Tuberculin skin test repetition after TNF-α inhibitors in patients with chronic inflammatory arthritis: a long-term retrospective cohort in endemic area.

OBJECTIVES: To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. METHODS: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). RESULTS: A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6-12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6-10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5-13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 - 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. CONCLUSION: These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

Reaction Rate Rules of Intramolecular H-Migration Reaction Class for RIORIIOO·Radicals in Ether Combustion.

The intramolecular H-migration reaction of RIORIIOO· radicals constitute a key class of reactions in the low-temperature combustion mechanism of ethers. Despite this, there is a dearth of direct computations regarding the potential energy surface and rate constants specific to ethers, especially when considering large molecular systems and intricate branched-chain structures. Furthermore, combustion kinetic models for large molecular ethers generally utilize rate constants derived from those of structurally similar alcohols or alkane fuels. Consequently, chemical kinetic studies involve the calculation of energy barriers and rate rules for the intramolecular H-migration reaction class of RIORIIOO· radicals, which are systematically conducted using the isodesmic reaction method (IRM). The geometries of the species participating in these reactions are optimized, and frequency calculations are executed using the M06-X method in tandem with the 6-31+G(d,p) basis set by the Gaussian 16 program. Moreover, the M06-2X/6-31+G(d,p) method acts as the low-level ab initio method, while the CBS-QB3 method is utilized as the high-level ab initio method for calculating single-point energies. Rate constants at the high-pressure-limit are computed based on the reaction class transition state theory (RC-TST) by ChemRate program, incorporating asymmetric Eckart tunneling corrections for intramolecular H-migration reactions across a temperature range of 500 to 2000 K. It was found that the isodesmic reaction method gives accurate energy barriers and rate constants, and the rate constants of the H-migration reaction for RIORIIOO· radicals diverge from those of comparable reactions in alkanes and alcohol fuels. There are significant disparities in energy barriers and rate constants across the entire reaction classes of the H-migration reaction for RIORIIOO· radicals, necessitating the subdivision of the H-migration reaction into subclasses. Rate rules are established by averaging the rate constants of representative reactions for each subclass, which is pivotal for the advancement of accurate low-temperature combustion reaction mechanisms for ethers.

Daily variation in sleepiness among firefighters while working the 24/48 and 48/96 shift schedules.

Objective: To assess the daily relationship between prior-night total sleep time (TST) and next-day, afternoon sleep propensity among firefighters operating from two popular fire department shift schedules. Methods: Dataset included 22 firefighters (24/48 shift schedule) and 20 firefighters (48/96 shift schedule). Daily TST was assessed using actigraphy and daily sleep propensity was assessed using the Epworth Sleepiness Scale (ESS), completed every afternoon. Results: Separate one-way repeated measures ANOVA indicated statistically significant differences among daily sleep propensity within each shift schedule. Separate Pearson product moment correlations indicated moderate relationships between prior-night TST and next-day, afternoon sleep propensity. Conclusion: When firefighters slept less, sleep propensity the following day increased. Least TSTs occurred on nights prior to commuting suggesting firefighters likely begin shifts without sufficient sleep and drive home without sufficient sleep, then experience greatest sleep propensity.

Autonomic impairment in primary lateral sclerosis.

PURPOSE: Prior studies reported evidence of autonomic involvement in motor neuron disease and suggested more severe dysfunction in upper motor neuron predominant syndromes. Hence, we sought to characterize autonomic impairment in primary lateral sclerosis. METHODS: Neurological evaluations, thermoregulatory sweat tests, and autonomic reflex screens were analyzed retrospectively in 34 primary lateral sclerosis patients (28 definite and 6 probable). Patients with other potential causes of autonomic failure and patients with autonomic testing results compromised by artifact were excluded. RESULTS: A total of 17 patients reported autonomic symptoms. Orthostatic lightheadedness was most frequent (8 patients), followed by bladder (7), bowel (5), and erectile dysfunction (3). The autonomic reflex screens of 33 patients were reviewed; 20 patients had abnormal studies. The thermoregulatory sweat tests of 19 patients were reviewed; 11 patients had abnormal studies. Composite Autonomic Severity Score was calculated for 33 patients and found abnormal in 20/33 patients (60.6%): 15/20 patients (75%) had mild impairment, and 5/20 patients (25%) had moderate impairment. The frequencies of testing abnormalities were: sudomotor 18/20 (90%), cardiovagal 9/20 (45%), and adrenergic 6/20 (30%). Sweat loss pattern analysis showed global, regional, and mixed patterns to be more common than length-dependent and distal patterns. CONCLUSION: We found evidence of frequent autonomic dysfunction in primary lateral sclerosis, which is generally of modest severity akin to prior reports for amyotrophic lateral sclerosis, but more commonly in a pattern consistent with preganglionic/ganglionic localization. This suggests that primary lateral sclerosis, as with amyotrophic lateral sclerosis, is a multisystem disease that affects the autonomic nervous system.

Unveiling Tst3, a Multi-Target Gating Modifier Scorpion α Toxin from Tityus stigmurus Venom of Northeast Brazil: Evaluation and Comparison with Well-Studied Ts3 Toxin of Tityus serrulatus.

Studies on the interaction sites of peptide toxins and ion channels typically involve site-directed mutations in toxins. However, natural mutant toxins exist among them, offering insights into how the evolutionary process has conserved crucial sequences for activities and molecular target selection. In this study, we present a comparative investigation using electrophysiological approaches and computational analysis between two alpha toxins from evolutionarily close scorpion species of the genus Tityus, namely, Tst3 and Ts3 from T. stigmurus and T. serrulatus, respectively. These toxins exhibit three natural substitutions near the C-terminal region, which is directly involved in the interaction between alpha toxins and Nav channels. Additionally, we characterized the activity of the Tst3 toxin on Nav1.1-Nav1.7 channels. The three natural changes between the toxins did not alter sensitivity to Nav1.4, maintaining similar intensities regarding their ability to alter opening probabilities, delay fast inactivation, and induce persistent currents. Computational analysis demonstrated a preference for the down conformation of VSD4 and a shift in the conformational equilibrium towards this state. This illustrates that the sequence of these toxins retained the necessary information, even with alterations in the interaction site region. Through electrophysiological and computational analyses, screening of the Tst3 toxin on sodium isoform revealed its classification as a classic α-NaTx with a broad spectrum of activity. It effectively delays fast inactivation across all tested isoforms. Structural analysis of molecular energetics at the interface of the VSD4-Tst3 complex further confirmed this effect.

Attenuated tuberculin skin test responses associated with Mycobacterium intracellulare sputum colonization in an adolescent TB prevalence survey in Western Kenya.

INTRODUCTION: Exposure to Non-tuberculous Mycobacteria (NTM) varies regionally and may partly explain the disparate outcomes of BCG vaccination and tuberculosis (TB) susceptibility. METHODS: We examined NTM sputum colonization, associations with clinical characteristics, and tuberculin skin test (TST) responses in an adolescent TB prevalence survey. RESULTS: Among 5004 adolescents screened, 2281 (45.5 %) were evaluated further. TB and NTM prevalence rates were 0.3 % and 8.0 %, respectively. Among 418 NTM isolates, 103 were unidentifiable, and 315 (75 %) comprised 15 species, the most frequent being M. intracellulare (MAC) (108, 26 %), M. scrofulaceum (96, 23 %) and M. fortuitum (51, 12 %). "NTM colonized" adolescents had less frequent chronic cough and night sweats (adjusted odds ratio [aOR] 0.62, 95 % confidence interval [CI] 0.44-0.87and aOR 0.61, CI 0.42-0.89 respectively), and lower TST induration (median 11 mm (interquartile range [IQR] 0-16) vs 13 mm (IQR 6-17; p = 0.006)) when compared to "NTM not colonized" participants. MAC, but not M. scrofulaceum or M. fortuitum, was associated with decreased TST induration (median 7.5 mm (IQR 0-15) vs 13 mm (IQR 6-17) among "MAC colonized" vs "not colonized", p = 0.001). CONCLUSION: We observed high NTM prevalence rates with species-specific associations with TST induration, consistent with a model of species-dependent heterologous immunity among mycobacteria.

Kinetics and mechanism of the gas-phase reaction of the hydroxyl radical with meta-aminotoluene compound.

CONTEXT: An ab initio investigation into the potential energy landscape of the meta-aminotoluene + •OH reaction has been conducted in this study. The calculated results reveal that the reaction channel leading to the product (NHC6H4CH3 + H2O) prevails under the 300-1700 K temperature range, while the reaction path forming the product (NH2C6H4CH2 + H2O) dominates in the higher-temperature region (T ≥ 1800 K). Within the specified temperature range, the product branching ratio for the former declines from 48 to 30%, while the latter shows an increase, reaching 29%. The overall second-order rate constants of the titled reaction obtained at the pressure 760 Torr (N2) can be illustrated by the modified Arrhenius expression of ktotal = 1.46 × 10-13 T0.58 exp[(-0.759 kcal.mol-1)/RT] cm3 molecule-1 s-1 and ktotal = 1.86 × 10-22 T3.24 exp[(-5.086 kcal.mol-1)/RT] cm3 molecule-1 s-1, covering the temperature range of T = 300-600 K and T > 600 K, respectively. The total rate constant at the ambient conditions in this work, 1.43 × 10-11 cm3 molecule-1 s-1, has been found to be roughly one order of magnitude lower than the available experimental data, ~ 1.2 × 10-10 cm3 molecule-1 s-1, measured by Atkinson et al., Rinke et al., and Witte et al., or the theoretical value, 4.4 × 10-10 cm3 molecule-1 s-1, and calculated by Abdel-Rahman and co-workers for the aniline + •OH reaction. METHODS: The structures of reactants, transition states, intermediate states, and products of the meta-aminotoluene + •OH reaction are calculated with the aug-cc-pVTZ basis set and the methods DFT/B3LYP and CCSD(T). The rate constants and branching ratios in the 300-2000 K temperature range are calculated with the statistical theoretical TST and RRKM master equation computations including tunneling corrections, with potential energy surface constructed by the CCSD(T)//B3LYP/aug-cc-pVTZ approach.

Combining a wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity.

STUDY OBJECTIVES: The gold standard for diagnosing obstructive sleep apnea (OSA) is polysomnography (PSG). However, PSG is a time-consuming method with clinical limitations. This study aimed to create a wireless radar framework to screen the likelihood of 2 levels of OSA severity (ie, moderate-to-severe and severe OSA) in accordance with clinical practice standards. METHODS: We conducted a prospective, simultaneous study using a wireless radar system and PSG in a Northern Taiwan sleep center, involving 196 patients. The wireless radar sleep monitor, incorporating hybrid models such as deep neural decision trees, estimated the respiratory disturbance index relative to the total sleep time established by PSG (RDIPSG_TST), by analyzing continuous-wave signals indicative of breathing patterns. Analyses were performed to examine the correlation and agreement between the RDIPSG_TST and apnea-hypopnea index, results obtained through PSG. Cut-off thresholds for RDIPSG_TST were determined using Youden's index, and multiclass classification was performed, after which the results were compared. RESULTS: A strong correlation (ρ = 0.91) and agreement (average difference of 0.59 events/h) between apnea-hypopnea index and RDIPSG_TST were identified. In terms of the agreement between the 2 devices, the average difference between PSG-based apnea-hypopnea index and radar-based RDIPSG_TST was 0.59 events/h, and 187 out of 196 cases (95.41%) fell within the 95% confidence interval of differences. A moderate-to-severe OSA model achieved an accuracy of 90.3% (cut-off threshold for RDIPSG_TST: 19.2 events/h). A severe OSA model achieved an accuracy of 92.4% (cut-off threshold for RDIPSG_TST: 28.86 events/h). The mean accuracy of multiclass classification performance using these cut-off thresholds was 83.7%. CONCLUSIONS: The wireless-radar-based sleep monitoring device, with cut-off thresholds, can provide rapid OSA screening with acceptable accuracy and also alleviate the burden on PSG capacity. However, to independently apply this framework, the function of determining the radar-based total sleep time requires further optimizations and verification in future work. CITATION: Lin S-Y, Tsai C-Y, Majumdar A, et al. Combining a wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity. J Clin Sleep Med. 2024;20(8):1267-1277.

The Applications of ELISpot in the Identification and Treatment of Various Forms of Tuberculosis and in the Cancer Immunotherapies.

ELISpot (enzyme-linked immunospot) is a powerful immunological tool for the detection of cytokine-secreting cells at a single-cell resolution. It is widely used for the diagnosis of various infectious diseases, e.g., tuberculosis and sarcoidosis, and it is also widely used in cancer immunotherapy research. Its ability to distinguish between active and latent forms of tuberculosis makes it an extremely powerful tool for epidemiological studies and contact tracing. In addition to that, it is a very useful tool for the research and development of cancer immunotherapies. ELISpot can be employed to assess the immune responses against various tumor-associated antigens, which could provide valuable insights for the development of effective therapies against cancers. Furthermore, it plays a crucial role to the evaluation of immune responses against specific antigens that not only could aid in vaccine development but also assist in treatment monitoring and development of therapeutic and diagnostic strategies. This chapter briefly describes some of the applications of ELISpot in tuberculosis and cancer research.

Tuberculous Pericarditis in Childhood: A Case Report and a Systematic Literature Review.

Tuberculous pericarditis (TBP) is an important cause of pericarditis worldwide while being infrequent in childhood, especially in low-TB-incidence countries. We report a case of TBP and provide a systematic review of the literature, conducted by searching PubMed, Scopus, and Cochrane to find cases of TBP in pediatric age published in the English language between the year 1990 and the time of the search. Of the 587 search results obtained, after screening and a backward citation search, 45 studies were selected to be included in this review, accounting for a total of 125 patients. The main signs and symptoms were fever, cough, weight loss, hepatomegaly, dyspnea, and increased jugular venous pressure or jugular vein turgor. A definitive diagnosis of TBP was made in 36 patients, either thanks to microbiological investigations, histological analysis, or both. First-line antitubercular treatment (ATT) was administered in nearly all cases, and 69 children underwent surgical procedures. Only six patients died, and only two died of TBP. TBP in childhood is relatively uncommon, even in high-TB-prevalence countries. Clinical manifestations, often suggestive of right-sided cardiac failure, are subtle, and diagnosis is challenging. TBP has an excellent prognosis in childhood; however, in a significant proportion of cases, invasive surgical procedures are necessary.

Prevalence of latent tuberculosis infection in Asian nations: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is a serious public health concern around the world including Asia. TB burden is high in Asian countries and significant population harbor latent tuberculosis infection(LTBI). AIM: This systematic review and meta-analysis aims to evaluate the prevalence of LTBI in Asian countries. METHOD: We performed a systematic literature search on PubMed, Embase, and ScienceDirect to identify relevant articles published between January 1, 2005, and January 1, 2023 investigating the overall prevalence of latent TB among people of Asia. Subgroup analysis was done for Asian subregions during the study period of 2011 to 2016 and 2017 to 2023, for tuberculin skin test (TST) and interferon gamma release assay (IGRA), respectively, as well as for QuantiFERON-TB (QFT) and TSPOT TB tests. Der Simonian and Laird's random-effects model was used to pool the prevalence of LTBI found using TST and IGRA. RESULT: A total of 15 studies were included after a systematic search from standard electronic databases. The analysis showed that the prevalence of latent TB in Asia was 21% (95% confidence interval [CI]: 19%-23%) and 36% (95% CI: 12%-59%) according to IGRAs and TSTs (cut off 10 mm) results, respectively. Based on IGRA, the prevalence of latent TB was 20% (95% CI: 13%-25%) in 2011 to 2016 and 21% (95% CI: 18%-24%) in 2017 to 2023. Using QFT, the prevalence was 19% (95% CI: 17%-22%) and using TSPOT, the prevalence was 26% (95% CI: 21%-31%). According to the United Nations division of Asia, the prevalence was higher for the Southern region and least for the Western region using TST and higher in the South-Eastern region and least in the Western region using the IGRA test. CONCLUSION: Almost a quarter of the Asian population has LTBI. Its diagnosis often poses a diagnostic challenge due to the unavailability of standard test in certain areas. Given this prevalence, a mass screening program is suggested with the available standard test and public awareness along with anti-TB regimen should be considered for individuals who test positive. However, for it to be implemented effectively, we need to take the affordability, availability, and cost-effectiveness of such interventions into account.

Tuberculosis prevention: current strategies and future directions.

BACKGROUND: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized. Elucidating determinants of transition between these states is crucial to decreasing the tuberculosis burden and reaching the END-TB Strategy goals as defined by the WHO. Vaccination, detection of infection, and provision of preventive treatment are key elements of tuberculosis prevention. OBJECTIVES: This review provides a comprehensive summary of recent evidence and state-of-the-art updates on advancements to prevent tuberculosis in various settings and high-risk populations. SOURCES: We identified relevant studies in the literature and synthesized the findings to provide an overview of the current state of tuberculosis prevention strategies and latest research developments. CONTENT: We present the current knowledge and recommendations regarding tuberculosis prevention, with a focus on M. bovis Bacille-Calmette-Guérin vaccination and novel vaccine candidates, tests for latent infection with M. tuberculosis, regimens available for tuberculosis preventive treatment and recommendations in low- and high-burden settings. IMPLICATIONS: Effective tuberculosis prevention worldwide requires a multipronged approach that addresses social determinants, and improves access to tuberculosis detection and to new short tuberculosis preventive treatment regimens. Robust collaboration and innovative research are needed to reduce the global burden of tuberculosis and develop new detection tools, vaccines, and preventive treatments that serve all populations and ages.

Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain.

Thiosulfate sulfurtransferase (TST, EC 2.8.1.1) was discovered as an enzyme that detoxifies cyanide by conversion to thiocyanate (rhodanide) using thiosulfate as substrate; this rhodanese activity was subsequently identified to be almost exclusively located in mitochondria. More recently, the emphasis regarding its function has shifted to hydrogen sulfide metabolism, antioxidant defense, and mitochondrial function in the context of protective biological processes against oxidative distress. While TST has been described to play an important role in liver and colon, its function in the brain remains obscure. In the present study, we therefore sought to address its potential involvement in maintaining cerebral redox balance in a murine model of global TST deficiency (Tst-/- mice), primarily focusing on characterizing the biochemical phenotype of TST loss in relation to neuronal activity and sensitivity to oxidative stress under basal conditions. Here, we show that TST deficiency is associated with a perturbation of the reactive species interactome in the brain cortex secondary to altered ROS and RSS (specifically, polysulfide) generation as well as mitochondrial OXPHOS remodeling. These changes were accompanied by aberrant Nrf2-Keap1 expression and thiol-dependent antioxidant function. Upon challenging mice with the redox-active herbicide paraquat (25 mg/kg i.p. for 24 h), Tst-/- mice displayed a lower antioxidant capacity compared to wildtype controls (C57BL/6J mice). These results provide a first glimpse into the molecular and metabolic changes of TST deficiency in the brain and suggest that pathophysiological conditions associated with aberrant TST expression and/or activity renders neurons more susceptible to oxidative stress-related malfunction.

Right to Occupational Safety: Prevalence of Latent Tuberculosis Infection in Healthcare Workers. A 1-Year Retrospective Survey Carried out at Hospital of Lecce (Italy).

BACKGROUND: Prevention of latent tuberculosis infection (LTBI) in healthcare workers (HCWs) to ensure the "Right to Occupational Safety" is a special challenge globally, as HCWs have a higher risk of acquiring the infection in hospital settings because of frequent close exposure to patients suffering from tuberculosis (TB). METHODS: Aretrospective study was performed with the aim of assessing the prevalence of LTBI related to demographical and occupational risk factors among HCWs employed in a large hospital in Italy. The study involved 1461 HCWs screened for LTBI by Mantoux tuberculin skin test (TST) and then confirmed with Interferon Gamma Release Assay (IGRA) test in case of positivity. Immunosuppressed and BGC-vaccinated workers were tested directly with IGRA. RESULTS: LTBI was diagnosed in 4.1% of the HCWs and the prevalence resulted lower than other studies conducted in low TB incidence countries. The variables significantly linked with higher frequency of the infection were: age ≥40 years (OR = 3.14; 95% CI: 1.13-8.74; p < 0.05), length of service ≥15 years (OR = 4.11; 95% CI: 1.48-11.43; p < 0.05) and not being trained on TB prevention (OR = 3.46; 95% CI: 1.85-6.46; p < 0.05). Not trained HCWs presented a higher risk of LTBI also after adjustment for age and length of service, compared to trained HCWs. CONCLUSIONS: screening of HCWs for LTBI should be always considered in routinely occupational surveillance in order to early diagnose the infection and prevent its progression. Safety policies in hospital settings centered on workers' training on TB prevention is crucial to minimize LTBI occurrence in HCWs.

Changes in the rate of bacillus tuberculosis infection in health workers in the first year of the COVID-19 epidemic in Kashan- Iran.

Objective: This cohort study aimed to determine the prevalence and risk factors of latent tuberculosis infection among healthcare workers during the COVID-19 pandemic. Methods: A one-year cohort study was conducted in a referral hospital in Kashan, involving 176 medical, educational, and cleaning personnel. Initial evaluations and tuberculin skin tests were performed, followed by a one-year follow-up period. Data were analyzed using SPSS version 26 software. Results: Among the participants, 26.1% (46 individuals) tested positive for latent tuberculosis infection. Age was a significant risk factor, with a 3.6% increase in latent tuberculosis infection risk with each advancing year. Men had 2.19 times (1.10-4.35) the chance of having a latent infection compared to women. Hospital staff were 3.7 times more at risk of tuberculosis infection than students. Among the hospital job categories, nursing assistants had the highest chance of tuberculosis infection, 6.77 times higher than medical students, followed by cleaning staff and nurses. The ICU, General, and Obstetrics and Gynecology departments had an infection chance of 2.46 (1.11-5.46) compared to other departments. No new positive cases were detected during the follow-up period. Conclusion: This study contributes to the understanding of latent tuberculosis infection prevalence and its risk factors among healthcare workers during the COVID-19 pandemic. The findings highlight the importance of infection control measures and targeted interventions to protect healthcare workers from occupational tuberculosis exposure.

Impact of Human Immunodeficiency Virus and Peripartum Period on Mycobacterium tuberculosis Infection Detection.

BACKGROUND: Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST). METHODS: Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP). RESULTS: 400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks' gestation [interquartile range, 24-30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P < .001), driven primarily by QFT-Plus-positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04-2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus-positive participants in pregnancy, Mycobacterium tuberculosis  (Mtb)-specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points. CONCLUSIONS: QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb-specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery.

Thiostrepton alleviates experimental colitis by promoting RORγt ubiquitination and modulating dysbiosis.

Thiostrepton (TST) is a natural antibiotic with pleiotropic properties. This study aimed to elucidate the therapeutic effect of TST on experimental colitis and identify its targets. The effect of TST on colon inflammation was evaluated in a dextran sulfate sodium (DSS)-induced colitis model and a T-cell transfer colitis model. The therapeutic targets of TST were investigated by cytokine profiling, immunophenotyping and biochemical approaches. The effect of TST on the gut microbiota and its contribution to colitis were evaluated in mice with DSS-induced colitis that were subjected to gut microbiota depletion and fecal microbiota transplantation (FMT). Alterations in the gut microbiota caused by TST were determined by 16S rDNA and metagenomic sequencing. Here, we showed that TST treatment significantly ameliorated colitis in the DSS-induced and T-cell transfer models. Specifically, TST targeted the retinoic acid-related orphan nuclear receptor RORγt to reduce the production of IL-17A by γδ T cells, type 3 innate lymphoid cells (ILC3s) and Th17 cells in mice with DSS-induced colitis. Similarly, TST selectively prevented the development of Th17 cells in the T-cell transfer colitis model and the differentiation of naïve CD4+ T cells into Th17 cells in vitro. Mechanistically, TST induced the ubiquitination and degradation of RORγt by promoting the binding of Itch to RORγt. Moreover, TST also reversed dysbiosis to control colonic inflammation. Taken together, these results from our study describe the previously unexplored role of TST in alleviating colonic inflammation by reducing IL-17A production and modulating dysbiosis, suggesting that TST is a promising candidate drug for the treatment of IBD.

The efficiency and safety of modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation in circumferential mixed hemorrhoids: a randomized controlled trial.

PURPOSE: This study aimed to explore the efficiency and safety of modified tissue-selecting therapy stapler combined with complete anal canal epithelial preservation operation (M-TST-CACP) in the treatment of circumferential mixed hemorrhoids. METHODS: This was a single-center, statistical analyst-blinded, randomized controlled trial (RCT). A total of 306 patients were finally included for analysis. The efficiency (efficacy, recurrence, anal smoothness, quality of life, and wound healing time) and safety (anal incontinence, pain level, anal stenosis, urinary retention, perianal edema, and postoperative bleeding) were evaluated. The statistical difference in continuous data between M-TST-CACP group and procedure for prolapse and hemorrhoids (PPH) group was compared using t-test or Mann-Whitney U test. The statistical difference in counting data between the two groups were compared using Pearson χ2 test. Difference within each group in different time points was evaluated using repeated-measures analysis of variance. RESULTS: M-TST-CACP group showed a higher cure rate (6 months: 74.51% vs. 64.71%, P = 0.044), lower recurrence (6 months: 0% vs. 4.58%, P = 0.015; 12 months: 0.65% vs. 5.88%, P = 0.010), lower anal incontinence score (1 month: 1.29 ± 1.17 vs. 1.93 ± 1.33; 3 months: 1.07 ± 0.87 vs. 1.59 ± 1.01; 6 months: 0.58 ± 0.61 vs. 1.00 ± 0.90; all P < 0.001), and lower rate of anal stenosis (1 month: 0% vs. 7.84%; 3 months: 0% vs. 9.80%; both P < 0.001) than the PPH group. CONCLUSIONS: M-TST-CACP had better efficiency and safety than the PPH, which could be a reasonable adoption for the surgeons to treat circumferential mixed hemorrhoids.

Screening for Latent Tuberculosis Infection in Solid Organ Transplant Recipients to Predict Active Disease: A Systematic Review and Meta-Analysis of Diagnostic Studies.

Background: This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Methods: Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. Results: A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179-2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731-1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. Conclusions: We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Diagnosis of Latent Tuberculosis Infection in Hemodialysis Patients: TST versus T-SPOT.TB.

Hemodialysis (HD) patients should be screened for latent tuberculosis (TB) infection. We aimed to determine the frequency of latent TB infection in HD patients and to compare the effectiveness of the tests used. The files of 56 HD patients followed between 1 January 2021 and 1 October 2022 were retrospectively analyzed. Demographic data, the presence of the Bacillus Calmette-Guerin (BCG) vaccine, whether or not the patients had previously received treatment for TB before, the status of encountering a patient with active TB of patients over 18 years of age, without active tuberculosis and who had a T-SPOT.TB test or a Tuberculin Skin Test (TST) were obtained from the patient files. The presence of previous TB in a posterior-anterior (PA) chest X-ray was obtained by evaluating PA chest X-rays taken routinely. Of the patients, 60.7% (n = 34) were male and their mean age was 60.18 ± 14.85 years. The mean duration of dialysis was 6.43 ± 6.03 years, and 76.8% (n = 43) had 2 BCG scars. The T-SPOT.TB test was positive in 32.1% (n = 18). Only 20 patients (35.7%) had a TST and all had negative results. While the mean age of those with positive T-SPOT.TB results was higher (p = 0.003), the time taken to enter HD was shorter (p = 0.029). T-SPOT.TB test positivity was higher in the group that had encountered active TB patients (p = 0.033). However, no significant difference was found between T-SPOT.TB results according to BCG vaccine, albumin, urea and lymphocyte levels. Although T-SPOT.TB test positivity was higher in patients with a previous TB finding in a PA chest X-ray, there was no statistically significant difference (p = 0.093). The applicability of the TST in the diagnosis of latent TB infection in HD patients is difficult and it is likely to give false-negative results. The T-SPOT.TB test is not affected by the BCG vaccine and immunosuppression. Therefore, using the T-SPOT.TB test would be a more appropriate and practical approach in the diagnosis of latent TB in HD patients.