Interferon-expressing oncolytic adenovirus + chemoradiation inhibited pancreatic cancer growth in a hamster model.

Past clinical trials of adjuvant therapy combined with interferon (IFN) alpha, fluorouracil, cisplatin, and radiation improved the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC). However, these trials also revealed the disadvantages of the systemic toxicity of IFN and insufficient delivery of IFN. To improve efficacy and tolerability, we have developed an oncolytic adenovirus-expressing IFN (IFN-OAd). Here, we evaluated IFN-OAd in combination with chemotherapy (gemcitabine + nab-paclitaxel) + radiation. Combination index (CI) analysis showed that IFN-OAd + chemotherapy + radiation was synergistic (CI <1). Notably, IFN-OAd + chemotherapy + radiation remarkably suppressed tumor growth and induced a higher number of tumor-infiltrating lymphocytes without severe side toxic effects in an immunocompetent and adenovirus replication-permissive hamster PDAC model. This is the first study to report that gemcitabine + nab-paclitaxel, the current first-line chemotherapy for PDAC, did not hamper virus replication in a replication-permissive immunocompetent model. IFN-OAd has the potential to overcome the barriers to clinical application of IFN-based therapy through its tumor-specific expression of IFN, induction of antitumor immunity, and sensitization with chemoradiation. Combining IFN-OAd with gemcitabine + nab-paclitaxel + radiation might be an effective and clinically beneficial treatment for PDAC patients.

Minor tropical fruits as a potential source of bioactive and functional foods.

Tropical fruits are defined as fruits that are grown in hot and humid regions within the Tropic of Cancer and Tropic of Capricorn, covering most of the tropical and subtropical areas of Asia, Africa, Central America, South America, the Caribbean and Oceania. Depending on the cultivation area covered, economic value and popularity these tropical fruits are divided into major and minor tropical fruits. There is an annual increment of 3.8% in terms of commercialization of the tropical fruits. In total 26 minor tropical fruits (Kiwifruit, Lutqua, Carambola, Tree Tomato, Elephant apple, Rambutan, Bay berry, Mangosteen, Bhawa, Loquat, Silver berry, Durian, Persimon, Longan, Passion fruit, Water apple, Pulasan, Indian gooseberry, Guava, Lychee, Annona, Pitaya, Sapodilla, Pepino, Jaboticaba, Jackfruit) have been covered in this work. The nutritional composition, phytochemical composition, health benefits, traditional use of these minor tropical fruits and their role in food fortification have been portrayed.

Lignocellulolytic extremozymes and their biotechnological applications.

Lignocellulolytic enzymes are used in different industrial and environmental processes. The rigorous operating circumstances of these industries, however, might prevent these enzymes from performing as intended. On the other side, extremozymes are enzymes produced by extremophiles that can function in extremely acidic or basic; hot or cold; under high or low salinity conditions. These severe conditions might denature the normal enzymes that are produced by mesophilic microorganisms. The increased stability of these enzymes has been contributed to a number of conformational modifications in their structures. These modifications may result from a few amino acid substitutions, an improved hydrophobic core, the existence of extra ion pairs and salt bridges, an increase in compactness, or an increase in positively charged amino acids. These enzymes are the best option for industrial and bioremediation activities that must be carried out under difficult conditions due to their improved stability. The review, therefore, discusses lignocellulolytic extremozymes, their structure and mechanisms along with industrial and biotechnological applications.

Population-wide genetic analysis of Ovar-DQA1 and DQA2 loci across sheep breeds in India revealed their evolutionary importance and fitness of sheep in a tropical climate.

Genetic variability at the major histocompatibility complex (MHC) is important in any species due to significant role played by MHC for antigen presentation. DQA locus has not been studied for its genetic variability across sheep population in India. In the present study, MHC of sheep at DQA1 and DQA2 loci were evaluated across 17 Indian sheep breeds. Results revealed high degree of heterozygosity (10.34% to 100% for DQA1 and 37.39 to 100% for DQA2). 18 DQA1 alleles and 22 DQA2 alleles were isolated in different breeds. Nucleotide content for DQA region revealed richness of AT content (54.85% for DQA1 and 53.89% for DQA2). DQA1 and DQA2 sequences clustered independently. We could see evidence of divergence of DQA as DQA1 and DQA2 across sheep breeds. Wu-Kabat variability index revealed vast genetic variation across DQA1 and DQA2, specifically at peptide binding sites (PBS) that consisted 21 residues for DQA1 and 17 residues for DQA2. Evolutionary analysis revealed the presence of positive and balancing selection for DQA1 locus, however DQA2 was under purifying selection across sheep breeds. Higher heterozygosity and large diversity at both loci especially at PBS indicated the fitness of the sheep population for evading pathogens and adapt to the harsh tropical climate.

Effect of (Ce, Dy) co-doping on the microstructural, optical, and photoluminescence characteristics of solution combustion synthesized ZnO nanoparticles.

Solution combustion synthesized ZnO nanoparticles that were Ce doped, Dy doped or co-doped at varying dopant concentrations were characterized for their microstructural, optical, and photoluminescence (PL) characteristics. The synthesized nanoparticles matched the standard hexagonal wurtzite structure of ZnO. The lattice fringes in the high-resolution transmission electron micrographs and the bright spotty rings in the selected area electron diffraction patterns authenticated the high crystallinity of the nanoparticles. The diffuse reflectance spectroscopy resolved the energy bandgap for the undoped ZnO as 3.18 eV, which decreased upon doping and co-doping. A sharp narrow ultraviolet emission peak at ~398 nm that originated from excitonic recombination was found in the PL spectra of the nanoparticles. The visible emission peaks in the PL spectra were assigned to the f-d and f-f electron transitions of Ce3+ and Dy3+ ions, respectively, in addition to different native defects in ZnO. The visible emissions (blue, yellow, and red) improved upon (Ce, Dy) co-doping, therefore (Ce, Dy) co-doped ZnO nanoparticles can be considered a promising luminescent material for the development of energy-saving light sources.

Structural, photoluminescence, and photocatalytic performances of Ce3+ -activated orthovanadate oxides M3 (VO4 )2 (M: Mg or Zn) synthesized by solution combustion route.

This paper presents a research investigation into the synthesis of vanadate oxides M3 (VO4 )2 (M: Mg or Zn) using the solution combustion method and investigates their structural, photoluminescence, and photocatalytic properties after introducing cerium (Ce) as a dopant. The resulting synthesized samples all display an orthorhombic crystalline structure with crystallite sizes ranging from 71 to 110 nm. Morphological diversity among the samples is revealed through field-emission scanning electron microscopy (FESEM) imagery. Diffuse reflectance spectroscopy discloses that the introduction of Ce3+ as a dopant leads to an increase in the band gap energy. Notably, when excited at a wavelength of 340 nm, the photoluminescence emission intensity reaches its peak across all samples. This intensity undergoes enhancement due to Ce3+ doping, causing a slight shift toward shorter wavelengths attributable to the augmented band gap resulting from the dopant. Markedly, among the investigated materials, Ce3+ -activated Mg3 (VO4 )2 stands out with the most pronounced emission intensity, positioning it as a highly promising luminescent material. Additionally, the incorporation of Ce3+ has a positive effect on the photocatalytic performance of Mg3 (VO4 )2 , resulting in notable improvement.

Can natural irrigants replace sodium hypochlorite? A systematic review.

CONTEXT: Sodium hypochlorite, a gold standard for irrigation in endodontics, has disadvantages like toxicity and root dentin weakening. Alternatives derived from natural products are being explored. AIMS: This systematic review was done to understand the clinical benefits of natural irrigants when compared with a standard irrigant, sodium hypochlorite. SETTINGS AND DESIGN REGISTRATION: This systematic review was registered with PROSPERO (2018 CRD42018112837) METHODS AND MATERIAL: This review was done in conformation to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA 2020) statement. In vivo studies using at least one natural irrigant and sodium hypochlorite (NaOCl) were included. Studies using them as medicaments were excluded. PubMed, Cochrane and SCOPUS were searched. RevMan tool for Risk of Bias 2 (RoB 2) and risk-of-bias tool to assess non-randomized studies of interventions (ROBINS-I) were used. GRADEpro was used to assess certainty of evidence. RESULTS: Ten articles (6 RCTs and 4 clinical studies) on approximately 442 patients were included. Seven natural irrigants were evaluated clinically. Due to the heterogeneity, meta-analysis could not be conducted. Antimicrobial efficacy was found to be similar for castor oil, neem, garlic-lemon, noni, papaine and NaOCl. Neem, papaine-chloramine, neem-NaOCl and neem-CHX were superior, while propolis, miswak and garlic were inferior to NaOCl. Post-operative pain was less for neem. There was no significant difference between papaine-chloramine, garlic extract and sodium hypochlorite in clinical/radiographic success. CONCLUSIONS: The studied natural irrigants are not more efficacious than NaOCl. At the moment, they cannot replace NaOCl routinely and may only substitute in select cases.

Utilising Emotion Monitoring for Developing Music Interventions for People with Dementia: A State-of-the-Art Review.

The demand for smart solutions to support people with dementia (PwD) is increasing. These solutions are expected to assist PwD with their emotional, physical, and social well-being. At the moment, state-of-the-art works allow for the monitoring of physical well-being; however, not much attention is delineated for monitoring the emotional and social well-being of PwD. Research on emotion monitoring can be combined with research on the effects of music on PwD given its promising effects. More specifically, knowledge of the emotional state allows for music intervention to alleviate negative emotions by eliciting positive emotions in PwD. In this direction, the paper conducts a state-of-the-art review on two aspects: (i) the effect of music on PwD and (ii) both wearable and non-wearable sensing systems for emotional state monitoring. After outlining the application of musical interventions for PwD, including emotion monitoring sensors and algorithms, multiple challenges are identified. The main findings include a need for rigorous research approaches for the development of adaptable solutions that can tackle dynamic changes caused by the diminishing cognitive abilities of PwD with a focus on privacy and adoption aspects. By addressing these requirements, advancements can be made in harnessing music and emotion monitoring for PwD, thereby facilitating the creation of more resilient and scalable solutions to aid caregivers and PwD.

The utilization of natural eco-benign sources for sustainable management to preserve hides and docking analysis of identified potential phytochemicals.

The industrial leather sector is one of the most ancient industries globally and continues to influence the global economic system in contemporary times significantly. Regardless of income, the leather sector is widely recognized as a significant environmentally detrimental sector because of the utilization of materials involved in preserving and processing leather. Raw hides, the primary ingredient in the leather industry, are highly susceptible to microbial attack once they have been flayed from animals. The current review provides information about the diverse operational processes employed in the beam house to produce leather goods. This paper primarily focuses on the preservation of various types of hides, including those derived from goats, cows, sheeps, deers, pigs, and other species, with particular emphasis on bio-based preservation methods. It also discusses various salt and salt-free curing methods along with their limitations. Furthermore, it reviews a viable and economically advantageous option for preserving animal hides using plant and microbial sources. Moreover, it focuses on investigating the molecular docking interactions between three critical enzymes in the phytochemical synthesis pathway, namely phenylalanine ammonia-lyase, phosphomevalonate kinase, and dihydroflavonol 4-reductase, and a set of specific modulators, followed by ADMET analyses. The objective was to determine the optimal binding affinity score for these enzyme-modulator complexes through virtual screening. The depiction of protein-ligand interactions offers potential benefits for future research endeavours, as well as valuable insights into the identification of modulators and the evaluation of the potency and efficacy of phytochemicals in the preservation of hides.

Awareness regarding the antitobacco laws and perceptions regarding interventions for effective tobacco control among young adults of Haryana, India.

Background: Tobacco is one of the major behavioral risk factors for noncommunicable diseases in India. Tobacco control depends on public awareness regarding prevalent antitobacco measures. Objectives: The present study documents the understanding of young adults (<25 years) regarding the antitobacco laws and their perception regarding interventions for effective tobacco control. Methods: A cross-sectional study was conducted in two districts of Haryana. A semistructured questionnaire was used to assess tobacco use, participants' awareness of sections 4, 5, 6 (a), and 8 of the Cigarette and Other Tobacco Products Act (COTPA, 2003), sources of information about antitobacco laws, and their implementation. The perception of participants about the effectiveness of laws and provisions was assessed using a three-point Likert scale. Results: Of the 1470 participants, 517 (35.2%) smoked or used smokeless products. They reported the media (84.6%) to be the most critical source of information about antitobacco laws, followed by the health department (57.6%) and family/peer group (44.9%). Most participants were aware of the prohibition of smoking in offices or banks, educational institutions, hospitals, and other public places. Both tobacco users and nonusers perceived health education programs to be an effective intervention to reduce tobacco use (P < 0.01). Conclusion: The awareness regarding COTPA has increased among the general population. The media could be a powerful tool to counteract the pro-tobacco cues in society. The need of the hour is to focus on improving compliance with antitobacco laws at the population level to achieve a tobacco-free India.

Optimizing Critical Care Documentation in a Pediatric Emergency Department.

OBJECTIVE: Emergency department (ED) physicians frequently provide critical care (CC) but document inconsistently. Variability in documentation can result in underbilling and is inconsistent with financial stewardship. We used admissions to the intensive care unit (ICU) as a proxy for CC provision. At baseline, CC notes were correctly documented for 20% of eligible visits, with potential missed charges of $1.8 million per year.Our objective was to increase CC note placement for eligible patients from 20% to 60% over 2 years. Additionally, we measured CC notes and the number of ICU admissions per 1000 ED visits, and change in facility fees. METHODS: We performed this project at a midwestern quaternary children's hospital with 2 EDs (combined volume 120,000 visits/year). We surveyed the ED physicians to inform our interventions. We used maintenance of certification points and financial incentives for quality improvement work to obtain buy-in. We used serial interventions with plan-do-study-act cycles: (1) CC note simplification, (2) education, (3) follow-up surveys, (4) additional location for CC note, and (5) timely reminders. We reviewed sample charts and used χ2 test and control charts for analysis. RESULTS: Critical care note placement for ICU admissions increased from 20% to 60% in 8 months, and further to greater than 75%. The CC notes increased from 4 to 16 per 1000 ED visits. Intensive care unit admissions increased but remained appropriate. The billed facility fee for CC increased by 263%. CONCLUSIONS: This project resulted in significant and sustained improvements in CC note completion. We believe providing education, simplifying the documentation process, automating reminders, and incentivizing optimal documentation were vital to success.

Improving Emergency Department Use of Safety-Net Antibiotic Prescriptions for Acute Otitis Media.

OBJECTIVES: Acute otitis media (AOM) is the most common reason for pediatric antibiotic prescriptions. The 2013 American Academy of Pediatrics' AOM guidelines recommend observation for nonsevere AOM. Our aim was to increase the percentage safety-net antibiotic prescription (SNAP) offered to patients 6 months of age or older diagnosed with AOM in 2 pediatric emergency departments (EDs) from a baseline of 0.5% to 15% in 20 months. METHODS: This is a quality improvement study at a quaternary pediatric medical center with 2 locations, both with EDs. A random chart review revealed that 27.5% of patients diagnosed with AOM in the ED would qualify for a SNAP, but only 0.5% were offered it. Quality improvement interventions were designed to improve safety-net antibiotic prescribing. Both EDs conducted multiple interventions, including algorithm development, provider education, and electronic medical record aids. The primary outcome measure was the percentage of patients offered a SNAP for AOM. RESULTS: A total of 8226 children 6 months of age or older were diagnosed with AOM in our 2 EDs during the 20-month intervention period. The percentage offered a SNAP increased at both EDs. One ED had a single shift in the mean to 7.9%, whereas the other had 2 shifts in the mean, an initial shift to 5.1% and a second to 7.3%. Providers consistently used the algorithm and electronic medical record aids. CONCLUSIONS: Safety-net antibiotic prescriptions in conjunction with parent education was effective in reducing the use of immediate antibiotic prescriptions in children with AOM in 2 pediatric EDs. Offering a SNAP can reduce unnecessary use of antibiotics, which in turn may decrease antibiotic-related adverse events and antibiotic resistance.

Preparation and Photocatalytic Performance of TiO2 Nanowire-Based Self-Supported Hybrid Membranes.

Nowadays, the use of hybrid structures and multi-component materials is gaining ground in the fields of environmental protection, water treatment and removal of organic pollutants. This study describes promising, cheap and photoactive self-supported hybrid membranes as a possible solution for wastewater treatment applications. In the course of this research work, the photocatalytic performance of titania nanowire (TiO2 NW)-based hybrid membranes in the adsorption and degradation of methylene blue (MB) under UV irradiation was investigated. Characterization techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), X-ray powder diffractometry (XRD) were used to study the morphology and surface of the as-prepared hybrid membranes. We tested the photocatalytic efficiency of the as-prepared membranes in decomposing methylene blue (MB) under UV light irradiation. The hybrid membranes achieved the removal of MB with a degradation efficiency of 90% in 60 min. The high efficiency can be attributed to the presence of binary components in the membrane that enhanced both the adsorption capability and the photocatalytic ability of the membranes. The results obtained suggest that multicomponent hybrid membranes could be promising candidates for future photocatalysis-based water treatment technologies that also take into account the principles of circular economy.

Diabetic Foot Care Knowledge and Practices in Rural North India: Insights for Preventive Podiatry.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the most dreaded complications of Type 2 Diabetes Mellitus (T2DM). Preventive podiatry is most efficient way of minimising DFU. The main aim of the study was to assess the knowledge and foot care practices among patients living with T2DM concerning the DFU. MATERIALS AND METHODS: We conducted a cross-sectional study in a rural-area of Haryana, India between January to March 2019 amongst 416 people living with T2DM after using multistage random sampling. A pre-tested, structured survey instrument prepared from the recommendation of the American College of Foot and Ankle Surgeons and the Diabetes UK was used after Hindi translation as per standard protocol. The knowledge and practices were classified as good, satisfactory and poor if the total score was between 8-11, 6-7 and <6. RESULTS: 14.2% had a previous history of DFU. The prevalence of good, satisfactory and poor knowledge was 63.5%, 12.5% and 24.0%. Further, 46.7%, 32.7% and 20.6% respondents depicted good, satisfactory and poor practices regarding foot care. On multivariate binary logistic regression analysis, younger age group, higher education, Per capita family income in INR, Blood glucose levels, HbA1c Levels, physical activity and previous history of DFU emerged as significant predictors of good foot-care knowledge and practices. CONCLUSION: There is an evident gap between foot-care knowledge and practices that should be addressed through comprehensive behaviour change strategies. Comprehensive risk-assessments for diabetes associated complications needs to be piloted at community level to assess the feasibility.

Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells.

Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8-145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from -17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.

"Nutrient-sensing" and self-renewal: O-GlcNAc in a new role.

Whether embryonic, hematopoietic or cancer stem cells, this metabolic reprogramming is dependent on the nutrient-status and bioenergetic pathways that is influenced by the micro-environmental niches like hypoxia. Thus, the microenvironment plays a vital role in determining the stem cell fate by inducing metabolic reprogramming. Under the influence of the microenvironment, like hypoxia, the stem cells have increased glucose and glutamine uptake which result in activation of hexosamine biosynthesis pathway (HBP) and increased O-GlcNAc Transferase (OGT). The current review is focused on understanding how HBP, a nutrient-sensing pathway (that leads to increased OGT activity) is instrumental in regulating self-renewal not only in embryonic and hematopoietic stem cells (ESC/HSC) but also in cancer stem cells.

Feasibility of implementing cervical cancer screening program using smartphone imaging as a training aid for nurses in rural India.

BACKGROUND: The Indian national program stresses implementation of cervical cancer screening by health workers/nurses using VIA (Visual Inspection under Acetic acid). We demonstrate its feasibility and reliability in rural setting, assessing the role of smartphone-imaging for continuous training of nurses. DESIGN: A cross-sectional design to assess the reliability of the nurse-led VIA test. To assess feasibility, VIA positive patients were observed till confirmative diagnosis was made. SAMPLE: Hospital-based purposive sampling was used to recruit participants. MEASURES: A structured questionnaire for recording participants' details, VIA findings and follow-up information; and an observational checklist to record implementation parameters during each clinic. An expert assessed the nurse's judgment using smartphone-images of cervix. RESULTS: During October 2016-June 2017, 2758 patients attended the weekly clinic; 238 (8.6%) met the criteria, of those 180 (75.6%) tested after consent. Nurse reported 25 (13.8%) VIA-positive cases, but only 19 accessed the referral service. Kappa statistic: 0.45 (CI: 0.26-0.63) suggested moderate nurse-expert agreement. Image retrieval and quality affected expert's evaluation. Implementation challenges include low awareness among the population and referral link-up. CONCLUSION: Appropriately trained nurses can reliably conduct screening. Real-time expert feedback might improve reporting. Rigorous awareness activities and on-site treatment can reduce drop-outs. The medical institute's involvement and administrative will were instrumental.

cGAS-STING Signaling Regulates Initial Innate Control of Cytomegalovirus Infection.

UNLABELLED: Several innate sensing pathways contribute to the control of early cytomegalovirus (CMV) infection, leading to a multiphasic type I interferon (IFN-I) response that limits viral replication and promotes host defenses. Toll-like receptor (TLR)-dependent pathways induce IFN-I production in CMV-infected plasmacytoid dendritic cells; however, the initial burst of IFN-I that occurs within the first few hours in vivo is TLR independent and emanates from stromal cells. Here we show that primary human endothelial cells mount robust IFN-I responses to human CMV that are dependent upon cyclic GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3) signaling. Disruption of STING expression in endothelial cells by clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 revealed that it is essential for the induction of IFN-I and restriction of CMV replication. Consistently, STING was necessary to mount the first phase of IFN-I production and curb CMV replication in infected mice. Thus, DNA sensing through STING is critical for primary detection of both human and mouse CMV in nonhematopoietic cells and drives the initial wave of IFN-I that is key for controlling early viral replication in vivo. IMPORTANCE: Cytomegalovirus (CMV) is one of the most common viral pathogens, with the majority of people contracting the virus in their lifetime. Although acute infection is mostly asymptomatic in healthy persons, significant pathology is observed in immunocompromised individuals, and chronic CMV infection may exacerbate a myriad of inflammatory conditions. Here we show that primary human endothelial cells mount robust IFN-I responses against CMV via a cGAS/STING/IRF3 pathway. Disruption of STING expression by CRISPRs revealed an essential role in eliciting IFN-I responses and restricting CMV replication. Consistently, in mice, STING is necessary for the first phase of IFN-I production that limits early CMV replication. Our results demonstrate a pivotal role for the cGAS-STING pathway in the initial detection of CMV infection.