How addicted are newly admitted undergraduate medical students to smartphones?: a cross-sectional study from Chitwan medical college, Nepal.

BACKGROUND: Increasing smartphone use among adolescents in todays' world has made this handy device an indispensable electronic tool, however, it comes at a price of problematic overuse or addiction. We aim to investigate the prevalence of smartphone addiction among undergraduate medical students and explore its association with various demographic and personal factors. METHODS: A pool of 250 undergraduate students completed a survey composed of socio-demographics information, smartphone-use related variables and 10-point Smartphone Addiction Scale-Short Version in February 2019. RESULTS: Smartphone addiction among medical students was estimated at around 36.8% with higher percentage of male smartphone addicts. Phubbing was reported by 37.6% participants with more than 60% reporting overuse. Statistically significant association was observed between smartphone addiction and gender and overuse. Self-acknowledgement of addiction was found to be the biggest predictor of smartphone addiction. CONCLUSION: This study provides preliminary insights into smartphone use, smartphone addiction and various factors predicting smartphone addiction among early undergraduate medical students from Nepal, which should be extended in future studies. Education policymakers and educators need to develop some strategies encouraging student's smartphone utilization to enhance academic performance.

Rare actinobacteria: a potential source of bioactive polyketides and peptides.

Polyketides and peptides obtained from actinobacteria are important therapeutic compounds which include front line antibiotics and anticancer drugs. Many screening programs are directed towards isolation of bioactive compounds from these organisms but the chances of finding novel antimicrobial leads among common actinobacteria are fast dwindling. As a result, the focus has shifted to the members of less exploited genera of rare actinobacteria. Three isolates, MMS8, MMS16 and KCR3 found to be potent polyketide and peptide producers were identified by 16S rRNA gene sequencing and their sequences deposited in the GenBank under the accession numbers MG407702, MG372012 and MG430204 respectively. MMS8 identified as Micromonospora auratinigra, yielded one potent compound determined to be chloroanthraquinone with an minimum inhibitory concentration (MIC) of 8 µg/ml against Bacillus subtilis and an IC50 value of 10 µg/ml and 4 µg/ml against HeLa and IMR cell lines respectively. This is the first report of the production of chloroanthraquinone by M. auratinigra. MMS16, identified as a member of the family Micromonosporaceae, yielded a potent compound MMS16B analyzed to be a novel bafilomycin analogue. The MIC of the compound was found to be 7 µg/ml against B.subtilis and IC50 value against HeLa and IMR was observed to be 9 µg/ml and 14 µg/ml respectively. MMS16B was also found to exhibit anti-quorum sensing (AQS) activity at sublethal concentrations. KCR3 identified as Kocuria kristinae yielded a novel antimicrobial peptide with antibacterial, antifungal and AQS activity. To the best of our knowledge, no antimicrobial activity has ever been reported from K. kristinae.

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

PURPOSE: Breast and/or ovarian cancers are among the most common cancers in women across the world. In the Indian population, the healthcare burden of breast and/or ovarian cancers has been steadily rising, thus stressing the need for early detection, surveillance, and disease management measures. However, the burden attributable to inherited mutations is not well characterized. METHODS: We sequenced 1010 unrelated patients and families from across India with an indication of breast and/or ovarian cancers, using the TruSight Cancer panel which includes 14 genes, strongly associated with risk of hereditary breast and/or ovarian cancers. Genetic variations were identified using the StrandNGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect mutations in 304 (30.1%) cases, of which, 56 mutations were novel. A majority (84.9%) of the mutations were detected in the BRCA1/2 genes as compared to non-BRCA genes (15.1%). When the cases were stratified on the basis of age at diagnosis and family history of cancer, the high rate of 75% of detection of hereditary variants was observed in patients whose age at diagnosis was below 40 years and had first-degree family member(s) affected by breast and/or ovarian cancers. Our findings indicate that in the Indian population, there is a high prevalence of mutations in the high-risk breast cancer genes: BRCA1, BRCA2, TP53, and PALB2. CONCLUSION: In India, socioeconomic inequality limiting access to treatment is a major factor towards increased cancer burden; therefore, incorporation of a cost-effective and comprehensive multi-gene test will be helpful in ensuring widespread implementation of genetic screening in the clinical practice for hereditary breast and/or ovarian cancers.

Detection of high frequency of mutations in a breast and/or ovarian cancer cohort: implications of embracing a multi-gene panel in molecular diagnosis in India.

Breast and/or ovarian cancer (BOC) are among the most frequently diagnosed forms of hereditary cancers and leading cause of death in India. This emphasizes on the need for a cost-effective method for early detection of these cancers. We sequenced 141 unrelated patients and families with BOC using the TruSight Cancer panel, which includes 13 genes strongly associated with risk of inherited BOC. Multi-gene sequencing was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. We were able to detect pathogenic mutations in 51 (36.2%) cases, out of which 19 were novel mutations. When we considered familial breast cancer cases only, the detection rate increased to 52%. When cases were stratified based on age of diagnosis into three categories, ⩽40 years, 40-50 years and >50 years, the detection rates were higher in the first two categories (44.4% and 53.4%, respectively) as compared with the third category, in which it was 26.9%. Our study suggests that next-generation sequencing-based multi-gene panels increase the sensitivity of mutation detection and help in identifying patients with a high risk of developing cancer as compared with sequential tests of individual genes.

Next-generation sequencing-based method shows increased mutation detection sensitivity in an Indian retinoblastoma cohort.

PURPOSE: Retinoblastoma (Rb) is the most common primary intraocular cancer of childhood and one of the major causes of blindness in children. India has the highest number of patients with Rb in the world. Mutations in the RB1 gene are the primary cause of Rb, and heterogeneous mutations are distributed throughout the entire length of the gene. Therefore, genetic testing requires screening of the entire gene, which by conventional sequencing is time consuming and expensive. METHODS: In this study, we screened the RB1 gene in the DNA isolated from blood or saliva samples of 50 unrelated patients with Rb using the TruSight Cancer panel. Next-generation sequencing (NGS) was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. RESULTS: We were able to detect germline pathogenic mutations in 66% (33/50) of the cases, 12 of which were novel. We were able to detect all types of mutations, including missense, nonsense, splice site, indel, and structural variants. When we considered bilateral Rb cases only, the mutation detection rate increased to 100% (22/22). In unilateral Rb cases, the mutation detection rate was 30% (6/20). CONCLUSIONS: Our study suggests that NGS-based approaches increase the sensitivity of mutation detection in the RB1 gene, making it fast and cost-effective compared to the conventional tests performed in a reflex-testing mode.

Correction: Visible-light acridinium-based organophotoredox catalysis in late-stage synthetic applications.

[This corrects the article DOI: 10.1039/D3RA01364B.].

From Theory to Practice: Implementing Next-Generation Sequencing and Public Health Genomics in Healthcare Systems.

If Europe's health systems make a conscious decision to increase their utilization of technology and techniques that can enhance prevention and expedite early-stage diagnosis, they can effectively address the growing challenges of disease. By embracing these advancements, these health systems can significantly improve their response to emerging health issues.However, at present the effective integration and exploitation of these opportunities remains hesitant and suboptimal, and health and health services underperform accordingly, with patients suffering from the continuing variations in diagnosis and access to innovation. This paper presents a comprehensive study that examines the current state of various influential disciplines and factors in European countries. It specifically focuses on the adoption of Next Generation Screening technologies and the development stage of Public Health Genomics. The assessment of these areas is presented in the context of a rapidly changing policy environment, which provides an opportunity for a fundamental reconsideration of how and where new tools can be integrated into healthcare systems and routine practices. Top of Form.

Tackling the implementation gap for the uptake of NGS and advanced molecular diagnostics into healthcare systems.

Next-generation sequencing (NGS) and liquid biopsy (LB) showed positive results in the fight against different cancer types. This paper aims to assess the uptake of advanced molecular diagnostics/NGS for quick and efficient genetic profiles of tumour cells. For that purpose, the European Alliance for Personalised Medicine conducted a series of expert interviews to ascertain the current status across member states. One stakeholder meeting was additionally conducted to prioritize relevant factors by stakeholders. Seven common pillars were identified, and twenty-five measures were defined based on these pillars. Results showed that a multi-faceted approach is necessary for successful NGS implementation and that regional differences may be influenced by healthcare policies, resources, and infrastructure. It is important to consider different correlations when interpreting the results and to use them as a starting point for further discussion.

Demographic Analysis of Cancer Research Priorities and Treatment Correlations.

Understanding the diversity in cancer research priorities and the correlations among different treatment modalities is essential to address the evolving landscape of oncology. This study, conducted in collaboration with the European Cancer Patient Coalition (ECPC) and Childhood Cancer International-Europe (CCI-E) as part of the "UNCAN.eu" initiative, analyzed data from a comprehensive survey to explore the complex interplay of demographics, time since cancer diagnosis, and types of treatments received. Demographic analysis revealed intriguing trends, highlighting the importance of tailoring cancer research efforts to specific age groups and genders. Individuals aged 45-69 exhibited highly aligned research priorities, emphasizing the need to address the unique concerns of middle-aged and older populations. In contrast, patients over 70 years demonstrated a divergence in research priorities, underscoring the importance of recognising the distinct needs of older individuals in cancer research. The analysis of correlations among different types of cancer treatments underscored the multidisciplinary approach to cancer care, with surgery, radiotherapy, chemotherapy, precision therapy, and biological therapies playing integral roles. These findings support the need for personalized and combined treatment strategies to achieve optimal outcomes. In conclusion, this study provides valuable insights into the complexity of cancer research priorities and treatment correlations in a European context. It emphasizes the importance of a multifaceted, patient-centred approach to cancer research and treatment, highlighting the need for ongoing support, adaptation, and collaboration to address the ever-changing landscape of oncology.

Aligning Cancer Research Priorities in Europe with Recommendations for Conquering Cancer: A Comprehensive Analysis.

Improvements in cancer care require a new degree of collaboration beyond the purely medical sphere, extending deeply into the world of other stakeholders-preeminently patients but also the other stakeholders in the hardware and software of care. Cancer remains a global health challenge, necessitating collaborative efforts to understand, prevent, and treat this complex disease. To achieve this goal, a comprehensive analysis was conducted, aligning the prioritization of cancer research measures in 13 European countries with 13 key recommendations for conquering cancer in the region. The study utilized a survey involving both patients and citizens, alongside data from IQVIA, a global healthcare data provider, to assess the availability and access to single-biomarker tests in multiple European countries. The results revealed a focused approach toward understanding, preventing, and treating cancer, with each country emphasizing specific research measures tailored to its strengths and healthcare objectives. This analysis highlights the intricate relationship between research priorities, access to biomarker tests, and financial support. Timely access to tests and increased availability positively influence research areas such as cancer prevention, early detection, ageing, and data utilization. The alignment of these country-specific measures with 13 recommendations for conquering cancer in Europe underscores the importance of tailored strategies for understanding, preventing, and treating cancer.

Visible-light acridinium-based organophotoredox catalysis in late-stage synthetic applications.

The field of photoredox catalysis has been transformed by the use of organic photocatalysts, which give access to re-activities that were previously only possible with transition-metal photocatalysts. Recent advancements in the use of an acridinium photocatalyst in organic synthesis are covered in this review. Both the late-stage functionalization of biorelevant molecules and the activation of inert chemical bonds are explored, with an emphasis on their mechanistic features.

Trios Lidisi Veneer, Transforming Smiles Using an Intraoral Scanner - A Case Report.

INTRODUCTION: The need to perform restorations with a natural appearance is one of the most challenging aspects of dentistry, and reproducing the colour of natural teeth in restorations is a clinical challenge due to the complex optical characteristics of dentition. Various procedures have been advocated in the literature to correct dental anomalies, particularly in the aesthetic region, such as tooth discoloration due to fluorosis or dentition spacing due to changes in tooth shape, such as peg laterals. CLINICAL APPLICATIONS: Veneer are one of the most commonly used treatment modalities in such cases. As the use of ceramics necessitates the use of more opaque restorative materials or different thickness, obtaining adequate results in terms of the final colour of the restoration becomes increasingly difficult. The purpose of this study is to present a clinical case of smile rehabilitation in the anterior region with facets made of lithium disilicate, with the goal of achieving colour uniformity and demonstrating the benefits and achieving smile aesthetics. TAKEAWAY LESSONS: Technological advancement such as intraoral scanner for impression making have significant improved the success of prosthesis. This case report presents conservative and aesthetic procedure in the management of closing the space in maxillary anterior region using lithium disilicate laminate veneers with trios software.

Oncocytoma of the parotid gland: A rare benign tumour.

Oncocytomas are one of the infrequent neoplasms seen in the oral cavity accounting for less than 2% of all neoplasms in the oral cavity with less than 1% chance of malignant transformation. They affect the major salivary glands and have a female predilection. The cognisance of the unique clinical and histopathological features is very important to conclude a confirmatory diagnosis. This paper reviews a case of oncocytoma presented in our department and also elucidates the diagnostic criteria for the same.

Evaluation of salivary oxidative stress in oral lichen planus using malonaldehyde.

Background: Oral lichen planus is a chronic, mucocutaneous, inflammatory disease, with an unknown etiology. Reactive oxygen species and oxidative damage to the tissues might be the cause. Malonaldehyde (MDA), a low molecular weight end product of lipid peroxidation reaction is a suitable biomarker of endogenous DNA damage. monitoring the oxidant-antioxidant status of saliva may serve as an efficient marker of disease development in oral lichen planus patients. Aim and Objectives: To evaluate salivary oxidative stress in oral lichen planus subject using MDA and compare it with control subjects. Furthermore, to compare MDA levels in erosive and hypertrophic lichen planus. Materials and Methods: The current study is case-control study. Unstimulated salivary samples in the morning hours were taken from oral lichen planus subjects (n = 25) and controls subjects without any oral disease (n = 25). The saliva was centrifuged at 900 g for 10 min at a temperature of 4°C. Then, the entire filtrate was transferred to Eppendorf test tubes and frozen at-80°C until analysis. Salivary MDA was done through thiobarbituric acid reactive substance assay as per the protocol laid down by the manufacturer (Sigma Aldrich Lipid Peroxidation Assay Kit). Results: The data were expressed as the mean ± standard deviation and the statistical analysis was done using Student's t-test using SPSS version 21 IBM software. The salivary level of MDA was significantly higher than that of controls (P < 0.05). Conclusion: The higher level of MDA in patients with oral lichen planus suggests that free radicals and the resulting oxidative damage may be important in the pathogenesis of oral lichen planus lesions.

Mitofusin-2 Negatively Regulates Melanogenesis by Modulating Mitochondrial ROS Generation.

Inter-organellar communication is emerging as one of the most crucial regulators of cellular physiology. One of the key regulators of inter-organellar communication is Mitofusin-2 (MFN2). MFN2 is also involved in mediating mitochondrial fusion-fission dynamics. Further, it facilitates mitochondrial crosstalk with the endoplasmic reticulum, lysosomes and melanosomes, which are lysosome-related organelles specialized in melanin synthesis within melanocytes. However, the role of MFN2 in regulating melanocyte-specific cellular function, i.e., melanogenesis, remains poorly understood. Here, using a B16 mouse melanoma cell line and primary human melanocytes, we report that MFN2 negatively regulates melanogenesis. Both the transient and stable knockdown of MFN2 leads to enhanced melanogenesis, which is associated with an increase in the number of mature (stage III and IV) melanosomes and the augmented expression of key melanogenic enzymes. Further, the ectopic expression of MFN2 in MFN2-silenced cells leads to the complete rescue of the phenotype at the cellular and molecular levels. Mechanistically, MFN2-silencing elevates mitochondrial reactive-oxygen-species (ROS) levels which in turn increases melanogenesis. ROS quenching with the antioxidant N-acetyl cysteine (NAC) reverses the MFN2-knockdown-mediated increase in melanogenesis. Moreover, MFN2 expression is significantly lower in the darkly pigmented primary human melanocytes in comparison to lightly pigmented melanocytes, highlighting a potential contribution of lower MFN2 levels to higher physiological pigmentation. Taken together, our work establishes MFN2 as a novel negative regulator of melanogenesis.

Function, structure, and evolution of the RubisCO-like proteins and their RubisCO homologs.

About 30 years have now passed since it was discovered that microbes synthesize RubisCO molecules that differ from the typical plant paradigm. RubisCOs of forms I, II, and III catalyze CO(2) fixation reactions, albeit for potentially different physiological purposes, while the RubisCO-like protein (RLP) (form IV RubisCO) has evolved, thus far at least, to catalyze reactions that are important for sulfur metabolism. RubisCO is the major global CO(2) fixation catalyst, and RLP is a somewhat related protein, exemplified by the fact that some of the latter proteins, along with RubisCO, catalyze similar enolization reactions as a part of their respective catalytic mechanisms. RLP in some organisms catalyzes a key reaction of a methionine salvage pathway, while in green sulfur bacteria, RLP plays a role in oxidative thiosulfate metabolism. In many organisms, the function of RLP is unknown. Indeed, there now appear to be at least six different clades of RLP molecules found in nature. Consideration of the many RubisCO (forms I, II, and III) and RLP (form IV) sequences in the database has subsequently led to a coherent picture of how these proteins may have evolved, with a form III RubisCO arising from the Methanomicrobia as the most likely ultimate source of all RubisCO and RLP lineages. In addition, structure-function analyses of RLP and RubisCO have provided information as to how the active sites of these proteins have evolved for their specific functions.

Molecular machinery regulating mitochondrial calcium levels: The nuts and bolts of mitochondrial calcium dynamics.

Mitochondria play vital role in regulating the cellular energetics and metabolism. Further, it is a signaling hub for cell survival and apoptotic pathways. One of the key determinants that calibrate both cellular energetics and survival functions is mitochondrial calcium (Ca2+) dynamics. Mitochondrial Ca2+ regulates three Ca2+-sensitive dehydrogenase enzymes involved in tricarboxylic acid cycle (TCA) cycle thereby directly controlling ATP synthesis. On the other hand, excessive Ca2+ concentration within the mitochondrial matrix elevates mitochondrial reactive oxygen species (mROS) levels and causes mitochondrial membrane depolarization. This leads to opening of the mitochondrial permeability transition pore (mPTP) and release of cytochrome c into cytosol eventually triggering apoptosis. Therefore, it is critical for cell to maintain mitochondrial Ca2+ concentration. Since cells can neither synthesize nor metabolize Ca2+, it is the dynamic interplay of Ca2+ handling proteins involved in mitochondrial Ca2+ influx and efflux that take the center stage. In this review we would discuss the key molecular machinery regulating mitochondrial Ca2+ concentration. We would focus on the channel complex involved in bringing Ca2+ into mitochondrial matrix i.e. Mitochondrial Ca2+ Uniporter (MCU) and its key regulators Mitochondrial Ca2+ Uptake proteins (MICU1, 2 and 3), MCU regulatory subunit b (MCUb), Essential MCU Regulator (EMRE) and Mitochondrial Ca2+ Uniporter Regulator 1 (MCUR1). Further, we would deliberate on major mitochondrial Ca2+ efflux proteins i.e. Mitochondrial Na+/Ca2+/Li+ exchanger (NCLX) and Leucine zipper EF hand-containing transmembrane1 (Letm1). Moreover, we would highlight the physiological functions of these proteins and discuss their relevance in human pathophysiology. Finally, we would highlight key outstanding questions in the field.

Expression of ß-catenin in oral leukoplakia and oral submucous fibrosis: An immunohistochemical study.

BACKGROUND: Oral potentially malignant disorders have increased propensity to turn malignant than its apparently normal counterparts. Histopathological examination, although gold standard, needs adjunct technique to give accurate diagnosis. Immunohistochemistry has proved to be a promising adjunct to aid in the diagnosis so far. The quest for a definitive marker is still on. Beta-catenin (ß-catenin), a structural protein has been evaluated to identify its likely role in malignant transformation of potentially malignant lesions and possibly designate it as one of the identifiable signature molecules in the transformation. AIM AND OBJECTIVE: To evaluate and estimate the expression of ß-catenin in different grades of dysplasia, oral submucous fibrosis (OSMF) and normal mucosa and compare the same. METHODOLOGY: A total number of 40 cases including different grades of dysplasia, OSMF and normal mucosa were immunohistochemically stained, location and intensity of its expression were evaluated for ß-catenin. The results were statistically analyzed using the one-way analysis of variance and Chi-square test. RESULTS: The expression of ß-Catenin in the cytoplasm as well as in the nucleus increased from mild-to-moderate dysplasia to OSMF and to severe epithelial dysplasia in an increasing order. The expression is seen to translocate from membranous to cytoplasm to nucleus indicating a proliferative potential in these group of lesions. CONCLUSION: ß-catenin is a promising marker which indicates the malignant transformation potential in the higher grades of dysplasia and OSMF.

Diagnostic efficacy of neutrophil to lymphocyte ratio (NLR) in oral potentially malignant disorders and oral cancer.

BACKGROUND AND AIMS: Inflammation is considered to be the seventh hallmark of cancer and plays a pivotal role in all stages of tumor development. Systemic inflammatory responses in particular neutrophil to lymphocyte ratio (NLR) have garnered immense attention of current researchers and its role is well proven in various solid malignancies. Its prognostic role in oral cancer have been extensively studied. However, its diagnostic role is yet to be explored. The current study aims to investigate diagnostic utility of NLR in oral potentially malignant disorders and oral cancer, when compared to normal subjects. METHODS: A total of 150 subjects were involved in the study, a total of 2.5 ml of blood was drawn from the median cubital vein of the patient in an EDTA vial and hematological parameters were assessed using Erba-Transasia B7256 Autoanalyzer and reassessed manually by two experts. STATISTICAL ANALYSIS: The NLR values were recorded and tabulated as Mean ± S.D. and comparisons were analyzed using Kruskal Wallis and Mann Whitney post hoc U test. ROC curve analysis was performed to estimate cut-off values. RESULTS: The NLR values when compared between the 3 groups were statistically significant (P < 0.001). The cut off value between disease and normal subject was 2.33, while the cut-off value between potentially malignant and malignant condition is 3.20. CONCLUSION: NLR can be a valuable diagnostic adjunct in oral cancer and potentially malignant disorders of oral cavity.

Roles of RubisCO and the RubisCO-like protein in 5-methylthioadenosine metabolism in the Nonsulfur purple bacterium Rhodospirillum rubrum.

Ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) catalyzes the assimilation of atmospheric CO(2) into organic matter and is thus central to the existence of life on earth. The beginning of the 2000s was marked by the discovery of a new family of proteins, the RubisCO-like proteins (RLPs), which are structural homologs of RubisCO. RLPs are unable to catalyze CO(2) fixation. The RLPs from Chlorobaculum tepidum, Bacillus subtilis, Geobacillus kaustophilus, and Microcystis aeruginosa have been shown to participate in sulfur metabolism. Whereas the precise function of C. tepidum RLP is unknown, the B. subtilis, G. kaustophilus, and M. aeruginosa RLPs function as tautomerases/enolases in a methionine salvage pathway (MSP). Here, we show that the form II RubisCO enzyme from the nonsulfur purple bacterium Rhodospirillum rubrum is also able to function as an enolase in vivo as part of an MSP, but only under anaerobic conditions. However, unlike B. subtilis RLP, R. rubrum RLP does not catalyze the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate. Instead, under aerobic growth conditions, R. rubrum RLP employs another intermediate of the MSP, 5-methylthioribulose-1-phosphate, as a substrate, resulting in the formation of different products. To further determine the interrelationship between RubisCOs and RLPs (and the potential integration of cellular carbon and sulfur metabolism), the functional roles of both RubisCO and RLP have been examined in vivo via the use of specific knockout strains and complementation studies of R. rubrum. The presence of functional, yet separate, MSPs in R. rubrum under both aerobic (chemoheterotrophic) and anaerobic (photoheterotrophic) growth conditions has not been observed previously in any organism. Moreover, the aerobic and anaerobic sulfur salvage pathways appear to be differentially controlled, with novel and previously undescribed steps apparent for sulfur salvage in this organism.