With the growing use of immunosuppressive therapies, clinicians are increasingly faced with the question of how to manage positive interferon-gamma release assays (IGRA). Atuberculosis infection (TBI, formerly referred to as "latent tuberculosis") is clinically silent and non-contagious but can reactivate as active tuberculosis under immunosuppressive conditions. Diagnosis involves either an IGRA or atuberculin skin test (TST), alongside microbiological and imaging studies to exclude active disease. Screening is recommended for individuals at increased risk, including those living with human immunodeficiency virus (HIV), those in close contact with tuberculosis patients, and those scheduled to receive certain immunosuppressive treatments, as well as individuals undergoing transplantation or dialysis, or those suffering from silicosis. Preventive therapy with tuberculostatic medication markedly reduces the risk of reactivation and should ideally be initiated at least 4weeks before starting immunosuppressive therapy.

Synapsis, the physical bridging of two broken DNA ends, is a critical step in non-homologous DNA end joining (NHEJ), the primary pathway for repairing DNA double-strand breaks (DSBs) in vertebrates. While NHEJ synapsis has been well characterized using blunt-ended DNA, how diverse DNA end configurations influence synaptic complex formation remains much less clear. Here, using single-molecule FRET, we show that end configurations play a decisive role in synapsis pathway choice, with end pairing compensating for XLF in facilitating synaptic complex transitions. Notably, 3-nucleotide (nt) microhomology at DNA ends significantly enhances close synaptic (CS) complex formation mediated by Ku70-Ku80 (Ku) and XRCC4-Ligase IV (X4L4), even in the absence of XLF. Although XLF is nonessential for synapsis with 3-nt microhomology, it further promotes CS formation when present. The FRET analysis reveals that the single-stranded and double-stranded junctions of the DNA ends are in close contact within the primary CS complex, while the overhangs flip out of the duplex, potentially stabilizing the complex. These findings underscore the pivotal role of DNA end configurations in regulating synapsis and their broader implications for NHEJ repair efficiency and fidelity.

Achieving balance in tendon repair is essential for restoring optimal function after tendon injuries, particularly in the hand and upper limb. We review and discuss key steps of 'balanced' flexor and extensor tendon repair and rehabilitation.Flexor tendon repair:To achieve optimal outcomes of tendon repair, the surgeon needs to consider the balance between mechanical strength and tendon nutrition. Strong multi-strand repairs provide security against gapping and rupture, but overly tight or running epitenon sutures may impair synovial and blood supply to epitenon. Pulley venting in zone 2 is another balance: too little venting risks the repair catching or rupturing, while too much venting risks bowstringing. In the wide-awake setting, intraoperative excursion testing shows the ideal venting length that allows a solid repair to glide freely without clinically significant bowstringing.In contaminated wounds, delayed repair avoids the risk of infection. Primary repairs are possible 1-2 weeks after injury, and even very late repairs can succeed if strong multi-strand core sutures are used and tension is carefully balanced. Repair tension should be sufficient to ensure that tendon ends are in close contact with slight bulkiness at the repair site to ensure a solid repair that allows early active digital motion.Extensor tendon repair and rehabilitation:Extensor tendon injuries proximal to the fingers also require balance between protection and movement. Immobilization risks stiffness, while early relative motion splinting with strong repairs allows safer functional use or early active motion exercise. Pain-guided active mobilization and patient education further help maintain glide without rupture. Successful treatment requires a balance of various aspects of the repair process, including anatomical prerequisites, surgical techniques and rehabilitation strategies, through a multifaceted approach that encompasses careful surgical planning, accurate surgical repairs, optimal therapy protocol design and patient engagement.

Domesticated dogs used for hunting come into close contact with humans, domestic animals and wildlife, exposing them to ticks and tick-borne pathogens. It is crucial to include them in surveillance activities to monitor the spread of zoonotic pathogens and formulate effective preventive and control measures. This study sought to examine the diversity of tick species infesting hunting dogs and to detect the DNA of tick-borne pathogens they carry. Ticks were collected from 28 hunting dogs, morphologically identified using available taxonomic keys, and their identifications confirmed by molecular methods. Total nucleic acid was extracted from individual tick species and screened for pathogens using PCR and Sanger sequencing. A total of 142 ticks were identified, with Rhipicephalus sanguineus (85.94%) as the predominant species. This study reports the first molecular confirmation and report of Amblyomma sparsum, Haemaphysalis parva, Rhipicephalus leporis and Rhipicephalus linnaei in Ghana. Pathogen DNA was detected in 31 (21.83%) of the ticks, with the occurring pathogens as Hepatozoon canis (13.28%), Uncultured Anaplasma sp. (7.75%), Ehrlichia canis (7.04%), Rickettsia africae (1.41%) and Uncultured Rickettsia sp. (0.7%). The findings of this study indicate that hunting dogs can be useful sentinels in monitoring tick populations and the spillover of zoonotic tick-borne pathogens from wildlife to humans and domestic animals. This study highlights the need for education, surveillance, and tick control strategies in Ghanaian dog populations to reduce the threat of zoonotic disease establishment and transmission.

Solid electrolytes are promising candidates for safe, high-energy battery systems. Composite solid electrolytes, in particular, hold the potential to combine high ionic conductivity with stable electrode interfaces. However, a fundamental trade-off often exists between ion conduction and mechanical properties. Here we present a composite solid electrolyte design that decouples ion conduction from mechanical flexibility, achieving a high ionic conductivity of 10.2 mS cm-1 at 25 °C while maintaining close mechanical contact with the electrode. The composite architecture consists of alternating layers of perpendicularly aligned (PA) Li0.3Cd0.85PS3 nanosheets, to establish continuous superionic conduction pathways, and Li-containing polyethylene oxide (PEO) layers, to ensure flexibility and interfacial compatibility. At 25 °C, this PA-Li0.3Cd0.85PS3/PEO electrolyte enables Li||LiNi0.8Co0.1Mn0.1O2 coin cells (stack pressure during assembly <0.5 MPa) to retain 92% discharge capacity after 600 cycles at 0.2 mA cm-2, with an average cycling Coulombic efficiency of 99.9%, and also facilitates practical use of pressure-less (stack pressure <0.1 MPa) Li||LiFePO4 pouch cells. This composite design strategy is further validated by substituting Cd with Mn in the inorganic sulfide nanosheets to produce a PA-Li0.46Mn0.77PS3/PEO electrolyte, exhibiting an ionic conductivity of 6.1 mS cm-1 at 25 °C and good mechanical flexibility.

In this paper we explore the interaction between Maghrebi Darijas and Romance languages from the perspective of both historical and contemporary evidence. As Caubet 2002, following Lahlou 1991 argues, among contemporary educated populations in urban centres across the Maghreb, bilingual/multilingual interaction is the norm not the exception. Historical evidence tells us this was also the case in 11th century al-Andalus, though it is of course impossible down the centuries to reconstruct the actual interaction. We will however argue that certain surviving texts can provide an indication when analysed in terms of the constraints on conversational codeswitching such as is provided by Aabi. We start from the position that Maghrebi Darija is a special case of linguistic permeability due to its politico-geographic location on the frontier and given its thousand year history of close contact with Romance. To investigate this phenomenon in both its historical and contemporary manifestations we draw on the current construct of translanguaging, an alternative perspective on multilingual interaction to code switching as expounded in Baynham &amp; Lee (2018) and the notion of convivencia as elaborated by Bossong in his study of linguistic conviviality and coexistence in mediaeval Andalusian poetry (Bossong 2010). We then go on to analyze this in two time slices: examining evidence of the productive convivencia/coexistence of romance and dialectal Arabic i) in the kharjas of 11th century al-Andalus as discussed by Bossong and others and ii) in the modern Maghreb music and performance scene (cf. Caubet 2002; Baynham &amp; Gintsburg 2022). We do this here through analysis of a song by the Algerian singer Talyani and a performance of the Moroccan comedian Hanane el-Fadhili, using in both time slices translanguaging and Bossong’s notion of convivencia in our analysis. We then conclude by arguing as Heath (2020) does that for effective research into such varieties as Maghrebi Arabic, both currently and historically, it is necessary for cross disciplinary work between researchers in Arabic and its Romance contact languages, in order to fully address its sociolinguistics. We understand this as a form of disciplinary translanguaging to be undertaken in order to establish the dynamics of the convivencia/coexistence of Arabic and Romance elements in this type of data.

Background Tuberculosis infection affects an estimated one-quarter of the global population and represents a key target for TB elimination strategies. While interferon-gamma release assays (IGRAs) such as QuantiFERON-TB Gold Plus (QFT-Plus) are WHO-endorsed, they remain logistically complex in low-resource settings. This study evaluates the performance of the AFIAS IGRA-TB, a qualitative fluorescence immunoassay (FIA), compared to QFT-Plus in Paraguay. Methods A cross-sectional diagnostic accuracy study was conducted from January to May 2025 among 210 individuals aged 18–59 years within the Barrio Obrero healthcare network in Asunción, Paraguay. Participants were stratified into three TB risk groups: low-risk (no known exposure), high-risk (close contacts and incarcerated individuals), and active TB cases. Blood samples were tested with both AFIAS and QFT-Plus assays. Discordant results were retested after six to eight weeks. Concordance was assessed using Cohen’s Kappa; quantitative correlations and ROC curves were also analysed. Results Of 210 participants, 75.2% were male. Overall positivity rates were 38.5% for QFT-Plus and 37.0% for AFIAS, with an agreement of 89.0% ( κ = 0.767; p &amp;lt; 0.0001). Strong concordance was observed in high-risk groups. Among 23 discordant cases, retesting confirmed the initial AFIAS result in 5 cases and QFT-Plus in 3; 7 remained discordant. Spearman correlation showed strong, significant association between quantitative values. ROC analysis yielded an AUC of 0.890 for AFIAS. Conclusion AFIAS IGRA-TB demonstrates comparable performance to QFT-Plus with operational advantages, suggesting it is a viable diagnostic alternative for TB infection, particularly in decentralized or resource-limited settings.

The West Africa Ebola virus disease (EVD) outbreak resulted in over 28,000 individuals infected, primarily in Liberia, Guinea, and Sierra Leone. Data from previous outbreaks indicate lasting health problems in survivors. The long-term neurologic impact of EVD remains largely unknown. The aim of this study was to characterize the neurologic and neurocognitive sequelae of EVD in pediatric survivors of the 2015 outbreak in Liberia. In this cross-sectional observational study conducted in Monrovia, Liberia, pediatric survivors of acute EVD aged younger than 18 years at the time of infection and older than 2 years at the time of the visit, along with their asymptomatic close contacts as controls, were seen at a median of 18 months after EVD. The single clinic visit included a neurologic history and symptom questionnaire, neurologic examination, and neurocognitive testing. Seropositive survivors and seronegative controls were included in analyses, with the t test used for continuous variables and the χ2 or Fisher exact test used for categorical variables. The cohort included 31 EVD cases and 41 controls, with a median age of 11 years (44% female). Neurologic symptoms that were reported significantly more frequently in cases than in controls included arm/leg weakness (67.7% vs 4.9%, p < 0.0001); problems with sitting, standing, or walking (22.6% vs 4.9%, p = 0.031); difficulty seeing (38.7% vs 9.8%, p = 0.003); difficulty understanding speech (32.3% vs 0%, p < 0.0001); fecal incontinence (19.4% vs 0%, p = 0.0051); and lack of motivation (22.2% vs 0%, p = 0.0052). EVD cases more often demonstrated disability than controls on the modified Rankin Scale. EVD cases "either sometimes or often" faced consequences for poor behavior, became upset for unknown reasons, and had difficulty completing tasks independently more often than controls on executive function assessment. There was no significant difference between groups in individual neurologic examination components, frequency of uveitis, or cognitive test scores. Numerous neurologic symptoms were reported more commonly in EVD cases than in controls, suggesting that EVD may have a lasting effect on the nervous system. Limitations included small sample size and reliance on participant self-report. Our findings highlight the importance of long-term clinical monitoring of pediatric EVD survivors, given the potential impact on childhood development.

Introduction Viral haemorrhagic fevers such as Rift Valley fever, Crimean-Congo haemorrhagic fever, and hantavirus disease continue to threaten public health in Africa. This study assessed the seroprevalence and associated factors of these infections in Senegal. Methods A cross-sectional survey was conducted from September 2022 to June 2024 among asymptomatic individuals living in close contact with livestock in two regions: Matam, a transboundary area; and Thiès, a non-transboundary area with high livestock density. Participants completed standardized questionnaires, and serum samples were screened for antibodies against Rift Valley fever virus, Crimean-Congo haemorrhagic fever virus, and Hantaan virus using a Luminex-based multiplex immunoassay. Logistic regression models were used to identify independent risk factors. Results Among 2,019 participants, crude seroprevalence was 15.1 percent (95 percent confidence interval: 13.5–16.7) for Rift Valley fever virus, 10.8 percent (9.4–12.2) for Crimean-Congo haemorrhagic fever virus, and 2.2 percent (1.6–3.0) for Hantaan virus. Exposure to Rift Valley fever virus was higher in Matam than in Thiès, whereas exposures to the other two viruses were higher in Thiès. Older age and male sex were consistently associated with infection, and exposure to Crimean-Congo haemorrhagic fever virus was also linked to raw milk consumption and slaughterhouse work. During the study, the national sentinel surveillance system detected only one case each of Rift Valley fever and Crimean-Congo haemorrhagic fever, indicating a substantial cases under-detection. Conclusions This study provides serological evidence of human hantavirus exposure in Senegal and confirms subclinical circulation of Rift Valley and Crimean-Congo haemorrhagic fevers. Our results suggest that routine surveillance is missing the vast majority of infections. These viruses circulate endemically within exposed populations, often in an asymptomatic or subclinical state, or manifesting with mild symptoms. This under-detection by the current monitoring system poses a significant challenge to the implementation of effective control strategies in endemic regions. This highlights the need to strengthen One Health surveillance to ensure early warning and public health preparedness.

Cementless femoral stem in arthroplasty for hip fracture: Early radiological subsidence at 3 months and predictive factor out of 117 cases.

BackgroundGlobal surges attributed to whooping cough, caused by Bordetella pertussis, are widespread. Maternal Tdap demonstrates success in preventing infant morbidity and mortality, however, cases predominate in adolescents. Unvaccinated individuals are at risk of infection. However, further exploration is warranted regarding waning immunity. This investigation outlines a whooping cough outbreak.Methods38 cases were identified from July 2024-December 2024 through health facilities, schools, families and the Michigan Disease Surveillance System (MDSS). Cases were investigated using the MDSS pertussis case investigation form for demographics, symptoms, hospitalization, vaccination, treatment and contact tracing. Close contacts were notified for mitigation. Immunizations and waiver data was obtained through the Michigan Care Improvement Registry (MCIR).Results38 cases were identified, 1-84 years old (median 14). 61% (n=23) of infections occurred in 11-18 years, 13% (n=5) each in 1-6, 7-10, and 19+ age cohorts. 61% were fully vaccinated (n=23), 26% unvaccinated (n=10), 14% outdated/unknown status (n=5). Average time since last dose among fully vaccinated was 23.5 months in 1-6 years (n=2), 66.25 in 7-10 (n=4), 48.5 in 11-18 (n=16) and 62 in 19+(n=1) cohorts. Primary symptoms were cough (100%), paroxysms of cough (68%), inspiratory whoop (21%), post-tussive vomiting (21%). 100% received treatment, 2 were hospitalized, no deaths and no cases in < 1-year olds. 11 schools and 1 daycare were affected. Among the top two schools with students impacted, immunization waiver percentages were 14% each, compared to county waivers of 8%.ConclusionTwo major factors are seen in our outbreak: 1) prolonged time since last dose for fully vaccinated individuals, and 2) non/under vaccinated people. Immunizations waivers place unvaccinated at high risk for infection. Efforts to encourage vaccination continue. However, the number of cases in fully vaccinated youth underscore the need to investigate waning immunity. The economic impact on individuals, families and society causing classroom shutdowns, sick time, lost wages, and over-utilization of healthcare and personnel resources persist. Consideration of boosters after adolescent Tdap or improved vaccine development are necessary.DisclosuresSeema Joshi, MD, Cephied: Grant/Research Support Marcus Zervos, MD, merck: Honoraria

BackgroundGroup A Streptococcus pyogenes (GAS) is a leading cause of infectious death globally. Hospital acquired (HA) GAS is particularly burdensome for infection preventionists, administrators, and involved healthcare workers (HCW). After a cluster of fulminant infections (death < / = 48 hrs. from symptom onset), we sought to evaluate the genetic relatedness of the isolates to an HA GAS outbreak that occurred at our facility in 2017and ascertain the genomic epidemiology of invasive GAS (iGAS).Figure 2Heat map showing virulence gene content of 36 Group A Streptococcus isolatesMethodsContact tracing and testing of all HWCs with close contact to any patient with possible HA iGAS and an ambidirectional approach were used. All iGAS one year preceding and one year following the index case were collected and underwent whole genome sequencing (WGS). Medical records of the cases prior and subsequent to the index case were retro- and prospectively reviewed. Additionally, six individual GAS colonies from the throat culture of the only positive HCW were sequenced to assess for intra-colony variation. Results were stratified according to outcome, strain type (ST), and emm type.Table 1Patient and Isolate Characteristics of Fulminant InfectionsResultsFrom 01/01/2023 to 04/01/2025, 40 isolates from 36 patients and the only positive HCW clustered into 13 lineages and 12 emm types. Within each lineage, clusters of high genetic relatedness were identified. However, all isolates from patients with any spatial-temporal or other epidemiologic connection were unrelated, including the ones from the 2017 outbreak (Figure 1). The index isolate belonged to ST-15 emm 3.1. Virulence gene content visually correlated with ST (Figure 2). Although some of isolates from fulminant infections were genetically related, there was no spatial, temporal, or epidemiologic connections among those isolates (Figure 1). There was no association between outcome and ST, or virulence gene content, or antibiotic resistance gene content (Figure 2, Table 1).ConclusionAll iGAS infections, including all fulminant infections, were community acquired. We found no citation explicitly reporting a ST 15 emm sub-type 3.1 in the U.S. Given the elusiveness of iGAS source attribution, these findings illustrate the importance of bolstering community surveillance efforts so that community data can inform outbreak investigation of HA GAS.DisclosuresAll Authors: No reported disclosures

Macrophages contribute to our immune defenses by phagocytosing pathogens and diseased cells. To accomplish this, they must first establish close contacts between receptors on their membranes and antibodies or other ligands decorating target cells. However, macrophage binding to the target can be disrupted by the presence of tall neighboring proteins and glycans-'bystander' molecules-that sterically prevent the two surfaces from coming into close contact. Counterintuitively, this inhibition can be overcome by the addition of even taller binding proteins between the macrophage and target cell, albeit at low concentrations. Using live cell and in vitro experiments, theory, and computer simulations, we show that tall binders can promote close contact that enables phagocytosis, even in the presence of bystander proteins that would normally block close contact.

The extracellular matrix (ECM) constitutes the bulk between cells, establishes barriers that separate tissue compartments, and defines the form and pliability of organs. The ECM is an integral part of the cellular microenvironment, conveying a multitude of biochemical (and mechanical) signals to associated cells, for example, by binding cytokines and chemotactic factors. All cells are in contact with the ECM, including immune cells in lymphoid organs and when they extravasate from blood vessels, as well as tissue-resident myeloid cells in close contact with the ECM of blood vessels. The past decade has seen technical advances in proteomics and transcriptomics that have provided large volumes of data on the diversity of the ECM and of the immune system. It is important to assess this rapidly growing body of data together with knowledge of the in vivo situation, particularly from more than a decade of intravital imaging studies. This Review summarizes both biochemical and imaging data that are relevant to leukocyte extravasation across the ECM - in particular, the basement membrane - to enter sites of inflammation, as well as the changes to the ECM that are associated with chronic inflammation, including tumour sites. It also discusses how this information may be exploited for the development of novel immunotherapies.

Abstract Cleaning mutualism between cleaner and client fish is fundamental to marine ecosystem health, significantly diminishing parasite burdens and enhancing host fitness. However, this interaction comes with epidemiological costs, as cleaner fish faces elevated infection risks due to close contact with clients, potentially destabilizing the mutualism. Despite its ecological significance, the cleaner-client mutualism remains to be analysed through mathematical model, in the context of disease dynamics. We develop a four-dimensional model that partitions cleaner and client fish into susceptible and infected classes, capturing both mutualistic benefits and infection costs. The system's boundedness is established, equilibrium points are identified, and their stability is analysed. Bifurcation analysis is performed to investigate threshold dynamics within the system. A rigorous analysis has been conducted to assess the impact of key parameters. Finally, numerical simulations are presented, and illustrative figures are provided to support the analytical findings.

Identification and phylogenetic analysis of a Brucella canis Isolate from an aborted canine fetus.

Bivalve planktonic development is a critical phase during which larvae must secrete the first calcium carbonate shell, the prodissoconch I (PD I). As PD I formation is in close contact with seawater, this process can be negatively affected by adverse seawater carbonate chemistry. It is hypothesized that bivalves can regulate shell formation under environmental stress through biologically controlled biomineralization involving a complex extracellular shell proteome. However, the plasticity of this regulatory mechanism during PD I development is unknown. We assessed the PD I shell proteome of the Hong Kong oyster (Magallana hongkongensis) in carbonate chemistry that was adverse or favorable for biomineralization to understand the regulatory capacity of larval shell formation. While survival rates were not affected in adverse carbonate chemistry, there were significant changes, including the upregulation of several calcium-binding proteins and downregulation of proton-generating processes and putative calcification inhibitors. With 198 sequences, the oyster larval shell proteome was twice to over six times larger than those reported for other bivalve species at the same developmental stage. However, in adverse carbonate chemistry, the oyster larval shells were thinner and smaller, and protein diversity decreased to 131 sequences, with overall lower functional redundancy and reduced expression of structural proteins, indicating potential trade-offs. The proteomic and shell structural data also suggest that direct cellular control and biologically induced mechanisms, which will require further investigation, may be involved in PD I formation.

Serosurveillance of Crimean-Congo hemorrhagic fever virus in zoo animals, Spain, 2007-2024.

To further improve the antibacterial performance of photocatalytic paper, a BiOBr/g-C3N4 photocatalyst was synthesized via a two-step method, involving calcination for g-C3N4 preparation followed by a solvothermal process for BiOBr/g-C3N4 composite formation. The BiOBr/g-C3N4 photocatalytic paper was fabricated by loading sunflower stalk pulp with a self-made hot-pressing device. In the composite, BiOBr and g-C3N4 form tight heterojunctions through close contact, facilitating efficient charge separation and enhancing visible-light utilization. The resulting photocatalytic paper exhibits excellent recyclability and strong antibacterial activity, achieving 99.99% antibacterial efficiency and extending the fruit preservation time by fourfold compared with the control group. This study provides a green and scalable approach for developing recyclable and biodegradable photocatalytic packaging materials with potential applications in sustainable food preservation.

We report a case of tsutsugamushi disease in a 41-year-old woman diagnosed during a non-endemic season in a previously low-incidence region without any history of outdoor exposure. The patient owned five cats with close contact that moved freely between the indoor and outdoor environments, suggesting the possibility that infected chiggers were carried indoors by the cats and transmitted Orientia tsutsugamushi to the patient. This case suggests that tsutsugamushi disease may be under-recognized and under-reported in such regions. Even in the absence of typical histories such as outdoor exposure, a detailed examination of pet ownership may help raise clinical suspicion.