Sternal tuberculosis: A rare manifestation of extrapulmonary disease.

Sternal tuberculosis is a rare and challenging diagnosis. We present a case of a 63-year-old woman who presented with a progressively enlarging anterior chest wall mass and nonspecific symptoms. Imaging studies revealed a destructive sternal lesion. A biopsy confirmed the tuberculosis diagnosis. The patient responded well to anti-tuberculosis treatment. This case highlights the importance of considering tuberculosis when making a differential diagnosis of sternal masses and emphasizes the need for early diagnosis and treatment.

The role of family support in medication adherence and quality of life among tuberculosis patients: A scoping review.

BACKGROUND: Tuberculosis (TB) remains one of the leading infectious diseases globally, causing high mortality rates. A significant factor contributing to this issue is nonadherence to treatment, which is influenced by family support and impacts the quality of life (QoL) of patients. AIM: The purpose of this study was to describe the role of family support in enhancing medication adherence and improving QoL in individuals with TB. METHODS: This study utilized a scoping review method to examine literature from the PubMed, Scopus, and EBSCO databases. The keywords used in the search included "social support OR online social support OR perceived social support OR family support" AND "Tuberculosis OR TB OR TBC" AND "medication adherence OR medication compliance OR drug adherence OR drug compliance OR adherence OR compliance OR lost to follow-up" AND "QoL OR HRQoL OR health-related QoL." The inclusion criteria were full-text articles in English, primary research studies, and publications from the last 10 years (2012-2022). RESULTS: Thirteen articles met the inclusion criteria, with sample sizes ranging from 50 to 1342 respondents, predominantly using cross-sectional methods. The study found that family support is crucial in promoting medication adherence and positively influencing the QoL of TB patients. Family members provide emotional and practical support, including supervision of medication intake and encouragement of healthy habits. This support enhances patients' confidence, motivation, and overall treatment outcomes. CONCLUSIONS: The findings underscore the indispensable role of family support in addressing the complex interplay between medication adherence and QoL for individuals with TB.

Pelvic-peritoneal pseudotumoral tuberculosis with elevated CA 125 mimicking ovarian cancer: A case report.

Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. It constitutes a public health problem, especially in developing countries. Pelvic localization is rare with tubal involvement being the most frequent. It presents clinically, radiologically, and biologically as an ovarian tumor. We report the case of a patient who presented to the emergency department with pelvic pain, an abdominal-pelvic mass, and a general state of deterioration. The patient had a high CA125 level, and imaging initially suggested a neoplastic origin. She underwent laparoscopy with histopathological examination, confirming the diagnosis of tuberculosis, showing giant cell granulomas with caseous necrosis. A favorable outcome was observed on all fronts after antitubercular treatment.

A disposable, portable electrochemical immunosensor for rapid in situ detection of bovine tuberculosis.

This contribution describes the development of a simple, fast, cost-effective, and sensitive impedimetric immunosensor for quantifying bovine tuberculosis (TB) in bovine serum samples. The construction of the immunosensor involved immobilizing the purified protein derivative (PPD) of M. bovis onto a screen-printed electrode that was modified with gold nanoparticles (AuNPs) and a polypyrrole (pPy) film synthesized electrochemically. The immunosensor exhibited a linear range from 0.5 µg mL-1 to 100 µg mL-1 and achieved a limit of detection (LD) of 100 ng mL-1 for the detection of anti-M. bovis antibody. The recovery percentages obtained in bovine serum samples were excellent, ranging between 98 % and 103 %. This device presents several advantages over alternative methods for determining TB in bovine serum samples. These include direct, in situ measurement without the need for pre-treatment, utilization of small volumes, thus avoiding harmful solvents and expensive reagents, and portability. In addition, the immunosensor exhibits both physical and chemical stability, retaining effectiveness even after 30 days of modification. This allows simultaneous incubations and facilitates large-scale detection. Hence, this immunosensor presents itself as a promising diagnostic tool for detecting anti-M. bovis antibodies in bovine serum. It serves as a viable alternative to tuberculin and ELISA tests.

Tuberculosis of the gastric cardia mimicking gastric carcinoma.

In this case report, a male patient in his 50's presented with right-sided neck swelling for 2 months and an acute episode of hematochezia along with vague abdominal and systemic symptoms for 2-3 years. The clinical suspicion was gastric carcinoma. Fine needle aspiration cytology (FNAC) from the neck swelling was inconclusive, and upper gastrointestinal (GI) endoscopy was normal. However, contrast enhanced CT neck, chest, and abdomen revealed focal, heterogeneously enhancing wall thickening in the cardia of the stomach with periportal and perigastric nodes showing peripheral rim enhancement; ascites and peritoneal thickening; a cold abscess in the right axilla; cervical and mediastinal lymph nodes with central hypodensity; and tree-in-bud opacities with sub-segmental consolidation in the lower lobe of the left lung. A diagnosis of disseminated tuberculosis was made, and the patient was successfully treated with empirical antitubercular therapy. This case highlights an uncommon presentation of tuberculosis of gastric cardia and a need to have a high index of suspicion, even in the absence of positive microbiological confirmation of the disease.

Factores relacionados con la adherencia al tratamiento de tuberculosis en el Departamento de Boyacá / Factors related with adherence to treatment of tuberculosis in the Department of Boyacá

Resumen Introducción: la tuberculosis es una enfermedad infecciosa crónica causada por Mycobacterium tuberculosis, capaz de afectar cualquier órgano o tejido siendo la forma más común la enfermedad pulmonar. Objetivo: identificar los factores que afectan la adherencia al tratamiento antituberculoso en pacientes del Departamento de Boyacá durante los años 2017-2019. Metodología: estudio descriptivo retrospectivo que utilizó como fuentes de información datos registrados en la base del programa departamental de Tuberculosis y SIVIGILA. Se realizó análisis univariado, determinando la distribución de las variables y análisis bivariado en el que se exploró la asociación entre la adherencia al tratamiento de tuberculosis y las variables independientes, se utilizó la prueba de Chi cuadrado. Resultados: se incluyeron 402 pacientes, la adherencia al tratamiento antituberculoso fue 96,5% y la no adherencia de 3,5%. El 66,7% eran de sexo femenino; 55,7% vivián en zona urbana; 66,5% pertenecían al régimen subsidiado; 89,7% mestizos; 91,2% correspondían a otros grupos poblacionales, seguido del 7,5% de población privada de la libertad y 1,3% habitantes de calle. Dentro de las comorbilidades la coinfección con VIH con 4,2% fue la de mayor presencia. Entre las causas de no adherencia al tratamiento fueron desinterés, cambio frecuente de domicilio, contrato finalizado con la EPS y suspensión del tratamiento por toxicidad hepática. El paciente con mayor probabilidad de abandonar el tratamiento pertenece al sexo masculino, al grupo poblacional de migrantes o habitantes de calle y se encuentra afiliado al régimen subsidiado, ​​​​se encontró una relación estadísticamente significativa entre estas variables y el resultado con la adherencia al tratamiento. Conclusiones: si bien el resultado obtenido en el presente trabajo no es elevado, es importante realizar vigilancia de la adherencia al tratamiento antituberculoso para disminuir el riesgo de complicaciones derivadas de su abandono como mayor mortalidad, desarrollo de resistencia bacteriana y un período de contagiosidad más prolongado.

Abstract Introduction: Tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis, capable of affecting any organ or tissue, the most common form being lung disease. Objective: Identify the factors that affect adherence to tuberculosis treatment in patients from the Department of Boyacá during the years 2017-2019. Methodology: Retrospective descriptive study that used as information sources data registered in the database of the departmental Tuberculosis program and SIVIGILA. A univariate analysis was carried out, determining the distribution of the variables and a bivariate analysis in which the association between adherence to tuberculosis treatment and the independent variables was explored, using the Chi-square test. Results: 402 patients were included, adherence to anti-tuberculosis treatment was 96.5% and non-adherence 3.5%. 66.7% were female; 55.7% lived in an urban area; 66.5% belonged to the subsidized regime; 89.7% mestizo; 91.2% corresponded to other population groups, followed by 7.5% of the population deprived of liberty and 1.3% homeless. Within the comorbidities, coinfection with HIV 4.2% was the one with the greatest presence. Among the causes of non-adherence to treatment were lack of interest; frequent change of address; Terminated contract with the EPS and suspension of treatment due to liver toxicity. The patient with the highest probability of abandoning treatment belongs to the male sex, to the population group of migrants or street dwellers and is affiliated with the subsidized regime, a statistically significant relationship was found between these variables and the result with adherence to treatment. Conclusions: Although the result obtained in this study is not high, it is important to monitor adherence to tuberculosis treatment to reduce the risk of complications derived from its abandonment, such as increased mortality, development of bacterial resistance, and a longer period of contagiousness.

Implementation of digital chest radiography for childhood tuberculosis diagnosis at district hospital level in six high tuberculosis burden and resources limited countries.

OBJECTIVES: Chest x-ray (CXR) plays an important role in childhood tuberculosis (TB) diagnosis, but access to quality CXR remains a major challenge in resource-limited settings. Digital CXR (d-CXR) can solve some image quality issues and facilitate their transfer for quality control. We assess the implementation of introducing d-CXR in 12 district hospitals (DHs) in 2021-2022 across Cambodia, Cameroon, Ivory Coast, Mozambique, Sierra Leone and Uganda as part of the TB-speed decentralisation study on childhood TB diagnosis. METHODS: For digitisation of CXR, digital radiography (DR) plates were setup on existing analogue radiography devices. d-CXR were transferred to an international server at Bordeaux University and downloaded by sites' clinicians for interpretation. We assessed the uptake and performance of CXR services and health care workers' (HCW) perceptions of d-CXR implementation. We used a convergent mixed method approach utilising process data, individual interviews with 113 HCWs involved in performing or interpreting d-CXRs and site support supervision reports. RESULTS: Of 3104 children with presumptive TB, 1642 (52.9%) had at least one d-CXR, including 1505, 136 and 1 children with one, two and three d-CXRs, respectively, resulting in a total of 1780 d-CXR. Of them, 1773 (99.6%) were of good quality and 1772/1773 (99.9%) were interpreted by sites' clinicians. One hundred and sixty-four children had no d-CXR performed despite attending the radiography department: 126, 37 and 1 with one, two and three attempts, respectively. d-CXRs were not performed in 21.6% (44/203) due to connectivity problem between the DR plate captor and the computer. HCW reported good perceptions of d-CXR and of the DR plates provided. The main challenge was the upload to and download from the server of d-CXRs due to limited internet access. CONCLUSION: d-CXR using DR plates was feasible at DH level and provided good quality images but required overcoming operational challenges.

Ibuprofen modulates macrophage polarization by downregulating poly (ADP-ribose) polymerase 1.

Ibuprofen, a non-steroidal drug, is well known for its anti-inflammatory activity. The effects of ibuprofen on the polarization of macrophages are still not clear. Herein, we used THP-1 monocyte-derived macrophages to find that ibuprofen has inhibitory effects on the polarization of both classically activated M1 macrophages and alternatively activated M2 macrophages by downregulating NF-κB and JAK/STAT signaling pathways. During M1 or M2 polarization, ibuprofen also downregulated the expression of poly (ADP-ribose) polymerase 1 (PARP1). Furthermore, knockdown of PARP1 by either small interfering RNA or PARP1 inhibitor PJ34 can exert inhibitory effects on the polarization of M1 and M2, and alter the immune response of macrophages to the infection of Mycobacterium tuberculosis H37Ra. The results demonstrate that PARP1 plays a regulatory role in the ibuprofen-modulated polarization of macrophage, revealing the interplay between the DNA repair response process and macrophage polarization.

Synthesis, Biological Evaluation, Molecular Docking Studies and ADMET Prediction of Oxindole-Based Hybrids for the Treatment of Tuberculosis.

INTRODUCTION: With a projected mortality toll of 1.4 million in 2019, tuberculosis (TB) continues to be a significant public health concern around the world. Studies of novel treatments are required due to decreased bioavailability, increased toxicity, increased side effects, and resistance of several first- and second-line TB therapies, including isoniazid and ethionamide. METHODS: This study reports the synthesis of oxindole-based hybrids as potent InhA inhibitors targeting Mycobacterium tuberculosis. The synthesized compounds (5a-5e and 8a-8c) were evaluated for their anti-mycobacterial activity against Mycobacterium tuberculosis and nontuberculous mycobacteria (NTMs), viz. M. abscessus (ATCC 19977), M. fortuitum (ATCC 6841), and M. chelonae (ATCC 35752) using the Microplate Alamar Blue Assay (MABA). Molecular docking studies were performed using AutoDock Vina to explore the binding interactions of these compounds with the InhA enzyme (PDB: 2NSD). Additionally, biochemical and histopathological studies were conducted to assess the hepatotoxicity of the lead compounds. Insilico molecular properties and ADMET properties of the synthesized compounds were predicted using SwissADME and Deep-PK online tools to assess their drug-likeness. RESULTS: Among the tested compounds, 8b exhibited significant anti-mycobacterial activity with a minimum inhibitory concentration (MIC = 1 µg/mL) comparable to the reference drug ethambutol. Further, the compound demonstrated a binding affinity and orientation similar to the reference inhibitor 4PI, indicating its potential as a potent InhA inhibitor, and was found to be stabilized within the binding pocket of InhA through H-bonding, hydrophobic and van der Waal's interactions. Besides, the compounds hepatotoxicity assessment studies depicted that 8b showed no significant liver dysfunction or damage to liver tissues. Additionally, 8b adhered to Lipinski's rule of five and Veber's rule, displaying favourable pharmacokinetic and drug-like properties, including high human intestinal absorption, distribution, and acceptable metabolic stability and excretion. CONCLUSION: Compound 8b emerged as a promising candidate for further optimization and development as a therapeutic agent for tuberculosis, offering a new avenue for tackling tuberculosis.

Dynamic modelling of improved diagnostic testing for drug-resistant tuberculosis in high burden settings.

BACKGROUND: Limited diagnostic testing for drug-resistant TB (DR-TB) may lead to high rates of misdiagnosis and undertreatment. Current diagnostic tests focus only on detection of rifampicin-resistant TB (RR-TB). This study aims to determine the impact of improved diagnostic testing for a wider range of drug resistance on DR-TB outcomes in high-burden TB settings, using the Philippines and Thailand as case studies. METHODS: A dynamic compartmental model was designed to simulate population level TB transmission, accounting for acquired drug resistance from treatment failure of drug susceptible TB. Three scenarios were analyzed: (1) Use of GeneXpert MTB/RIF on all presumptive TB cases (Status Quo); (2) GeneXpert MTB/RIF + GeneXpert XDR, (3) GeneXpert MTB/RIF + targeted Next Generation Sequencing (tNGS). Scenarios were modelled over a 10-year period, from 2025 to 2034. RESULTS: Compared to the status quo, Scenario 2 results in a fourfold increase in annual DR-TB cases diagnosed in the Philippines and a fivefold increase in Thailand. DR-TB treatment failure decreases by 20% in the Philippines and 23% in Thailand. Scenario 3 further increases DR-TB case detection, reducing DR-TB treatment failure by 26% in the Philippines and 29% in Thailand. Reductions in DR-TB incidence and mortality ranged from 3 to 6%. CONCLUSION: The use of GeneXpert XDR or tNGS as an additional diagnostic test for DR-TB significantly improves DR-TB case detection and reduces treatment failure, supporting their consideration for use in high burden settings. These findings highlight the importance of detecting a wider range of TB resistance in addition to RR-TB, the potential impact these improved diagnostic tests can have on DR-TB outcomes, and the need for additional research on cost-effectiveness of these interventions.

Association between toxin-antitoxin system mutations and global transmission of MDR-TB.

BACKGROUND: The emergence of Multidrug-Resistant Tuberculosis (MDR-TB) poses a significant threat to global tuberculosis control efforts. This study aimed to examine the influence of mutations in Toxin-Antitoxin system genes on the global transmission of MDR-TB caused by Mycobacterium tuberculosis (M. tuberculosis). METHODS: Whole-genome sequencing was conducted on 13,518 M. tuberculosis isolates. Genes of the Toxin-Antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Techniques such as Random Forest, Gradient Boosting Decision Tree, and Generalized Linear Mixed Models were employed to identify mutation sites in Toxin-Antitoxin system-related genes that facilitated the transmission of MDR-TB. RESULTS: 4,066 (30.08%) were identified as MDR-TB strains of all analyzed isolates. We found significant associations between specific gene mutations and MDR-TB transmission clusters including mutations in Rv0298 (G213A), Rv1959c (parE1, C88T), Rv1960c (parD1, C134T), Rv1991A (maze, G156A), Rv2547 (vapB, C54G), Rv2862A (vapB23, T2C), and Rv3385c (vapB46, G70A). Additionally, several gene mutations associated with MDR-TB transmission clades such as Rv1956 (higA, G445T), Rv1960c (parD1, C134T), and Rv1962A (vapB35, G99A) were noted. Certain gene mutations including vapB35 (G99A), higA (G445T), and parD1 (C134T) correlated with cross-regional transmission clades. CONCLUSION: This study highlights the significant association between specific gene mutations in the Toxin-Antitoxin system and the global transmission of MDR-TB, providing valuable insights for developing targeted interventions to control MDR-TB.

Out-of-pocket payment and catastrophic health expenditure of tuberculosis patients in accessing care at public-private mix clinics in Myanmar, 2022.

BACKGROUND: The financial burden of tuberculosis (TB) can hinder patients and their families, creating obstacles throughout the care cascade, despite TB prevention and control being provided free of charge. In Myanmar, patients can visit private providers operating under public-private mix (PPM) schemes, where TB services (diagnosis and treatment) are typically offered at no cost. The study focused on quantifying the financial burden faced by TB patients seeking care from Myanmar's PPM providers. METHODS: This cross-sectional telephone survey included 695 adults seeking TB treatment [drug-susceptible TB (DS-TB) and retreatment TB] from various private providers in four states and regions with high TB burden in Myanmar. Telephone interviews were conducted in May and June 2022. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2022 and estimated throughout pre- and post-TB treatment episodes. The TB-affected households were defined as experiencing catastrophic health expenditure if their expenditure due to TB exceeded 20% of their capacity to pay, as recommended by the World Health Organization. All cost data were collected in Myanmar Kyats (MMK) and converted to USD (1 USD = 1850 MMK as of July 20, 2022). Logistic regression analysis was done to identify the determinants of catastrophic health expenditure. RESULTS: The findings showed patients made a median of 7 times for clinic visits throughout their treatment, with the median total cost for the entire TB treatment being 53.4 US dollars (USD), including direct medical and testing costs (11.9 USD) and direct non-medical patient expenditure (11.6 USD). Pre-treatment costs were higher compared to post-treatment costs (the intensive phase and continuation phase). During the intensive phase, TB care cost was nearly free, but during the continuation phase, it was a median of 2.6 USD. About 34.5% of patients experienced catastrophic health expenditure due to TB treatment, with expenses exceeding 20% of their capacity to pay. Multivariate regression analysis revealed that patients with a history of hospitalization (aOR = 14.84; P < 0.01), seeking care from regions other than Yangon (aOR = 2.6; P < 0.01), and using coping strategies (aOR = 12.53; P < 0.01), were more likely to face catastrophic financial burdens. Higher monthly household income (over 162 USD) was associated with a decreased risk of incurring catastrophic health expenditure (aOR = 0.38; P < 0.01). CONCLUSIONS: TB patients and their households in Myanmar faced risk of catastrophic costs, even when treated in the private sector with free diagnostic charges and anti-TB medicine. The study highlighted the need for additional strategies or policies to make TB care affordable and mitigate the financial burden of TB-affected households.

Mycobacterium tuberculosis evolution from monoresistance to pre-extensive drug resistance during a prolonged household outbreak.

Whole genome sequencing (WGS) is sensitive tool for the analysis of tuberculosis transmission and drug-resistance. We used WGS to analyze the Mycobacterium tuberculosis evolution from isoniazid monoresistance to MDR/preXDR during a prolonged household outbreak. The outbreak started with a isoniazid resistant strain (katG S315T mutation) and evolve in two cases to pre-XDR phenotype (with mutations in katG, rpoB, embB, pncA and gyrA genes). Based on WGS data and epidemiological interview we proposed a possible chain of transmission an evolution of the strains. Similar intra-patient and inter-patient acquisition of variability was observed, making difficult to distinguish reinfection or reactivation. Analysis of WGS data together with epidemiological clinical history are discussed in order to distinguish between prolonged infections or transition from latency to reactivation. Classical interview and clinical history taking should be consider to fully understanding WGS data. With a still low incidence of TB cases, Uruguay could use universal WGS of all isolates to reduce time of diagnosis, detect outbreaks and perform public actions to reduce TB incidence.

Treatment outcomes among patients with isoniazid mono-resistant tuberculosis in Mumbai, India: A retrospective cohort study.

Background: Tuberculosis (TB) remains a significant cause of mortality globally, with India accounting for 27% of the estimated number of people with TB. Multidrug-resistant TB (MDR-TB) and isoniazid (INH) resistance pose additional challenges to effective treatment. We aimed to describe treatment outcomes of INH mono-resistant TB patients under programmatic conditions in Mumbai, India. Methods: This retrospective cohort study was conducted at Shatabdi Hospital in Mumbai between 2019-2021.We described the clinical and demographic characteristics, treatment outcomes, and risk factors for unfavourable outcomes among patients with INH mono-resistant TB treated with rifampicin, ethambutol, pyrazinamide, and levofloxacin (LfxREZ) for a duration of 6 months. Results: Among 3105 patients with drug-resistant TB initiated on treatment, 217 (7 %) had INH mono-resistant TB. Of these, 54 % (117/217) were female, with a median age of 26 years (interquartile range: 20-40). The majority (88 %; 191/217) presented with pulmonary TB, and most (87 %; 188/217) had favourable treatment outcomes, including treatment completion (52 %; 112/217) and cure (35 %; 76/217). Unfavourable outcomes, including treatment failure (2.3 %; 5/217), loss to follow-up (9.2 %; 20/217), or death (1.8 %; 4/217), were observed in 13 % (29/217) of patients. A total of ten (5 %) patients experienced at least one non-severe adverse drug reaction. Factors associated with unfavourable outcomes included severe thinness (p = 0.019) and male gender (p = 0.012). Conclusion: Treating INH mono-resistant patients with LfxREZ resulted in satisfactory outcomes and low toxicity. It is important to rule out drug resistance to INH while determining the treatment regimen.

Vitamin D Receptor Gene Polymorphisms Differentiated Between Tuberculosis Disease and Infection: Causal Association Study.

Purpose: Latent tuberculosis infection (LTBI) is a critical stage in tuberculosis (TB)control, and few studies have addressed the role of vitamin D receptor(VDR) gene polymorphisms in differentiating between TB and late-onset TB from an immunogenetic perspective. Patients and Methods: Recruitment of tuberculosis patients and latently infected population in Urumqi, Xinjiang, and use of propensity score matching(PSM) to match the two groups and control confounding to further construct a Bayesian network to analyze causal associations between VDR polymorphisms and tuberculosis disease status. Results: 137 LTBI and 237 TB were obtained through PSM. Logistic regression showed that the VDR gene BsmI locus, TaqI locus, and ApaI locus were associated with a higher risk of TB in a codominant model (P<0.05). Further Bayesian network construction showed that occupation and being a VDR gene BsmI locus were direct influences on TB disease status, and the VDR gene TaqI locus played an indirect role through the BsmI locus, and the probability of TB risk was highest in individuals with manual labour and BsmI locus of the C/T type, which was 84.15%. Conclusion: Bayesian network modelling intuitively revealed that individuals with a C/T type of BsmI locus and physical labour are at high risk of TB compared with TB infection, and they are key factors between with TB disease, providing reference evidence for controlling TB progression.

sRNAdeep: a novel tool for bacterial sRNA prediction based on DistilBERT encoding mode and deep learning algorithms.

BACKGROUND: Bacterial small regulatory RNA (sRNA) plays a crucial role in cell metabolism and could be used as a new potential drug target in the treatment of pathogen-induced disease. However, experimental methods for identifying sRNAs still require a large investment of human and material resources. METHODS: In this study, we propose a novel sRNA prediction model called sRNAdeep based on the DistilBERT feature extraction and TextCNN methods. The sRNA and non-sRNA sequences of bacteria were considered as sentences and then fed into a composite model consisting of deep learning models to evaluate classification performance. RESULTS: By filtering sRNAs from BSRD database, we obtained a validation dataset comprised of 2438 positive and 4730 negative samples. The benchmark experiments showed that sRNAdeep displayed better performance in the various indexes compared to previous sRNA prediction tools. By applying our tool to Mycobacterium tuberculosis (MTB) genome, we have identified 21 sRNAs within the intergenic and intron regions. A set of 272 targeted genes regulated by these sRNAs were also captured in MTB. The coding proteins of two genes (lysX and icd1) are implicated in drug response, with significant active sites related to drug resistance mechanisms of MTB. CONCLUSION: In conclusion, our newly developed sRNAdeep can help researchers identify bacterial sRNAs more precisely and can be freely available from https://github.com/pyajagod/sRNAdeep.git .

The progress of Mycobacterium tuberculosis drug targets.

Tuberculosis (TB) has been troubling humans for hundreds of years, is a highly infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, Mtb can infect almost all organs of the body and is one of the deadly infectious diseases in the world. At present, the first-line treatment regimen has a long treatment cycle and is prone to multiple drug resistance. Anti-tuberculosis drugs and latent tuberculosis infection (LTBI) resistance are increasing year by year, and new targets and new bioactive compounds are urgently needed to treat this disease. This review focuses on the latest reported anti-TB drug targets and related compounds in recent years, reviews the current TB drug regimen and major defects, outlines the key drug targets developed to date in Mtb, and the current situation of newly discovered anti-TB resistant forms of drugs. To provide a reference for the research and development of new anti-TB drugs and bring new treatment strategies for TB patients.

Disseminated Tuberculosis Masquerading as a Uterine Cervical Mass in an Immunocompetent Young Female: A Case Report.

Concurrent tubercular involvement of two or more non-contiguous organs is termed disseminated tuberculosis (TB) and is rare in immunocompetent patients. We describe the case of a young immunocompetent woman with disseminated TB who presented with primary complaints of amenorrhea and dysuria. Abdominal ultrasound showed a uterine cervical mass, which on histopathological evaluation revealed epithelioid granulomata with Langhans giant cells and acid-fast bacilli (AFB). Her chest radiograph showed scattered air space opacities bilaterally, and contrast-enhanced computed tomography of the abdomen revealed the involvement of bilateral kidneys, para-aortic lymph nodes, adrenals, sacroiliac regions, and the gastrointestinal tract. A colonoscopy picked up an ulcer in the terminal ileum, which on histopathology was positive for AFB. The patient was started on anti-tubercular treatment.

Can Primary Knee Tuberculosis Simulate the Clinical and Radiological Profile of Pigmented Villonodular Synovitis?

When faced with clinical and radiological findings suggestive of villonodular synovitis, tuberculosis is not often considered a differential diagnosis, especially when the patient is not a known tuberculosis carrier. In this paper, we present an exceptional case of a patient who had a tumefaction (measuring 17 cm in length) in the anterointernal region of her left knee, with a clinical and radiological picture in favor of villonodular synovitis. However, after tumor resection, the anatomopathological study of the surgical specimen came back in favor of a tuberculous lesion. This exceptional case shows that tuberculosis should be retained as a diagnostic possibility in the presence of clinical and radiological findings in favor of villonodular synovitis, even if the patient is not known to have a tuberculous lesion elsewhere.

Non-tuberculous mycobacteria enhance the tryptophan-kynurenine pathway to induce immunosuppression and facilitate pulmonary colonization.

The increasing prevalence of non-tuberculous mycobacterium (NTM) infections alongside tuberculosis (TB) underscores a pressing public health challenge. Yet, the mechanisms governing their infection within the lung remain poorly understood. Here, we integrate metagenomic sequencing, metabolomic sequencing, machine learning classifiers, SparCC, and MetOrigin methods to profile bronchoalveolar lavage fluid (BALF) samples from NTM/TB patients. Our aim is to unravel the intricate interplay between lung microbial communities and NTM/Mycobacterium tuberculosis infections. Our investigation reveals a discernible reduction in the compositional diversity of the lung microbiota and a diminished degree of mutual interaction concomitant with NTM/TB infections. Notably, NTM patients exhibit a distinct microbial community characterized by marked specialization and notable enrichment of Pseudomonas aeruginosa and Staphylococcus aureus, driving pronounced niche specialization for NTM infection. Simultaneously, these microbial shifts significantly disrupt tryptophan metabolism in NTM infection, leading to an elevation of kynurenine. Mycobacterium intracellulare, Mycobacterium paraintracellulare, Mycobacterium abscessus, and Pseudomonas aeruginosa have been implicated in the metabolic pathways associated with the conversion of indole to tryptophan via tryptophan synthase within NTM patients. Additionally, indoleamine-2,3-dioxygenase converts tryptophan into kynurenine, fostering an immunosuppressive milieu during NTM infection. This strategic modulation supports microbial persistence, enabling evasion from immune surveillance and perpetuating a protracted state of NTM infection. The elucidation of these nuanced microbial and metabolic dynamics provides a profound understanding of the intricate processes underlying NTM and TB infections, offering potential avenues for therapeutic intervention and management.