People who inject drugs (PWID) have high rates of bloodstream infections (BSI) with Staphylococcus aureus (SA) and group A streptococcus (GAS). Little is known about health-related quality of life outcomes after BSI.
Methods
We performed a prospective pilot cohort study of patients with BSI due to SA or GAS. Health-related quality of life, anxiety, depression and cognitive function were assessed using validated tools (EQ5-5D-5L), Hospital Anxiety and Depression Score (HADS) and Montreal Cognitive Assessment (MOCA) at baseline, 28 days post-discharge and 6 months post-infection.
Findings
66 patients were recruited over a 12-month period, including 17 PWID. For the whole cohort, global health rank improved from baseline to day 28 (median 40 to 60, p=0.002), with no significant improvement from day 28 to day 168 (median 60 to 75, p=0.161). At baseline, PWID had lower overall health-related quality of life than non-PWID (median 25 vs 45, p=0.229), persisting at day 28 (non-PWID median 65, PWID median 43, p=0.036) and day 168 (non-PWID median 75, PWID median 40, p=0.035). This difference was driven by worse scores in the EQ-5D-5L mental health component and HADS, with HADS scores being significantly impaired in PWID at baseline (p=0.001) and day 28 (p=0.007).
Conclusion
PWID have impaired health-related quality of life after SA and GAS BSI that persists for up to 6 months. Poor mental health is the major component of this, and further studies could clarify if this is a target for intervention.
Extrapulmonary tuberculosis (EPTB) remains diagnostically challenging due to its paucibacillary nature and variable presentation. Xpert and culture are limited in EPTB diagnosis due to sampling challenges, low sensitivity, and long turnaround times. This study evaluated the performance of the MPT64 antigen detection test for diagnosing EPTB, particularly tuberculous lymphadenitis (TBLN) and tuberculous pleuritis (TBP), in a high-TB, low-HIV setting. Conducted at Gulab-Devi Hospital, Lahore, Pakistan, this study evaluated the MPT64 test’s performance against conventional diagnostic methods, including culture, histopathology, and the Xpert MTB/RIF assay. Lymph node biopsies were collected, and cell blocks were made from aspirated pleural fluid from patients clinically presumed to have EPTB. Of 338 patients, 318 (94%) were diagnosed with EPTB. For TBLN, MPT64 demonstrated higher sensitivity (84%) than Xpert (48%); for TBP, the sensitivity was 51% versus 7%, respectively. Among histopathology-confirmed TBLN cases, MPT64 outperformed both culture and Xpert (85% vs. 58% and 47%). Due to the low number of non-TB cases, specificity could not be reliably assessed. The MPT64 test shows promise as a rapid, sensitive diagnostic tool for EPTB, particularly TBLN, in routine settings. While sensitivity is notably superior to Xpert, further studies are needed to evaluate its specificity and broader diagnostic utility.
The diagnostic challenges of extrapulmonary tuberculosis (EPTB) are multifaceted and stem from a combination of biological, logistical, and infrastructural issues. Accurate diagnosis of EPTB requires specific tests to detect mycobacteria, but medical professionals face challenges due to diverse clinical manifestations, the paucibacillary nature of the disease, and the fact that its diagnosis typically requires invasive procedures to obtain tissue samples, which depend on skilled personnel and functional laboratory system resources that are often limited in low- and middle-income countries (LMICs) [1,2].
EPTB accounts for approximately 20–30% of all active tuberculosis (TB) cases globally, with this proportion rising to 50% among individuals co-infected with human immunodeficiency virus (HIV) infections [3,4,5]. Tuberculous lymphadenitis (TBLN) is the most common expression, comprising 35–50% of cases, while tuberculous pleuritis (TBP) is the second most predominant manifestation, which accounts for 10–16% [3,6,7]. Combined, these two forms represent about half (50%) of all EPTB presentations. Globally, 8–10 million people are infected with TB annually, with EPTB accounting for up to 17% of all TB cases reported in 2023 [8]. The majority (80%) of incident TB cases and mortalities occur in low- and middle-income countries. Pakistan is among the high-TB-burden countries; 428,600 TB cases were notified in 2023, with 18% (77,148) being EPTB [8,9].
Despite significant advances in the field of TB diagnosis over the last decade, including advancements in microscopy, culture, and molecular techniques, the diagnosis of EPTB remains a major challenge [10,11]. The clinical and histological diagnostic criteria utilized have low sensitivity and specificity, which might lead to missed or overdiagnosis [12]. The Xpert MTB/RIF assay (Xpert), a significant milestone in TB diagnostics, shows reduced efficacy for EPTB due to variability in specimen types, limited tissue availability, and the need for complex sample processing [13,14]. Isolation of Mycobacterium tuberculosis (MTB) from clinical samples by culture remains the “gold standard” due to its high specificity, ability to detect viable bacilli (10–100 bacilli/mL) from biological samples, and ability to identify species. However, low sensitivity and long turnaround times limit the use of culture in resource-limited settings [1,15]. Due to the absence of a low-cost, robust, rapid, and accurate diagnostic method, diagnosis of EPTB is often delayed or misdiagnosed, resulting in increased disease severity and mortality. Therefore, there is an urgent need for a better diagnostic test that is feasible and sustainable in resource-limited settings.MPT64 is one of the major culture filtrate proteins (24 kDa) encoded by the RD2 region genes, secreted by MTB complex species, and is a specific antigen that differentiates it from the Mycobacterium other than tuberculosis species. The diagnostic potential of an immunochemistry-based MPT64 antigen detection test (MPT64 test) has demonstrated greater sensitivity compared with conventional methods and the Xpert. Its sensitivity and specificity are also comparable with the nested polymerase chain reaction (nested-PCR) [15,16,17,18]. Results from earlier research indicate that MPT64 has a unique capacity for intracellular accumulation that enables the detection of smaller numbers of mycobacteria in the lesion, which is not achievable using other conventional methods for the diagnosis of TB [15,19].
The synthesis and characterization of Ipomoea aquatica herbal extract gold nanoparticles (IA-AuNPs) are of great interest due to their antioxidant and anticancer properties. Current study reflects simplest procedure to synthesize IA-AuNPs. Its MTT and cytotoxicity assay was evaluated in HepG2 cells with an IC50 value of 69.62 ± 5 µg/ml after 24 h of incubation. Apoptosis was done using ROS/, MMP and live-dead cell examination using AO/EtBr staining. In spectrophotometric analysis a single peak was observed at 542 nm which represents the SPR absorption band of gold nanoparticles. The IA-AuNPs were spherical with 5–40 nm size, with an average size of 10 nm, based on HR-TEM and HR-SEM. The existence of gold in IA-AuNPs was confirmed by EDX data. FTIR confirmed presence of various bioactive compounds in IA-AuNPs, with peaks at 3344cm−1, 2897cm−1, 2168cm−1, 1765cm−1, 1640cm−1, and 1275cm−1 corresponding to the-OH group and stretches of CH, C = H, C = O, and CO, respectively. At pH9 and 5Msalt concentration, significant stability of IA-AuNPs was observed. The zeta (ζ) potential value of IA-AuNPs at 25 °C and pH9 was -37.7 mV, showing its good quality and greater stability compared to pH6 and pH7 having zeta (ζ) potential value of -13.1 mV and -20.2 mV respectively. IA-AuNPs exhibited dose-dependent cytotoxicity, and ROS/MMP mediated apoptosis assay. DPPH radical scavenging activities was measured at 517 nm in respect to ascorbic acid in which IA-AuNPs exhibited stronger antioxidant properties than plant extract. Overall, our results suggested that IA-AuNPs have anticancer/ antioxidant properties that may be useful for the treatment of hepatic cancer as future drug.
Optical nanoparticles and functional nanomaterials, which have an ability to transport drugs and detect diseases, have recently attracted considerable interest among scientists. Achieving efficient delivery in both healthy and target cells is of utmost importance. Gold nanoparticles (AuNPs) have received considerable interest because of their unique characteristics, such as ease of synthesis, tunable optical and magnetic properties, controlled surface functionalization, and immobilization [1]. Nano-biotechnology has emerged as a significant subfield in the biotechnology. Nanoparticles can be synthesized in several ways, including thermal decomposition; photochemically mediated reduction into micelles; reduction in solutions; and other chemical, biological, electrochemical, and microwave-based techniques [2]. Currently, "green synthesis of nanoparticles" has attracted attention because they are both cost effective, environment friendly and could be used as potential drug
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia primarily affecting lung interstitium (Leon-Roman et al., 2022). Lung interstitium refers to structures between lung parenchyma (e.g., alveoli and bronchi), including alveolar wall tissues and regions between capillary endothelium and alveolar epithelium (Doshi et al., 2022). Hallmark of IPF is fibrosis of lung interstitium, which represents end stage of interstitial lung disease. This leads to progressive deterioration of respiratory function, manifesting as clinical symptoms such as dry cough, fatigue, and progressive exertional dyspnea (Huang and Tang, 2021, Podolanczuk et al., 2023, Glass et al., 2022). Although current treatment options for IPF are limited and prognosis remains poor (Benegas Urteaga et al., 2022), early diagnosis can effectively delay disease progression, making early identification crucial (Benegas Urteaga et al., 2022). According to 2022 clinical practice guidelines for IPF and progressive pulmonary fibrosis jointly issued by ATS/ERS/JRS/ALAT, diagnosis of IPF typically integrates clinical symptoms, imaging studies (particularly high-resolution computed tomography, HRCT), pulmonary function tests, histological examinations (e.g., lung biopsy), and exclusion of other diseases. HRCT imaging and characteristic pulmonary function changes are key diagnostic criteria (Raghu et al., 2022). However, despite importance of HRCT in IPF diagnosis, its imaging changes remain incompletely understood (Yazaki et al., 2021), which limits early and accurate diagnosis. Therefore, exploring characteristics of IPF and developing novel diagnostic biomarkers are of paramount importance for improving diagnostic accuracy and clinical management.
DNA damage repair (DDR) is the cellular process that repairs DNA damage caused by internal and external environmental factors (e.g., reactive oxygen species, radiation, chemicals, oxidative stress). It involves multiple repair mechanisms, including direct repair, base excision repair, nucleotide excision repair, double-strand break repair, and crosslink repair (De Bont and van Larebeke, 2004, Wang et al., 2023a, Sancar et al., 2004, Souliotis et al., 2019). These repair mechanisms are essential for maintaining genomic stability (Smith et al., 2021). Given that the lungs are directly exposed to external environment and often encounter harmful substances, they are particularly susceptible to DNA damage, which can impact lung health (Zhang et al., 2024). Typically, the body initiates a series of DNA repair mechanisms in response to DNA damage. However, if repair is insufficient or fails, damaged DNA may attack lung tissues, leading to pulmonary diseases such as IPF (Zhu et al., 2022), pulmonary hypertension (Sharma and Aldred, 2020), chronic obstructive pulmonary disease (COPD) (Sauler et al., 2018), and even lung cancer (Zhang et al., 2022). Thus, DDR plays a critical role in IPF pathogenesis. However, diagnostic value of DDR genes in IPF has not been fully explored. Therefore, investigating role of DDR in IPF is of great significance for understanding its pathogenesis and developing novel diagnostic approaches.
The present study aimed to identify DDR-related core genes involved in the progression of IPF and to assess their diagnostic potential and immunological associations. In this regard, we conducted a comprehensive analysis of multiple IPF transcriptomic datasets to characterize diagnostic value of DDR genes and determine their relationship with IPF immune microenvironment. We predicted several miRNAs that may regulate DDR genes. These findings hold important implications for early diagnosis and targeted progression of IPF.
The increasing incidence of emerging infectious diseases emphasizes the urgent need for timely and accurate global surveillance and early warning systems. In recent years, infectious disease surveillance has become more diversified, and early warning technologies have seen significant advancements in sensitivity and timeliness. This review outlines the evolution and application of infectious disease surveillance and focuses on the potential of the One Health approach. By integrating data across human, animal, and environmental domains, the One Health approach provides a more comprehensive and effective framework for addressing future pandemics. Furthermore, this review systematically introduces key concepts in infectious disease early warning that include the selection of warning thresholds and the categorization of warning models. This review also summarizes representative global early warning systems for infectious diseases, discusses their prospects, and offers insights for developing intelligent, multi-source data-driven monitoring and early warning systems globally.
In recent years, the incidence and impact of emerging infectious diseases have increased significantly, with notable outbreaks such as the 2003 severe acute respiratory syndrome (SARS), the 2009 swine flu pandemic, the 2012 Middle East respiratory syndrome (MERS), and, most recently, the coronavirus disease 2019 (COVID-19) pandemic.1 These events highlight the urgent need for more robust and holistic infectious disease surveillance and early warning systems that allow the timely monitoring, detection, and assessment of emerging health threats.2, 3
Surveillance systems made significant advancements during the COVID-19 pandemic, particularly in the use of wastewater surveillance and digital methods such as mobility tracking and infodemiology.4 However, notable gaps still remain. One major issue is that existing systems continue to focus primarily on human health, with hospital-based surveillance forming the backbone. However, hospital-based systems often experience delays in detecting anomalies, emphasizing the need for further enhancements to address future pandemic risks.5 Another challenge is the disparity in monitoring capabilities across countries. Whereas some nations have well-established infrastructures, others face barriers, including limited resources, a lack of laboratory capabilities, political instability, and inadequate data-sharing systems, which further hamper global efforts in detecting and responding to emerging infectious diseases.6, 7 For example, since October 2024, the Democratic Republic of the Congo has been struck by an undiagnosed disease that includes symptoms of fever, headache, cough, runny nose, and body ache. However, the cause was not identified until 2 months later, in December, as an acute respiratory infection complicated by malaria, further indicating regional disparities in resources and diagnostic capabilities.
The performance of early warning systems is closely linked to the effectiveness of disease surveillance because these systems transform data into actionable insights. Early warning techniques have also evolved considerably with the expansion of data sources and advancements in computational power. Today, multi-channel surveillance data are integrated to assess factors that influence the spatiotemporal spread of diseases, expanding the range of indicators to include symptoms, risk factors (e.g., meteorological conditions, vector density, and pathogen data), population mobility, and even internet queries.8 Moreover, the scope of early warning has broadened to include spatial and spatiotemporal warnings, thus offering a more comprehensive view of disease dynamics.9 Furthermore, earlier warning techniques have relied primarily on time series models that issue real-time alerts. However, modern systems now employ a range of advanced algorithms, including machine learning and deep learning,10 to forecast trends and provide proactive alerts that enable earlier resource preparation and better allocation.
The soil ecosystem is a dynamic environment teeming with life, where countless microorganisms engage in complex interactions that regulate nutrient cycling, plant health, and ecosystem stability. Among these microorganisms, fungi and bacteria represent two dominant groups that play pivotal roles in soil nitrogen dynamics. Their intricate competition and cooperation over nitrogen — an essential nutrient for plant growth — have significant implications for soil fertility, agricultural productivity, and environmental sustainability. This fascinating interplay is often described as a "nitrogen battle," a silent yet crucial contest that shapes the health and function of terrestrial ecosystems.
Nitrogen is a key component of amino acids, proteins, nucleic acids, and chlorophyll, making it indispensable for both plants and microorganisms. Despite being abundant in the atmosphere as dinitrogen (N₂), most plants cannot directly utilize this inert form. It is through microbial activity in the soil that nitrogen becomes bioavailable, undergoing transformations via processes such as nitrogen fixation, ammonification, nitrification, and denitrification. Bacteria and fungi both contribute significantly to these pathways, albeit with distinct strategies, enzymatic capabilities, and ecological niches.
Bacteria are renowned for their ability to fix atmospheric nitrogen. Nitrogen-fixing bacteria, such as Rhizobium species, establish symbiotic relationships with leguminous plants, converting atmospheric nitrogen into ammonia (NH₃), a form plants can assimilate. Free-living nitrogen fixers like Azotobacter and Clostridium also contribute to this process in the soil. In addition, bacterial communities play a central role in nitrification — the oxidation of ammonia to nitrite (NO₂⁻) and subsequently to nitrate (NO₃⁻) — primarily conducted by nitrifying bacteria such as Nitrosomonas and Nitrobacter. These transformations increase nitrogen availability but can also lead to nitrogen losses through leaching and denitrification under certain conditions.
Fungi, on the other hand, are traditionally recognized for their roles in decomposing complex organic matter and recycling nutrients within the soil. Saprophytic fungi break down lignin, cellulose, and other resistant organic compounds, releasing organic nitrogen in the form of ammonium (NH₄⁺) through the process of ammonification. Mycorrhizal fungi, particularly arbuscular mycorrhizal fungi (AMF), form mutualistic associations with plant roots, enhancing nitrogen and phosphorus uptake while receiving carbohydrates from the host plant. Certain ectomycorrhizal fungi can also access organic nitrogen pools that are otherwise unavailable to plants, positioning fungi as key players in nitrogen mineralization and uptake.
Fleas are wingless ectoparasites that feed on the blood of warm-blooded animals and play a significant role as vectors of several medically and veterinary-relevant diseases. The oriental cat flea, Ctenocephalides orientis, is endemic to Asia and infests dogs more frequently than cats. However, its presence in small ruminants remains largely unexplored. Between January 2017 and October 2023, flea surveys were conducted on goat farms across seven different provinces in Thailand. Initially, flea specimens were identified using morphological keys and, subsequently, confirmed through molecular analysis of the mitochondrial genes cytochrome c oxidase subunit 1 (cox1, 450 bp) and cytochrome c oxidase subunit 2 (cox2, 678 bp), the nuclear ribosomal internal transcribed spacer 1 (ITS1, 828 bp) and the elongation factor-1 alpha (EF-1α, 904 bp) gene. In addition to characterizing these markers, the mitochondrial genome, including all protein-coding genes (PCGs), was amplified, analyzed, and subjected to comparative analyses. Among 500 goats examined, 33 (6.6%) were infested with fleas, which belonged to only one species, C. orientis. Pairwise genetic distance analysis and phylogenetic reconstruction strongly supported the placement of C. orientis within a distinct clade, consistent with the reference sequences. Of the four genetic markers analyzed, EF-1α exhibited the highest diversity. The partial mitochondrial genome of C. orientalis (14,315 bp) encoding 34 genes, including 13 PCGs, 19 transfer RNA genes, and two ribosomal RNA genes, was sequenced. Phylogenetic and genetic distance analyses based on multiple molecular markers and the mitochondrial genome revealed a close evolutionary relationship between C. orientis and C. canis. These findings confirmed that C. orientis is not only restricted to companion animals but also infests goats, suggesting its potential role in disease transmission to other animals. Furthermore, the study findings provide a dataset of both nuclear and mitochondrial molecular markers, which would facilitate future research on the taxonomy, phylogeny, and evolutionary relationships of fleas.
Protein-based therapeutics have garnered increasing attention across various medical fields for their substantial benefits to human health. Existing strategies for intracellular protein delivery, such as cell-penetrating peptide (CPP)-based approaches, including the transactivator of transcription (TAT) peptide, have shown promising results but also present limitations, particularly due to the need for recombinant protein manufacturing and daily invasive administration. To overcome such hindrances and develop delivery tools that are able to foster the production of the protein directly inside the body of patients, we engineered the lactic acid bacterium, Lactococcus lactis, to express and secrete TATκ-GFP protein. After oral administration of the recombinant L. lactis in mice, we found the presence of the TATκ-GFP protein not only in the intestinal wall but also in the mouse liver, heart, and brain
Thermotolerance has been viewed as an uncommon characteristic among the fungi and one of the reasons that less than 1% of the described species operate as opportunistic pathogens of humans. Growth at 37°C is certainly a requirement for a fungus that invades the body core, but tens of thousands of nonpathogenic species are also able to grow at this temperature. Ergo, body temperature does not serve as a thermal barrier to the development of infections by many harmless fungi. The absence of other virulence factors must be more demanding. This observation raises questions about the hypothetical links between climate change and the increasing number of life-threatening human mycoses. Given the widespread distribution of fungal thermotolerance and the 1°C (2°F) increase in global temperature over the last 140 years it seems unlikely that the warming climate has driven the evolution of more virulent strains of fungi. More compelling explanations for the changes in the behavior of fungi as disease agents include their adaptation to the widening use of azoleantifungals in hospitals and the wholesale application of millions of tons of the same class of heterocyclic chemicals in agriculture. On the other hand, climate change is having a significant effect on the spread of human mycoses by extending the geographical range of pathogenic fungi. A related increase in fungal asthma caused by spore inhalation is another likely consequence of planetary change.
