The Candida auris Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence.

Candida auris , a multidrug-resistant human fungal pathogen, was first identified in 2009 in Japan. Since then, systemic C. auris infections have now been reported in more than 50 countries, with mortality rates of 30-60%. A major contributing factor to its high inter- and intrahospital clonal transmission is that C. auris, unlike most Candida species, displays unique skin tropism and can stay on human skin for a prolonged period. However, the molecular mechanisms responsible for C. auris skin colonization, intradermal persistence, and systemic virulence are poorly understood. Here, we report that C. auris Hog1 mitogen-activated protein kinase (MAPK) is essential for efficient skin colonization, intradermal persistence, as well as systemic virulence. RNA-seq analysis of wildtype parental and hog1 Δ mutant strains revealed marked down-regulation of genes involved in processes such as cell adhesion, cell-wall rearrangement, and pathogenesis in hog1 Δ mutant compared to the wildtype parent. Consistent with these data, we found a prominent role for Hog1 in maintaining cell-wall architecture, as the hog1 Δ mutant demonstrated a significant increase in cell-surface ß-glucan exposure and a concomitant reduction in chitin content. Additionally, we observed that Hog1 was required for biofilm formation in vitro and fungal survival when challenged with primary murine macrophages and neutrophils ex vivo . Collectively, these findings have important implications for understanding the C. auris skin adherence mechanisms and penetration of skin epithelial layers preceding bloodstream infections. Importance: Candida auris is a World Health Organization (WHO) fungal priority pathogen and an urgent public health threat recognized by the Centers for Disease Control and Prevention (CDC). C. auris has a unique ability to colonize human skin. It also persists on abiotic surfaces in healthcare environments for an extended period of time. These attributes facilitate the inter- and intrahospital clonal transmission of C. auris . Therefore, understanding C. auris skin colonization mechanisms are critical for infection control, especially in hospitals and nursing homes. However, despite its profound clinical relevance, the molecular and genetic basis of C. auris skin colonization mechanisms are poorly understood. Herein, we present data on the identification of the Hog1 MAP kinase as a key regulator of C. auris skin colonization. These findings lay foundation for further characterization of unique mechanisms that promote fungal persistence on human skin.

One-step simultaneous liquid phase exfoliation-induced chirality in graphene and their chirality-mediated microRNA delivery.

Graphene (G) has established itself as an exciting prospect for a broad range of applications owing to its remarkable properties. Recent innovations in chiral nanosystems have led to sensors, drug delivery, catalysis, etc. owing to the stereospecific interactions between various nanosystems and enantiomers. As the molecular structure of G itself is achiral introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications. Herein, we demonstrate direct liquid phase exfoliation and chiral induction in G nanosheets abbreviated as l-graphene and d-graphene in the presence of chiral l-tyrosine and d-tyrosine and by applying high-temperature sonication. The obtained exfoliated nanosheets demonstrated stable chirality confirmed by circular dichroism. Fourier transform infrared (FTIR) spectra, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and differential scanning calorimetry (DSC) showed functional, structural, morphological, surface, and thermal characteristics of l-graphene and d-graphene. The hemo-compatibility of these chiral graphenes was evaluated for the very first time utilizing human red blood cells. Lastly, for the very first time, an attempt was made to explore enantiomeric binding between chiral l-graphene and d-graphene with microRNA (miR-205) and their possibility towards chirality-mediated gene delivery in prostate cancerous cells.

The Predominance of Tobacco Propensities and Tobacco-Related Oral Lesions in Textile Mill Workers of Bhopal: A Cross-Sectional Study.

INTRODUCTION: Low wages, long work hours, and stressful working conditions predominantly affect the oral and general health of industrial workers, which in turn result in their tobacco consumption. This cross-sectional study examined the prevalence of tobacco use and its associated oral lesions among textile mill workers in Bhopal, India. Oral cancer and premalignant lesions are significantly increased by smoking and chewing tobacco. The study's objective was to assess and record the prevalence of oral mucosal lesions linked to tobacco use in different age groups among Bhopal textile industry workers. METHODOLOGY: A cross-sectional study was conducted among 583 textile mill workers. Data were collected using a questionnaire and the WHO Oral Health Assessment Form 2013. IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States) was used for the statistical analysis. Variables were compared using the mean, percentage, and standard deviation. The chi-square test and Fisher's exact test were used to compare the distribution of gender, tobacco habits, and oral mucosal lesions in different age groups. RESULTS: Males made up 69.1% of the workforce. A clear male preference was noted (P ≤ 0.001). About 64.7% of the workers did not have any tobacco-related habits, 20.8% used smokeless tobacco, 7.9% used a smoking form of tobacco, and 6.7% used both. Older age groups, 31-45 and >46 years old, had a higher proportion of users of smokeless tobacco (P ≤ 0.001). The most commonly reported oral mucosal lesions were ulcerative conditions in 6.9%, followed by oral submucous fibrosis (OSMF), keratotic lesions, and leukoplakia in 5.0%, 4.1%, and 3.6% of the study population, respectively. Leukoplakia and OSMF were prevalent in the 31-45-year age group, while ulcerative lesions were more prevalent in the 18-30-year age group (P ≤ 0.001). CONCLUSION: Workers at textile mills were more likely to use a smokeless form of tobacco. Older age groups had higher rates of smokeless tobacco use as compared to smoking, which was more prevalent in the younger age group. Oral mucosal lesions in older age groups frequently include OSMF and leukoplakia. The main reasons for engaging in the tobacco use habit were stress and a lack of awareness. Oral hygiene was a neglected entity among workers.

Candida auris Genetics and Emergence.

Candida auris is a multidrug-resistant fungal pathogen that presents a serious threat to global human health. Since the first reported case in 2009 in Japan, C. auris infections have been reported in more than 40 countries, with mortality rates between 30% and 60%. In addition, C. auris has the potential to cause outbreaks in health care settings, especially in nursing homes for elderly patients, owing to its efficient transmission via skin-to-skin contact. Most importantly, C. auris is the first fungal pathogen to show pronounced and sometimes untreatable clinical drug resistance to all known antifungal classes, including azoles, amphotericin B, and echinocandins. In this review, we explore the causes of the rapid spread of C. auris. We also highlight its genome organization and drug resistance mechanisms and propose future research directions that should be undertaken to curb the spread of this multidrug-resistant pathogen.

Indocyanine Green-based Glow Nanoparticles Probe for Cancer Imaging.

Indocyanine green (ICG) is one of the FDA-approved near infra-red fluorescent (NIRF) probes for cancer imaging and image-guided surgery in the clinical setting. However, the limitations of ICG include poor photostability, high concentration toxicity, short circulation time, and poor cancer cell specificity. To overcome these hurdles, we engineered a nanoconstruct composed of poly (vinyl pyrrolidone) (PVP)-indocyanine green that is cloaked self-assembled with tannic acid (termed as indocyanine green-based glow nanoparticles probe, ICG-Glow NPs) for the cancer cell/tissue-specific targeting. The self-assembled ICG-Glow NPs were confirmed by spherical nanoparticles formation (DLS and TEM) and spectral analyses. The NIRF imaging characteristic of ICG-Glow NPs was established by superior fluorescence counts on filter paper and chicken tissue. The ICG-Glow NPs exhibited excellent hemo and cellular compatibility with human red blood cells, kidney normal, pancreatic normal, and other cancer cell lines. An enhanced cancer-specific NIRF binding and imaging capability of ICG-Glow NPs was confirmed using different human cancer cell lines and human tumor tissues. Additionally, tumor-specific binding/accumulation of ICG-Glow NPs was confirmed in MDA-MB-231 xenograft mouse model. Collectively, these findings suggest that ICG-Glow NPs have great potential as a novel and safe NIRF imaging probe for cancer cell/tumor imaging. This can lead to a quicker cancer diagnosis facilitating precise disease detection and management.

Structural and Functional Characterization of Rv0792c from Mycobacterium tuberculosis: Identifying Small Molecule Inhibitor against HutC Protein.

In order to adapt in host tissues, microbial pathogens regulate their gene expression through a variety of transcription factors. Here, we have functionally characterized Rv0792c, a HutC homolog from Mycobacterium tuberculosis. In comparison to the parental strain, a strain of M. tuberculosis with a Rv0792c mutant was compromised for survival upon exposure to oxidative stress and infection in guinea pigs. RNA sequencing analysis revealed that Rv0792c regulates the expression of genes involved in stress adaptation and virulence of M. tuberculosis. Solution small-angle X-ray scattering (SAXS) data-steered model building confirmed that the C-terminal region plays a pivotal role in dimer formation. Systematic evolution of ligands by exponential enrichment (SELEX) resulted in the identification of single-strand DNA (ssDNA) aptamers that can be used as a tool to identify small-molecule inhibitors targeting Rv0792c. Using SELEX and SAXS data-based modeling, we identified residues essential for Rv0792c's aptamer binding activity. In this study, we also identified I-OMe-Tyrphostin as an inhibitor of Rv0792c's aptamer and DNA binding activity. The identified small molecule reduced the growth of intracellular M. tuberculosis in macrophages. The present study thus provides a detailed shape-function characterization of a HutC family of transcription factor from M. tuberculosis. IMPORTANCE Prokaryotes encode a large number of GntR family transcription factors that are involved in various fundamental biological processes, including stress adaptation and pathogenesis. Here, we investigated the structural and functional role of Rv0792c, a HutC homolog from M. tuberculosis. We demonstrated that Rv0792c is essential for M. tuberculosis to adapt to oxidative stress and establish disease in guinea pigs. Using a systematic evolution of ligands by exponential enrichment (SELEX) approach, we identified ssDNA aptamers from a random ssDNA library that bound to Rv0792c protein. These aptamers were thoroughly characterized using biochemical and biophysical assays. Using SAXS, we determined the structural model of Rv0792c in both the presence and absence of the aptamers. Further, using a combination of SELEX and SAXS methodologies, we identified I-OMe-Tyrphostin as a potential inhibitor of Rv0792c. Here we provide a detailed functional characterization of a transcription factor belonging to the HutC family from M. tuberculosis.

ELOVL4 Mutations That Cause Spinocerebellar Ataxia-34 Differentially Alter Very Long Chain Fatty Acid Biosynthesis.

The FA Elongase-4 (ELOVL4) enzyme mediates biosynthesis of both very long chain (VLC)-PUFAs and VLC-saturated FA (VLC-SFAs). VLC-PUFAs play critical roles in retina and sperm function, whereas VLC-SFAs are predominantly associated with brain function and maintenance of the skin permeability barrier. While some ELOVL4 mutations cause Autosomal Dominant Stargardt-like Macular Dystrophy (STGD3), other ELOVL4 point mutations, such as L168F and W246G, affect the brain and/or skin, leading to Spinocerebellar Ataxia-34 (SCA34) and Erythrokeratodermia variabilis. The mechanisms by which these ELOVL4 mutations alter VLC-PUFA and VLC-SFA biosynthesis to cause the different tissue-specific pathologies are not well understood. To understand how these mutations alter VLC-PUFA and VLC-SFA biosynthesis, we expressed WT-ELOVL4, L168F, and W246G ELOVL4 variants in cell culture and supplemented the cultures with VLC-PUFA or VLC-SFA precursors. Total lipids were extracted, converted to FA methyl esters, and quantified by gas chromatography. We showed that L168F and W246G mutants were capable of VLC-PUFA biosynthesis. W246G synthesized and accumulated 32:6n3, while L168F exhibited gain of function in VLC-PUFA biosynthesis as it made 38:5n3, which we did not detect in WT-ELOVL4 or W246G-expressing cells. However, compared with WT-ELOVL4, both L168F and W246G mutants were deficient in VLC-SFA biosynthesis, especially the W246G protein, which showed negligible VLC-SFA biosynthesis. These results suggest VLC-PUFA biosynthetic capabilities of L168F and W246G in the retina, which may explain the lack of retinal phenotype in SCA34. Defects in VLC-SFA biosynthesis by these variants may be a contributing factor to the pathogenic mechanism of SCA34 and Erythrokeratodermia variabilis.

Current status of biopsy markers for the breast in clinical settings.

INTRODUCTION: A breast biopsy marker is a very small object that is introduced into the breast to serve as a tissue marker. The placement of a breast marker following a biopsy or to mark an abnormality in the breast has become standard practice in the clinical setting. Breast biopsy markers offer a wide range of benefits which includes the prevention of re-biopsy of a benign tumor, differentiating multiple lesions within the breast, evaluation of the extent of a tumor, and increased precision during surgery. AREAS COVERED: This review article presents a range of breast biopsy markers used in clinical practice. First, an overview of the necessity of breast markers in healthy breast management. Second, it summarizes the diversity in composition, shape, unique properties and features, and bio-absorbable carriers of breast biopsy markers. Finally, it also discusses the possible use of clinically approved breast biopsy markers in various scenarios and their implications. EXPERT OPINION: This review serves as a guide in the selection of an appropriate breast marker. We believe that some of the common drawbacks associated with current breast biopsy markers can be overcome by developing novel polymer-metal and composite-based breast biopsy markers.

microRNA-205 in prostate cancer: Overview to clinical translation.

Prostate cancer (PrCa) is the most common type of cancer among men in the United States. The metastatic and advanced PrCa develops drug resistance to current regimens which accounts for the poor management. microRNAs (miRNAs) have been well-documented for their diagnostic, prognostic, and therapeutic roles in various human cancers. Recent literature confirmed that microRNA-205 (miR-205) has been established as one of the tumor suppressors in PrCa. miR-205 regulates number of cellular functions, such as proliferation, invasion, migration/metastasis, and apoptosis. It is also evident that miR-205 can serve as a key biomarker in diagnostic, prognostic, and therapy of PrCa. Therefore, in this review, we will provide an overview of tumor suppressive role of miR-205 in PrCa. This work also outlines miR-205's specific role in targeted mechanisms for chemosensitization and radiosensitization in PrCa. A facile approach of delivery paths for successful clinical translation is documented. Together, all these studies provide a novel insight of miR-205 as an adjuvant agent for reducing the widening gaps in clinical outcome of PrCa patients.

A Proteomic Approach for the Quantification of Posttranslational Protein Lysine Acetylation in Candida albicans.

Candida albicans is a normal component of the human microflora that colonizes mucosal/epithelial surfaces and the gastrointestinal tract as a commensal organism. However, in an immunocompromised host, it can cause life-threatening infections of high mortality and morbidity. Virulence as well as antifungal drug resistance of C. albicans is often regulated by posttranslational modifications (PTM) of proteins via lysine acetylation by lysine acetyltransferases. Here, we report an experimental approach using tandem mass tag (TMT) labeling for the detection and quantification of lysine acetylation of histone and nonhistone proteins in C. albicans.

Transcriptomics and Phenotyping Define Genetic Signatures Associated with Echinocandin Resistance in Candida auris.

Candida auris emerged as a human fungal pathogen only during the past decade. Remarkably, C. auris displays high degrees of genomic diversity and phenotypic plasticity, with four major clades causing hospital outbreaks with high mortality and morbidity rates. C. auris can show clinical resistance to all classes of antifungal drugs, including echinocandins that are usually recommended as first-line therapies for invasive candidiasis. Here, we exploit transcriptomics coupled with phenotypic profiling to characterize a set of clinical C. auris isolates displaying pronounced echinocandin resistance (ECN-R). A hot spot mutation in the echinocandin FKS1 target gene is present in all resistant isolates. Moreover, ECN-R strains share a core signature set of 362 genes differentially expressed in ECN-R isolates. Among others, mitochondrial gene expression and genes affecting cell wall function appear to be the most prominent, with the latter correlating well with enhanced adhesive traits, increased cell wall mannan content, and altered sensitivity to cell wall stress of ECN-R isolates. Moreover, ECN-R phenotypic signatures were also linked to pathogen recognition and interaction with immune cells. Hence, transcriptomics paired with phenotyping is a suitable tool to predict resistance and fitness traits as well as treatment outcomes in pathogen populations with complex phenotypic diversity. IMPORTANCE The surge in antimicrobial drug resistance in some bacterial and fungal pathogens constitutes a significant challenge to health care facilities. The emerging human fungal pathogen Candida auris has been particularly concerning, as isolates can display pan-antifungal resistance traits against all drugs, including echinocandins. However, the mechanisms underlying this phenotypic diversity remain poorly understood. We identify transcriptomic signatures in C. auris isolates resistant to otherwise fungicidal echinocandins. We identify a set of differentially expressed genes shared by resistant strains compared to unrelated susceptible isolates. Moreover, phenotyping demonstrates that resistant strains show distinct behaviors, with implications for host-pathogen interactions. Hence, this work provides a solid basis to identify the mechanistic links between antifungal multidrug resistance and fitness costs that affect the interaction of C. auris with host immune defenses.

Inositol Phosphoryl Transferase, Ipt1, Is a Critical Determinant of Azole Resistance and Virulence Phenotypes in Candida glabrata.

In this study, we have specifically blocked a key step of sphingolipid (SL) biosynthesis in Candida glabrata by disruption of the orthologs of ScIpt1 and ScSkn1. Based on their close homology with S. cerevisiae counterparts, the proteins are predicted to catalyze the addition of a phosphorylinositol group onto mannosyl inositolphosphoryl ceramide (MIPC) to form mannosyl diinositolphosphoryl ceramide (M(IP)2C), which accounts for the majority of complex SL structures in S. cerevisiae membranes. High throughput lipidome analysis confirmed the accumulation of MIPC structures in ΔCgipt1 and ΔCgskn1 cells, albeit to lesser extent in the latter. Noticeably, ΔCgipt1 cells showed an increased susceptibility to azoles; however, ΔCgskn1 cells showed no significant changes in the drug susceptibility profiles. Interestingly, the azole susceptible phenotype of ΔCgipt1 cells seems to be independent of the ergosterol content. ΔCgipt1 cells displayed altered lipid homeostasis, increased membrane fluidity as well as high diffusion of radiolabeled fluconazole (3H-FLC), which could together influence the azole susceptibility of C. glabrata. Furthermore, in vivo experiments also confirmed compromised virulence of the ΔCgipt1 strain. Contrarily, specific functions of CgSkn1 remain unclear.

Prevalence of Early Childhood Caries among the 3-5-year-old Children in Jeddah, Saudi Arabia.

Introduction: Dental caries is a significant dental public health issue and it is the world's most common oral health condition among children. In the Kingdom, the prevalence and severity of early childhood caries has been rising. Aim: The aim of the study is to establish the prevalence of early childhood caries among children aged 3-5 years in Jeddah as well as the associated risk factor of visiting a dentist. Methodology: The research is based on a cross-sectional observational design. Children from both private and public schools were randomly selected from schools in all of Jeddah's regions until a sufficient sample size was attained. For the diagnosis of early childhood caries, the American Academy of Pediatric Dentistry criteria were used. Results: In Jeddah, the prevalence of early childhood caries is 57% among children aged 3-5 years. Conclusion: Caries in young children is a public health issue. There should be an increased emphasis to the parents that the child should visit the dentist by 12 months of age as recommended by many professional organizations. Regular dental appointments would then help to lessen the caries burden on children at an early age. The Four A's treatment regimen is recommended to aid in the prevention and early detection of early childhood caries. How to cite this article: Vanka S, Vanka A, Wali O, et al. Prevalence of Early Childhood Caries among the 3-5-year-old Children in Jeddah, Saudi Arabia. Int J Clin Pediatr Dent 2022;15(S-2):S197-S200.

Comparative Transcriptomics Reveal Possible Mechanisms of Amphotericin B Resistance in Candida auris.

Candida auris is an emerging multidrug-resistant human fungal pathogen often refractory to treatment by all classes of antifungal drugs. Amphotericin B (AmB) is a fungicidal drug that, despite its toxic side effects, remains a drug of choice for the treatment of drug-resistant fungal infections, including those caused by C. auris. However, the molecular mechanisms underlying AmB resistance are poorly understood. In this study, we present data that suggests membrane lipid alterations and chromatin modifications are critical processes that may contribute to or cause adaptive AmB resistance in clinical C. auris isolates. To determine the plausible cause of increased AmB resistance, we performed RNA-seq of AmB-resistant and sensitive C. auris isolates. Remarkably, AmB-resistant strains show a pronounced enrichment of genes involved in lipid and ergosterol biosynthesis, adhesion, drug transport as well as chromatin remodeling. The transcriptomics data confirm increased adhesion and reduced lipid membrane permeability of AmB-resistant strains compared to the sensitive isolates. The AmB-resistant strains also display hyper-resistance to cell wall perturbing agents, including Congo red, calcofluor white and caffeine. Additionally, we noticed an increased phosphorylation of Mkc1 cell integrity MAP kinase upon AmB treatment. Collectively, these data identify differences in the transcriptional landscapes of AmB-resistant versus AmB-sensitive isolates and provide a framework for the mechanistic understanding of AmB resistance in C. auris.

Tumor tissue-specific bacterial biomarker panel for colorectal cancer: Bacteroides massiliensis, Alistipes species, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, Corynebacterium appendicis.

Human microbiome studies have shown diversity to exist among different ethnic populations. However, studies pertaining to the microbial composition of CRC among the Indian population have not been well explored. We aimed to decipher the microbial signature in tumor tissues from North Indian CRC patients. Next-generation sequencing of tumor and adjacent tissue-derived bacterial 16S rRNA V3-V4 hypervariable regions was performed to investigate the abundance of specific microbes. The expression profile analysis deciphered a decreased diversity among the tumor-associated microbial communities. At the phyla level, Proteobacteria was differentially expressed in CRC tissues than adjacent normal. Further, DeSeq2 normalization identified 4 out of 79 distinct species (p < 0.005) only in CRC, Bacteroides massiliensis, Alistipes onderdonkii, Bifidobacterium pseudocatenulatum, and Corynebacterium appendicis. Thus, the findings suggest that microbial signatures can be used as putative biomarkers in diagnosis, prognosis and treatment management of CRC.

In Situ Nanoparticle Self-Assembly for Combination Delivery of Therapeutics to Non-Small Cell Lung Cancer.

Chemotherapy often experiences several challenges including severe systemic toxicity and adverse effects. The combination chemotherapy arose as an effective clinical practice aimed at reducing doses of drugs to achieve synergistic actions with low toxicity. Our recent efforts demonstrated a synergistic therapeutic benefit of gambogic acid (GA) and gemcitabine (Gem) against lung cancer. However, simultaneous delivery of these two drugs at the tumor site is highly challenging. Therefore, the development of an injectable formulation that can effectively deliver both hydrophobic (GA) and hydrophilic (Gem) drugs in one formulation is a clinically unmet need. Herein, this study reports an in situ human serum albumin (HSA)- and tannic acid (TA)-mediated complexed GA and Gem nanoparticles (G-G@HTA NPs). G-G@HTA NP formation was confirmed by the particle size, Fourier transform infrared spectroscopy, and 1H NMR spectroscopy. The superior therapeutic activity of G-G@HTA NPs was demonstrated by multiple in vitro functional assays. Additionally, G-G@HTA NPs revealed an obvious and precise targeting of tumors in vivo. The promoted and more synergistic anti-tumor efficacy of G-G@HTA NPs was attained than that of combined treatments and single drug treatments. These events have resulted in no apparent systemic and organ toxicities. Together, this study suggests that in situ HSA-TA-based combinatorial treatment strategy is a suitable approach for application in lung cancer treatment.

HigB1 Toxin in Mycobacterium tuberculosis Is Upregulated During Stress and Required to Establish Infection in Guinea Pigs.

The extraordinary expansion of Toxin Antitoxin (TA) modules in the genome of Mycobacterium tuberculosis has received significant attention over the last few decades. The cumulative evidence suggests that TA systems are activated in response to stress conditions and are essential for M. tuberculosis pathogenesis. In M. tuberculosis, Rv1955-Rv1956-Rv1957 constitutes the only tripartite TAC (Toxin Antitoxin Chaperone) module. In this locus, Rv1955 (HigB1) encodes for the toxin and Rv1956 (HigA1) encodes for antitoxin. Rv1957 encodes for a SecB-like chaperone that regulates HigBA1 toxin antitoxin system by preventing HigA1 degradation. Here, we have investigated the physiological role of HigB1 toxin in stress adaptation and pathogenesis of Mycobacterium tuberculosis. qPCR studies revealed that higBA1 is upregulated in nutrient limiting conditions and upon exposure to levofloxacin. We also show that the promoter activity of higBA1 locus in M. tuberculosis is (p)ppGpp dependent. We observed that HigB1 locus is non-essential for M. tuberculosis growth under different stress conditions in vitro. However, guinea pigs infected with higB1 deletion strain exhibited significantly reduced bacterial loads and pathological damage in comparison to the animals infected with the parental strain. Transcriptome analysis suggested that deletion of higB1 reduced the expression of genes involved in virulence, detoxification and adaptation. The present study describes the role of higB1 toxin in M. tuberculosis physiology and highlights the importance of higBA1 locus during infection in host tissues.

Bay Leaf Extract-Based Near-Infrared Fluorescent Probe for Tissue and Cellular Imaging.

The development of fluorescence dyes for near-infrared (NIR) fluorescence imaging has been a significant interest for deep tissue imaging. Among many imaging fluoroprobes, indocyanine green (ICG) and its analogues have been used in oncology and other medical applications. However, these imaging agents still experience poor imaging capabilities due to low tumor targetability, photostability, and sensitivity in the biological milieu. Thus, developing a biocompatible NIR imaging dye from natural resources holds the potential of facilitating cancer cell/tissue imaging. Chlorophyll (Chl) has been demonstrated to be a potential candidate for imaging purposes due to its natural NIR absorption qualities and its wide availability in plants and green vegetables. Therefore, it was our aim to assess the fluorescence characteristics of twelve dietary leaves as well as the fluorescence of their Chl extractions. Bay leaf extract, a high-fluorescence agent that showed the highest levels of fluorescence, was further evaluated for its tissue contrast and cellular imaging properties. Overall, this study confirms bay-leaf-associated dye as a NIR fluorescence imaging agent that may have important implications for cellular imaging and image-guided cancer surgery.

Comparative Study of Dental Health Status and Its Determinants among Children Attending Government and Private Schools in Kanpur City.

The purpose of this study was to evaluate the prevalence of dental caries and gingivitis and its relation to various determinants like dietary habits, habits related to oral health, and oral hygiene practice among private and government school children of age 6-12 years in Kanpur City. A total of 1,550 children (775 from government school and 775 from private school) were selected. Overall, 60% children presented with caries. Prevalence of caries was significantly more associated with government school children (63.1%) compared with private school children (56.9%). The mean deft scores were high in government school children (1.08 ± 1.91) compared with private school children (0.93 ± 1.53). This was statistically significant (p < 0.05). The DMFT scores were also high among government school children (0.84 ± 1.25) compared with private school children (0.67 ± 1.19). This was statistically significant (p < 0.05). On the whole, out of 1,550 children only 17.8% children presented with gingivitis, in which majority had mild form of gingivitis when compared with moderate and severe forms. The prevalence of gingivitis was relatively high among government school children (55%) compared with private school children (45%). This was statistically significant (p < 0.05). Summing up, a conclusion could be drawn that the prevalence of both dental caries and gingivitis depends on the state of the oral hygiene habits and practices, correspondingly, due to schoolchildren's knowledge of individual oral hygiene and skills. HOW TO CITE THIS ARTICLE: Singh N, Gaur S, Kumar M, et al. Comparative Study of Dental Health Status and Its Determinants among Children Attending Government and Private Schools in Kanpur City. Int J Clin Pediatr Dent 2021;14(5):666-673.

Intron distribution and emerging role of alternative splicing in fungi.

Spliceosomal introns are noncoding sequences that are spliced from pre-mRNA. They are ubiquitous in eukaryotic genomes, although the average number of introns per gene varies considerably between different eukaryotic species. Fungi are diverse in terms of intron numbers ranging from 4% to 99% genes with introns. Alternative splicing is one of the most common modes of posttranscriptional regulation in eukaryotes, giving rise to multiple transcripts from a single pre-mRNA and is widespread in metazoans and drives extensive proteome diversity. Earlier, alternative splicing was considered to be rare in fungi, but recently, increasing numbers of studies have revealed that alternative splicing is also widespread in fungi and has been implicated in the regulation of fungal growth and development, protein localization and the improvement of survivability, likely underlying their unique capacity to adapt to changing environmental conditions. However, the role of alternative splicing in pathogenicity and development of drug resistance is only recently gaining attention. In this review, we describe the intronic landscape in fungi. We also present in detail the newly discovered functions of alternative splicing in various cellular processes and outline areas particularly in pathogenesis and clinical drug resistance for future studies that could lead to the development of much needed new therapeutics.