Viral nanoparticles: Current advances in design and development.

Viral nanoparticles (VNPs) are self-assembling, adaptable delivery systems for vaccines and other therapeutic agents used in a variety of biomedical applications. The potential of viruses to invade and infect various hosts and cells renders them suitable as potential nanocarriers, possessing distinct functional characteristics, immunogenic properties, and improved biocompatibility and biodegradability. VNPs are frequently produced through precise genetic or chemical engineering, which involves adding diverse sequences or functional payloads to the capsid protein (CP). Several spherical and helical plant viruses, bacteriophages, and animal viruses are currently being used as VNPs, or non-infectious virus-like particles (VLPs). In addition to their broad use in cancer therapy, vaccine technology, diagnostics, and molecular imaging, VNPs have made important strides in the realms of tissue engineering, biosensing, and antimicrobial prophylaxis. They are also being used in energy storage cells due to their binding and piezoelectric properties. The large-scale production of VNPs for research, preclinical testing, and clinical use is fraught with difficulties, such as those relating to cost-effectiveness, scalability, and purity. Consequently, many plants- and microorganism-based platforms are being developed, and newer viruses are being explored. The goal of the current review is to provide an overview of these advances.

Inhibitory effect of garlic and omam extracts on Mucor circinelloides, a fungus causing mucormycosis: An in vitro study.

Context: Mucor circinelloides is reported to be the second among the most common causative agents of emerging mucormycosis. It is intrinsically resistant to most known antifungals. Further the use of antifungals cause side effects. Traditional knowledge system for treating various ailments is stronger in India and it also backs deriving various bioactive compounds from herbal sources, in the modern system of medicine. Therefore, two most commonly used culinary herbal materials viz., ginger and omam were studied in vitro against M. circinelloides, as an alternate to antifungal drugs. Aims: To explore the traditional herbal resources as alternate to Amphotericin B to use against M. circinelloides, a fungus causing mucormycosis. Methods and Material: Aqueous extracts of garlic and omam were prepared and tested against M. circinelloides, at different concentrations. A positive control with Amphotericin B and negative control without any supplements were also maintained. The inhibitory effect was assessed by adopting optical density (OD) measurement method in SD broth and SD Agar Well Plate using spore suspension as inoculum. Statistical Analysis Used: Paired student T test was employed using SPSS Version 1.6. Results and Conclusions: Both garlic and omam extracts were found to inhibit the M. circinelloides and their MICs were 600 and 700 µL/mL. It is comparable with the MIC of Amphotericin B, 200 µg/mL. Thus, the regular use of garlic and omam can reduce the risk of possible mucormycosis and these herbs can be explored for drug formulations against M. circinelloides.

The First Differentiated TB Care Model From India: Delays and Predictors of Losses in the Care Cascade.

To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.

--Eleven tips for operational researchers working with health programmes: our experience based on implementing differentiated tuberculosis care in south India.

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.

A non-invasive ultrasensitive diagnostic approach for COVID-19 infection using salivary label-free SERS fingerprinting and artificial intelligence.

Clinical diagnostics for SARS-CoV-2 infection usually comprises the sampling of throat or nasopharyngeal swabs that are invasive and create patient discomfort. Hence, saliva is attempted as a sample of choice for the management of COVID-19 outbreaks that cripples the global healthcare system. Although limited by the risk of eliciting false-negative and positive results, tedious test procedures, requirement of specialized laboratories, and expensive reagents, nucleic acid-based tests remain the gold standard for COVID-19 diagnostics. However, genetic diversity of the virus due to rapid mutations limits the efficiency of nucleic acid-based tests. Herein, we have demonstrated the simplest screening modality based on label-free surface enhanced Raman scattering (LF-SERS) for scrutinizing the SARS-CoV-2-mediated molecular-level changes of the saliva samples among healthy, COVID-19 infected and COVID-19 recovered subjects. Moreover, our LF-SERS technique enabled to differentiate the three classes of corona virus spike protein derived from SARS-CoV-2, SARS-CoV and MERS-CoV. Raman spectral data was further decoded, segregated and effectively managed with the aid of machine learning algorithms. The classification models built upon biochemical signature-based discrimination method of the COVID-19 condition from the patient saliva ensured high accuracy, specificity, and sensitivity. The trained support vector machine (SVM) classifier achieved a prediction accuracy of 95% and F1-score of 94.73%, and 95.28% for healthy and COVID-19 infected patients respectively. The current approach not only differentiate SARS-CoV-2 infection with healthy controls but also predicted a distinct fingerprint for different stages of patient recovery. Employing portable hand-held Raman spectrophotometer as the instrument and saliva as the sample of choice will guarantee a rapid and non-invasive diagnostic strategy to warrant or assure patient comfort and large-scale population screening for SARS-CoV-2 infection and monitoring the recovery process.

Insights into the capsid structure of banana bunchy top virus.

Banana is the major staple food crop for approximately 400 million people. Bunchy top disease of banana is one of the most devastating diseases caused by banana bunchy top virus (BBTV), which results in stunting of plants, bunchy appearance of leaves and a significant loss of yield. While many isolates of BBTV from various regions of India have been characterized by different groups, no structural study exists for this important virus. To bridge this gap, the pET28a clone of the coat protein (CP) gene from BBTV isolate of Hill banana grown in lower Pulney Hills (Virupakshi) of Tamilnadu was expressed in BL21 (DE3) pLysS. Purification of the CP was achieved by Ni-NTA affinity chromatography. In vitro capsid assembly studied using sucrose density gradient centrifugation suggested that the CP did not assemble as a virus-like particle (VLP), but remained as smaller oligomers. Studies using dynamic light scattering (DLS) indicate that the purified protein is poly-dispersed, represented majorly as pentamers. Homology modeling studies provided useful insights into the probable fold of the CP suggesting that it is a ß-sandwich, similar to that seen in the majority of plant viruses. In silico capsid reconstruction aided the understanding of the quaternary organization of subunits in the capsid and their molecular interactions. The location of the aphid-binding EAG motif was identified on the surface loops close to the pentameric axis indicating its role in vector-mediated transmission. Comparison with the CP and capsid structure of geminiviruses provided useful insights into the mode of nucleic acid binding and the role of genome during capsid assembly. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03204-4.

Modelling and simulation of food waste bio-drying.

Bio-drying of food waste is an attractive aerobic treatment method for moisture removal and producing refuse-derived fuel (RDF) beneficial for waste utilization as an energy source. Understanding the mechanism of process and interaction of key variables is necessary for optimizing the parameters to improve the water removal rate. In the present study, an attempt was made to develop mass and energy balances using the first principles to predict the variation of key variables namely concentration of degradable matter, moisture, oxygen concentration, and temperature based on process kinetics. The simulation of the developed first-order ordinary differential equations combined for three horizontal layers of the waste pile was carried out using Simulink software in MATLAB R2020b interface. The predicted output was compared with experimental data of the pilot-scale plant for food waste with different municipal solid waste components including paper and plastic and with literature data for food waste with a bulking agent (BA). A good prediction of bio-drying performance was achieved using the proposed model and the experimental data.

Development of mathematical model and experimental Validation for batch bio-drying of municipal solid waste: Mass balances.

Bio-drying of solid waste is a complex process that involves anoxic hydrolysis, aerobic oxidation, evaporation, absorption, and condensation. To understand the interaction between different variables (concentration of volatile matter, moisture, microbial biomass, and temperature) and to predict the system performance, a powerful tool is necessary for improved drying rates. Hence, a mathematical model of mass balances of the batch bio-drying of municipal solid waste (MSW), associated with rate equations of evaporation of moisture from the waste matrix and absorption of leachate on absorbents is developed which is the novelty of the present study. This model integrates 18 first-order differential equations based on process kinetics for mass balances of components in the solid, liquid, and gas phases, comprising the specific degradability of food, paper, and inert material of the MSW. The proposed model is simulated using MATLAB ode15s solver and validated with experimental data from the pilot-scale bio-drying reactor. The model predicted values are in good agreement with experimental values with a deviation of ±10%.

Analysis of ENAM gene single-nucleotide polymorphism rs3796704 with caries susceptibility in young adult Tamil population.

BACKGROUND: Dental caries is as primeval as humanity, but still, investigations are undergoing regarding the etiopathogenesis behind this multifactorial disease. Genetics is known to play a vital role in the etiology behind dental caries in addition to environmental and socioeconomic factors. Genetic variations like single-nucleotide polymorphisms (SNPs) were extensively studied in the past decade to portray the etiopathogenesis contributing to dental caries. AIM: This investigation was undertaken to analyze the ENAM gene SNP rs3796704 with caries susceptibility in ethnic young adult Tamil population of India. MATERIALS AND METHODS: Out of 370 patients included, 215 patients belonged to the high caries group (Decayed, Missing and Filled Tooth [DMFT] ≥2) and 155 patients belonged to the low caries group (DMFT ≤ 1). DNA was extracted from the blood of all the individuals. SNP genotyping was performed utilizing tetra-primer amplification refractory mutation system-polymerase chain reaction with specific primers. RESULTS: The genotyping results showed that there were no differences in allelic (P = 0.114) and genotypic frequencies (P = 0.159) between the high caries and low caries groups. CONCLUSION: Future studies can be conducted in larger samples and different ethnicities around the globe to analyze the role played by SNPs of enamel formation genes in cariogenesis.

Cytotoxic activity of cholesterol oxidase produced by Streptomyces sp. AKHSS against cancerous cell lines: mechanism of action in HeLa cells.

Re-occurrence of cancer is the major drawback for the currently available anticancer therapies. Therefore, study of an efficient enzyme, cholesterol oxidase produced by various kinds of microbes especially obtained from unexplored marine actinobacterial species against human cancer cell lines and understanding its mechanism of action helps to identify an irreversible and potent anticancer agent. The cytotoxic potential of cholesterol oxidase produced by a marine Streptomyces sp. AKHSS against four different human cancer cell lines was demonstrated through MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Fluorescent confocal microscopy and flow cytometry based experiments were performed to understand the efficiency of the enzymatic action on HeLa cells. Further, the apoptotic related proteins were detected through western blotting. Interestingly, the enzyme exhibited potent cytotoxicity at very low concentrations (0.093-0.327 µM) against all the cells tested. Fluorescent confocal microscopy revealed the morphological variations induced by the enzyme on cancer cell lines such as the formation of lipid droplets and condensation of nuclei. The enzyme treated cell-free extracts of HeLa cells analyzed through gas chromatography mass spectrometry showed the depletion of membrane cholesterol and the presence of substituted enzyme oxidized product, cholest-4-ene-3-one. The enzyme had induced significant inhibitory effects on the cell viability such as cell cycle arrest (G1 phase), apoptosis and rise of reactive oxygen species as evident through flow cytometry. Besides, hyperpolarization of mitochondrial membrane, reduced rates of phosphorylation of pAkt and the expression of apoptotic death markers like Fas, Fas L, caspases (8 and 3) and PARP-1 were recorded in the enzyme treated HeLa cells. Thus, cholesterol oxidase purified from a marine Streptomyces sp. AKHSS exhibits potent cytotoxicity at very low concentrations against human cancer cell lines. All the ex vivo experiments portrayed the substantial inhibitory effect of the enzyme on HeLa cells suggesting that cholesterol oxidase of Streptomyces sp. AKHSS could be a prominent cancer chemotherapeutic agent.

Double-Silicate Derived Hybrid Foams for High-Capacity Adsorption of Textile Dye Effluent: Statistical Optimization and Adsorption Studies.

In this work, a lightweight inorganic-organic hybrid foam adsorbent is processed out of economically cheap "double-silicate" precursors employing natural bentonite and water glass through a facile cross-linking and polymerization technique. Poly(vinyl alcohol) was used to provide structural strength to the three-dimensional framework. The foam adsorbent possessed an apparent density of 0.083 g cm-3, indicating its internetworks and exposed surface area for the uptake of dyes. The foam was systematically studied for the treatment of textile dye effluent. Multivariate optimization process was carried out using response surface methodology. The Box-Behnken model was used for the design of experiments and to study the interplay between the variables. Batch adsorption and continuous column adsorption studies were carried out at respective levels of initial concentration (200-1000 µM), adsorbent dose (1-10 g L-1), and contact time (0-120 min). The results revealed that the hybrid silicate foam exhibits adsorption capacity as high as 99.9, 98.9, and 98.2% for 200, 600, and 1000 µM concentrations of methylene blue in 120 min, respectively, and 100% adsorption for 200, 600, and 1000 µM concentrations of crystal violet in 120 min for 10 g L-1 of adsorbent. Adsorption equilibrium data fitted well to Langmuir isotherm, and the kinetics followed second-order kinetic model. Synthetic industrial effluent with 1000 µM dye concentration was also prepared and studied with continuous column for determining the working capacity of the adsorbent, and the results are presented. The silicate hybrid foam is a cheap adsorbent that does not produce any secondary waste and can be repeatedly used making it attractive for dye industries.

Experimental and modelling of Arthrospira platensis cultivation in open raceway ponds.

In this study, the growth of Arthrospira platensis was studied in an open raceway pond. Furthermore, dynamic model for algae growth and CFD modelling of hydrodynamics in open raceway pond were developed. The dynamic behaviour of the algal system was developed by solving mass balance equations of various components, considering light intensity and gas-liquid mass transfer. A CFD modelling of the hydrodynamics of open raceway pond was developed by solving mass and momentum balance equations of the liquid medium. The prediction of algae concentration from the dynamic model was compared with the experimental data. The hydrodynamic behaviour of the open raceway pond was compared with the literature data for model validation. The model predictions match the experimental findings. Furthermore, the hydrodynamic behaviour and residence time distribution in our small raceway pond were predicted. These models can serve as a tool to assess the pond performance criteria.

Effect of geographical and ethnic variation on Dysphonia Severity Index: a study of Indian population.

Dysphonia Severity Index (DSI) is a widely used multiparametric approach to objectively quantify the voice quality. Few research groups have investigated the test-retest, interobserver variability, and influence of age and gender. They have also verified the application of DSI in various voice rehabilitation conditions. However, all these studies have been conducted on European population. There is a possibility of variation in the basic parameters of DSI across geographical and ethnic groups. Hence, the present study evaluated DSI in Indian population. One hundred twenty voluntary participants (60 males, 60 females) who had G(0) on the Grade, Roughness, Breathiness, Aesthenia, Strain (GRBAS) scale participated in the study (age range of 18-25 years, M=21.8, standard deviation=2.7). Maximum phonation time (MPT), frequency intensity, and jitter measurements were made using CSL 4500 (Kay Elemetrics, Pine Brook, NJ). Results showed noticeable difference between Indian and European population on MPT, Highest frequency (F(0)-High), and DSI values. Significant gender difference was also observed on MPT and F(0)-High. Test-retest reliability showed >95% for all the parameters. The MPT decrement lead to a reduction in the overall DSI value in both the genders. These results of the study caution voice professionals to reinvestigate and establish their own norms for their geographical and ethnic groups.

Timing in speech: a review of Sanskrit literature and its verification.

The concept of timing in speech as held by the ancient Sanskrit Scholars is described. This has been verified by spectrographically analyzing 109 Sanskrit sentences as spoken by ten Sanskrit speakers. The results seem to partly support the notion of Sanskrit grammarians in that their concept regarding the vowel durations gain support from this study. The information obtained from this study and such reviews could be of great importance in the understanding of human speech production and perception.

Management of carcinoma breast with conservative surgery and radiation therapy-experience in a developing country.

Between 1980 and 1987, 14 patients with breast cancer who refused mastectomy were treated at the V.N. Cancer Centre, Coimbatore, with excision of the lump, followed by radiation therapy and adjuvant chemotherapy/hormonal therapy. No attempt was made to boost the tumour bed with interstitial implants or electron beam for want of these facilities. No patient developed local or loco-regional disease or distant metastases during the period of follow-up which ranged between 10 and 76 months. Ten of the 14 patients have been followed up for more than two years. Most published data on breast-conserving treatment for cancer breast are from the U.S., UK and Europe. There are not many papers published from the developing countries. This paper gives an insight into this subject in the developing countries.

Speech pathology in ancient India--a review of Sanskrit literature.

This paper aims at highlighting the knowledge of the Sanskrit scholars of ancient times in the field of speech and language pathology. The information collected here is mainly from the Sanskrit texts written between 2000 B.C. and 1633 A.D. Some aspects of speech and language that have been dealt with in this review have been elaborately described in the original Sanskrit texts. The present paper, however, being limited in its scope, reviews only the essential facts, but not the details. The purpose is only to give a glimpse of the knowledge that the Sanskrit scholars of those times possessed. In brief, this paper is a review of Sanskrit literature for information on the origin and development of speech and language, speech production, normality of speech and language, and disorders of speech and language and their treatment.