Identification of DPP-IV inhibitory peptides derived from buffalo colostrum: Mining through bioinformatics, in silico and in vitro approaches.

Bioactive peptides derived from foods provide physiological health benefits beyond nutrition. This study focused on profiling small peptide inhibitors against two key serine proteases, dipeptidyl peptidase-IV (DPP-IV) and prolyl oligopeptidase (POP). DPP-IV is a well-known protein involved in diverse pathways regulating inflammation, renal, cardiovascular physiology, and glucose homeostasis. POP is yet another key target protein for neurodegenerative disorders. The study evaluated peptide libraries of buffalo colostrum whey and fat globule membrane proteins derived from pepsin and pepsin-pancreatin digestion through in silico web tools and structure-based analysis by molecular docking and binding free-energy estimation, followed by in vitro assay for DPP-IV inhibition for the lead peptides. The bioinformatic study indicated 49 peptides presented motifs with DPP-IV inhibition while 5 peptides with sequences for POP inhibition. In the molecular docking interactions study, 22 peptides interacted with active site residues of DPP-IV and 3 peptides with that of POP. The synthesized peptides, SFVSEVPEL and LTFQHNF inhibited DPP-IV in vitro with an IC50 of 193.5 µM and 1.782 mM, respectively. The study revealed the key residues for inhibition of DPP-IV and POP thus affirming the DPP-IV inhibitory potential of milk-derived peptides.

A scoping review exploring oral health inequalities in India: a call for action to reform policy, practice and research.

INTRODUCTION: Reduction in health inequalities and providing universal access to health care have been identified as two important global milestones by the World Health Organization for countries to achieve by 2030. Therefore, recognizing the magnitude of oral health inequalities in India has become a pressing priority to improve access to dental care within the country. This scoping review was conducted with the aim of reviewing, collating and analysing the current knowledge base on oral health inequalities in India. METHODOLOGY: The scoping review followed Arksey and O'Malley's approach, and reporting was performed in accordance with the PRISMA-ScR guidelines. A systematic search was conducted on Scopus, PubMed, Web of Science, and EMBASE to identify literature addressing one or more dimensions of oral health inequalities in India, published in English between January 2002 and April 2022. The data were charted, and qualitative analysis was performed to derive themes, highlighting the key concepts emerging from this review. RESULTS: In accordance with the eligibility criteria, a total of 71 articles retrieved through database search and backward citation search were included in this scoping review. The major themes ranged from individual to diverse sociodemographic factors acting as barriers to and facilitators of access to dental care. Deficiencies in human resources for oral health, along with a wide diversity in dental service provision and dental education were other major themes contributing to inequality. Subsequently, this has resulted in recommendations on restructuring the dental workforce and their development and modifications in oral health care policies and practices. The qualitative synthesis demonstrates the intertwined nature of the multiple factors that influence the goal of achieving an affordable, accessible, extensive and inclusive oral healthcare system in India. CONCLUSIONS: This comprehensive review provides a broad perspective on oral health inequalities in India, providing valuable insights for both researchers and policymakers in this area and guiding their efforts towards achieving universal oral health coverage in the Indian context.

Regulation of microtubule disassembly by spatially heterogeneous patterns of acetylation.

Microtubules (MTs) are bio-polymers, composed of tubulin proteins, involved in several functions such as cell division, transport of cargoes within cells, maintaining cellular structures etc. Their kinetics are often affected by chemical modifications on the filament known as Post Translational Modifications (PTMs). Acetylation is a PTM which occurs on the luminal surface of the MT lattice and has been observed to reduce the lateral interaction between tubulins on adjacent protofilaments. Depending on the properties of the acetylase enzyme αTAT1 and the structural features of MTs, the patterns of acetylation formed on MTs are observed to be quite diverse. In this study, we present a multi-protofilament model with spatially heterogeneous patterns of acetylation, and investigate how the local kinetic differences arising from heterogeneity affect the global kinetics of MT filaments. From the computational study we conclude that a filament with spatially uniform acetylation is least stable against disassembly, while ones with more clustered acetylation patterns may provide better resistance against disassembly. The increase in disassembly times for clustered pattern as compared to uniform pattern can be up to fifty percent for identical amounts of acetylation. Given that acetylated MTs affect several cellular functions as well as diseases such as cancer, our study indicates that spatial patterns of acetylation need to be focused on, apart from the overall amount of acetylation.

Derivation & validation of glycosylated haemoglobin (HbA 1c ) cut-off value as a diagnostic test for type 2 diabetes in south Indian population.

BACKGROUND & OBJECTIVES: Glycosylated haemoglobin (HbA 1c ) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA 1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA 1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India. METHODS: In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA 1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA 1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341). RESULTS: On applying HbA 1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set,sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8 , 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant. INTERPRETATION & CONCLUSIONS: HbA 1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India.

Comparison of Dental Caries Risk Assessment Using CaRisk- A Simple Mobile Based Application and WHO deft, DMFT Scores: A Cross Sectional Study.

Statement of the Problem: It is essential to address caries risk at an early stage for the prevention of dental caries. Mobile application CaRisk is designed in a particular way to self-assess the dental caries risk by the individual's themselves. Purpose: The current study aimed to assess the dental caries risk among age groups 5-6 and 35-44 using self-assessment caries risk mobile application CaRisk and compare it with the deft and DMFT values. Materials and Method: This cross-sectional study was conducted in Chennai, India; to evaluate the risk of dental caries in children aged 5 to 6 and adults aged 35 to 44. The scores of the mobile application CaRisk and the decayed- extracted- filled teeth (deft)/ decayed-missing-filled-teeth (DMFT) caries risk assessment were evaluated. Descriptive statistics were performed. The risk category was determined by frequency. Chi-square analysis was done to determine whether the DMFT scores and the CaRisk mobile app were associated. The correlation was performed between the CaRisk mobile application and DMFT scores. Results: Association was found between the caries risk assessment score of the mobile application CaRisk and the DMFT and deft scores of the adults and children for both the age groups 5-6 and 35-44 years respectively and it indicates that it was found to be statistically significant. Pearson's correlation was performed to assess the strength of association and R-values obtained for the age group 5-6 and 35-44 years respectively, which was statistically significant (0.892 and 0.840). Conclusion: This CaRisk mobile application scores correlate with the deft and DMFT scores and it is an effective self-diagnosis tool for assessing dental caries risk assessment. Further, it is suggested that the mobile application CaRisk should be tested among a huge population.

Layer-by-layer assembled graphitic carbon nitride membranes for water treatment.

Meeting societal demand for potable water supply remains one of the prioritized challenges faced in the modern era. The anthropogenic intervention has led to a dire situation threatening ecological balance and human health. There is an inevitable need for the development of new technologies and innovations in existing technologies for water treatment. Photocatalytic Membrane technology, encompassing the merits of membrane filtration and photocatalytic degradation has evolved as a potential and reliable technology for sustainable water treatment. Innovations in photocatalytic materials and membrane fabrication techniques can lead to the goal of commercialization of membrane water treatment technology. Herein, we demonstrate the potential of graphitic carbon nitride (g-C3N4) and its functionalized analog as photocatalytic membranes for sustainable water treatment. g-C3N4 and Tetracarboxyphenylporphyrin sensitized g-C3N4 (g-C3N4/TCPP) was introduced onto commercial nylon membrane surface via a layer-by-layer (LBL) assembly method using chitosan and sodium salt of polystyrene sulphonic acid as polyelectrolytes. The fabricated membranes were characterized to ensure the integration of the photocatalysts. The performance of the membranes for water treatment was assessed by selecting some common dyes as model pollutants. The modified membranes exhibited excellent flux recovery and could afford high rejection rates upon irradiation indicating the prospects for sustainable filtration.

Association between dental caries experience and salivary profile among autoimmune thyroid disease subjects - a cross-sectional comparative study.

Background: Autoimmune thyroid disease (AITD) is an inflammatory condition that primarily affects women between the ages of 30 and 50. It has been hypothesised that AITD causes salivary glands to produce less saliva due to its endocrine effects. Studies showing the effect of AITD on salivary glands are very scarce. The aim of this study was to compare AITD patients with controls who were of a similar age and gender in terms of salivary metrics and the prevalence of dental caries. Methods: 200 subjects in Bangalore city (100 AITD subjects and 100 healthy subjects as controls) participated in a cross-sectional study. Subjective oral dryness was assessed using Farsi's criteria. Salivary parameters and caries were assessed using GC Saliva-Check BUFFER kit and WHO caries criteria respectively. Descriptive and analytical statistics were done. Significant data was defined as a p value of <0.05. Results: When compared to controls, the AITD group had substantially more subjective mouth dryness and dental caries. Unstimulated (USFR) and stimulated salivary flow rate (SFR), pH and buffering capacity were reduced in AITD group whereas viscosity was high. There was a significant negative correlation between USFR, SFR, subjective oral dryness and dental caries. In a linear regression, there was no association between age, gender, socioeconomic status (SES), thyroid stimulating hormone (TSH), salivary viscosity, pH, buffering capacity and dental caries. Dental caries, USFR and SFR demonstrated a substantial relationship. Conclusions: The present research may indicate an underlying association between thyroid and salivary gland dysfunction resulting in oral dryness and high dental caries experience.

Correction: Effectiveness of Silver Diamine Fluoride for Early Childhood Caries Among Children Aged 24 to 72 Months: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/46144.].

Effectiveness of Silver Diamine Fluoride for Early Childhood Caries Among Children Aged 24 to 72 Months: Protocol for a Randomized Controlled Trial.

BACKGROUND: Dental caries is a serious public health issue globally. It is one of the most prevalent chronic disease in children worldwide. An important public health concern is the existence of one or more decayed, missing, or filled tooth surfaces in any primary teeth of preschool children. Early childhood caries (ECC) can be halted with the use of silver diamine fluoride (SDF) solution. Previous research has indicated that it may have a preventive impact in the treatment of ECC. It is well known that 38% silver diamine fluoride (SDF) is helpful at preventing dental caries. On the other hand, there is not enough evidence on SDF's ability to prevent caries in primary teeth. To date, no well-planned clinical study has been carried out to investigate SDF's impact on caries protection. OBJECTIVE: The study's objective is to evaluate and compare the efficacy of 12%, 30%, and 38% silver diamine fluoride in preventing ECC in children aged 24 to 72 months in Mangaluru Taluk. METHODS: This is a single-center, randomized, active-controlled, parallel-group pragmatic trial. Children attending preschool in Mangalore Taluk aged 24 to 72 months will be included in the study. There will be three study groups: group 1 will receive 12% SDF semiannually; group 2 will receive 30% SDF semiannually; and group 3 will receive 38% SDF semiannually. After 6 and 12 months, the principal examiner will conduct a clinical examination of the teeth with a visual and tactile assessment. The effectiveness of the various concentrations of SDF will be determined after 12 months. RESULTS: The research was funded in September 2020, and data collection started in September 2022. As of February 2023, 150 participants have enrolled in the study. The project is still underway, and it is expected to be completed in December 2023. CONCLUSIONS: Uncertainty surrounds the efficacy of 38% SDF in preventing ECC. Consensus-Based Clinical Case Reporting (CARE) guidelines recommending the use of SDF for ECC prevention will be modified if the findings are as expected. Additionally, since the findings will be broadly disseminated, more nations will implement the use of SDF, easing the burden of ECC on the entire world. Future research on the treatment and prevention of ECC will benefit from the study results. If SDF is successful in preventing caries in a classroom or community context, it will mark an important turning point for preventive dentistry. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/2020/02/023420; https://tinyurl.com/3ju2apab. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46144.

Microplastic content of over-the-counter toothpastes - a systematic review.

Background: Microplastic particles are used as ingredients in personal care products such as face washes, shower gels and toothpastes and form one of the main sources of microplastic pollution, especially in the marine environment. In addition to being a potential pollutant to the environment, the transfer of microplastics to humans can become a severe threat to public health. This systematic review was conceptualized to identify evidence for the presence of and characteristics of microplastics in toothpaste formulations. Methods: The PICOS Criteria was used for including studies for the review. Electronic databases of Scopus, Embase, Springer Link, PubMed, Web of Science and Google Scholar were searched, as well as hand and reference searching of the articles was carried out. The articles were screened using the software application, Covidence® and data was extracted. Results: This systematic review showed that toothpastes from China, Vietnam, Myanmar and the UAE, reported no evidence of microplastics and those from Malaysia, Turkey and India reported the presence of microplastics. The shape of the microplastics present in these toothpastes were found to be granular, irregular with opaque appearance and also in the form of fragments and fibers and the percentage weight in grams ranged from 0.2 to 7.24%. Malaysia releases 0.199 trillion microbeads annually from personal care products into the environment and toothpastes in Turkey release an average of 871 million grams of microplastics annually. Similarly, in India, it has been reported that 1.4 billion grams of microplastic particles are emitted annually from toothpaste. Conclusions: The findings of this systematic review provide evidence that toothpastes, at least in some parts of the world, do contain microplastics and that there is a great risk of increase in the addition of microplastics to the environment by the use of toothpaste.

FnCas9-based CRISPR diagnostic for rapid and accurate detection of major SARS-CoV-2 variants on a paper strip.

The COVID-19 pandemic originating in the Wuhan province of China in late 2019 has impacted global health, causing increased mortality among elderly patients and individuals with comorbid conditions. During the passage of the virus through affected populations, it has undergone mutations, some of which have recently been linked with increased viral load and prognostic complexities. Several of these variants are point mutations that are difficult to diagnose using the gold standard quantitative real-time PCR (qRT-PCR) method and necessitates widespread sequencing which is expensive, has long turn-around times, and requires high viral load for calling mutations accurately. Here, we repurpose the high specificity of Francisella novicida Cas9 (FnCas9) to identify mismatches in the target for developing a lateral flow assay that can be successfully adapted for the simultaneous detection of SARS-CoV-2 infection as well as for detecting point mutations in the sequence of the virus obtained from patient samples. We report the detection of the S gene mutation N501Y (present across multiple variant lineages of SARS-CoV-2) within an hour using lateral flow paper strip chemistry. The results were corroborated using deep sequencing on multiple wild-type (n = 37) and mutant (n = 22) virus infected patient samples with a sensitivity of 87% and specificity of 97%. The design principle can be rapidly adapted for other mutations (as shown also for E484K and T716I) highlighting the advantages of quick optimization and roll-out of CRISPR diagnostics (CRISPRDx) for disease surveillance even beyond COVID-19. This study was funded by Council for Scientific and Industrial Research, India.

SARS-CoV-2, the virus responsible for COVID-19, has a genome made of RNA (a nucleic acid similar to DNA) that can mutate, potentially making the disease more transmissible, and more lethal. Most countries have monitored the rise of mutated strains using a technique called next generation sequencing (NGS), which is time-consuming, expensive and requires skilled personnel. Sometimes the mutations to the virus are so small that they can only be detected using NGS. Finding cheaper, simpler and faster SARS-CoV-2 tests that can reliably detect mutated forms of the virus is crucial for public health authorities to monitor and manage the spread of the virus. Lateral flow tests (the same technology used in many pregnancy tests) are typically cheap, fast and simple to use. Typically, lateral flow assay strips have a band of immobilised antibodies that bind to a specific protein (or antigen). If a sample contains antigen molecules, these will bind to the immobilised antibodies, causing a chemical reaction that changes the colour of the strip and giving a positive result. However, lateral flow tests that use antibodies cannot easily detect nucleic acids, such as DNA or RNA, let alone mutations in them. To overcome this limitation, lateral flow assays can be used to detect a protein called Cas9, which, in turn, is able to bind to nucleic acids with specific sequences. Small changes in the target sequence change how well Cas9 binds to it, meaning that, in theory, this approach could be used to detect small mutations in the SARS-CoV-2 virus. Kumar et al. made a lateral flow test that could detect a Cas9 protein that binds to a nucleic acid sequence found in a specific mutant strain of SARS-CoV-2. This Cas9 was highly sensitive to changes in its target sequence, so a small mutation in the target nucleic acid led to the protein binding less strongly, and the signal from the lateral flow test being lost. This meant that the lateral flow test designed by Kumar et al. could detect mutations in the SARS-CoV-2 virus at a fraction of the price of NGS approaches if used only for diagnosis. The lateral flow test was capable of detecting mutant viruses in patient samples too, generating a colour signal within an hour of a positive sample being run through the assay. The test developed by Kumar et al. could offer public health authorities a quick and cheap method to monitor the spread of mutant SARS-CoV-2 strains; as well as a way to determine vaccine efficacy against new strains.

Fourteen-year-old boy with decreased appetite and pedal swelling.

CLINICAL INTRODUCTION: A 14-year-old boy presented with history of decreased appetite and bilateral swelling of feet for 6 months. He did not give any associated history of orthopnoea or paroxysmal nocturnal dyspnoea. He was born by a normal delivery after a non-consanguineous marriage. He had an unremarkable birth and childhood health history. There was no family history of significant cardiovascular illness or sudden death. Clinical examination showed an average built boy with elevated jugular venous pressure with prominent v wave and bilateral pitting pedal oedema. Cardiovascular examination showed normal first (S1) and second (S2) heart sounds and a short early systolic murmur over tricuspid region. Other systems examination was remarkable for soft tender hepatomegaly.ECG showed sinus rhythm with tall, peaked p waves. Chest X-ray revealed enlargement along the right cardiac border. Transthoracic echocardiographic images are shown in figure 1A (apical four-chamber view) and figure 1B (tricuspid inflow Doppler). There was no colour Doppler evidence of interatrial shunt.heartjnl;105/5/405/F1F1F1Figure 1(A) Transthoracic echocardiographic apical four-chamber view. (B) Tricuspid inflow continuous wave Doppler image. QUESTION: What is the most likely diagnosis of his condition? Endomyocardial fibrosis (EMF)Ebstein's anomalyArrhythmogenic right ventricular dysplasia (ARVD)Idiopathic dilatation of right atriumRestrictive cardiomyopathy.

Blue emitting copper nanoclusters as colorimetric and fluorescent probe for the selective detection of bilirubin.

Hurdles to develop point of care diagnostic methods restrict the translation of progress in the health care sector from bench side to bedside. In this article a simple, cost effective fluorescent as well as colorimetric nanosensor was developed for the early and easy detection of hyperbilirubinemia. A stable, water soluble bovine serum albumin stabilised copper nanocluster (BSA CuNC) was used as the fluorescent probe which exhibited strong blue emission (404nm) upon 330nm excitation. The fluorescence of the BSA CuNC can be effectively quenched by the addition of bilirubin by the formation of copper-bilirubin complex. Meanwhile the copper-bilirubin complex resulted in an observable colour change from pale violet to green facilitating colorimetric detection. The prepared sensor displayed good selectivity and sensitivity over other co-existing molecules, and can be used for quantifying bilirubin with a detection limit down to 257fM. Additionally, the as-prepared probe was coated on a paper strip to develop a portable paper strip sensor of bilirubin. Moreover, the method was successfully applied in real sample analysis and obtained promising result.

Inhibitory potential of Buffalo (Bubalus bubalis) colostrum immunoglobulin G on Klebsiella pneumoniae.

The unique components of colostrum like free oligosaccharides and glycoconjugates are known to offer resistance to enzymatic digestion in the gastrointestinal tract and have the ability to inhibit the localized adherence of enteropathogens to the digestive tract of the neonates. In this context, we have evaluated the in vitro effect of buffalo colostrum immunoglobulin G on human pathogen Klebsiella pneumoniae, a predominant multidrug resistant pathogen associated with nasocomial infections. The investigation revealed growth inhibitory potential of immunoglobulin G in a dose dependent manner supported by scanning electron microscopic studies. The N-glycan enriched fraction of immunoglobulin G after PNGase treatment was found more effective, comparable to ampicillin than native immunoglobulin G supporting the fact that colostrum derived oligosaccharides is crucial and act as ideal substrates for undesirable and pathogenic bacteria. The MALDI TOF/TOF analysis confirmed the glycostructures of abundant N-glycans of immunoglobulin G exerting antibacterial activity. The proteomic analysis revealed variations between control and treated cells and expression of chemotaxis-CheY protein (14kDa) was evidenced in response to immunoglobulin G treatment. Hence, it would be interesting to investigate the mode of inhibition of multidrug-resistant K. pneumoniae by buffalo colostrum immunoglobulin G with the identification of a newly expressed signalling protein.

SufE transfers sulfur from SufS to SufB for iron-sulfur cluster assembly.

Iron-sulfur (Fe-S) clusters are key metal cofactors of metabolic, regulatory, and stress response proteins in most organisms. The unique properties of these clusters make them susceptible to disruption by iron starvation or oxidative stress. Both iron and sulfur can be perturbed under stress conditions, leading to Fe-S cluster defects. Bacteria and higher plants contain a specialized system for Fe-S cluster biosynthesis under stress, namely the Suf pathway. In Escherichia coli the Suf pathway consists of six proteins with functions that are only partially characterized. Here we describe how the SufS and SufE proteins interact with the SufBCD protein complex to facilitate sulfur liberation from cysteine and donation for Fe-S cluster assembly. It was previously shown that the cysteine desulfurase SufS donates sulfur to the sulfur transfer protein SufE. We have found here that SufE in turn interacts with the SufB protein for sulfur transfer to that protein. The interaction occurs only if SufC is present. Furthermore, SufB can act as a site for Fe-S cluster assembly in the Suf system. This provides the first evidence of a novel site for Fe-S cluster assembly in the SufBCD complex.