Diagnosis of extra pulmonary tuberculosis: An update on novel diagnostic approaches.

Tuberculosis (TB) remains a major global public health problem worldwide. Though Pulmonary TB (PTB) is mostly discussed, one in five cases of TB present are extrapulmonary TB (EPTB) that manifests conspicuous diagnostic and management challenges with respect to the site of infection. The diagnosis of EPTB is often delayed or even missed due to insidious clinical presentation, pauci-bacillary nature of the disease, and lack of laboratory facilities in the resource limited settings. Culture, the classical gold standard for the diagnosis of tuberculosis, suffers from increased technical and logistical constraints in EPTB cases. Other than culture, several other tests are available but their feasibility and effciacy for the detection of EPTB is still the matter of interest. We need more specific and precise test/s for the various forms of EPTB diagnosis which can easily be applied in the routine TB control program is required. A test that can contribute remarkably towards improving EPTB case detection reducing the morbidity and mortality is the utmost requirement. In this review we described the scenario of molecular and other noval methods available for laboratory diagnosis of EPTB, and also discussed the challenges linked with each diagnostic method. This review will make the readers aware of new emerging diagnostic techniques in the field of EPTB diagnosis. They can make an informed decision to choose the appropriate one according to the test availability, their clinical settings and financial considerations.

T-cell signature cytokines distinguish pulmonary sarcoidosis from pulmonary tuberculosis.

Sarcoidosis is a systemic inflammatory disorder characterized by tissue infiltration due to mononuclear phagocytes and lymphocytes and associated noncaseating granuloma formation. Pulmonary sarcoidosis (PS) shares a number of clinical, radiological, and histopathological characteristics with that of pulmonary tuberculosis (PTB). Due to this, clinicians face issues in differentiating between PS and PTB in a substantial number of cases. There is a lack of any specific biomarker that can diagnose PS distinctively from PTB. We compared T-cell-based signature cytokines in patients with PS and PTB. In this study, we proposed a serum biomarker panel consisting of cytokines from cells: T helper (Th) 1 [interferon-gamma (IFN-γ); tumor necrosis factor-alpha (TNF-α)], Th9 [interleukin (IL)-9], Th17 [IL-17], and T regulatory (Treg) [IL-10; transforming growth factor-beta (TGF-ß)]. We performed the principal component analysis that demonstrated that our serum cytokine panel has a significant predictive ability to differentiate PS from PTB. Our results could aid clinicians to improve the diagnostic workflow for patients with PS in TB endemic settings where the diagnosis between PS and PTB is often ambiguous.

A Comparative Evaluation of Xylitol Chewing Gum and a Combination of IgY + Xylitol Chewable Tablet on Salivary Streptococcus mutans Count in Children: A Double-blind Randomized Controlled Trial.

Aim: The study was designed for evaluation and comparison of the efficacy of Xylitol chewing gum and a combination of IgY + Xylitol chewable tablet (Nodecay TM) against the "salivary Streptococcus mutans " count in children. Materials and methods: About 120 children belonging to 6-12 years age-group were enrolled into this "double-blind randomized control clinical trial" according to the selection criteria. They were randomly assigned to three groups of 40 each: Group I-Xylitol chewing gum, Group II-IgY + Xylitol Chewable tablet (Nodecay TM), and Group III-Control. Children in all the groups had to chew the gum/tablet twice daily for 5 minutes during the 15-day period. The salivary samples at baseline, 15 days, 1, 2, and 3 months were inoculated on mitis salivarius bacitracin agar with potassium tellurite medium and the number of colony-forming units (CFUs) of Streptococcus mutans were determined. The data obtained was subjected to statistical analysis. Result: There was a "significant" difference in the number of "S. mutans CFUs" amongst the three groups at 15 days, 1st month, 2nd month, 3rd month with highest levels of S. mutans CFUs in Group III-Control and least in Group II-IgY + Xylitol (NodecayTM). Conclusion: The combination of IgY + Xylitol (NodecayTM) when administered for 15 days had significant efficacy against "S. mutans" when compared to Xylitol and control group. Clinical significance: Passive immunization with immunoglobulin Y is known not only to decrease the S. mutans count but also confers extended immunity by preventing recolonization of the tooth surface by persistence of the antibodies in saliva. How to cite this article: Jain RL, Tandon S, Rai TS, et al. A Comparative Evaluation of Xylitol Chewing Gum and a Combination of IgY + Xylitol Chewable Tablet on Salivary Streptococcus mutans Count in Children: A Double-blind Randomized Controlled Trial. Int J Clin Pediatr Dent 2022;15(S-2):S212-S220.

Psychometric approach to evaluate periodontal disease using Revised Illness Perception Questionnaire.

INTRODUCTION: Illness perception is the cognitive representation of an illness, which determines how a person responds to it. The Revised Illness Perception Questionnaire (IPQ-R) assesses seven components of illness representation in various chronic diseases, but queries prevail about its factor structure. The study assesses the components of illness representation in patients with chronic periodontitis. MATERIALS AND METHODS: A total of 625 voluntary, consecutive dental patients with a clinical diagnosis of periodontitis were recruited into the study. The Hindi version of IPQ-R was used, consisting of three parts-identity scale, structured scale, and perceived causes of the patient's ailment. RESULTS: Of the 625 participants, 44.0% reported cyclical disease pattern, 30.4% said their disease was a mystery. Only 1.6% predicted it to remain throughout their life. A total of 44.0% of participants reported the disease to impact their day-to-day life severely. A significant difference was observed between males and females across seven components of IPQ-R. While 21.6% of participants attributed stress to be a major cause for their diseased state, 20.8% reported workload to be a major cause, but 42.4% attributed poor medical care in the past to be a major cause for their state. CONCLUSIONS: A sensible approach to treating a disease is to measure the patient's illness perception and target specific interventions accordingly. It would be cost-effective and break misconceptions about diseases in patients, ultimately providing them with better overall health and satisfaction.

Inhibiting OX40 Restores Regulatory T-Cell Function and Suppresses Inflammation in Pulmonary Sarcoidosis.

BACKGROUND: Pulmonary sarcoidosis (PS) is a noncaseating granulomatous disease of unknown origin. Despite conflicting reports, it is considered that the regulatory T (Treg) cells are functionally impaired in PS, but the underlying mechanisms remain unclear. OX40, a pivotal costimulatory molecule, is essential for T-cell functions and memory development, but its impact on Treg cells is ambiguous. RESEARCH QUESTION: Does the OX40 pathway influence the suppressive functions of Treg cells in PS? STUDY DESIGN AND METHODS: Fifty treatment-naïve patients with PS and 30 healthy control participants were recruited for this study. Polychromatic flow cytometry-based immunologic assays were performed to enumerate effector T helper (Th) cells and Treg cells along with their functions. Using real-time polymerase chain reaction analysis, small interfering RNA, and pharmacologic inhibitors, the impact of OX40 on Treg cell function was investigated. RESULTS: We observed enrichment of Th-9 cells perhaps for the first time along with Th-1, Th-17, and Treg cells in patients' BAL fluid (BALF) compared with peripheral blood. However, Treg cells were observed to be functionally defective at the pathological site. We observed higher expression of OX40 on both T effector (CD4+Foxp3-) and Treg (CD4+Foxp3+) cells obtained from the BALF of patients with PS. However, OX40 exerted contrasting impact on these T-cell subsets, enhancing effector T-cell functions (interferon γ, tumor necrosis factor α) while inhibiting Treg cell function (IL-10, transforming growth factor ß). OX40 silencing or blocking on Treg cells resulted in restoration of their impaired functions. INTERPRETATION: We propose that inhibiting the OX40 pathway may constitute a therapeutic strategy for controlling inflammatory T cells by restoring Treg cell functions in patients with PS.

Effect of engineered superparamagnetic iron oxide nanoparticles in targeted cardiac precursor cell delivery by MRI.

A scientific approach is presented describing the fabrication of nanoprobe (GloTrack) that can act as cardiac precursor label to segregate cells from cardiac/non cardiac origins and traced by magnetic resonance imaging (MRI). Signal regulatory protein alpha (SIRPA) and kinase domain receptor (KDR) recognizing antibodies, form a layer on super paramagnetic iron oxide nanoparticle - poly-ethylene glycol (SPION-PEG) complex, and bind to protein expressed on the surface of cardiac muscle cells. Physical attributes size, distribution, labelling efficiency, echocardiogram (ECG) changes and bio-distribution by MRI were analysed. The results indicate that GloTrack has an average size of 471 nm, exhibits negative potential and promotes labelling efficiency. The bio-distribution of GloTrack in in vivo experiments was traceable in 7T MRI showing high accumulation of GloTrack in cardiac muscles as compared to the liver and spleen. ECG data revealed that GloTrack segregated cardiac precursors has the potential benefit in treating heart failure, thereby paving way in the development of minimal cell manipulation with targeted cell delivery approaches.

"How was tuberculosis known to the world?"

Tuberculosis is a well-known disease in the Indian subcontinent. This disease always poses challenges in front of the clinician for its proper treatment. However, its discovery was equally challenging. It took a great effort of many clinicians after which this disease was known to the world. History of tuberculosis is not only extensive but dramatic as well.

Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19.

The outbreak of severe acute respiratory syndrome coronavirus-2 is causing a serious disaster through coronavirus disease-19 (COVID-19) around the globe. A large segment of the population from every corner of the world is already infected with this dreadful pathogen with a high mortality rate. These numbers are increasing drastically causing a situation of a global pandemic. Although after the continuous scientific efforts, we are still not having any specific drug or vaccine for the SARS-CoV-2 pathogen to date and there is an urgent need to develop a newer therapy to counter the COVID-19 global pandemic. Thus, in the current study, a framework for computational drug repurposing is established, and based on their safety profile, metocurine was chosen as a safe and effective drug candidate for developing therapy against the viral Mpro enzyme of SARS-CoV-2 for the treatment of COVID-19.

Sarcoidosis: Causes, Diagnosis, Clinical Features, and Treatments.

Sarcoidosis is a multisystem granulomatous disease with nonspecific clinical manifestations that commonly affects the pulmonary system and other organs including the eyes, skin, liver, spleen, and lymph nodes. Sarcoidosis usually presents with persistent dry cough, eye and skin manifestations, weight loss, fatigue, night sweats, and erythema nodosum. Sarcoidosis is not influenced by sex or age, although it is more common in adults (< 50 years) of African-American or Scandinavians decent. Diagnosis can be difficult because of nonspecific symptoms and can only be verified following histopathological examination. Various factors, including infection, genetic predisposition, and environmental factors, are involved in the pathology of sarcoidosis. Exposures to insecticides, herbicides, bioaerosols, and agricultural employment are also associated with an increased risk for sarcoidosis. Due to its unknown etiology, early diagnosis and detection are difficult; however, the advent of advanced technologies, such as endobronchial ultrasound-guided biopsy, high-resolution computed tomography, magnetic resonance imaging, and 18F-fluorodeoxyglucose positron emission tomography has improved our ability to reliably diagnose this condition and accurately forecast its prognosis. This review discusses the causes and clinical features of sarcoidosis, and the improvements made in its prognosis, therapeutic management, and the recent discovery of potential biomarkers associated with the diagnostic assay used for sarcoidosis confirmation.

New vision for improving oral hygiene status of visually impaired students aged from 9 to 17 years.

BACKGROUND: Visually impaired patients are at a higher risk of developing periodontal disease because of greater difficulty in attaining good oral hygiene. This study aims to assess and compare the oral hygiene status of visually impaired students before and after oral health education interventions using special customized methods. METHODS: The present study was a randomized control trial of 180 visually impaired students divided into three groups. Each group includes 60 students selected randomly from blind school. Oral health education was given using Braille in Group 1, Audio Tactile performance (ATP) technique in Group 2, and a combination of Braille and ATP technique in Group 3. Plaque index (PI) scores and gingival index (GI) scores were calculated and evaluated at baseline and after 3 months. Intergroup comparison and intragroup comparison of PI and GI at baseline and 3 months was by using one way ANOVA and Paired t test, respectively. RESULTS: There was a highly significant difference seen for the intergroup comparison of post PI (P < 0.01) and post GI (P < 0.01) with least mean in Group 3. There was a statistically highly significant difference seen for the intra group comparison of pre and post PI and GI (P < 0.01) with lesser means in post as compared to pre in all three groups. CONCLUSIONS: Visually impaired children could maintain an acceptable level of oral hygiene when taught using combination of Braille and ATP technique.

Connectome of the Suprachiasmatic Nucleus: New Evidence of the Core-Shell Relationship.

A brain clock, constituted of ∼20,000 peptidergically heterogeneous neurons, is located in the hypothalamic suprachiasmatic nucleus (SCN). While many peptidergic cell types have been identified, little is known about the connections among these neurons in mice. We first sought to identify contacts among major peptidergic cell types in the SCN using triple-label fluorescent immunocytochemistry (ICC). To this end, contacts among vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and calretinin (CALR) cells of the core, and arginine vasopressin (AVP) and met-enkephalin (ENK) cells of the shell were analyzed. Some core-to-shell and shell-to-core communications are specialized. We found that in wild-type (WT) mice, AVP fibers make extremely sparse contacts onto VIP neurons but contacts in the reverse direction are numerous. In contrast, AVP fibers make more contacts onto GRP neurons than conversely. For the other cell types tested, largely reciprocal connections are made. These results point to peptidergic cell type-specific communications between core and shell SCN neurons. To further understand the impact of VIP-to-AVP communication, we next explored the SCN in VIP-deficient mice (VIP-KO). In these animals, AVP expression is markedly reduced in the SCN, but it is not altered in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). Surprisingly, in VIP-KO mice, the number of AVP appositions onto other peptidergic cell types is not different from controls. Colchicine administration, which blocks AVP transport, restored the numbers of AVP neurons in VIP-KO to that of WT littermates. The results indicate that VIP has an important role in modulating AVP expression levels in the SCN in this mouse.

Sarcoidosis vs tuberculosis: Diagnostic mystery still unresolved.

Sarcoidosis and tuberculosis are chronic, multisystemic, granulomatous disease of alike clinical, radiological and histopathological manifestations. Idiopathic nature of the disease and a strong clinical similarity with tuberculosis make the effectiveness of various clinical examinations for the diagnosis of sarcoidosis difficult in a tuberculosis endemic area. Presently confirmation of a diagnosis of sarcoidosis in most cases requires a biopsy which is often not confirmatory. A variety of novel medical approaches is under research to replace invasive diagnostic procedures for a simple non-invasive investigation for the identification of sarcoidosis. Here we discussed the studies focussing on the features that can be useful for distinguishing sarcoidosis from tuberculosis. Multiple studies have found molecular, cellular, immunological and clinical biomarkers efficient to lead the way of clinicians for the exact diagnosis of sarcoidosis.

Synthesis and Biological Activities of Oxadiazole Derivatives: A Review.

Recently, there has been wide interest in compounds containing the oxadiazole scaffold because of their unique chemical structure and their broad spectrum of biological properties. This review provides readers with an overview of the main synthetic methodologies for oxadiazoles and of their broad spectrum of pharmacological activities such as, anti-microbial, anti-fungal activity, antiviral, anti-tubercular, anti-inflammatory, anti-convulsant, anti-angiogenic, anti-proliferative, analgesic, anti-oedema and in alzheimer activity, which were reported over the past years.

Particle filtering for arrival time tracking in space and source localization.

Locating and tracking a source in an ocean environment and estimating environmental parameters of a sound propagation medium are critical tasks in ocean acoustics. Many approaches for both are based on full field calculations which are computationally intensive and sensitive to assumptions on the structure of the environment. Alternative methods that use only select features of the acoustic field for localization and environmental parameter estimation have been proposed. The focus of this paper is the development of a method that extracts arrival times and amplitudes of distinct paths from measured acoustic time-series using sequential Bayesian filtering, namely, particle filtering. These quantities, along with complete posterior probability density functions, also extracted by filtering, are employed in source localization and bathymetry estimation. Aspects of the filtering methodology are presented and studied in terms of their impact on the uncertainty in the arrival time estimates. Using the posterior probability densities of arrival times, source localization and water depth estimation are performed for the Haro Strait Primer experiment; the results are compared to those of conventional methods. The comparison demonstrates a significant advantage in the proposed approach.

Osteogenic differentiation of human dental pulp stem cells on ß-tricalcium phosphate/poly (l-lactic acid/caprolactone) three-dimensional scaffolds.

Functional tissue engineering for bone augmentation requires the appropriate combination of biomaterials, mesenchymal stem cells, and specific differentiation factors. Therefore, we investigated the morphology, attachment, viability, and proliferation of human dental pulp stem cells cultured in xeno-free conditions in human serum medium seeded on ß-tricalcium phosphate/poly(l-lactic acid/caprolactone) three-dimensional biomaterial scaffold. Additionally, osteogenic inducers dexamethasone and vitamin D(3) were compared to achieve osteogenic differentiation. Dental pulp stem cells cultured in human serum medium maintained their morphology; furthermore, cells attached, remained viable, and increased in cell number within the scaffold. Alkaline phosphatase staining showed the osteogenic potential of dental pulp stem cells under the influence of osteogenic medium containing vitamin D(3) or dexamethasone within the scaffolds. Maintenance of dental pulp stem cells for 14 days in osteogenic medium containing vitamin D(3) resulted in significant increase in osteogenic markers as shown at mRNA level in comparison to osteogenic medium containing dexamethasone. The results of this study show that osteogenic medium containing vitamin D(3) osteo-induced dental pulp stem cells cultured in human serum medium within ß-tricalcium phosphate/poly(l-lactic acid/caprolactone) three-dimensional biomaterial, which could be directly translated clinically.

A particle filtering approach for spatial arrival time tracking in ocean acoustics.

The focus of this work is on arrival time and amplitude estimation from acoustic signals recorded at spatially separated hydrophones in the ocean. A particle filtering approach is developed that treats arrival times as "targets" and tracks their "location" across receivers, also modeling arrival time gradient. The method is evaluated via Monte Carlo simulations and is compared to a maximum likelihood estimator, which does not relate arrivals at neighboring receivers. The comparison demonstrates a significant advantage in using the particle filter. It is also shown that posterior probability density functions of times and amplitudes become readily available with particle filtering.

Vitamin D(3) metabolites induce osteogenic differentiation in human dental pulp and human dental follicle cells.

Vitamin D(3) metabolites regulate the bone metabolism and 1α,25-dihydroxyvitamin D(3) (1α,25(OH)(2)D(3)) is known to play an important role in teeth mineralization. However, little is known about the potential of vitamin D as an osteogenic inducer in human dental pulp (hDPCs) and dental follicle cells (hDFCs) in vitro. Therefore, we investigated the effects of vitamin D(3) metabolites 1α,25(OH)(2)D(3) and 25-hydroxyvitamin D(3) (25OHD(3)) on proliferation and osteogenic differentiation of hDPCs and hDFCs in vitro. We also examined whether vitamin D(3) metabolic enzymes were regulated in hDFCs and hDPCs. Cell proliferation was decreased by both metabolites in hDPCs and hDFCs. Vitamin D(3) metabolites increased ALP activity and induced mineralization when osteogenic supplements (OS; l-ascorbic acid-2-phosphate+ß-glycerophosphate) were added, though the expression of osteocalcin (OC) and osteopontin (OPN) were regulated without the addition of OS. CYP24 and CYP27B1 expressions were upregulated by vitamin D(3) metabolites and 25OHD(3) was converted into 1α,25(OH)(2)D(3) in the culture medium. These results confirm that 1α,25(OH)(2)D(3) (10 and 100 nM) and 25OHD(3) (500 nM) can be used as osteogenic inducers synergistically with osteogenic supplements for differentiation of hDPCs and hDFCs. Furthermore, our findings strengthen our knowledge about the role of hDPCs and hDFCs as vitamin D(3) target cells.

Addition of BMP-2 or BMP-6 to dexamethasone, ascorbic acid, and ß-glycerophosphate may not enhance osteogenic differentiation of human periodontal ligament cells.

This study was designed to investigate the potential merits of the combined use of bone morphogenetic protein (BMP)-2 or BMP-6 and osteogenic supplements (OS) [dexamethasone, ascorbic acid (AA), and ß-glycerophosphate] on osteogenic differentiation of periodontal ligament cells (PDLCs). Osteogenic differentiation was evaluated by quantitative alkaline phosphatase (ALP) assay, alizarin red staining, quantitative calcium assay, and the qRT-PCR analysis for the expression of collagen type I, runt-related transcription factor-2, osteopontin (OPN), and osteocalcin in PDLCs. Culture with BMP-2 or BMP-6+AA increased ALP activity of PDLCs, suggesting their osteo-inductive effects. However, longer duration of culture showed neither of the BMPs induced in vitro mineralization. In contrast, OS were able to increase ALP activity and OPN expressions, and also induced in vitro mineralization. The mineralization ability was not enhanced by the addition of BMP-2 or BMP-6. These findings suggest that the addition of BMP-2 or BMP-6 to OS may not enhance an osteogenic differentiation of hPDLCs.