, an overburden sandstone layer, and a coal seam of thickness ~ 4.5 m, ~ 14 m, and ~ 11 m, respectively. The wideness of the gallery boundary has been evaluated using the composite lineament map and found to be surpassing approved limits for underground mining, signifying evidence of rat hole mining practices. The thin pillars in the coal seam and fractures observed on the surface indicate the failure of overburdened rock masses, leading to land subsidence in the nearby villages. The study reinforces the urgency of shifting the local population to a safer environment to avoid unfortunate situations. [ABSTRACT FROM AUTHOR]

Underground galleries possess random subsidence threats if they are not treated well. Threats even become multifold when these galleries are located somewhere in the vicinity of the railway tracks. So, checking the stable ground formation or the health of the subsurface formation near railway tracks and mapping the galleries are very important tasks for the sake of the environment, economy and lives. Galleries under the present study are associated with the coal seam-X and seam-XA of the Jogidih Colliery of Jharia Coalfield. Seven electrical resistivity tomography (ERT) profiles and magnetic surveys were performed at a side of the railway track to characterize the subsurface formation near railway tracks and to detect the gallery and its extension. Both ERT and magnetic data analysis suggest the presence of some galleries at a certain distance from the railway tracks. Moreover, combined analysis of ERT and magnetic data suggests that ground within ~20 m from the railway tracks is found to be stable with homogeneous compact formation. [ABSTRACT FROM AUTHOR]

Bosutinib (BOS) is a BCS class IV drug that shows low oral bioavailability and high fast-fed variability. Various pharmaceutical formulations have been explored thus far in order to improve its bioavailability while avoiding fast-fed variability. In the present study, we explored cyclodextrin (CD) complexation strategy to overcome the aforementioned disadvantages associated with BOS. CD complexation is a simple, versatile and economic approach that enables formation of inclusion complexes, thereby improving aqueous solubility while nullifying pH-dependent solubility and fast-fed variability for poorly soluble drugs. Initially, we performed molecular dynamics and docking studies to select appropriate CD derivative. The results of in silico studies revealed that sulfo-butyl ether β-cyclodextrin (SBE-CD) offered superior binding affinity with BOS. Further, Job's plot revealed that 1:1 stoichiometry of BOS and CD resulted in enhancement of BOS solubility up to ~ 132.6-folds. In vitro release studies in bio-relevant media (fasted and fed state simulated gastric and intestinal fluids) revealed higher drug release while overcoming its pH-dependent solubility. In vitro studies on K562 cells demonstrated a 1.83-fold enhancement in cytotoxicity due to enhanced ROS production and G2/M phase arrest.In vivo pharmacokinetic studies in Sprague-Dawley rats revealed insignificant fast-fed variability with AUCfast/fed 0.9493 and Cmaxfast/fed 0.8291 being closer to 1 in comparison with BOS. Hence, we conclude that SBE-CD complexation could be a promising approach in diminishing fast-fed variability of BOS. [ABSTRACT FROM AUTHOR]

This work presents a reliable communication system tailored for post-disaster scenarios, where the existing terrestrial communication infrastructure is entirely disrupted by natural calamities. To encounter the situation, a Temporary Base Station (TBS) is deployed in the heart of the disaster-stricken area. However, due to the limited coverage area of the TBS, reaching far users becomes unattainable. To address this, Unmanned Aerial Vehicles (UAVs) are proposed as flying relays with indirect connectivity, utilizing Half-Duplex/Full-Duplex (HD/FD) Non-Orthogonal Multiple Access (NOMA) schemes, abbreviated as HDU/FDU-NOMA. The UAVs, strategically positioned around the TBS on a circular path, can move radially outward or inward based on far user throughput demands and also serve as near-users. Moreover, a Weibull fading distribution (WD) is taken into account for both links, encompassing transmissions from far-users to UAVs and from UAVs to TBS. To assess communication reliability, exact and closed-form expressions for outage probability and throughput performance are derived. These expressions aid in identifying optimal UAV locations to achieve throughput fairness for both far-users and near-users, as well as maximizing throughput for far-users. Additionally, the proposed scheme's outage and throughput performance is demonstrated to surpass that of corresponding Orthogonal Multiple Access (OMA) schemes in the uplink. Simulation results conform to the analytical results. [ABSTRACT FROM AUTHOR]

In this paper, a novel geometric progression (GP)-based approach for dynamic power allocation (PA) in a single-carrier multi-user power-domain non-orthogonal multiple access (PD-NOMA) network is proposed. The mathematical analysis of the proposed model furnishes the PA coefficients that satisfy the basic PA as well as successive interference cancellation (SIC) constraints. The model requires a minimum signal-to-noise power ratio (SNR) that depends only on the channel conditions of the strongest-user. With this SNR, the model ensures each of the cluster users experiences at least a constant, desired minimum target throughput. Further, the PA coefficients obtained with the proposed GP-based fair power allocation (FPA) algorithm are analyzed for a multi-user scenario of four, five, and six users, respectively. A comparative analysis of performance metrics, such as the obtained sum-rate, user fairness index, complexity, coefficient's nature, and the throughput is carried out, that verifies the efficacy of the proposed model. The simulations reveal a fairness index up to unity along with error-free SIC. For a six-user case with a GP ratio of 10, the minimum target throughput unity, and operational SNR 3927.63 (35.94 dB), the proposed algorithm provides a network sum-rate of 16.76 bps and a high fairness index of 91.64%. Furthermore, the geometric progression-based fair power allocation (GPFPA) algorithm provides a trade-off between the sum-rate and fairness index and can be tuned for higher network throughput or higher fairness index. Hence, the proposed model justifies its appropriateness for the sixth-generation (6G) massive connection density and ultra-reliability scenarios. [ABSTRACT FROM AUTHOR]

Oral carcinoma (OC) is the leading cause of mouth deformation and mortality in the world. It is the 6th most frequent cancer globally. OC is aggressive cancer-forming tumors that invade nearby tissues, leading to locoregional spread. Surgical ablation of large tumors leads to removal of a large chunk of the mouth leading to loss of function and aesthetics. Hence, the use of neoadjuvant and adjuvant chemotherapy is common for the shrinking of tumors and the prevention of tumor recurrence. In this research, we have developed niclosamide (NIC)-loaded nanoparticles-impregnated gelatin nanofibers (NNPF) for local action. The developed nanoparticles demonstrated superior cytotoxicity in the oral cancer cell line compared to the free drug. Cell staining studies demonstrated increased apoptosis and reactive oxygen species generation after treatment with NIC-loaded nanoparticles (NNP). Cell cycle analysis demonstrated cell cycle inhibition in the G0/G1 phase. Cytotoxicity studies in 3D tumoroids demonstrated the ability of NNP to prevent cancer cell growth in 3D arrangement. Thus, NNPF could prove to be a boon for localized delivery as implant-based systems for sustained release in various cancer therapeutic applications. [ABSTRACT FROM AUTHOR]

The darker side of food behavior is that millions of tons of food have been shown the doors of garbage. Therefore, food waste behavior needs an eye to look upon. The purpose of this research is to inculcate the concept of systematic literature review along with meta-analysis in order to examine the Theory of Planned Behavior (TPB) with respect to food waste behavior. The methodology includes Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) that is conducted for the identification, screening, and inclusion of studies. In all, twenty-six independent studies with (N = 13373) met the inclusion criteria. For validating the related literature, random-effects meta-analysis has been applied for ascertaining the average correlation among the variables. More specifically, the present study also examines the sub-group analysis effect among TPB variables. The findings reveal that the strongest association was observed between Attitude and Intention followed by Subjective Norm (SN) and Intention (INT), Perceived Behavioral Control (PBC) and Intention, and Intention and Behavior. Furthermore, the subgroup analysis using multi-cultural groups explores the highest composite correlation in the case of other cultural groups that included countries like Canada. The outcomes of the present study seek to serve in the best interest of households, event management stakeholders, and food policy makers. [ABSTRACT FROM AUTHOR]

Psoriasis is a non-contagious, chronic, relapsing inflammatory skin disease with cutaneous manifestations such as red, raised scaly plaques. Current treatment approaches for psoriasis comprise topical therapy, systemic therapy, phototherapy, psoralen with UVA(PUVA) and biologics. Regardless of the progression in therapeutic approaches (novel therapies like biologics) in psoriasis, phototherapy is also an economical, compelling and safe treatment option that lacks the immunosuppressive properties as well as the toxicities of traditional modalities. It can be combined safely with other therapeutic options such as topical therapies and novel biologics and provide effective therapy. The aim of the current review is to analyze the literature on the safety as well as the efficacy of phototherapy with various treatment modalities in the management of psoriasis. This review summarizes randomized controlled clinical trials addressing combinations of phototherapy with other treatment modalities for the management of psoriasis. The findings of these clinical studies are elaborated. [ABSTRACT FROM AUTHOR]

Introduction: Reduction of zygomaticomaxillary (ZMC) fracture is often difficult to evaluate intraoperatively because of it peculiar anatomy and limited accessibility. The purpose of this study is to evaluate the efficacy of use of C-arm as a tool for intraoperative monitoring of ZMC fracture reduction. Materials and Methods: Group I (C-Arm) and Group II (control group) comprised of patients with isolated unilateral displaced Zygomatic complex (ZMC) fractures and having orbital volume change. The efficacy of use of C-arm intra-operatively was evaluated to analyse the reduction of fracture. Results: It was observed that mean change in ocular volume was around 1.07cm2 for Group I and 1.51cm2 in Group II. Thus post-operative eye volume was near to normal in Group I than Group II. The change in ocular volume post-operatively was observed to be statistically significant (p-value < 0.05) in both the groups. Post HOC Tukey statistical analysis determined the intergroup relation in change in eye volume between normal, pre- and post-operative and was found to be statistically significant (p-value < 0.05). The intergroup comparison between Group I and Group II was done using ANOVA statistical analysis and was found to be statistically significant (p-value < 0.05). Discussion: Our study revealed that C-arm is definitively an effective tool in the oral and maxillofacial surgery armamentarium, giving better results with minimal surgical exposure and by eliminating operator related error. [ABSTRACT FROM AUTHOR]

Osteoarthritis is one of the foremost disabling disorders in the world. There is no definitive treatment to prevent the progression of osteoarthritis. Hence, palliative treatment aims at minimizing pain, disability and improving function, performance and quality of life. Oral administration of nonsteroidal anti-inflammatory drug is associated with number of adverse effects and reduced therapeutic efficacy. Intra-articular injection has been the preferred route of drug administration. However, the clearance of drug from the arthritic site, risk of infections, cost and the pain associated with frequent injections make this route highly non-compliant to patients. Since osteoarthritis is a chronic condition which requires treatment for prolonged duration, there is an urgent need for another administration route which circumvents the hindrances linked with intra-articular route. Transdermal route across the skin locally at the osteoarthritis site could help in surpassing the disadvantages associated with intra-articular route. However, traversing skin barrier and reaching the chondrocytes with sufficient amount of the drug is extremely difficult. Nanocarrier-based approaches could hold an answer to the said shortcomings owing to their reduced size, targeting tunability and site specificity. In this article, we discuss the pathophysiology of osteoarthritis, molecular targets, and utilization of nanocarrier-based approaches to strategize the treatment of osteoarthritis in a new direction, i.e. topical delivery of nanocarriers in osteoarthritis. [ABSTRACT FROM AUTHOR]

The utility of andrographolide (AN) in visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) is limited owing to poor solubility, hindered permeation, and unstable structure under physiological conditions. The present study mainly focuses on synthesizing of andrographolide-Soya-L-α-phosphatidyl choline (ANSPC) complex in ethanol and its characterization using various spectral and analytical techniques. Results from FT-IR, 1H NMR, ROSEY, and in silico docking techniques suggest ANSPC complex formation due to inter-molecular interaction between the hydrophilic head of SPC and hydroxyl group of AN present at 24th position. ANSPC complex demonstrated the solubility of 113.93 ± 6.66 μg/mL significantly (P < 0.05) greater than 6.39 ± 0.47 μg/mL of AN. The particle size of ANSPC complex was found to be 182.2 ± 2.69 nm. The IC50 value of AN suspension (PBS, pH ~ 7.4) at 24, 48, and 72 h against Leishmania donovani (L. donovani) was noticed to be 32.76 ± 4.53, 20.87 ± 2.37, and 17.71 ± 3.06 μM/mL, respectively. Moreover, augmented aqueous solubility of ANSPC complex led to significant (P < 0.05) reduction in IC50 value, i.e., 25.02 ± 4.35, 11.31 ± 0.60, and 8.33 ± 2.71 μM/mL at 24, 48, and 72 h, respectively. The IC50 values for miltefosine were noted to be 9.84 ± 2.65, 12.13 ± 7.26, and 6.56 ± 0.61 μM/mL at similar time periods. Moreover, ANSPC complex demonstrated augmented cellular uptake at 24 h as compared to 6 h in L.donovani. We suppose that submicron size and phospholipid-mediated complexation might have endorsed the permeation of ANSPC complex across the plasma membrane of L.donovani parasite by transport mechanisms such as P-type ATPase. ANSPC complex warrants further in-depth in vivo studies under a set of stringent parameters for translating the product into a clinically viable form. [ABSTRACT FROM AUTHOR]

Drawing on institutional theory and resource dependence theory, this study examines whether mandating gender quotas for corporate boards is associated with a greater presence of women on boards, better accounting-based and market-based performance, more innovativeness, and more external female directors. Based on a cross-country comparative sample of companies from 18 countries, our results suggest that organizations in countries where gender quotas are implemented show better market-based performance and better board vigilance through a higher number of external directors than organizations in countries where quotas are not implemented. The direct impact of gender quotas on innovativeness and accounting performance is not observed. Our findings add to the institutional theory literature by suggesting that companies respond strategically and show acquiescence in their strategic response when institutional pressure addresses ethical concerns (gender diversity). The results support institutional theory's contentions that companies from countries mandating gender quotas are valued more highly by the market. Nevertheless, the impacts on accounting performance and innovativeness are not apparent. Additionally, adopting a resource dependence approach, we find that the presence of women on boards is associated with more efficient corporate governance practices. The results of this study demonstrate the positive implications of gender quotas for company boards. The upper echelons of companies and country policymakers may better understand the importance of diversity and the presence of female directors on company boards. [ABSTRACT FROM AUTHOR]

Purpose: Oral cancer is the most common cancer among the Indian men and the second most common cancer among the Indian women. Such high incidence of oral cancer in India is due to consumption of tobacco in different form including smoking of cigarette. Smoke of tobacco contains different carcinogens which causes DNA damage. Such DNA damage if remain unrepaired due to faulty DNA repair system can cause mutation and eventual development of cancer. Methodology: In the present study, we aimed to check the role of smoking as well as interaction of smoking and XPC polymorphism in risk modulation of oral cancer. Total of 372 subjects including 300 healthy controls and 72 patients of oral cancers been genotyped for the XPC PAT D/I, A/C and C/T polymorphisms with PCR based or PCR–RFLP based method. Genotype frequency was analyzed by chi-square test and strength of associations by odds ratio with 95% confidence intervals. Results: The present study showed that compared to nonsmokers, smokers are at five times higher risk to develop oral cancer (p value= 0.001, OR= 5.03, 95% CI 2.91–8.69) and three times higher risk to develop node-positive (p value= 0.01, OR= 3.66, 95% CI 1.34–9.95) oral cancer. It has also been observed that individuals who were smokers and carrier of variant allele genotypes (AC and CC) for XPC A/C polymorphism were at threefold higher risk (p value= 0.01, OR=2.97, 95% CI 1.29–6.86) to develop oral cancer compared to individual who were smokers but do not carry the C allele (AA genotype). This observation indicates that C allele of XPC A/C polymorphism interacts with smoking and significantly increases the risk of oral cancer. Conclusion: This study demonstrates a possible role of smoking and gene–smoking interaction in risk enhancement of oral cancer. [ABSTRACT FROM AUTHOR]

Vaccines are designed to leverage the immune system and produce long-lasting protection against specific diseases. Peptide vaccines are regarded as safe and effective way of circumventing problems such as mild allergic reactions associated with conventional vaccines. The biggest challenges associated with formulation of peptide vaccines are stability issues and conformational changes which lead to destruction of their activity when exposed to lyophilization process that may act as stressors. Lyophilization process is aimed at removal of water which involves freezing, primary drying and secondary drying. To safeguard the peptide molecules from such stresses, cryoprotectants are used to offer them viability and structural stability. This paper is an attempt to understand the physicochemical properties of peptide vaccines, mechanism of cryoprotection under the shed of water replacement, water substitution theory and cation-pi interaction theory of amino acids which aims at shielding the peptide from external environment by formation of hydrogen bonds, covalent bonds or cation-pi interaction between cryoprotectant and peptide followed by selection criteria of cryoprotectants and their utility in peptide vaccines development along with challenges and opportunities. [ABSTRACT FROM AUTHOR]

The human race is consistently striving for achieving good health and eliminate disease-causing factors. For the last few decades, scientists have been endeavoring to invent and innovate technologies that can substitute the conventional dosage forms and enable targeted and prolonged drug release at a particular site. The novel multi-matrix technology is a type of matrix formulation where the formulation is embraced to have a matrix system with multiple number of matrices. The MMX technology embraces with a combination of outer hydrophilic layer and amphiphilic/lipophilic core layer, within which drug is encapsulated followed by enteric coating for extended/targeted release at the required site. In comparison to conventional oral drug delivery systems and other drug delivery systems, multi-matrix (MMX) technology formulations afford many advantages. Additionally, it attributes for targeting strategy aimed at the colon and offers modified prolonged drug release. Thus, it has emerged rapidly as a potential alternative option in targeted oral drug delivery. However, the development of this MMX technology formulations is a exigent task and also has its own set of limitations. Due to its promising advantages and colon targeting strategy over the other colon targeted drug delivery systems, premier global companies are exploiting its potential. This article review deep insights into the formulation procedures, drug delivery mechanism, advantages, limitations, safety and efficacy studies of various marketed drug formulations of MMX technology including regulatory perspectives and future perspectives. [ABSTRACT FROM AUTHOR]

Purpose: The rectovaginal fistula (RVF) is a type of female ARM in which the rectum terminates in the vagina. Due to its rarity, there are limited reports on its presentation, management, and follow-up. This paper deals with the clinical presentation, management, and outcome of RVF.Methods: It was a retrospective cohort study of 10 years. The patients were evaluated for age, clinical presentation, associated anomalies, any prior surgical interventions performed elsewhere, and complications. After workup, the patients underwent three stages of surgery.Results: Fifty-six patients of RVF were managed. The median age was 13.48 months. The associated anomalies were present in 37 (66%) patients. Posterosagittal and anterosagittal anorectoplasty (PSARP and ASARP) were performed in 29 and 6 patients, respectively. Abdominoperineal pull-through (APPT) was performed in 16 patients of congenital pouch colon. The complications of the first stage included stomal stenosis (4) and stomal prolapse (3). Constipation was present in 39 patients 2 years after the third surgery.Conclusions: RVF is a distinct entity, which needs careful clinical examination. With proper planning for diagnosis and treatment, it can be managed at specialized centers. Care may be needed for the associated anomalies. The follow-up is an integral part of its management. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is considered to be a triggering factor for deterioration of health related quality of life. In present study we assessed hearing loss consequent to metabolic syndrome. A total of 100 patients diagnosed for metabolic syndrome (IDF criteria) were included in the study. All the patients underwent pure tone audiometry and impedance audiometry. All the patients underwent anthropometric measurements, lipid profile, blood sugar and blood pressure assessments. Data was analyzed using SPSS 21.0 software. A total of 62% patients had sensorineural hearing loss. Maximum (35%) had mild hearing loss, followed by moderate hearing loss (23%). Only 4 (4%) cases had severe hearing loss. Older age, wider waist circumference, higher fasting blood glucose levels and lower blood pressure were found to be significantly associated with sensorineural hearing loss and its severity on univariate analysis. However, on multivariate assessment only age and waist circumference showed a significant association with hearing loss. [ABSTRACT FROM AUTHOR]

The first coal mining in India was started in the seventeenth century with an unplanned way in Raniganj coalfield, the coal capital of India. The coalfield was possessed by several small private companies which were nationalized in 1973. A part plan of Chanch/Victoria Area, Victoria West Colliery, BCCL, Raniganj Coalfield, India, indicates an underground coal mine gallery/goaf in the Begunia Coal-seam that connects to a Light Casting Factory. It was established as "Barakar Iron Works" in the year 1881 by the government at that time. It is understood that the approaching gallery was used for coal supply to the "Light Casting Factory" by the mining of "Begunia Coal-Seam". Mostly, these are uncharted and very poorly documented with scarce mine plans. So, the present study attempts to explore the location, depth, extension, and condition of the old working gallery through time-lapse monitoring using a combined study comprising of Self-Potential (SP) and Electrical Resistivity Tomography (ERT) techniques. Four SP profiles data along a line and thirteen ERT profiles data in four different lines were collected across the expected site with different station/electrode spacing covering different profile length in four seasons, viz., Summer (May 2016), Monsoon (August 2016), Post-Monsoon (October 2016) and Summer (April 2017). SP data were analysed using simulated annealing (SA) optimization technique for the evaluation of model parameters. The ERT data were acquired using Wenner, Dipole–Dipole and Schlumberger arrays and inversion of the combined data set was performed using the 2.5D ZZRESINV inversion software. Prominent negative SP signature with equivalent low resistivity anomaly have been delineated that possibly indicate the presence of the old mine working/mine gallery. However, the overall results of time-lapse study inferred that the ground is stable. All results are corroborated with available lithology and field photographs. [ABSTRACT FROM AUTHOR]

Introduction: The tobacco use and the dietary intake/levels of vitamin C and E, and the trace elements, iron, copper, zinc, and selenium are interrelated with the development of oral precancer. These micronutrients are necessary for maintaining good oral health. Aims: To estimate the nutritional status, vitamin E, C and micronutrient level of zinc, iron, copper, and selenium, and basic vitals in all study groups. Material Method: The study sample is comprised of 384 subjects. There were three study groups, and in each study group, there were 128 subjects. Group A was tobacco users without oral precancer/dysplasia. Group B was tobacco users with oral precancer (H/P confirmed). Group C was healthy individuals with no history of tobacco or areca nut use and oral precancer. Data have been collected using a standard structured predesigned questionnaire for evaluation of the nutrition level of the subject; 5 mL blood has been collected for estimation of micronutrients; and basic vitals such as pulse rate and blood pressure have been examined using the digital machine. Questionnaire data will also be entered in the worksheet for the purpose of analysis. The analysis will be performed using the commercially available Statistical Package SPSS. Result: The serum level of zinc, iron, selenium, vitamin E and C was decreasing in Groups A and B, i.e., users with precancer and users without precancer as compared to Group C, i.e., controls. But serum copper level was increasing in Groups A and B, i.e., users with precancer and users without precancer, and the level was found to be decreased in Group C, i.e., controls. Later on, in the present study, basic vitals such as blood pressure and pulse rate of all the study subjects in all the three groups were clinically examined. No significant differences were found in blood pressure, pulse rate (radial pulse), and height in all groups. But the weight was slightly higher in Groups A and B as compared to Group C. Discussion: Diet plays an aggressive role in the development of oral precancer. The deficiency of certain micro nutrients may lead to disease progression. We can say that a healthy diet comprising of vegetarian and plain food may lead to solving issues of oral health. Conclusion: The above-highlighted text shows that micronutrients play dominant role in maintenance of oral health and its deficiency may result in the growth of oral precancer. So involving diet rich in zinc, iron, selenium, vitamin E and C may help in maintaining healthy nation. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) encompasses a group of metabolic disorders characterized by elevated levels of plasma glucose leading to macro- and micro-vascular damages to target organs. According to IDF, India had 73 million population of diabetes in 2017, and this figure may rise to 134 million adults by 2045 International Diabetes Federation, 2017. Since the alveolar capillary network in the lung is a large micro-vascular unit, microangiopathy may be targeting lungs along with other organs. Objective: To correlate pulmonary function tests with duration of type 2 diabetes mellitus. Method: The cross-sectional study was conducted on one hundred six patients of type 2 diabetes mellitus who met the inclusion and exclusion criteria. Diabetic cases were categorized on the basis of duration of disease. RMS Helios 401 computerized spirometer was used to assess pulmonary functions. Statistical tests employed include t test, ANOVA, and correlation coefficient analysis. Result: The mean duration of disease for patients with diabetes was 10.17 ± 5.16 year. There was a significant negative correlation between the parameters of lung function test (p value < 0.05) with duration of diabetes. Conclusion: We found that pulmonary functions have inverse relationship with increase in duration of type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Structure-property correlations were investigated for LaxCe1−xO2−δ (x = 0.05, 0.15) system (for both nanoparticles and ceramic). The nanoparticles were synthesized by the co-precipitation route and characterized for their structural, catalytic and visible light driven photocatalytic properties. Synthesised LaxCe1−xO2−δ nanopowders depicted phase purity with excellent compositional control as confirmed by various structural characterisation tools. The 15% La3+-doped ceria nanoparticles portrayed superior photocatalytic properties; complete degradation (99%) of the methylene blue dye was observed within 60 min of visible light irradiation under an alkaline medium. High density (> 96%) of the ceramics (sintered at 1580 °C for 2 h) confirmed promising sinterability of the synthesised powders. The ionic conductivities of the LaxCe1−xO2−δ ceramics increased with temperature and frequency owing to enhanced oxygen vacancies in the ceria matrix as a result of doping (of La3+-ions); a maximum conductivity of ~ 8.4 × 10−2 S cm−1 was obtained at 900 °C for the 15% La3+-doped ceria ceramics at 1 MHz frequency. [ABSTRACT FROM AUTHOR]

Purpose: The chemotherapeutics agent, 5-fluorouracil (5-FU), and curcumin (Cur), a natural antioxidant, has a wide pharmacological window to treat oral carcinoma; however, both drugs have limited bioavailability. This research study designs to develop a nanoemulsions (NEs) formulation by combining 5-FU and Cur to improve anticancer activity against oral cavity squamous cell carcinoma (OSCC) cells from the diversified origin for in vitro analysis, SCC090 (human tongue) and SCC152 (human hypo-pharynx). Methodology: NEs formulated through homogenization, applying high-energy ultrasonication technique. The prepared 5-FUNE/Cur-NE/5-FU-Cur-NE were characterized and optimized by different in vitro assays to evaluate release system and treatment of OSCC cells to monitor cellular acceptability, such as in vitro anticancer activity by MTT assay, cell uptake studies and protein expression associated apoptotic study.Results: 5-FUNE/Cur-NE/5-FU-Cur-NE successfully formulated and show mean-value of the particle size (150-200 nm), surface charge (− 25.70 to − 37.91 mV), and PDI (0.194). In vitro release of 5-FUNE/Cur-NE/5-FU-Cur-NEs was monitored over a course of 04 days, where acidic pH shows higher release as compared to alkaline pH, along with acceptable stability data. Cytotoxicity study has shown higher-dose-dependent anticancer effect with a reduced IC50 value of NEs as compared to BLNE. Cellular uptake study of 5-FUNE/Cur-NE/5-FU-Cur-NEs upgraded many folds, comparatively BLNE and show potential cell arrest. Additionally, the cell protein (Blc2, Bax, P53, and P21) expression was revised and raised cell apoptosis.Conclusion: The combinational loaded, 5-FU and Cur in nanoformulation system have proven their potency to deliver improved anticancer activity, against oral cancer. [ABSTRACT FROM AUTHOR]

MD2, a 160-residue accessory glycoprotein, is responsible for the recognition and binding of Gram-negative bacterial membrane component, lipopolysaccharide (LPS). Internalization of pathogen inside the mononuclear phagocytes has also been attributed to MD2 which leads to the clearance of pathogens from the host. However, not much is known about the segments in MD2 that are responsible for LPS interaction or internalization of pathogen inside the defense cells. A 16-residue stretch (MD54) from MD2 protein has been identified that possesses a short heptad repeat sequence and four cationic residues enabling it to participate in both hydrophobic and electrostatic interactions with LPS. An MD54 analog of the same size was also designed in which a leucine residue at a heptadic position was replaced with an alanine residue. MD54 but not its analog, MMD54 induced aggregation of LPS and aided in its internalization within THP-1 monocytes. Furthermore, MD54 inhibited LPS-induced nuclear translocation of NF-κB in PMA-treated THP-1 and TLR4/MD2/CD14-transfected HEK-293T cells and the production of pro-inflammatory cytokines. In addition, in in vivo experiments, MD54 showed marked protection and survival of mice against LPS-induced inflammation and death. Overall, we have identified a short peptide with heptad repeat sequence from MD2 that can cause aggregation of LPS and abet in its internalization within THP-1 cells, resulting in attenuation of LPS-induced pro-inflammatory responses in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The functional polymorphism A1082G in the gene ( IL10) for interleukin-10 associated with risk of oral squamous cell carcinoma (OSCC). The present case-control study was to evaluate the possible association between IL10 A1082G gene and OSCC in north Indian population. Analysis of IL10 A1082G genotype in 232 OSCC cases and 221 healthy controls of comparable age, gender, smokers, tobacco chewing and alcohol consumption. IL10 A1082G status in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The frequencies of IL10 A1082G polymorphism AA, AG, GG genotypes were 29.74, 68.10 and 2.15% in OSCC cases and 57.46, 42.08 and 0.45% in healthy controls. The average frequency of G mutant allele was 36.20% in OSCC cases compared with 21.50% among the controls and this allele was associated with increased risk for OSCC cases. Heterozygous AG genotype was found statistically significant in OSCC cases than in controls (OR = 1.6, 95% CI = 1.1-2.2, P = 0.003), whereas homozygous mutant GG genotype was not found significant (OR = 4.7, 95% CI = 0.55-41.1, P = 0.2). Moreover, we found that G allele was significant in OSCC cases of tobacco chewing. The frequency of IL10 A1082G polymorphism G allele and AG genotype is associated with OSCC cases as compared with controls; this may be due to smoking and tobacco chewing. Our findings showed that in IL10 A1082G gene polymorphism AG genotype and G allele may participate in the progression of OSCC. [ABSTRACT FROM AUTHOR]

Background: Intestinal tuberculosis (ITB) and Crohn's disease (CD) have clinical, radiological, endoscopic, and histological resemblance. There is paucity of literature regarding differentiation of CD and ITB based on radiology using computed tomography (CT). Aims: The present study was designed to compare CT features of ITB and CD and develop a predictive model to differentiate ITB and CD. Methods: Patients with ITB and CD, who underwent CT enteroclysis/CT enterography/CT abdomen before starting treatment, were recruited. Specific findings were noted by a radiologist who was blinded to the diagnosis. A predictive model was developed based on the features which were significantly different in these diseases. Results: Fifty-four patients with CD and 50 patients with ITB were compared. On univariate analysis, left colonic involvement, ileocecal involvement, long-segment involvement, comb sign, presence of skip lesions, involvement of ≥3 segments and ≥1-cm sized lymph nodes were significantly different between CD and ITB. On multivariate analysis, ileocecal involvement, long-segment involvement and the presence of lymph node ≥1 cm were statistically significant. Based upon the latter three variables, a risk score (with values ranging from 0 to 3) was generated, with scores 0 and 1 having specificity of 100 % and 87 %, respectively, and positive predictive values (PPV) of 100 % and 76 %, respectively, for ITB and scores 2 and 3 having specificity of 68 % and 90 %, respectively, and PPV of 63 % and 80 %, respectively, for CD. Conclusions: A predictive model based on the presence of long-segment involvement, ileocecal involvement and lymph nodes sized ≥1 cm on CT could differentiate ITB and CD with good specificity and PPV. [ABSTRACT FROM AUTHOR]

Background: Extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD), as well as intestinal tuberculosis (ITB) from Asia, are underreported. We, therefore, describe the prevalence of EIMs in Indian IBD and ITB patients and study their relationship with disease extent and severity in IBD. Methods: This retrospective single-center study included all IBD and ITB patients evaluated from January 2005 to July 2012. Disease profile and frequencies of arthropathies (peripheral and central) and ocular (episcleritis, iritis/uveitis), oral (aphthous stomatitis), skin (erythema nodosum, pyoderma gangrenosum, psoriasis), hepatobiliary (primary sclerosing cholangitis), and thromboembolic manifestations were analyzed. Results: Of 1,652 patients (1146 UC, 303 CD, 203 ITB), frequency of any EIM was 33.2 %, 38.3 %, and 14.3 % in UC, CD, and ITB patients, respectively. Thromboembolism was more common among UC patients with pancolitis than proctitis ( p < 0.001) and left-sided colitis ( p = 0.02). Primary sclerosing cholangitis was seen in 0.4 % UC patients. Steroid-dependent UC patients had higher frequency of any EIM, peripheral arthropathy, or thromboembolism than patients with no or infrequent steroid requirement ( p < 0.05). Peripheral arthropathy ( p = 0.02), erythema nodosum ( p = 0.01), and aphthous stomatitis ( p = 0.004) were more common with CD than with UC patients. Patients with colonic CD had higher frequency of peripheral arthropathy, any EIM, and multiple EIMs than ileal or ileocolonic disease ( p < 0.05). Relative to ITB, CD patients had higher frequencies of peripheral arthropathy ( p < 0.001), aphthous stomatitis ( p = 0.01), any EIM ( p < 0.001), and multiple EIMs ( p < 0.001). Conclusions: In Indian IBD and ITB patients, EIMs appear to be related to disease severity in UC and disease location in CD and are significantly more common in CD than in ITB. Overall prevalence of EIMs in these patients is similar to that of the West. [ABSTRACT FROM AUTHOR]

Design of antimicrobial peptides with selective activity towards microorganisms is an important step towards the development of new antimicrobial agents. Leucine zipper sequence has been implicated in cytotoxic activity of naturally occurring antimicrobial peptides; moreover, this motif has been utilized for the design of novel antimicrobial peptides with modulated cytotoxicity. To understand further the impact of substitution of amino acids at 'a' and/or 'd' position of a leucine zipper sequence of an antimicrobial peptides on its antimicrobial and cytotoxic properties four short peptides (14-residue) were designed on the basis of a leucine zipper sequence without or with replacement of leucine residues in its 'a' and 'd' positions with d-leucine or alanine or proline residue. The original short leucine zipper peptide (SLZP) and its d-leucine substituted analog, DLSA showed comparable activity against the tested Gram-positive and negative bacteria and the fungal strains. The alanine substituted analog (ASA) though showed appreciable activity against the tested bacteria, it showed to some extent lower activity against the tested fungi. However, the proline substituted analog (PSA) showed lower activity against the tested bacterial or fungal strains. Interestingly, DLSA, ASA and PSA showed significantly lower cytotoxicity than SLZP against both human red blood cells (hRBCs) and murine 3T3 cells. Cytotoxic and bactericidal properties of these peptides matched with peptide-induced damage/permeabilization of mammalian cells and bacteria or their mimetic lipid vesicles suggesting cell membrane could be the target of these peptides. As evidenced by tryptophan fluorescence and acrylamide quenching studies the peptides showed similarities either in interaction or in their localization within the bacterial membrane mimetic negatively charged lipid vesicles. Only SLZP showed localization inside the mammalian membrane mimetic zwitterionic lipid vesicles. The results show significant scope for designing antimicrobial agents with selectivity towards microorganisms by substituting leucine residues at 'a' and/or 'd' positions of a leucine zipper sequence of an antimicrobial peptide with different amino acids. [ABSTRACT FROM AUTHOR]

We report results of the studies relating to the fabrication of a highly sensitive label free biosensor based on graphene oxide (GO) platform for the detection of aflatoxin B1 (AFB) which is most toxic and predominant food toxin, using electrochemical impedance spectroscopy. The structural and optical characterization of GO/Au and anti-AFB/GO/Au has been done by electron microscopy, Raman, X-ray diffraction (XRD), UV-vis and electrochemical impedance spectroscopy (EIS). The impedimetric sensing response of immunoelectrode as a function of AFB concentration reveals wider linear detection range (0.5-5 ng/ml), high sensitivity (639 Ω ng ml), improved detection limit (0.23 ng ml) and good stability (5 weeks) for the label-free detection. Association constant ( k) for antigen-antibody interaction obtained as 0.46 ng ml indicates high affinity. [ABSTRACT FROM AUTHOR]

We have fabricated an immunosensor based on carbon nanotubes and chitosan (CNT-CH) composite for detection of low density lipoprotein (LDL) molecules via electrochemical impedance technique. The CNT-CH composite deposited on indium tin oxide (ITO)-coated glass electrode has been used to covalently interact with anti-apolipoprotein B (antibody: AAB) via a co-entrapment method. The biofunctionalization of AAB on carboxylated CNT-CH surface has been confirmed by Fourier transform infrared spectroscopic and electron microscopic studies. The covalent functionalization of antibody on transducer surface reveals higher stability and reproducibility of the fabricated immunosensor. Electrochemical properties of the AAB/CNT-CH/ITO electrode have been investigated using cyclic voltammetric and impedimetric techniques. The impedimetric response of the AAB/CNT-CH/ITO immunoelectrode shows a high sensitivity of 0.953 Ω/(mg/dL)/cm in a detection range of 0-120 mg/dL and low detection limit of 12.5 mg/dL with a regression coefficient of 0.996. The observed low value of association constant (0.34 Ms) indicates high affinity of AAB/CNT-CH/ITO immunoelectrode towards LDL molecules. This fabricated immunosensor allows quantitative estimation of LDL concentration with distinguishable variation in the impedance signal. [ABSTRACT FROM AUTHOR]