Detection and characterization of autoreactive memory stem T-cells in children with acute immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by an isolated decrease in platelets below 100 × 109/l after the exclusion of other conditions associated with thrombocytopenia. We investigated the role of different memory T-cell subsets, including T stem cell memory (TSCM), in children diagnosed with primary ITP and its association with therapeutic duration. This case-control study included 39 pediatric patients with acute ITP admitted to the Children's Hospital at Assiut University. Using a FACSCanto flow cytometer, CD8 + and CD4 + T-lymphocytes were gated. Five different subsets were characterized in each of these cells according to CD45RO and CD45RA expression. Afterward, gating was performed based on CCR7, CD95, and CD27. Examination of the CD8 + T cells subpopulation showed that Central memory T (TCM) and CD8+ Naïve T (TN) cells were significantly lower in ITP patients than in healthy children (p < 0.0001) and (p = 0.01), respectively. In addition, CD8 + TEMRA was significantly higher in ITP children than in controls (p = 0.001). CD4 + TCM cells were significantly lower in the ITP patient group (p = 0.04). However, CD4 + TEM was significantly higher in patients than controls (p = 0.04). Our research found that ITP patients had an imbalance in the ratio of CD4+ to CD8+ T cells in the peripheral blood and that TCM cells may be involved in the pathogenetic mechanism of ITP. TCMs could help in prediction of patients with higher risk of developing ITP.

Potential role of immunotherapy and targeted therapy in the treatment of cancer: A contemporary nursing practice.

Immunotherapy and targeted therapy have emerged as promising therapeutic options for cancer patients. Immunotherapies induce a host immune response that mediates long-lived tumor destruction, while targeted therapies suppress molecular mechanisms that are important for tumor maintenance and growth. In addition, cytotoxic agents and targeted therapies regulate immune responses, which increases the chances that these therapeutic approaches may be efficiently combined with immunotherapy to ameliorate clinical outcomes. Various studies have suggested that combinations of therapies that target different stages of anti-tumor immunity may be synergistic, which can lead to potent and more prolonged responses that can achieve long-lasting tumor destruction. Nurses associated with cancer patients should have a better understanding of the immunotherapies and targeted therapies, such as their efficacy profiles, mechanisms of action, as well as management and prophylaxis of adverse events. Indeed, this knowledge will be important in establishing care for cancer patients receiving immunotherapies and targeted therapies for cancer treatment. Moreover, nurses need a better understanding regarding targeted therapies and immunotherapies to ameliorate outcomes in patients receiving these therapies, as well as management and early detection of possible adverse effects, especially adverse events associated with checkpoint inhibitors and various other therapies that control T-cell activation causing autoimmune toxicity. Nurses practice in numerous settings, such as hospitals, home healthcare agencies, radiation therapy facilities, ambulatory care clinics, and community agencies. Therefore, as compared to other members of the healthcare team, nurses often have better opportunities to develop the essential rapport in providing effective nurse-led patient education, which is important for effective therapeutic outcomes and continuance of therapy. In this article, we have particularly focused on providing a detailed overview on targeted therapies and immunotherapies used in cancer treatment, management of their associated adverse events, and the impact as well as strategies of nurse-led patient education.

The Influence of Nurse-Led Interventions on Diseases Management in Patients with Diabetes Mellitus: A Narrative Review.

The global prevalence of people with diabetes mellitus (PWD) is rapidly increasing. Nurses can provide diabetes care for PWD in several areas. Interventions led by nurses can support PWD for effective management of diabetes, which can positively improve clinical outcomes. Nurse-led diabetes self-management education (DSME) is an effective strategy to manage diabetes mellitus (DM) since it improves self-care practice and knowledge regarding diabetes. PWD often need to stay in hospitals longer, which involves poorer patient satisfaction and clinical outcomes. Nurse-led clinics for DM management are a new strategy to possibly ameliorate the disease management. Diabetes specialist nurses can play an important role in improving diabetes care in inpatient settings. Various studies have revealed that nurses can independently provide care to PWD in collaboration with various other healthcare providers. Studies also demonstrated that the nurse-led education-receiving group showed a significantly reduced level of average glycosylated haemoglobin A1c level. Moreover, nurse-led interventions often result in significant improvements in diabetes knowledge, psychological outcomes, self-management behaviours, and physiological outcomes. The purpose of this literature review was to identify the impact of nurse-led interventions on diabetes management. Moreover, in this review, a number of nursing interventions and the nurses' roles as educators, motivators as well as caregivers in DM management have been extensively discussed. This article also summarises the outcomes that are measured to evaluate the impact of nursing interventions and the strategies to overcome the existing and emerging challenges for nurses in diabetes care.

Bridging autoimmunity and epigenetics: The influence of lncRNA MALAT1.

Autoimmune disorders represent a heterogeneous spectrum of conditions defined by an immune system's atypical reactivity against endogenous constituents. In the complex anatomy of autoimmune pathogenesis, lncRNAs have appeared as pivotal arbiters orchestrating the mechanisms of ailment initiation, immune cascades, and transcriptional modulation. One such lncRNA, MALAT1, has garnered attention for its potential association with the aetiology of several autoimmune diseases. MALAT1 has been shown to influence a wide spectrum of cellular processes, which include cell multiplication and specialization, as well as apoptosis and inflammation. In autoimmune diseases, MALAT1 exhibits both disease-specific and shared patterns of dysregulation, often correlating with disease severity. The molecular mechanisms underlying MALAT1's impact on autoimmune disorders include epigenetic modifications, alternative splicing, and modulation of gene expression networks. Additionally, MALAT1's intricate interactions with microRNAs, other lncRNAs, and protein-coding genes further underscore its role in immune regulation and autoimmune disease progression. Understanding the contribution of MALAT1 in autoimmune pathogenesis across different diseases could offer valuable insights into shared pathways, thereby clearing a path for the creation of innovative and enhanced therapeutic approaches to address these complex disorders. This review aims to elucidate the complex role of MALAT1 in autoimmune disorders, encompassing rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), type 1 diabetes, systemic lupus erythematosus, and psoriasis. Furthermore, it discusses the potential of MALAT1 as a diagnostic biomarker, therapeutic target, and prognostic indicator.

The emerging role of noncoding RNAs in the EGFR signaling pathway in lung cancer.

Noncoding ribonucleic acids (ncRNAs) have surfaced as essential orchestrators within the intricate system of neoplastic biology. Specifically, the epidermal growth factor receptor (EGFR) signalling cascade shows a central role in the etiological underpinnings of pulmonary carcinoma. Pulmonary malignancy persists as a preeminent contributor to worldwide mortality attributable to malignant neoplasms, with non-small cell lung carcinoma (NSCLC) emerging as the most predominant histopathological subcategory. EGFR is a key driver of NSCLC, and its dysregulation is frequently associated with tumorigenesis, metastasis, and resistance to therapy. Over the past decade, researchers have unveiled a complex network of ncRNAs, encompassing microRNAs, long noncoding RNAs, and circular RNAs, which intricately regulate EGFR signalling. MicroRNAs, as versatile post-transcriptional regulators, have been shown to target various components of the EGFR pathway, influencing cancer cell proliferation, migration, and apoptosis. Additionally, ncRNAs have emerged as critical modulators of EGFR signalling, with their potential to act as scaffolds, decoys, or guides for EGFR-related proteins. Circular RNAs, a relatively recent addition to the ncRNA family, have also been implicated in EGFR signalling regulation. The clinical implications of ncRNAs in EGFR-driven lung cancer are substantial. These molecules exhibit diagnostic potential as robust biomarkers for early cancer detection and personalized treatment. Furthermore, their predictive value extends to predicting disease progression and therapeutic outcomes. Targeting ncRNAs in the EGFR pathway represents a novel therapeutic approach with promising results in preclinical and early clinical studies. This review explores the increasing evidence supporting the significant role of ncRNAs in modulating EGFR signalling in lung cancer, shedding light on their potential diagnostic, prognostic, and therapeutic implications.

From inflammation to metastasis: The central role of miR-155 in modulating NF-κB in cancer.

Cancer is a multifaceted, complex disease characterized by unchecked cell growth, genetic mutations, and dysregulated signalling pathways. These factors eventually cause evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, which makes it difficult for targeted therapeutic interventions to be effective. MicroRNAs (miRNAs) are essential gene expression regulators linked to several biological processes, including cancer and inflammation. The NF-κB signalling pathway, a critical regulator of inflammatory reactions and oncogenesis, has identified miR-155 as a significant participant in its modulation. An intricate network of transcription factors known as the NF-κB pathway regulates the expression of genes related to inflammation, cell survival, and immunological responses. The NF-κB pathway's dysregulation contributes to many cancer types' development, progression, and therapeutic resistance. In numerous cancer models, the well-studied miRNA miR-155 has been identified as a crucial regulator of NF-κB signalling. The p65 subunit and regulatory molecules like IκB are among the primary targets that miR-155 directly targets to alter NF-κB activity. The molecular processes by which miR-155 affects the NF-κB pathway are discussed in this paper. It also emphasizes the miR-155's direct and indirect interactions with important NF-κB cascade elements to control the expression of NF-κB subunits. We also investigate how miR-155 affects NF-κB downstream effectors in cancer, including inflammatory cytokines and anti-apoptotic proteins.

Imbalance of Follicular Helper and Follicular Regulatory T Cells in Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Data regarding the imbalance in follicular helper T (Tfh) and follicular regulatory T (Tfr) cell responses in patients having chronic rhinosinusitis with nasal polyps (CRSwNP) is so far limited. Thus, we aimed to assess the changes in circulating Tfh and Tfr in CRSwNP patients. METHODS: This case-control study included 21 patients having CRSwNP and 20 age and sex-matched healthy blood donors as a control group. Lund-Mackay staging system was used for radiologic scoring of chronic rhinosinusitis. Two milliliters of peripheral blood samples were collected from all participants into EDTA-containing vacutainer tubes to assess the levels of Tfh and Tfr cells using flow cytometry. RESULTS: Patients having CRSwNP did not show significant differences in the percentages of CD4+ T cells and total CD4+CXCR5+ T cells from healthy controls. Meanwhile, levels of both activated circulating Tfh and Tfr showed a marked rise in patients than controls. In addition, a positive correlation was observed between the levels of both activated Tfh and Tfr cells. CONCLUSION: An imbalance in circulating Tfh/Tfr levels was detected in patients having CRSwNP. A significant rise in the levels of Tfh and Tfr was detected in patients proposing a possible role of this imbalance in disease pathogenesis.

Could the Crosstalk Between Myeloid-Derived-Suppressor Cells and Regulatory T Cells Have a Role in Beta-Thalassemia?

Background: Secondary iron overload, alloimmunization, and increased risk of infection are common complications in patients with transfusion-dependent thalassemia (TDT). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune response. This research aimed to study the interaction between Tregs and MDSCs in TDT patients and to evaluate the association of these cell types with disease severity. Methods: This case-control study included 26 patients with TDT and 23 healthy, age- and sex-matched controls. All patients were investigated for complete blood count (CBC), serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets. Results: A significant increase was observed in the frequencies of Tregs and MDSCs, particularly monocytic MDSCs (MO-MDSCs), in TDT patients compared with controls. The frequencies of these cells showed a direct association with ferritin level and total leukocyte count and an inverse association with hemoglobin level. Furthermore, a positive correlation was observed between Tregs and each of the total MDSCs and MO-MDSCs. Conclusions: Levels of Tregs and MDSCs increased in TDT and may probably have a role in suppressing the active immune systems of TDT patients.

Biodegradable Electrospun Scaffolds as an Emerging Tool for Skin Wound Regeneration: A Comprehensive Review.

Skin is designed to protect various tissues, and because it is the largest and first human bodily organ to sustain damage, it has an incredible ability to regenerate. On account of extreme injuries or extensive surface loss, the normal injury recuperating interaction might be inadequate or deficient, bringing about risky and disagreeable circumstances that request the utilization of fixed adjuvants and tissue substitutes. Due to their remarkable biocompatibility, biodegradability, and bioactive abilities, such as antibacterial, immunomodulatory, cell proliferative, and wound mending properties, biodegradable polymers, both synthetic and natural, are experiencing remarkable progress. Furthermore, the ability to convert these polymers into submicrometric filaments has further enhanced their potential (e.g., by means of electrospinning) to impersonate the stringy extracellular grid and permit neo-tissue creation, which is a basic component for delivering a mending milieu. Together with natural biomaterial, synthetic polymers are used to solve stability problems and make scaffolds that can dramatically improve wound healing. Biodegradable polymers, commonly referred to as biopolymers, are increasingly used in other industrial sectors to reduce the environmental impact of material and energy usage as they are fabricated using renewable biological sources. Electrospinning is one of the best ways to fabricate nanofibers and membranes that are very thin and one of the best ways to fabricate continuous nanomaterials with a wide range of biological, chemical, and physical properties. This review paper concludes with a summary of the electrospinning (applied electric field, needle-to-collector distance, and flow rate), solution (solvent, polymer concentration, viscosity, and solution conductivity), and environmental (humidity and temperature) factors that affect the production of nanofibers and the use of bio-based natural and synthetic electrospun scaffolds in wound healing.

Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease.

Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies.

Vitamin E TPGS-Based Nanomedicine, Nanotheranostics, and Targeted Drug Delivery: Past, Present, and Future.

It has been seventy years since a water-soluble version of vitamin E called tocophersolan (also known as TPGS) was produced; it was approved by USFDA in 1998 as an inactive ingredient. Drug formulation developers were initially intrigued by its surfactant qualities, and gradually it made its way into the toolkit of pharmaceutical drug delivery. Since then, four drugs with TPGS in their formulation have been approved for sale in the United States and Europe including ibuprofen, tipranavir, amprenavir, and tocophersolan. Improvement and implementation of novel diagnostic and therapeutic techniques for disease are goals of nanomedicine and the succeeding field of nanotheranostics. Specifically, imaging and treating tumors with nanohybrid theranostics shows promising potential. Docetaxel, paclitaxel, and doxorubicin are examples of poorly bioavailable therapeutic agents; hence, much effort is applied for developing TPGS-based nanomedicine, nanotheranostics, and targeted drug delivery systems to increase circulation time and promote the reticular endothelial escape of these drug delivery systems. TPGS has been used in a number of ways for improving drug solubility, bioavailability improvement, and prevention of drug efflux from the targeted cells, which makes it an excellent candidate for therapeutic delivery. Through the downregulation of P-gp expression and modulation of efflux pump activity, TPGS can also mitigate multidrug resistance (MDR). Novel materials such as TPGS-based copolymers are being studied for their potential use in various diseases. In recent clinical trials, TPGS has been utilized in a huge number of Phase I, II, and III studies. Additionally, numerous TPGS-based nanomedicine and nanotheranostic applications are reported in the literature which are in their preclinical stage. However, various randomized or human clinical trials have been underway for TPGS-based drug delivery systems for multiple diseases such as pneumonia, malaria, ocular disease, keratoconus, etc. In this review, we have emphasized in detail the review of the nanotheranostics and targeted drug delivery approaches premised on TPGS. In addition, we have covered various therapeutic systems involving TPGS and its analogs with special references to its patent and clinical trials.

One-pot green synthesis of silver nanoparticles using brittle star Ophiocoma scolopendrina: Assessing biological potentialities of antibacterial, antioxidant, anti-diabetic and catalytic degradation of organic dyes.

In the current study, aqueous extract of O. scolopendrina (OSE) was used to synthesize AgNPs in a simple and environmentally friendly manner. The biosynthesized OSE-AgNPs were also assessed for its catalytic, antibacterial, anti-diabetic, antioxidant and dye degradation properties. The techniques like UV-visible spectroscopic examinations, TEM, SEM, TGA, zeta potential and FT-IR were used in the characterization investigations. The bioproduction of OSE-AgNPs was preliminary confirmed by UV-visible spectroscopic based investigation followed by microscopic visualization. The synthesized OSE-AgNPs exhibited a reddish brown colour and nearly spherical forms with sizes between 5 and 50 nm quantified by TEM and SEM. The attendance of functional groups like -OH and -NH present in OSE caps on the AgNPs surface was confirmed by FTIR analysis. Interestingly, in the presence of OSE-AgNPs, the degradation of dyes (CV, 95% and EY, 96% in 15 min) were noticeably accelerated. Further, OSE-AgNPs demonstrated substantial antibacterial activity; robust antioxidant properties andnotable anti-diabetic activities. This is the first account on the biosynthetic process of AgNPs using the aqueous extract of O. scolopendrina.

Elucidating the promising role of traditional Chinese medicine in neuroprotection against oxidative stress encompassing Alzheimer's disease.

Medicinal plants are being used from time immemorial for their therapeutic benefits and have immense value in the therapy of neurodegenerative disorders. One of the most important neurological disorders is Alzheimer's disease (AD) which is a major contributor to dementia and is accompanied by abundant oxidative stress in the brain tissue. A critical pathway to target the increased oxidative stress is to administer agents with antioxidant potential. Despite currently available clinical treatments to treat AD such as cholinesterase inhibitors or NMDA antagonists which address only the symptoms and cannot hamper disease progression, no efficient available clinical treatment can break the vicious cycle of oxidative stress and neurodegeneration till date. The main objective of presenting this review is that traditional Chinese medicine (TCM) acts as a promising candidate in breaking this vicious cycle and improves the quality of life of the debilitating patients. The active constituents of various herbs in TCM including Angelica sinensis, Radix polygalae, Polygala tenuifolia, and members of the Lamiaceae family have acquired experience of managing oxidative stress as indicated in the review for more than a thousand years now, and the preclinical and clinical evidence of their therapeutic potential has been highlighted in the review. Most importantly, Chinese herbs provide a multiple-target approach rather than a single-target approach and thus can target multiple pathways involved in AD at once. The Chinese herbs can definitely untangle the issues in the current therapy regimen of AD.

Cow's Milk-related Symptom Score for cow's milk allergy assessment: a meta-analysis for test accuracy.

BACKGROUND: We aimed to assess the ability of Cow's Milk-related Symptom Score (CoMiss) in screening cow's milk protein allergy (CMPA) and assess validation of its sensitivity and specificity. METHODS: We searched the PubMed, WOS, Embase, and Ovid databases using broad terms and keywords for the concepts of the symptom-based score (CoMiss) and cow's milk allergy. We performed the meta-analyses using a meta-package of R software and Meta-DiSc software. RESULTS: Fourteen studies were included with a total of 1238 children. At cut-off value 12, CoMiss had a pooled sensitivity of 0.64 and a pooled specificity of 0.75. The PLR and NLR were 3.05 and 0.5, respectively. The AUC value of the sROC curve was 0.7866. CoMiss showed a significant difference in CMPA patients at baseline and after milk elimination for 2-4 weeks (MD, 7.18), as well as between the CMPA-positive group compared with the CMPA-negative group, however, the statistical significancy was obtained after leave study of Selbuz et al. out of the analysis (MD, 4.61). CONCLUSIONS: CoMiss may be a promising symptom score in the Awareness of the symptoms related to cow's milk allergy and a useful tool in monitoring the response to a cow's milk-free diet. IMPACT: Cow's milk protein allergy (CMPA) is the most frequent food allergy in children under the age of 3 years. Cow's Milk-related Symptom Score (CoMiss) is a clinical scoring system to assist primary healthcare providers in early detection of CMPA We performed a meta-analysis of CoMiss test accuracy. Our findings reflect that CoMiss may be a promising symptom score in CMPA awareness and a useful tool in monitoring the response to a cow's milk-free diet.

Incidence of diabetic ketoacidosis during COVID-19 pandemic: a meta-analysis of 124,597 children with diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. This study will not only shed light on such life-threatening complications but also be a step to increase the awareness of healthcare providers about such complications in the upcoming pandemic waves and increased dependence on telemedicine. Thus, we aimed to further investigate the increase of DKA in pediatrics. METHODS: PubMed, Web of Science, and Scopus were broadly searched for studies assessing the incidence of DKA in pediatrics during the COVID-19 pandemic. RESULTS: Our study included 24 papers with a total of 124,597 children with diabetes. A statistically significant increase occurred in the risk of DKA among newly diagnosed T1DM patients during the pandemic (RR 1.41; 95% CI 1.19, 1.67; p < 0.01; I2 = 86%), especially in the severe form of DKA (RR 1.66: 95% CI 1.3, 2.11) when compared to before. CONCLUSION: DKA in newly diagnosed children with T1DM has increased during the pandemic and presented with a severe form. This may reflect that COVID-19 may have contributed not only to the development but also the severity of DKA. IMPACT: Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus (T1DM) that has increased during the COVID-19 pandemic. Our study included 25 papers with a total of 124,597 children with diabetes. A statistically significant increase occurred in the risk of DKA among newly diagnosed T1DM patients during the pandemic. Our findings reflect that COVID-19 may have an altered presentation in T1DM and can be related to DKA severity.

Potential of Therapeutic Small Molecules in Apoptosis Regulation in the Treatment of Neurodegenerative Diseases: An Updated Review.

Neurodegenerative disorders (NDs) include Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) and the common feature of NDs is the progressive death of specific neurons in the brain. Apoptosis is very important in developing the nervous system, nonetheless an elevated level of cell death has been observed in the case of NDs. NDs are different in terms of their neuronal vulnerability and clinical manifestations, however they have some overlapping neurodegenerative pathways. It has been demonstrated by several studies with cell lines and animal models that apoptosis has a significant contribution to make in advancing AD, ALS, HD, and PD. Numerous dying neurons were also identified in the brains of individuals with NDs and these conditions were found to be linked with substantial cell loss along with common characteristics of apoptosis including activation of caspases and cysteine-proteases, DNA fragmentation, and chromatin condensation. It has been demonstrated that several therapeutic agents including antioxidants, minocycline, GAPDH ligands, p53 inhibitors, JNK (c-Jun N-Terminal Kinase) inhibitors, glycogen synthase kinase-3 inhibitor, non-steroidal anti-inflammatory drugs, D2 dopamine receptor agonists, FK506, cell cycle inhibitors, statins, drugs targeting peroxisome proliferator-activated receptors, and gene therapy have the potential to provide protection to neurons against apoptosis. Therefore, the use of these potential therapeutic agents might be beneficial in the treatment of NDs. In this review, we have summarized the pathways that are linked with apoptotic neuronal death in the case of various NDs. We have particularly focused on the therapeutic agents that have neuroprotective properties and the potential to regulate apoptosis in NDs.

Molecular and Serological Diagnostic Approach to Define the Microbiological Origin of Blood Culture-Negative Infective Endocarditis.

Blood culture-negative infective endocarditis (BCNIE) poses a significant challenge in determining the best antibiotic regimen for this life-threatening infection, which should be treated with as specific and effective a regimen as feasible. The goal of this study was to determine the prevalence of BCNIE among definite infective endocarditis (IE) cases and to study the impact of a molecular and serological diagnostic approach in defining the microbiological origin of BCNIE. This study included 94 definite IE cases. Serum and blood samples from BCNIE patients were tested using serological, broad-range PCR, and sequencing assays. Valve tissue sections obtained from 42 operated patients were subjected to culture and molecular studies. BCNIE accounted for 63 (67%) of the cases. Of these cases, blood PCR followed by sequencing could diagnose 11 cases. Zoonotic infective endocarditis was detected in 7 (11%) patients by serology and PCR (four Brucella, two Bartonella, and one Coxiella). Sequencing of valve PCR bands revealed 30 positive cases. Therefore, the percentage of BCNIE with unidentified etiology was reduced from 67% to 27.7% through a combination of all diagnostic procedures utilized in our study. Blood and valve PCR and sequencing assays are valuable techniques for the etiological diagnosis of BCNIE, especially in cases with previous antibiotic therapy. However, these tests should be used as part of a larger diagnostic strategy that includes serology, microscopy, and valve culture. The use of an automated blood culture system, and proper blood culture collection before ordering antibiotics, will guide IE etiological diagnosis.

Mobile Health (mHealth) Technology in Early Detection and Diagnosis of Oral Cancer-A Scoping Review of the Current Scenario and Feasibility.

Objective: Oral cancer is one of the most common types of cancer with dreadful consequences. But it can be detected early without much expensive equipment. Screening and early detection of oral cancer using Mobile health (mHealth) technology are reported due to the availability of the extensive network of mobile phones across populations. Therefore, we aimed to explore the existing literature regarding mHealth feasibility in the early detection of oral cancer. Materials and Method. An extensive search was conducted to explore the literature on the feasibility of mobile health for early oral cancer. Clinical studies reporting kappa agreement between on-site dentists and offsite health care workers/dentists in the early detection of oral cancer were included in this review. Studies describing the development of a diagnostic device, app development, and qualitative interviews among practitioners trained in using mobile health were also included in this review for a broader perspective on mHealth. Results: While most of the studies described various diagnostic accuracies using mHealth for oral cancer early detection, few studies reported the development of mobile applications, novel device designs for mHealth applications, and the feasibility of a few mHealth programs for early oral cancer detection. Community health workers equipped with a mobile phone-based app could identify "abnormal" oral lesions. Overall, many studies reported high sensitivity, specificity, and Kappa value of agreement. Effectiveness, advantages, and barriers in oral cancer screening using mHealth are also described. Conclusion: The overall results show that remote diagnosis for early detection of oral cancer using mHealth was found useful in remote settings.

Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review.

Chronic obstructive pulmonary disease (COPD) is an increasing and major global health problem. COPD is also the third leading cause of death worldwide. Oxidative stress (OS) takes place when various reactive species and free radicals swamp the availability of antioxidants. Reactive nitrogen species, reactive oxygen species (ROS), and their counterpart antioxidants are important for host defense and physiological signaling pathways, and the development and progression of inflammation. During the disturbance of their normal steady states, imbalances between antioxidants and oxidants might induce pathological mechanisms that can further result in many non-respiratory and respiratory diseases including COPD. ROS might be either endogenously produced in response to various infectious pathogens including fungi, viruses, or bacteria, or exogenously generated from several inhaled particulate or gaseous agents including some occupational dust, cigarette smoke (CS), and air pollutants. Therefore, targeting systemic and local OS with therapeutic agents such as small molecules that can increase endogenous antioxidants or regulate the redox/antioxidants system can be an effective approach in treating COPD. Various thiol-based antioxidants including fudosteine, erdosteine, carbocysteine, and N-acetyl-L-cysteine have the capacity to increase thiol content in the lungs. Many synthetic molecules including inhibitors/blockers of protein carbonylation and lipid peroxidation, catalytic antioxidants including superoxide dismutase mimetics, and spin trapping agents can effectively modulate CS-induced OS and its resulting cellular alterations. Several clinical and pre-clinical studies have demonstrated that these antioxidants have the capacity to decrease OS and affect the expressions of several pro-inflammatory genes and genes that are involved with redox and glutathione biosynthesis. In this article, we have summarized the role of OS in COPD pathogenesis. Furthermore, we have particularly focused on the therapeutic potential of numerous chemicals, particularly antioxidants in the treatment of COPD.

Exploring the role of astrocytic dysfunction and AQP4 in depression.

Aquaporin-4 (AQP4) is the water regulating channel found in the terminal processes of astrocytes in the brain and is implicated in regulating the astrocyte functions, whereas in neuropathologies, AQP4 performs an important role in astrocytosis and release of proinflammatory cytokines. However, several findings have revealed the modulation of the AQP4 water channel in the etiopathogenesis of various neuropsychiatric diseases. In the current article, we have summarized the recent studies and highlighted the implication of astrocytic dysfunction and AQP4 in the etiopathogenesis of depressive disorder. Most of the studies have measured the AQP4 gene or protein expression in the brain regions, particularly the locus coeruleus, choroid plexus, prefrontal cortex, and hippocampus, and found that in these brain regions, AQP4 gene expression decreased on exposure to chronic mild stress. Few studies also measured the peripheral AQP4 mRNA expression in the blood and AQP4 autoantibodies in the blood serum and revealed no change in the depressed patients in comparison with normal individuals.