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Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms. [ABSTRACT FROM AUTHOR]

Adrenomedullin has emerged as a promising biomarker in the field of viral diseases. Numerous studies have demonstrated its potential in assessing disease severity, predicting clinical outcomes, and monitoring treatment response. Adrenomedullin (AM) is a multifaceted peptide implicated in vasodilation, hormone secretion, antimicrobial defense, cellular growth, angiogenesis, and, importantly, chronic pain. AM and related peptides interface with cytoskeletal proteins within neuronal contexts, influencing microtubule dynamics. AM has primarily been utilized in diagnosing diseases of bacterial origin, including sepsis. Nevertheless, there are reports suggesting its utility in diseases of viral origin, and this is the focus of the present study. Furthermore, adrenomedullin has been shown to be elevated in various viral infections, suggesting its role in immune response modulation. Furthermore, AM may contribute to neuronal dysfunction through mechanisms involving immune and inflammatory responses, apoptosis, and disruptions in calcium homeostasis. This review aims to consolidate current knowledge regarding AM and its potential implications in viral diseases, elucidating its diverse roles in neurological pathophysiology. This review highlights the growing importance of adrenomedullin as a biomarker in viral diseases and the need for further functional studies to understand the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

The plant vascular system is not only a transportation system for delivering nutrients but also a highway transport network for spreading viruses. Tomato spotted wilt orthotospovirus (TSWV) is among the most destructive viruses that cause serious losses in economically important crops worldwide. However, there is minimal information about the long-distance movements of TSWV in the host plant vascular system. In this this study, we confirm that TSWV virions are present in the xylem as observed by transmission electron microscopy (TEM). Further, a quantitative proteomic analysis based on label-free methods was conducted to reveal the uniqueness of protein expression in xylem sap during TSWV infection. Thus, this study identified and quantified 3305 proteins in two groups. Furthermore, TSWV infection induced three viral structural proteins, N, Gn and Gc, and 315 host proteins differentially expressed in xylem (163 up-regulated and 152 down-regulated). GO enrichment analysis showed up-regulated proteins significantly enriched in homeostasis, wounding, defense response, and DNA integration terms, while down-regulated proteins significantly enriched in cell wall biogenesis/xyloglucan metabolic process-related terms. KEGG enrichment analysis showed that the differentially expressed proteins (DEPs) were most strongly associated with plant-pathogen interaction, MAPK signaling pathway, and plant hormone signal transduction. Cluster analysis of DEPs function showed the DEPs can be categorized into cell wall metabolism-related proteins, antioxidant proteins, PCD-related proteins, host defense proteins such as receptor-like kinases (RLKs), salicylic acid binding protein (SABP), pathogenesis related proteins (PR), DNA methylation, and proteinase inhibitor (PI). Finally, parallel reaction monitoring (PRM) validated 20 DEPs, demonstrating that the protein abundances were consistent between label-free and PRM data. Finally, 11 genes were selected for RT-qPCR validation of the DEPs and label-free-based proteomic analysis concordant results. Our results contribute to existing knowledge on the complexity of host plant xylem system response to virus infection and provide a basis for further study of the mechanism underlying TSWV long-distance movement in host plant vascular system. [ABSTRACT FROM AUTHOR]

Background/Objectives: As a primary source of mortality and disability, bacterial infections continue to develop a severe threat to humanity. Nuclear medicine imaging (NMI) is known for its promising potential to diagnose deep-seated bacterial infections. This work aims to develop a new technetium-99m (99mTc) labeled tigecycline radiopharmaceutical as an infection imaging agent. Methods: Reduced 99mTc was used to make a coordinate complex with tigecycline at pH 7.7–7.9 at room temperature. Instantaneous thin-layer chromatography impregnated with silica gel (ITLC-SG) and ray detector equipped high-performance liquid chromatography (ray-HPLC) was performed to access the radiolabeling yield and radiochemical purity (RCP). Results: More than 91% labeling efficiency was achieved after 25 min of mild shaking of the reaction mixture. The radiolabeled complex was found intact up to 4 h in saline. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) infection-induced rats were used to record the biodistribution of the radiopharmaceutical and its target specificity; 2 h' post-injection biodistribution revealed a 2.39 ± 0.29 target/non-target (T/NT) ratio in the E. coli infection-induced animal model, while a 2.9 ± 0.31 T/NT value was recorded in the S. aureus bacterial infection-induced animal model. [99mTc]Tc-tigecycline scintigraphy was performed in healthy rabbits using a single photon emission computed tomography (SPECT) camera. Scintigrams showed normal kidney perfusion and excretion into the bladder. Conclusion: In conclusion, the newly developed [99mTc]Tc-tigecycline radiopharmaceutical could be considered to diagnose broad-spectrum bacterial infections. [ABSTRACT FROM AUTHOR]

Fracture-related infection (FRI) is a devastating event, directly affecting fracture healing, impairing patient function, prolonging treatment, and increasing healthcare costs. Time plays a decisive role in prognosis, as biofilm maturation leads to the development of antibiotic resistance, potentially contributing to infection chronicity and increasing morbidity and mortality. Research exploring the association between biofilm maturation and antibiotic resistance in orthopaedics primarily addresses aspects related to quality of life and physical function; however, little exists on life-threatening conditions and mortality. Understanding the intrinsic relationship between biofilm maturation, bacterial resistance, and mortality is critical in all fields of medicine. In the herein narrative review, we summarize recent evidence regarding biofilm formation, antibiotic resistance, and infection chronicity (BARI), the three basic components of the "triangle of death" of FRI, and its implications. Preoperative, perioperative, and postoperative prevention strategies to avoid the "triangle of death" of FRI are presented and discussed. Additionally, the importance of the orthopaedic trauma surgeon in understanding new tools to combat infections related to orthopaedic devices is highlighted. [ABSTRACT FROM AUTHOR]

Background/Objectives: Acute exacerbation (AE) of interstitial lung disease (ILD) is a major challenge. This study aimed to retrospectively investigate occurrences of AEs in patients with ILDs, including idiopathic pulmonary fibrosis (IPF), non-IPF (iNSIP: idiopathic nonspecific interstitial pneumonia), and connective tissue disease (CTD)-associated ILDs (CTD-ILDs), at a single tertiary center before and after the coronavirus disease 2019 (COVID-19) pandemic. The study aimed to clarify the seasonal and regional trends of AEs of ILDs, assess the roles of viral and bacterial infections, and identify key prognostic factors for patient outcomes. Methods: We conducted a retrospective review of hospitalized adult patients with AEs of ILDs from January 2019 to February 2024. Results: A total of 93 patients were enrolled: IPF (n = 42), iNSIP (n = 37), and CTD-ILDs (n = 14). The median age was 80 years (interquartile range: 74.0–86.0 years), with males comprising 64.5% (n = 60). AEs of ILDs predominantly occurred in winter and were particularly notable after summer 2023, coinciding with the lifting of COVID-19-related travel restrictions in Japan. Patient referrals from different areas (Northern Tama, East and/or Southern Tama, and other Tokyo metropolitan areas) were evenly distributed throughout the study period. Viral infections were detected in only two patients (SARS-CoV-2), and bacterial infections included methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. The Cox regression analysis identified serum lactate dehydrogenase levels ≥350 IU/L and tachypnea (respiratory rate ≥ 30 breaths per min) on admission as prognostic factors for mortality, with a hazard ratio [HR] of 2.783 (95% confidence interval [CI]: 1.480–5.235, p = 0.001) and an HR of 3.332 (95% CI: 1.710–6.492, p < 0.001), respectively. Conclusions: AEs of ILDs predominantly occur in winter, and viral and bacterial infections are infrequently detected. Elevated serum LDH levels and tachypnea are crucial prognostic markers for mortality. This study highlights the seasonal trend in the AE of ILD and emphasizes the importance of specific prognostic indicators in clinical practice. [ABSTRACT FROM AUTHOR]

Background: medical teams continue to face challenges with infections following hip replacement surgery, whether they occur shortly after the procedure or months or years later. Certain medical conditions like diabetes, rheumatoid arthritis, and obesity are risk factors that make patients more susceptible to infections. Traditional intervention methods such as DAIR, one-step, or two-step procedures are being enhanced and refined to ensure quicker and more effective treatment. Some cases present particularly difficult challenges, featuring persistent fistulas and unpredictable responses to treatment. Methods: in our article, we share two unique cases, detailing their histories, progressions, and treatment decisions. We explore the use of antibiotic-impregnated calcium biocomposite as a local adjuvant therapy and the application of negative pressure therapy to expedite healing. The system of NWPT has seen widespread uptake and is now implemented routinely for open wounds, such as open fractures, fasciotomies, ulcers, and infected wounds. Results: our findings demonstrate that surgical debridement and calcium sulfate bead insertion successfully treat bone and joint infections without causing any side effects or complications. As a particularity, in the first case, we encountered the exteriorization of Stimulan pearls after surgery, without other complications related to the biocomposite. Conclusions: we have found that NPWT is a beneficial tool in managing complex wounds in both acute and chronic stages, after the infection is cured, reducing the need for frequent dressing changes, shortening hospital stays, and enhancing patient comfort. [ABSTRACT FROM AUTHOR]

Background: Biofilm formation in Helicobacter pylori (H. pylori) helps bacteria survive antibiotic exposure and supports bacterial colonization and persistence in the stomach. Most of the published articles have focused on one aspect of the biofilm. Therefore, we conducted the current study to better understand the mechanism of biofilm formation, how the biofilm contributes to antibiotic resistance, and how the biofilm modifies the medication delivery mechanism. Methods: We conducted a literature review analysis of the published articles on the Helicobacter pylori biofilm between 1998 and 2024 from the PubMed database to retrieve eligible articles. After applying the inclusion and exclusion criteria, two hundred and seventy-three articles were eligible for our study. Results: The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles. Conclusions: This infrastructure is responsible for the increased survival of bacteria, especially in harsh environments or in the presence of antibiotics. Therefore, understanding the biofilm formation for H. pylori is crucial. This study illustrates biofilm formation in H. pylori to help improve the treatment of H. pylori infection. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections are still a challenge in orthopedics and traumatology. Nowadays, genomics comes to the aid of diagnosis and treatment, in addition to traditional methods. Recently, a key role of the intestinal microbiota has been postulated, and great efforts are aimed at discovering its interconnection, which shows to be at different levels. Firstly, the gut microbiome influences the immune system through the gut-associated lymphoid tissue (GALT). A balanced microbiome promotes a strong immune response, which is essential to prevent all local and systemic infections, including PJI. Thus, a dysbiosis, i.e., the disruption of this system, leads to an imbalance between the various strains of microorganisms co-existing in the gut microbiome, which can result in a weakened immune system, increasing susceptibility to infections, including PJI. Additionally, the dysbiosis can result in the production of pro-inflammatory mediators that enter the systemic circulation, creating a state of chronic inflammation that can compromise the immune system's ability to fend off infections. Furthermore, the microbiome maintains the integrity of the gut barrier, preventing the translocation of harmful bacteria and endotoxins into the bloodstream; dysbiosis can compromise this protective "wall". In addition, the gut microbiome may harbor antibiotic-resistance genes; during antibiotic treatment for other infections or prophylaxis, these genes may be transferred to pathogenic bacteria, making the treatment of PJI more difficult. In this complex landscape, next-generation sequencing (NGS) technology can play a key role; indeed, it has revolutionized the study of the microbiome, allowing for detailed and comprehensive analysis of microbial communities. It offers insights into the functional potential and metabolic capabilities of the microbiome, studies the collective genome of the microbiome directly from environmental samples sequencing DNA without isolating individual organisms, analyzes the RNA transcripts to understand gene expression and functional activity of the microbiome, analyzes the RNA transcripts to understand gene expression and functional activity of the microbiome, investigates the metabolites produced by the microbiome and studies the entire set of proteins produced by the microbiome. NGS technology, the study of the micromyoma and its implications in the field of orthopedic trauma are innovative topics on which few publications are yet to be found in the international scientific literature. The costs are still high, the focus of research is maximum, and it will certainly change our approach to infections. Our study is an up-to-date review of the hot topic application of NGS in the study and investigation of periprosthetic infections and the microbiome. [ABSTRACT FROM AUTHOR]

Outbreaks of furunculosis cause significant losses in salmonid aquaculture worldwide. With a recent rise in antimicrobial resistance, regulatory measures to minimize the use of antibiotics in animal husbandry, including aquaculture, have increased scrutiny and availability of veterinary medical products to control this disease in production facilities. In such a regulatory environment, the utility of autogenous vaccines to assist with disease prevention and control as a veterinary-guided prophylactic measure is of high interest to the producers and veterinary services alike. However, evolving concepts of epidemiological units and epidemiological links need to be considered during approval and acceptance procedures for the application of autogenous vaccines in multiple aquaculture facilities. Here, we present the results of solid-state nanopore sequencing (Oxford Nanopore Technologies, ONT) performed on 54 isolates of Aeromonas salmonicida ssp. salmonicida sampled during clinical outbreaks of furunculosis in different aquaculture facilities from Bavaria, Germany, from 2017 to 2020. All of the performed analyses (phylogeny, single nucleotide polymorphism and 3D protein modeling for major immunogenic proteins) support a high probability that all studied isolates belong to the same epidemiological unit. Simultaneously, we describe a cost/effective method of whole genome analysis with the usage of ONT as a viable strategy to study outbreaks of other pathogens in the field of aquatic veterinary medicine for the purpose of developing the best autogenous vaccine candidates applicable to multiple aquaculture establishments. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore molecular measures of P. falciparum malaria burden (FOI and MOI) in the context of seasonal malaria chemoprevention. We analyzed malaria cases collected as part of a longitudinal cohort study. The cohort included P. falciparum-negative children aged 1.5 to 12, as confirmed by PCR 21 days after a radical cure using DHA-PQ or AS. Children were followed up for six months using active and passive case detection methods. At each visit, dried blood spots and blood smears were collected by finger prick, along with clinical data. Parasite DNA was extracted and analyzed by nested PCR for detection and genotyping of P. falciparum parasites. A total of 458 P. falciparum isolates collected during follow-up from October 2020 to March 2021 were genotyped. During the follow-up, children contracted 1.05 (95% IC [0.81–1.30]) new P. falciparum infections/child/time of exposure, and the MOI value was 3.00 (SD 1.60). Age is a protective factor (IRR: 0.74; 95% CI: 0.61, 0.90) against the occurrence of an episode of malaria, unlike an increase in MOI (IRR: 1.63; 95% CI: 1.04, 1.99), which is a favorable factor (p < 0.05). This study confirms the reduction in malaria transmission in our study area, probably due to the massive deployment of control tools. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes is responsible for 20–30% of pharyngitis in children and 5–15% in adults. The ineffective treatment of group A Streptococcus (GAS) infections can result in postinfectious sequelae. This study aims to evaluate the frequency of GAS pharyngitis and assess the management of patients with pharyngitis and antibiotic use. We conducted a multicenter, retrospective analysis of medical records from nine primary care centers in Poland. The study enrolled 1949 medical records of patients (children 67.4%, adults 32.6%). An infection of Streptococcus pyogenes, based on a rapid strep test, was diagnosed in 830 patients (42.6%). In the comprehensive study group of 1949 patients, 1054 (54.1%) were given antibiotics. Notably, 224 patients had a negative rapid strep test result but still received antibiotic treatment, underscoring the complexity of treatment decisions. The most commonly used antibiotics were oral penicillin V in 431 cases (41%) and amoxicillin in 219 cases (20.8%). We observed no significant difference between positive rapid strep test results and patients' sociodemographic data and comorbidities. The prevalence of GAS was 42.6% in the analyzed records of patients with pharyngitis, and 54.1% were prescribed antibiotics. Antibiotics were overprescribed for sore throats. Strategies are needed to promote rational antibiotic use. [ABSTRACT FROM AUTHOR]

Vegetables are an essential component of a balanced diet. The consumption of ready-to-eat foods may lead to the risk of infections and illnesses due to microbial contamination. To mitigate the potential of microbial contamination risks, it is critical to promote safe handling practices among consumers. In this study, our research evaluated the efficacy of different vegetable washing methods, specifically with lettuce, tomato, and cucumber, to establish optimal practices for reducing microbial contamination. This study consisted of two phases. Initially, a survey was distributed to 150 volunteers using snowball sampling to assess everyday vegetable handling and washing methods. The survey's results identified four predominant methods: washing with a 5% vinegar solution for 3 min followed by tap water rinse (37.3% of participants), rinsing with tap water for 1 min (29.3%), washing with a 5% salt solution (vegetable soap) for 3 min followed by a tap water rinse (16.6%), and a 3 min tap water rinse (14%). A minor segment (3.33%) reported not washing their vegetables at all. The survey's findings guided the second phase, which tested the aforementioned washing protocols' effectiveness in reducing Escherichia coli (E. coli) levels on spiked contaminated salad vegetables. The tested vegetables were sterilized using UV light, inoculated with 0.5 McFarland E. coli, and then washed using the four identified methods. After that, E. coli enumeration after washing was performed using 3M™ Petrifilm and the comparison was analyzed via one-way ANOVA. During this study, it was revealed that the cucumbers had the highest E. coli contamination levels in comparison to the lettuce and tomato after washing. Interestingly, by comparing the three washing methods, it was found that washing the vegetables with vinegar proved to be the most effective solution for reducing microbial presence on both lettuce and cucumbers. Notably, the natural smoothness of tomato skin led to no significant differences in contamination levels across washing methods. In summary, vinegar washing effectively reduces microbial contamination from salad vegetables, highlighting the need for informed consumer practices to prevent foodborne outbreaks. This study emphasizes the importance of monitoring contamination sources and using safe washing techniques. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we reported a peste des petits ruminants virus infection case in wild animals, and a virus strain was subsequently sequenced. Our results showed the existence of peste des petits ruminants virus in wild small ruminants in China, which was found to be closely related to the peste des petits ruminants virus isolated in China between 2013 and 2014. Our findings indicated that more attention should be paid to the prevention and control of wildlife diseases because there is the possibility of wild animals infecting domestic animals. In 2013, the second outbreak of peste des petits ruminants occurred in China, leading to a spillover in more than 20 provinces and municipalities over the next few months. Thereafter, the epidemic situation was stable owing to strict prevention and control measures. In February 2024, several bharals and argali with suspected symptoms of PPR were discovered in Rutog country, Tibet Autonomous Region. Samples collected from these animals were delivered to our laboratory for diagnosis; the results of fluorescence quantitative reverse-transcription (RT) PCR indicated that all samples were positive for PPR viral RNA. The N and F gene fragments were amplified successfully via RT-PCR, and these results confirmed that these animals were infected with PPRV. A PPRV strain (subsequently named ChinaTibet2024) was sequenced, and its genome length was 15,954 nucleotides. A phylogenetic tree analysis using N and F genes and viral genomes showed that the ChinaTibet2024 genome was classified into lineage IV of the PRRV genotypes. The genome of the ChinaTibet2024 strain was found to be closely related to PPRVs isolated in China between 2013 and 2014. A base insertion and a base deletion were detected in the M gene 5′ untranslated region. Results indicated that the prevalent PPRV strains in China did not show significant changes and that special attention should be paid to the surveillance of wild animals as an important part of PPR prevention and control. [ABSTRACT FROM AUTHOR]

We consider a space–time SI epidemic model with infection age dependent infectivity and non-local infections constructed on a grid of the torus T d = [ 0 , 1) d , where the individuals may migrate from node to node. The migration processes in either of the two states are assumed to be Markovian. We establish a functional law of large numbers by letting the initial approximate number of individuals on each node, N, to go to infinity and the mesh size of the grid, ε , to go to zero jointly. The limit is a system of parabolic PDE/integral equations. The constraint on the speed of convergence of the parameters N and ε is that N ε d → ∞ as (N , ε) → (+ ∞ , 0) . [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors (TETs) are uncommon malignancies uniquely associated with autoimmunity and immunodeficiency. Previous studies among patients with primary immunodeficiency diseases have shown that a low calculated globulin (CG) level, obtained by subtracting albumin from total protein level, is associated with infection risk. We investigated this association among patients with TET. Methods: A cross-sectional retrospective study was performed based on electronic medical records of patients with TET treated during 2002–2024 at a tertiary care institution. For each patient, their lowest CG level and the date of occurrence were identified. The incidence of serious infection requiring hospitalization during 6 months before and 6 months after the index date was recorded. Multivariable Poisson regression models were constructed. Results: Among 101 TET patients, 96 patients (95%) had the information available to derive at least one CG level. The median lowest CG level was 2.65 g/dL (range 1.0–4.2). There were 33 serious infection episodes. Pneumonia was the most prevalent type of infection in 52% of episodes. In a multivariable analysis, a CG level below 2.0 was independently associated with the prevalence of infection with a prevalence ratio of 6.18 (95% CI: 3.12–12.23, p < 0.001). Furthermore, thymectomy was significantly associated with infection. Conclusions: Among patients with TET, a low CG level was associated with an increased prevalence of serious infections. Our limited experiences suggest that it is feasible to derive the CG level for most patients during routine clinical care. [ABSTRACT FROM AUTHOR]

Background/Objectives: Human cytomegalovirus (HCMV) is the most frequent cause of congenital infections. The HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection in pregnancy. In this study, the antigen-specific T-cell response against different HCMV proteins (IE-1, pp65, gB, gHgLpUL128L) was investigated in pregnant women with primary infection and in control subjects with remote infection to identify possible components of a vaccine. Methods: Blood samples from 35 pregnant women with HCMV primary infection and 30 HCMV-seropositive healthy adult subjects with remote infection were tested. The antigen-specific T-cell response was measured using cytokine intracellular staining after stimulation with IE-1, pp65, gB and gHgLpUL128L peptides pool. Results: The pp65-specific CD4+ T-cell response was higher in pregnant women with HCMV primary infection at the late time point and in control subjects with remote infection, while the pregnant women at the early time point showed a higher gB-specific CD8+ T-cell response. Regarding the CD4+ and CD8+ T-cell phenotypes, we observed that HCMV-specific CD4+ and CD8+ T cells expressing CD45RA+ remained constant in pregnant women with primary infection at the early and late time points and in subjects with remote infection, while HCMV-specific CD4+ and CD8+ T cells expressing IL-7R+ or producing IL-2 were higher in control subjects with remote infection than in pregnant women with HCMV primary infection. Conclusions: The T-cell response was higher against gB in the early phase of infection and against pp65 in the late phase. Therefore, these proteins should be taken into consideration as candidates for a vaccine. [ABSTRACT FROM AUTHOR]

A series of conditions can mimic musculoskeletal infections on imaging, complicating their diagnosis and affecting the treatment. Depending on the anatomical location, different conditions can manifest with clinical and imaging findings that mimic infections. Herein we present a wide spectrum of the musculoskeletal disorders of the axial skeleton, long bones, peripheral joints, and soft tissue that may manifest as infectious processes, and we focus on the potential mimics of osteomyelitis, septic arthritis, and infectious spondylodiscitis that are common in clinical practice. We present the typical imaging characteristics of each musculoskeletal infection, followed by mimicking conditions. [ABSTRACT FROM AUTHOR]

Background/Objectives: In this study, we aimed to compare the predictive power of non-conventional (neutrophil/lymphocyte ratio—NLR; platelet/lymphocyte ratio—PLR) and conventional markers (C-reactive protein—CRP; procalcitonin—PCT; interleukin-6—IL-6) in terms of disease progression and mortality in severe SARS-CoV-2 patients. Methods: In this prospective observatory study, blood samples were collected daily, focusing on the established inflammatory markers. Critically ill COVID-19 patients who required ICU admission were included. Patient treatment followed established COVID-19 protocols, and the data analysis was performed using SPSS with non-normal distribution methods. The study cohort primarily included patients infected with the delta variant. Results: A mortality rate of 76.6% was observed among 167 patients during the study period. Significant differences in conventional and non-conventional markers between survivor and non-survivor groups were observed. The PCT levels were significantly elevated (p < 0.005) in the deceased group. Among the non-conventional markers, the NLR was consistently higher in non-survivors and emerged as a significant predictor of mortality, whereas the PLR was not elevated among the non-survivors. ROC analyses indicated that PCT and the NLR were the markers with the highest predictive power for mortality. The multivariate logistic regression analysis identified NLR, PCT, CRP, and IL-6 as significant predictors of mortality across different days. The NLR showed a consistent, though not always statistically significant, association with increased mortality risk, particularly on Days 2 and 5. Conclusions: The NLR's accessibility and simplicity of determination make it a valuable and practical tool for monitoring inflammatory processes in viral infections. Our findings suggest that incorporating NLR analysis into routine clinical practice could enhance the early identification of high-risk patients, thereby improving patient management and outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with chronic lymphocytic leukemia (CLL) are more susceptible to infections, which are also the most common cause of death in these patients. Previous studies in patients with CLL described elevated levels of FOXP3+ regulatory T cells (Tregs), which also correlated with decreased T cell responses to microbial antigens. As the activation of the STAT5 transcription factor induces the expression of FOXP3 and human CD4+FOXP3+ T cells that also contain nonsuppressive T cells, we analyzed STAT5 phosphorylation (pSTAT5) and suppressive subpopulations, including activated Tregs (aTregs). We found a significantly increased frequency of aTregs in patients with advanced stages, which significantly correlated with the total tumor mass score. aTreg expansion in vitro was associated with significantly higher aTreg pSTAT5 responses to SARS-CoV-2 antigen-specific stimulation in vitro. Finally, a subgroup of patients characterised by an increased aTreg percentage among CD4+FOXP3+ T cells experienced a more severe disease course with serious grade ≥3 infections during follow-up. Introduction: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA−FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic signalling in Treg subsets. Materials and Methods: In this study, by using conventional and imaging flow cytometry, we monitored STAT5 signalling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and the disease course during a follow-up of 37 patients with CLL. Results: The aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was characterised by more frequent episodes of severe infections during follow-up. Conclusions: The results suggesting that an aTreg fraction could represent a possible marker of a severe disease course with infectious complications. Augmented homeostatic STAT5 signalling could support aTreg expansion, as higher pSTAT5 levels were significantly correlated with an increased aTreg frequency among CD4+FOXP3+ T cells during the follow-up of patients on therapy, as well as following SARS-CoV-2 antigen-specific stimulation in vitro. [ABSTRACT FROM AUTHOR]

Pandemics from viral respiratory tract infections in the 20th and early 21st centuries were associated with high mortality, which was not always caused by a primary viral infection. It has been observed that severe course of infection, complications and mortality were often the result of co-infection with other pathogens, especially Staphylococcus aureus. During the COVID-19 pandemic, it was also noticed that patients infected with S. aureus had a significantly higher mortality rate (61.7%) compared to patients infected with SARS-CoV-2 alone. Our previous studies have shown that S. aureus strains isolated from patients with COVID-19 had a different protein profile than the strains in non-COVID-19 patients. Therefore, this study aims to analyze S. aureus strains isolated from COVID-19 patients in terms of their pathogenicity by analyzing their virulence genes, adhesion, cytotoxicity and penetration to the human pulmonary epithelial cell line A549. We have observed that half of the tested S. aureus strains isolated from patients with COVID-19 had a necrotizing effect on the A549 cells. The strains also showed greater variability in terms of their adhesion to the human cells than their non-COVID-19 counterparts. [ABSTRACT FROM AUTHOR]

Kidney transplantation significantly improves the survival of patients with end-stage kidney disease (ESKD) compared to other forms of kidney replacement therapy. However, kidney transplant recipients' outcomes are not fully satisfactory due to increased risk of cardiovascular diseases, infections, and malignancies. Immune-related complications remain the biggest challenge in the management of kidney graft recipients. Despite the broad spectrum of immunosuppressive agents available and more detailed methods used to monitor their effectiveness, chronic allograft nephropathy remains the most common cause of kidney graft rejection. The kynurenine (KYN) pathway is the main route of tryptophan (Trp) degradation, resulting in the production of a plethora of substances with ambiguous properties. Conversion of Trp to KYN by the enzyme indoleamine 2,3-dioxygenase (IDO) is the rate-limiting step determining the formation of the next agents from the KYN pathway. IDO activity, as well as the production of subsequent metabolites of the pathway, is highly dependent on the balance between pro- and anti-inflammatory conditions. Moreover, KYN pathway products themselves possess immunomodulating properties, e.g., modify the activity of IDO and control other immune-related processes. KYN metabolites were widely studied in neurological disorders but recently gained the attention of researchers in the context of immune-mediated diseases. Evidence that this route of Trp degradation may represent a peripheral tolerogenic pathway with significant implications for transplantation further fueled this interest. Our review aimed to present recent knowledge about the role of the KYN pathway in the pathogenesis, diagnosis, monitoring, and treatment of kidney transplant recipients' complications. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing resistance. However, many AMPs fail to progress into clinics due to unexpected difficulties found in preclinical in vivo phases. Our research has focused on crotalicidin (Ctn), an AMP from snake venom, and a fragment thereof, Ctn[15-34], with improved in vitro antimicrobial and anticancer activities and remarkable serum stability. As the retroenantio versions of both AMPs maintained favorable profiles, in this work, we evaluate the in vivo efficacy of both the native-sequence AMPs and their retroenantio counterparts in a murine infection model with Acinetobacter baumannii. A significant reduction in bacterial levels is found in the mice treated with Ctn[15-34]. However, contrary to expectations, the retroenantio analogs either exhibit toxicity or lack efficacy when administered to mice. Our findings underscore the critical importance of in vivo infection model evaluation to fully calibrate the therapeutic potential of AMPs. [ABSTRACT FROM AUTHOR]

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD. [ABSTRACT FROM AUTHOR]

Unlike the well-documented bothropic and crotalid snakebites in Brazil, lachetic envenomings (i.e., triggered by the bushmaster snake) are rare and present significant diagnostic challenges. This case describes a severe envenoming induced by a Lachesis muta snake in a 26-year-old Brazilian man who was bitten near a forest in November 2022. Characteristic symptoms such as sweating and bradycardia pointed towards lachetic envenoming, but initial misdiagnosis as a bothropic bite resulted in a delay in appropriate antivenom therapy. Despite later receiving the correct treatment, the severity of the envenoming necessitated the amputation of a finger and triggered a severe infection. This report highlights the challenges of diagnosing and treating Lachesis spp. bites due to their rarity. Moreover, an overview of lachetic-induced signs and symptoms was explored. This study emphasizes that further reports are warranted to improve understanding of Lachesis muta envenoming and to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

In this article, a diffusion component in an SIR model is introduced, and its impact is analyzed using fractional calculus. We have included the diffusion component in the SIR model. in order to illustrate the variations. Here, we have applied the general fractional derivative to analyze the impact. The Laplace decomposition technique is employed to obtain the numerical outcomes of the model. In order to observe the effect of the diffusion component in the SIR model, graphical solutions are also displayed. [ABSTRACT FROM AUTHOR]

Introducing genetic material into hard-to-transfect mammalian cell lines and primary cells is often best achieved through retroviral infection. An ideal retroviral vector should offer a compact, selectable, and screenable marker while maximizing transgene delivery capacity. However, a previously published retroviral vector featuring an EGFP/Puromycin fusion protein failed to meet these criteria in our experiments. We encountered issues such as low infection efficiency, weak EGFP fluorescence, and selection against infected cells. To address these shortcomings, we developed a novel retroviral vector based on the Moloney murine leukemia virus. This vector includes a compact bifunctional EGFP and Puromycin resistance cassette connected by a 2A peptide. Our extensively tested vector demonstrated superior EGFP expression, efficient Puromycin selection, and no growth penalty in infected cells compared with the earlier design. These benefits were consistent across multiple mammalian cell types, underscoring the versatility of our vector. In summary, our enhanced retroviral vector offers a robust solution for efficient infection, reliable detection, and effective selection in mammalian cells. Its improved performance and compact design make it an ideal choice for a wide range of applications involving precise genetic manipulation and characterization in cell-based studies. [ABSTRACT FROM AUTHOR]

Pelvic inflammatory disease is an infectious condition affecting women's upper genital tract, including the uterus, fallopian tubes, and ovaries. It primarily arises from an infection that spreads upward from the lower genital area. The relationship between chronic pelvic pain and coexisting conditions is a key focus in its diagnosis and treatment. This type of pain is also considered a form of reflex dystrophy, involving both neurological and psychological components, the first line treatment consists in antibiotherapy. For patients with complex or severe pelvic abscesses, surgical intervention may be considered in selected cases. The primary surgical techniques employed are open and laparoscopic surgery, both aimed for abscess removal. MRI or Doppler ultrasonography may be employed when there is a suspicion of adnexal torsion, adenomyosis or deep pelvic endometriosis, especially if the ultrasound results are unclear or inconclusive Laparoscopic surgery has increasingly become favored by both healthcare professionals and patients. Moreover, laparoscopy has emerged as the most valuable tool for diagnosing chronic pelvic pain. The approach to treating pelvic abscesses in women of reproductive age depends greatly on clinical assessments, individual patient factors, and the desire to preserve fertility. However, laparoscopy may present technical difficulties in patients with severe pelvic abscesses, particularly those with extensive adhesions or a closed-off pelvic area, requiring advanced surgical expertise. Women with associated conditions such as endometriosis often experience a more severe form of pelvic inflammatory disease, which is less responsive to antibiotics and more frequently requires surgical resolution. The surgical treatment should be performed individualized to the clinical condition of the patient and the time of intervention must be carefully chosen. [ABSTRACT FROM AUTHOR]

Background/Objectives: PET imaging of bacterial infection could potentially provide added benefits for patient care through non-invasive means. [68Ga]Ga-desferrioxamine B—a radiolabelled siderophore—shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa and sufficient serum stability for clinical application. In this report, we present data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette-based synthesis modules (Modular-Lab PharmTracer and GRP 3V) utilising commercially obtainable cassettes together with a licensed 68Ge/68Ga radionuclide generator. Methods: Quality control, including the determination of radiochemical purity, as well as a system suitability test, was set up via RP-HPLC on a C18 column. The two described production processes use an acetic acid/acetate buffer system with ascorbic acid as a radical scavenger for radiolabelling, yielding ready-to-use formulations with sufficient activity yield. Results: Batch data analysis demonstrated radiochemical purity of >95% by RP-HPLC combined with ITLC and excellent stability up to 2 h after synthesis. Specifications for routine production were set up and validated with four masterbatches for each synthesis module. Conclusions: Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable automated production of [68Ga]Ga-desferrioxamine B in-house with high reproducibility for clinical application. [ABSTRACT FROM AUTHOR]

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (99mTc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99mTc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh2), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99mTc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97–98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD7.4 values (1.6–2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac-[99mTc(CO)3(Cip-DTC)(PPh3)] (2′) showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac-[99mTc(CO)3(Cip-DTC)(TMPP)] (3′) demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99mTc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

The increasing incidence of antibiotic resistance in bacteria is a major problem in terms of therapeutic options, especially in immunocompromised patients, such as patients from intensive care units (ICUs), HIV-positive patients, patients with malignancies or transplant patients. Commensal bacteria, especially anaerobes, serve to maintain microbial stability by preventing overpopulation with pathogenic bacteria. In immunocompromised patients, microbiota imbalance caused by antibiotic therapy and decreased host immunity favors intestinal overpopulation with pathogenic species, leading to increased bacterial translocation and susceptibility to systemic infections. Infections with multidrug-resistant (MDR) bacteria pose major challenges to the establishment of appropriate treatment and lead to increased mortality. Asymptomatic colonization with MDR bacteria usually precedes infection and tends to persist for long periods of time, and in immunocompromised patients, colonization with MDR bacteria is a risk factor for systemic infections. This review aims to assess the relation between colonization and infection with MDR bacteria in immunocompromised patients such as ICU patients, HIV-positive patients and cancer patients and to identify the prevalence and patterns of MDR bacterial colonization and infection in this category of patients. [ABSTRACT FROM AUTHOR]

The severity of adenovirus infection or the success of adenovirus-vectorized gene therapy largely depends on the efficiency of viral entry into cells. Various drugs can alter viral entry. This study evaluated the effects of dexamethasone, paracetamol, diclofenac, ibuprofen, and ketorolac on adenovirus entry into cells in vitro and in vivo. SiHa cell cultures pretreated with dexamethasone, paracetamol, diclofenac, ibuprofen, ketorolac, or no drug were exposed to the Ad-BGal vector. The percentage of cells showing vector entry was quantified microscopically. In vivo, BALB-C mice pretreated for 7 days with the drugs or no drug were exposed to the Ad-BGal vector intravenously (IV) or via oral (VO). Organs showing vector entry were identified by X-Gal staining and eosin counterstaining. Hepatic areas with adenovirus entry were quantified in µm2. Dexamethasone, paracetamol, and ibuprofen increased adenovirus entry both in vitro and in vivo. Diclofenac increased entry only in vitro. Ketorolac did not affect adenoviral entry. The liver exhibited the most significant changes, with dexamethasone, paracetamol, and ibuprofen increasing adenovirus entry the most. Oral administration of the vector showed that dexamethasone increased its entry into the pharynx. Some physicochemical properties of the drugs (MW (g/mol), LogP, MR [cm3/mol], tPSA, CMR, LogS, and ClogP) were analyzed, and their possible implications on cell membrane properties that could potentially influence adenovirus entry through mechanisms independent of cellular receptors were discussed. Anti-inflammatory drugs could alter adenoviral infections and adenovirus vector-based gene therapies, necessitating further research. [ABSTRACT FROM AUTHOR]

Insect-specific viruses (ISVs) include viruses that are restricted to the infection of mosquitoes and are spread mostly through transovarial transmission. Despite using a distinct mode of transmission, ISVs are often phylogenetically related to arthropod-borne viruses (arboviruses) that are responsible for human diseases and able to infect both mosquitoes and vertebrates. ISVs can also induce a phenomenon called "superinfection exclusion", whereby a primary ISV infection in an insect inhibits subsequent viral infections of the insect. This has sparked interest in the use of ISVs for the control of pathogenic arboviruses transmitted by mosquitoes. In particular, insect-specific flaviviruses (ISFs) have been shown to inhibit infection of vertebrate-infecting flaviviruses (VIFs) both in vitro and in vivo. This has shown potential as a new and ecologically friendly biological approach to the control of arboviral disease. For this intervention to have lasting impacts for biological control, it is imperative that ISFs are maintained in mosquito populations with high rates of vertical transmission. Therefore, these strategies will need to optimise vertical transmission of ISFs in order to establish persistently infected mosquito lines for sustainable arbovirus control. This review compares recent observations of vertical transmission of arboviral and insect-specific flaviviruses and potential determinants of transovarial transmission rates to understand how the vertical transmission of ISFs may be optimised for effective arboviral control. [ABSTRACT FROM AUTHOR]

The herpes simplex viruses consist of the strains, HSV-1 and HSV-2, which are prevalent worldwide and lack a definitive cure. We aimed to explore the specific characteristics of HSV 1 and 2 infections, such as differences between gender assigned at birth, age at infection, site of infection, comorbidities, and effect of pregnancy, through a data analysis. Between 2011 and 2018, the Israeli Central Virology Laboratory diagnosed 9189 samples using multiplexed real-time PCR. In addition, we extracted all of the medical data for 287 females hospitalized at the Sheba Medical Center with HSV-1 (161) or HSV-2 (126) genital infections. HSV-2 was almost absent in the orofacial samples from both genders, while in other lesion sites, HSV-2 was significantly more abundant in females than in males (p < 0.05,). HSV-2 was initially detected at puberty. In the hospitalized females' malignancies, both HSV-1 and HSV-2 were found with a non-significant difference. Simultaneously, pregnancies were more common in females who were HSV-2-positive compared with those who were HSV-1-positive (27.8% vs. 12.4%, respectively, p < 0.01). Primary infections occur more with HSV-1 than with HSV-2 (15.6% vs. 3.2%, respectively). Our findings demonstrate that genital HSV-2 infection episodes are more frequent during pregnancy, suggesting that pregnancy may serve as a risk factor for HSV-2 reactivation or infection. [ABSTRACT FROM AUTHOR]

Sepsis is caused by a dysregulated host response to an infection that leads to cascading cell death and eventually organ failure. In this study, the role of inflammatory response serum secretory phospholipase A2 (sPLA2) and albumin in sepsis was investigated by determining the activities of the two proteins in serial serum samples collected on different days from patients with sepsis after enrollment in the permissive underfeeding versus standard enteral feeding protocols in an intensive care unit. Serum sPLA2 and albumin showed an inverse relationship with increasing sPLA2 activity and decreasing albumin membrane-binding activity in patients with evolving complications of sepsis. The activities of sPLA2 and albumin returned to normal values more rapidly in the permissive underfeeding group than in the standard enteral feeding group. The inverse sPLA2–albumin activity relationship suggests a complex interplay between these two proteins and a regulatory mechanism underlying cell membrane phospholipid homeostasis in sepsis. The decreased albumin–membrane binding activity in patients' serum was due to its fatty acid-binding sites occupied by pre-bound fatty acids that might alter albumin's structure, binding capacities, and essential functions. The sPLA2–albumin dual serum assays may be useful in determining whether nutritional intervention effectively supports the more rapid recovery of appropriate immune responses in critically ill patients with sepsis. [ABSTRACT FROM AUTHOR]

The murine model is invaluable for studying intricate interactions among gut microbes; hosts; and diseases. However; the impact of genetic variations in the murine microbiome; especially in disease contexts such as Klebsiella pneumoniae (Kp) infection; still needs to be explored. Kp; an opportunistic global pathogen; is becoming increasingly prevalent in regions like Asia; especially China. This study explored the role of the gut microbiota during Kp infection using mouse model; including wild-type and rpoS mutants of Kp138; KpC4; and KpE4 from human; maize; and ditch water; respectively. Under stress conditions; RpoS reconfigures global gene expression in bacteria; shifting the cells from active growth to survival mode. Our study examined notable differences in microbiome composition; finding that Lactobacillus and Klebsiella (particularly in WKp138) were the most abundant genera in mice guts at the genus level in all wild-type treated mice. In contrast; Firmicutes were predominant in the healthy control mice. Furthermore; Clostridium was the dominant genus in all mutants; mainly in ∆KpC4; and was absent in wild-type treated mice. Differential abundance analysis identified that these candidate taxa potentially influence disease progression and pathogen virulence. Functional prediction analysis showed that most bacterial groups were functionally involved in biosynthesis; precursor metabolites; degradation; energy generation; and metabolic cluster formation. These findings challenge the conventional understanding and highlight the need for nuanced interpretations in murine studies. Additionally; this study sheds light on microbiome–immune interactions in K. pneumoniae infection and proposes new potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus acts both as a colonizing commensal bacterium and invasive pathogen. Nasal colonization is associated with an increased risk of infection caused by the identical strain. In patients with atopic dermatitis (AD), the degree of S. aureus colonization is associated with the severity of the disease. Here, we comparatively analyzed the in vivo transcriptional profile of S. aureus colonizing the nose and non-diseased skin (non-lesional skin) as opposed to the diseased skin (lesional skin—defined here as infection) of 12 patients with AD. The transcriptional profile during the asymptomatic colonization of the nose closely resembled that of the lesional skin samples for many of the genes studied, with an elevated expression of the genes encoding adhesion-related proteins and proteases. In addition, the genes that modify and remodel the cell wall and encode proteins that facilitate immune evasion showed increased transcriptional activity. Notably, in a subgroup of patients, the global virulence regulator Agr (accessory gene regulator) and downstream target genes were inactive during nasal colonization but upregulated in the lesional and non-lesional skin samples. Taken together, our results demonstrate a colonization-like transcriptional profile on diseased skin and suggest a role for the peptide quorum sensing system Agr during the transition from asymptomatic nasal colonization to skin colonization/infection. [ABSTRACT FROM AUTHOR]

Introduction: Vault particles are large cytoplasmic ribonucleoprotein particles that participate in inflammation. The aim of this study was to assess the diagnostic and prognostic value of major vault protein (MVP) in patients with inflammation, in order to determine whether MVP could be used as a biomarker for infection or inflammation. We also aimed to compare the diagnostic impact of MVP compared to other conventional measurements, such as CRP or white blood cell (WBC) counts. Methods: CRP and MVP levels were measured in 111 sera samples from 85 patients with inflammation admitted to a tertiary-care hospital and 26 healthy individuals during an 18-month period (2019–2020), using nephelometry and a custom MVP sandwich ELISA assay, respectively. In addition, WBC counts were measured using a commercial assay. Results: MVP levels were found to be elevated in patients with inflammation compared to healthy individuals (p < 0.0001). Moreover, MVP levels were higher in patients with inflammation due to an infectious etiology compared to those with non-infectious etiology (p = 0.0006). MVP levels significantly decreased during the first four days of infection in response to antibiotic treatment, while CRP levels showed a less-sensitive decline. An ROC curve analysis demonstrated that MVP and CRP have similarly high diagnostic accuracy, with AUCs of 0.955 and 0.995, respectively, followed by WBCs with an AUC of 0.805. Conclusions: The ROC curves demonstrated that MVP has the potential to serve as a diagnostic biomarker for inflammation and infection. Additionally, MVP levels may reflect the efficacy of antibiotic treatment. [ABSTRACT FROM AUTHOR]

Background: This communication summarizes our single-center experience with the use of anti-IL-1 biologic response modifiers for treating autoimmune and autoinflammatory conditions in children. Methods: We outline our rationale for the off-label use of anakinra and discuss emerging treatment paradigms that necessitate further research and validation. Results: Anakinra has enabled personalized treatment, whether used as a single agent on an as-needed basis, as part of a background treatment regimen, or in combination with colchicine. Our data also highlight the significance of anakinra in treating post-infectious inflammatory diseases, demonstrating its high efficacy in novel applications such as rheumatic fever and post-viral arthritis. Canakinumab, on the other hand, has provided long-term remission. Both medications were well-tolerated, with no serious adverse effects reported. Conclusions: Based on our observations and successful outcomes, we advocate for future collaborative efforts to improve access to anti-IL-1 medications to better manage excessive and harmful inflammation in children. [ABSTRACT FROM AUTHOR]

Simple Summary: Viral rhinotracheitis is an acute upper respiratory (URT) disease caused by feline herpesvirus type 1 (FHV-1). Cats remain in a latent infectious condition after healing from the primary infection. Therefore, there is no viable treatment for FHV-1 infection. This disease is widely distributed worldwide and poses a threat to the health of pet cats and the protection of rare felines. To further understand the current epidemic trend of FHV-1, we isolated the virus from Yanji City for the first time, revealing the genetic evolution direction of FHV-1 by comparing the gD gene sequences between 33 positive samples and those uploaded worldwide. This study provides a theoretical foundation for the prevention and treatment of feline viral bronchitis by conducting an epidemiological investigation. Epidemiological surveys revealed that 33 of the 93 samples were positive for FHV-1, with the gD gene of these 33 samples exhibiting low variation, high homology, and no critical amino acid mutation. Feline herpesvirus type 1 (FHV-1), also known as feline viral rhinotracheitis (FVR) virus, is one of the main causes of URT disease in cats. All cats can become hosts of FHV-1, and the spread of this disease affects the protection of rare feline animals. Nasal swabs from cats with URT disease were collected at five veterinary clinics in Yanji City from 2022 to 2024. The purpose of this study was to isolate and investigate the epidemiology of FHV-1. The gD gene of the FHV-1 strain was cloned and inserted into the pMD-18T vector and transformed into a competent Escherichia coli strain. Subsequently, the gD gene of the positive samples was sequenced and phylogenetic analysis was performed to determine the genetic evolution relationship between the strains. We successfully isolated the FHV-1 strain YBYJ-1 in Yanji City for the first time. The diameter of the virus is approximately 150–160 nm. After 48 h of virus inoculation, the cells were round, isolated, and formed grape-like clusters. The gD gene of the virus was sequenced, and the length was 1125 bp, which proved the isolate was FHV-1. This study found that the genetic evolution of the FHV-1 gD gene was stable, expanding the molecular epidemiological data on FHV-1 in cats in Yanji City. [ABSTRACT FROM AUTHOR]

Infectious spondylodiscitis is a life-threatening disease and has some challenges in terms of diagnostic, differentiative, and therapeutic processes. Therefore, rapid and effective management of infectious spondylodiscitis is necessary. Hematological inflammation indices (HIIs) such as the neutrophil/lymphocyte ratio and aggregate index of systemic inflammation are derived from blood cells and used as diagnostic, prognostic, predictive, and treatment monitoring indicators. This study aimed to evaluate HIIs for discriminating between infectious spondylodiscitis pathogens. This retrospective comparative study included 116 patients with infectious spondylodiscitis. According to the responsible infectious pathogens, three types of infectious spondylodiscitis were defined: Brucella (n = 51), pyogenic (n = 43), and tuberculous (n = 22). The HIIs were derived from baseline complete blood counts. The three types of infectious spondylodiscitis were statistically compared for the HII scores. We found that the Brucella group had significantly lower HII scores than the pyogenic group (p < 0.05). Also, the Brucella group had significantly lower HII scores than the tuberculous group (p < 0.05). However, no significant differences were found between the pyogenic and tuberculous groups regarding HIIs (p > 0.05). In conclusion, the HIIs may be considered in the differentiation between Brucella spondylodiscitis and other types of infectious spondylodiscitis. [ABSTRACT FROM AUTHOR]

Neonatal infectious disease continues to result in high rates of infant morbidity and mortality. Early- and late-onset disease represent difficult to detect and difficult to treat illnesses, particularly when antimicrobial resistant pathogens are present. Newborns are immunodeficient and are at increased risk of vertical and horizontal infection, with preterm infants increasingly susceptible. Additional risk factors associated with infection include prolonged use of a central catheter and/or ventilation, congenital abnormalities, admittance to intensive care units, and the use of broad-spectrum antibiotics. There is increasing recognition of the importance of the host microbiome and dysbiosis on neonatal infectious disease, including necrotising enterocolitis and sepsis in patients. Current diagnostic methods rely on blood culture, which is unreliable, time consuming, and can result in false negatives. There is a lack of accurate and reliable diagnostic tools available for the early detection of infectious disease in infants; therefore, efficient triage and treatment remains challenging. The application of biomarkers, machine learning, artificial intelligence, biosensors, and microfluidics technology, may offer improved diagnostic methodologies. Point-of-care devices, such diagnostic methodologies, may provide fast, reliable, and accurate diagnostic aids for neonatal patients. This review will discuss neonatal infectious disease as impacted by antimicrobial resistance and will highlight novel point-of-care diagnostic options. [ABSTRACT FROM AUTHOR]

Background and Objectives: Infections are the most common and potentially life-threatening complications of the treatment of children with acute lymphoblastic leukemia (ALL). The aim of this study was to determine epidemiological, clinical, and microbiological characteristics of infections in pediatric patients with ALL. Materials and Methods: Twenty-three children (16 males and 7 females, with a mean age of 5.9 years (range of 1.3 to 12.2 years)) with ALL, treated at the Division of Hematology, Oncology, and Clinical Genetics, Department of Pediatrics, Clinical Hospital Center Rijeka, Croatia, from 1 January 2015 to 31 December 2020, were included in the study. Results: One hundred and four infectious episodes (IEs) were reported (an average of 4.5 IE per patient). IEs were more frequent in the intensive phases of antileukemic treatment. Neutropenia was present in 48 IEs (46.2%) with a duration greater than 7 days in 28 IEs (58.3%). The respiratory tract was the most common infection site (48.1%). We documented 49 bacterial (47.1%), 4 viral (3.9%), 4 fungal (3.9%), and 10 mixed isolates (9.6%), while in 37 IEs (35.6%), a pathogen was not isolated. The most common causes of bacteremia were coagulase-positive staphylococci. The most frequent empirical therapy was third- and fourth-generation cephalosporins, followed by piperacillin/tazobactam. The modification of first-line antimicrobial therapy was performed in 56.9% of IEs. Granulocyte-colony stimulating factor was administered in 53.8% of IEs, and intravenous immunoglobulins were administered in 62.5% of IEs. One patient required admission to the intensive care unit. No infection-related mortality was reported. Conclusions: ALL patients have frequent IEs. Close monitoring, the identification of risk factors, the rapid empirical use of antibiotics in febrile neutropenia, and the timely modification of antimicrobial therapy play key roles in reducing infection-related morbidity and mortality in children with ALL. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) infections are significantly associated with multiple adverse reproductive outcomes such as miscarriages. Pregnant women are more susceptible to an HPV infection and its prevalence increases as pregnancy progresses. In this present review, we summarize the existing evidence indicating the potential impact of an HPV infection on the occurrence of recurrent pregnancy loss (RPL). Comprehensive research of the literature was performed in the Medline/PubMed and Scopus databases. A total of 185 articles were identified and 40 full-text articles were assessed. Four studies were eligible to be included in this literature review. To our knowledge, this is the first review aiming to summarize the current state of evidence regarding the possible association of HPV infections and RPL. Recurrent pregnancy loss constitutes a distressing reproductive event and scientific research has made significant efforts to determine the causes and mechanisms that could lead to RPL. It is still unclear whether the papillomavirus infection is associated with an increased risk for recurrent miscarriages. Research in the field revealed conflicting results and their deductions are limited by methodological limitations. Given the high prevalence of HPV infections and their potential role in the occurrence of adverse outcomes during pregnancy, further research is required to clarify the possibility of an HPV infection being a potential risk factor for recurrent miscarriages. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS, Streptococcus agalactiae) is a pathogen of increasing importance in adults. Severe and invasive cases in non-pregnant adults were collected during the period 2015–2019 by voluntary-based surveillance. In total, 108 GBS strains were phenotypically and genotypically characterized for the serotype, antimicrobial resistance, pili, surface protein genes, and the hyper-virulent adhesin hvgA. Patients were divided into two age groups: adults (18–64 years; n = 32) and older adults (≥65 years; n = 72). The average age was 70.8 years, with a male/female ratio of 1.7. Most isolates were recovered from cases of bacteremia (blood, n = 93), and a higher frequency of invasive GBS infections (iGBS) was found among older adults (66.7%). Serotype III was the most frequent (n = 41, 38%), followed by type Ia and type V (n = 20 each, 18.5%). Serotypes Ia, Ib, II, III, IV, and V accounted for all but one isolates (99.1%). The iGBS isolates were universally susceptible to penicillin, while the prevalence of resistance to clindamycin, erythromycin, tetracycline, and high-level gentamicin resistance was 26.8%, 24.1%, 85.2%, and 5.5%, respectively, with the predominance of the erm(B) gene for macrolide resistance and the tet(M) gene for tetracycline resistance. The associations between the serotypes/antimicrobial resistance/virulence traits underlined the increasing importance of serotype III and its contribution to antimicrobial resistance as well as the steady increase over time of serotype IV. This nationwide study confirmed the need for monitoring the GBS epidemiology in non-pregnant adults through continuous surveillance of GBS infections. [ABSTRACT FROM AUTHOR]

Background: Due to its distinct vascular tropism, Campylobacter fetus is recognized as a significant cause of severe systemic infections, especially in immunocompromised individuals, while it is rarely reported as a cause of gastrointestinal infections. Methods: A rare case of mycotic abdominal aortic aneurysm associated with Campylobacter fetus detected on the aneurysm wall itself was described. Results: A 68-year-old male was admitted to the hospital due to severe abdominal pain. The patient was afebrile, hemodynamically stable with elevated C-reactive protein levels. A physical examination revealed a palpable, pulsatile, tender mass located in the periumbilical region. Ultrasonography and multi-slice computer tomography angiography (MSCTA) identified an infrarenal abdominal aortic aneurysm with a maximum diameter of 6.5 cm, showing suspicious signs of dissection. Aneurysmectomy with Dacron tube graft interposition was performed. Although the blood cultures remained negative, the culture of the aneurysmal wall grew Campylobacter fetus, enabling early diagnosis and targeted antibiotic therapy. The patient was treated with meropenem for two weeks, followed by amoxicillin-clavulanate for another two weeks after hospital discharge. Conclusions: Campylobacter fetus associated with abdominal aortic aneurysms represents a life-threatening condition, posing a significant challenge in vascular surgery. Due to the lack of clear guidelines on antibiotic susceptibility testing and the treatment of infections associated with this pathogen, enhanced surveillance of Campylobacter fetus is necessary in both human and veterinary medicine. [ABSTRACT FROM AUTHOR]

Bacterial infections pose significant global health challenges, often underestimated due to difficulties in accurate diagnosis, especially when culture-based diagnostics fail. This study assesses the effectiveness of 16S-based metagenomic next generation sequencing (NGS) for identifying pathogens in culture-negative clinical samples across various medical settings. Overall, 48% of samples were collected from orthopedics, 15% from neurosurgery, and 12% in cardiac surgery, among others. The detection rate of monomicrobial infections was 68.6%, and 5.7% for polymicrobial infections. In addition, NGS detected bacteria in all samples from the lungs, head and neck, and eye specimens. Cutibacterium acnes (11%, 12/105) was the most frequent microorganism, followed by Staphylococcus epidermidis (10.4%, 11/105), and Staphylococcus aureus (9.5%, 10/105). In conclusion, 16S-targeted metagenomic sequencing enhances pathogen detection capabilities, particularly in instances where traditional cultures fail. By the combination of NGS and bacterial cultures, microbiologists might provide a more accurate diagnosis, guiding more effective treatments and potentially reducing healthcare costs associated with empirical treatments. [ABSTRACT FROM AUTHOR]