Journal of Medical Virology, Volume 96, Issue 7, July 2024.

Journal of Medical Virology, Volume 96, Issue 7, July 2024.

Journal of Medical Virology, Volume 96, Issue 7, July 2024.

Journal of Medical Virology, Volume 96, Issue 7, July 2024.

Journal of Medical Virology, Volume 96, Issue 7, July 2024.

In recent years, vector-borne infectious diseases have emerged as a significant global public health concern [1]. The expansion of the geographic range of the tick vectors has led to a notable increase in tick-borne diseases (TBDs), which now account for more than 75% of all reported vector-borne diseases in the United States annually [2-4]. Among these tick-borne diseases is human babesiosis, an emerging infectious disease caused by intraerythrocytic apicomplexan parasites of the Babesia genus [5].

The coronavirus disease 2019 (COVID-19) would affect multiple systems with numerous complications, especially severe and irreversible lung parenchymal damage [1]. A significant proportion (6-10%) of patients with COVID-19 infection can progress to respiratory failure and require mechanical ventilation (MV) due to the development of acute respiratory distress syndrome (ARDS) [2,3], which is associated with high mortality exceeding 20% to 40% [4,5]. Additionally, some patients with COVID-19–associated ARDS develop pulmonary fibrosis (PF), which leads to prolonged MV or extracorporeal membrane oxygenation (ECMO) [6,7].

Implementing integrated service delivery for communities living in the same areas and facing multiple neglected tropical diseases (NTDs) is advocated as a key approach in the fight against NTDs by the World Health Organization (WHO). [1,2] Two groups of NTDs are often targeted for integrated delivery of interventions: NTDs requiring preventive chemotherapy (PC) through mass drug administration (MDA) campaigns; and skin-related NTDs (skin NTDs) requiring similar control strategies. [3-7,8]…

IntroductionThe COVID-19 pandemic has raised concerns about the persistence of symptoms after infection, commonly referred to as ‘post-COVID’ or ‘long-COVID’. While countries in high-resource countries have highlighted the increased risk of disadvantaged communities, there is limited understanding of how COVID-19 and post-COVID conditions affect marginalised populations in low-income and middle-income countries. We study the longitudinal patterns of COVID-19, post-COVID symptoms and their impact on the health-related quality of life through the IndiQol Project. Methods and analysisThe IndiQol Project conducts household surveys across India to collect data on the incidence of COVID-19 and multidimensional well-being using a longitudinal design. We select a representative sample across six states surveyed over four waves. A two-stage sampling design was used to randomly select primary sampling units in rural and urban areas of each State. Using power analysis, we select an initial sample of 3000 household and survey all adult household members in each wave. The survey data will be analysed using limited dependent variable models and matching techniques to provide insights into the impact of COVID-19 pandemic and post-COVID on health and well-being of individuals in India. Ethics and disseminationEthics approval for the IndiQol Project was obtained from the Macquarie University Human Research Ethics Committee in Sydney, Australia and Institutional Review Board of Morsel in India. The project results will be published in peer-reviewed journals. Data collected from the IndiQol project will be deposited with the EuroQol group and will be available to use by eligible researchers on approval of request. …

IntroductionTransitioning patients from their paediatric centres to adulthood is an important subject for many of these patients living with different chronic pathologies. There are few studies that assess its effectiveness in paediatric surgical pathologies. The overall objective of this scoping review is to assess the extent of the literature describing transitional programmes dedicated to young patients living with surgical conditions. The primary question will look to assess what transitional programmes are available for young patients living with surgical conditions either operated or not. Methods and analysisThe proposed scoping review will follow guidelines described by the Joanna Briggs Institute manual described by Peters et al in 2020. This protocol will employ the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols checklist. The concept that will be included in this review is the exposure of these patients to a transition of care pathway or care programmes. Patients between the ages of 16 and 30 with a surgical condition will be included. There will be no comparator. No specific outcomes will be assessed, however, the outcomes that will be found from the transition programmes will be reviewed. A knowledge synthesis librarian will search MEDLINE All (Ovid), Embase (Ovid), Web of Science Core Collection (Clarivate) and CINAHL Complete (EBSCOhost). The literature search will be limited to 2000 onwards publications. No language or age group limitation will be applied. The reference list of all included sources of evidence will be screened for additional studies. Screening of search results and data extraction from included studies will be completed in Covidence by two independent reviewers. We will also use the PAGER (Patterns, Advances, Gaps, Evidence for practice and Research recommendations) framework to report and summarise the results. Ethics and disseminationThis review does not require ethics approval. Our dissemination strategy includes peer review publication, conference presentation, co-constructed guidelines with stakeholders and policymakers. Trial registrationThis review is registered on OSF …

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 2, Page 136-138, July 15, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 2, Page 143-144, July 15, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 2, Page 222-233, July 15, 2024.

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 2, Page 240-242, July 15, 2024.

Abstract Background Ruthenibacterium lactatiformans, a Gram-stain-negative, rod-shaped, obligate anaerobic bacterium of the Oscillospiraceae family, has not been previously reported in human infections. This study reports the first case of bacteraemia and potential vertebral osteomyelitis caused by Ruthenibacterium lactatiformans. Case presentation An 82-year-old man with a history of diabetes, chronic renal failure, and prior spinal surgery for spondylolisthesis and spinal stenosis presented with fever and lower back pain. Magnetic resonance imaging revealed multiple vertebral osteomyelitis lesions. Initial blood cultures identified methicillin-resistant Staphylococcus aureus (MRSA), which prompted vancomycin treatment. However, repeated blood cultures not only confirmed persistent MRSA, but also detected Gram-negative bacilli (GNB). Despite surgical removal of the spinal hardware and antimicrobial therapy, the patient’s osteomyelitis worsened, necessitating transfer for further management. Subsequent analysis using 16S rRNA gene sequencing identified the GNB as Ruthenibacterium lactatiformans. Conclusions This is the first documented instance of human infection with Ruthenibacterium lactatiformans, signifying its pathogenic potential in vertebral osteomyelitis. The involvement of anaerobic bacteria and the possibility of polymicrobial infections complicate the diagnosis and treatment of vertebral osteomyelitis. This report underscores the need for caution when identifying the causative organism and selecting an appropriate treatment. …

Abstract Introduction Infective endocarditis is a rare but potentially severe disease, associated with significant morbidity and mortality. Our study aims to describe the epidemiology and management aspects of endocarditis in northern Morocco and compare it with international management guidelines. Materials and Methods This is a retrospective study involving all patients hospitalized in the cardiology department of the University Hospital of Tangier for infective endocarditis over a period of 4 years and 7 months, from May 2019 to February 2024. Results Eighty patients were hospitalized for IE during the study period. The average age of the patients was 46 years, with an even sex ratio. IE concerned native valves in 77% of cases, mechanical prostheses in 19% of cases, and on bio prostheses in 4%. The average diagnostic delay was 25 days. Blood cultures were negative in 59% of cases. The predominant infective microorganism was the bacteria Staphylococcus (65.6%). Imaging results showed vegetations in 76.3% of cases, predominantly on the mitral valve (39.3%), followed by the aortic valve (21.3%). The main complications included heart failure (51.2%), peripheral arterial embolisms (22.5%) and splenic infarction (17.5%). Management wise, the most commonly used antibiotic therapy was a combination of ceftriaxone and gentamicin. Clinical and biological improvement was observed in 70% of cases, with a mortality rate of 12.5%. Twelve patients underwent surgery (15%). Urgent surgery was indicated in 66,7% of the operated patients. Conclusion Our study highlights the challenges in managing infective endocarditis in northern Morocco. The prognosis of infective endocarditis can be improved through multidisciplinary management within the implementation of an Endocarditis Team. …

Leukocyte telomere length is a highly polygenic trait that has been associated with a complex range of lifestyle factors and disease risk. McQuillan et al.’s results comparing telomere length to malaria incidence rates suggest that infections may be another important factor, possibly through permanent shortening of telomeres in hematopoietic progenitor cells.

This May marked the 20th anniversary of the BioMalPar conference at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. The meeting originated as part of a European network of excellence but has evolved to a world-leading conference on the biology and pathology of malaria parasites. Ally Olotu (Ifakara Health Institute, Tanzania) kicked off the conference this year with a keynote presentation on malaria prevention, emphasizing current and emerging vaccine strategies. Another highlight was the presentation of the BioMalPar Lifetime Achievement Award to Andy Waters (University of Glasgow, UK).

The protozoan parasites Plasmodium, Leishmania, and Trypanosoma are transmitted by hematophagous insects and cause severe diseases in humans. These infections pose a global threat, particularly in low-resource settings, and are increasingly extending beyond the current endemic regions. Tropism of parasites is crucial for their development, and recent studies have revealed colonization of noncanonical tissues, aiding their survival and immune evasion. Despite receiving limited attention, cumulative evidence discloses the respiratory system as a significant interface for host–pathogen interactions, influencing the course of (co)infection and disease onset. Due to its pathophysiological and clinical implications, we emphasize that further research is needed to better understand the involvement of the respiratory system and its potential to improve prevention, diagnosis, treatment, and interruption of the chain of transmission.

Our study highlighted the potential for reduced risk of mortality, ICU admission, or the need for ventilatory support in patients hospitalised with COVID-19 treated with nirmatrelvir–ritonavir as a monotherapy compared with treatment regimens based on nirmatrelvir–ritonavir and remdesivir combination therapy or remdesivir monotherapy. Further randomised controlled trials are needed to support the validity of the current results.

Tropical Medicine &International Health, EarlyView.

Abstract Background Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question.Methods We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers.Results From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight.Conclusions Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.

Abstract Background Diagnosing infective endocarditis (IE) poses a significant challenge. This study aimed to compare the diagnostic accuracy of the 2015 and 2023 Duke clinical criteria introduced by the European Society of Cardiology (ESC) in a cohort of patients suspected of having IE.Methods Conducted retrospectively at two Swiss University Hospitals between 2014-2023, the study involved patients with suspected IE. Each hospitals’ Endocarditis Team categorized case as either IE or not IE. The performance of each iteration of the Duke-ESC clinical criteria was assessed based on the agreement between definite IE and the diagnoses made by the Endocarditis Team.Results Among the 3127 episodes with suspected IE, 1177 (38%) were confirmed to have IE. Using the 2015 Duke-ESC clinical criteria, 707 (23%) episodes were deemed definite IE, with 696 (98%) receiving a final IE diagnosis. With the 2023 Duke-ESC clinical criteria, 855 (27%) episodes were classified as definite IE, of which 813 (95%) were confirmed as IE. The 2015 and 2023 Duke-ESC clinical criteria categorized 1039 (33%) and 1034 (33%) episodes, respectively, as possible IE. Sensitivity for the 2015 Duke-ESC and the 2023 Duke-ESC clinical criteria was calculated at 59% (95% CI: 56-62%), and 69% (66-72%), respectively, with specificity at 99% (99-100%), and 98% (97-98%), respectively.Conclusions The 2023 ESC criteria demonstrated significant improvements in sensitivity compared to the 2015 version, although one-third of episodes were classified as possible IE by both versions.

Abstract Background Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4–5 years; 6–11 years; or 12–16 years).Methods Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically-confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers; GMTs); and safety were evaluated per age group through ∼4 years post-vaccinationResults VE against VCD across serotypes was 43.5% (95% confidence interval: 25.3%, 57.3%) for 4–5 year-olds; 63.5% (56.9%, 69.1%) for 6–11 year-olds, and 67.7% (57.8%, 75.2%) for 12–16 year-olds. VE against hospitalized VCD was 63.8% (21.1%, 83.4%), 85.1% (77.1%, 90.3%), and 89.7% (77.9%, 95.2%), for the three age groups, respectively. GMTs remained elevated against all four serotypes for ∼4 years post-vaccination, with no evident differences across age groups. No clear differences in safety by age were identified.Conclusions This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4-16 years of age living in dengue endemic areas. Relatively lower VE in 4–5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group.

by Emmanuel O. Adewuyi, Asa Auta, Mary I. Adewuyi, Aaron Akpu Philip, Victory Olutuase, Yun Zhao, Vishnu Khanal Introduction Antenatal care (ANC) is crucial for positive pregnancy outcomes, but it is underutilised in Nigeria, suggesting unmet needs, and potentially contributing to the country’s high burden of maternal and neonatal mortalities. This study comprehensively assesses ANC utilisation and receipt of its components in Nigeria, focusing on disparities between rural and urban areas. Methods We used the data disaggregation approach to analyse the Nigeria Demographic and Health Survey 2018. We estimated ANC utilisation, assessed the receipt of ANC components, and identified factors associated with eight or more (≥ 8) ANC contacts nationally and across rural and urban residences. Results Nationwide, only 20.3% of women had ≥ 8 ANC contacts, with a significant disparity (P < 0.001) between urban (35.5%) and rural (10.4%) areas in Nigeria. The North-East region had the lowest ANC utilisation nationally (3.7%) and in urban areas (3.0%), while the North-West had the lowest in rural areas (2.7%). Nationally, 69% of mothers received iron supplements, 70% had tetanus injections, and 16% received medicines for intestinal parasites, with urban residents having higher proportions across all ANC components. Maternal and husband education, health insurance, and maternal autonomy were associated with increased ANC odds at the national, rural, and urban residences. However, differences exist, with all ethnicities having higher ANC odds than the Hausa/Fulanis in urban areas and the Yorubas demonstrating greater odds than other ethnicities in rural settings. Internet use was significant only in the national context, watching television only in urban settings, while maternal working status, wealth, birth type, religion, and radio listenership were significant in rural areas. Conclusion Our study reveals significant disparities in ANC utilisation and components across Nigeria, with rural residents, particularly in northern regions, as well as socioeconomically disadvantaged and teenage mothers facing notable challenges. A multifaceted approach prioritising the interplay of intersectional factors like geography, socioeconomic status, education, religion, ethnicity, and gender dynamics is essential. Key strategies should include targeted interventions to promote educational opportunities, expand health insurance coverage, leverage internet and context-specific media, and foster socioeconomic empowerment, with priority for underserved populations. …

by Wuttipong Phumrattanaprapin, Nitima Tatiya-apiradee, Pattana Jantaban, Wiriya Mahikul Background Taeniasis and cysticercosis are parasitic infections caused by Taenia spp., mainly transmitted through the consumption of undercooked pork. Prevention requires increasing knowledge and awareness, improving meat inspection and hygiene, and promoting safe food handling and sanitation. The aim of this study was to evaluate the knowledge and practice (KP) of residents in Pak Chong District, Nakhon Ratchasima, Thailand, regarding taeniasis and cysticercosis. Methods A cross-sectional study was conducted in Pak Chong District, Nakhon Ratchasima, Thailand, and its 11 subdistrict municipalities. Study participants were selected using a stratified random sampling design. A validated questionnaire (Cronbach’s alpha = 0.70) was used to collect socio-demographic information and assess knowledge and practices related to taeniasis and cysticercosis. Descriptive statistics and multiple linear regression were used for the analysis. Results Of the 360 survey respondents, 65.0% (n = 234) were women, 82.2% (n = 296) were aged under 60 years, 99.2% (n = 357) identified as Buddhist, 87.5% (n = 315) had less than a bachelor’s degree education level, 54.2% (n = 195) had monthly family income ≥10,000 Thai baht, 10.6% (n = 38) were unemployed, and 26.1% (n = 93) lived in a town municipality. The survey revealed that 98.3% (n = 354) of participants were categorized as having less accurate knowledge and 83.6% (n = 301) were classified as more frequently engaging in correct prevention practices. Our study revealed that pig farmers (1.7%) occasionally permitted the pigs to forage freely. The results of multiple linear regression analysis revealed that knowledge scores were positively associated with household income ≥10,000 Thai baht (βadj = 1.50, 95% confidence interval [CI] 0.65 to 2.36). Practice scores were negatively associated with age over 60 years (βadj = −1.77, 95% CI −3.14 to −0.40) and living in a subdistrict municipality (βadj = −2.58, 95% CI −3.77 to −1.39). There was no association between KP regarding taeniasis and cysticercosis in the population of Pak Chong. Conclusions Overall, participants’ knowledge was lacking. Public education interventions are recommended to improve knowledge among residents with low socioeconomic status. These findings can inform the development of targeted interventions and educational programs in Pak Chong District, especially among elderly people in subdistrict municipalities, to improve practices for the prevention and control of these parasitic infections. …

by Jolien Van den Bossche, Maxime De Laere, Koen Deschepper, Paul Germonpré, Yvan Valcke, Jan Lamont, Barbara Stein, Kirsten Van Camp, Charlotte Germonpré, Griet Nijs, Ella Roelant, Sébastien Anguille, Eva Lion, Zwi Berneman Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms’ tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8–10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8–10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial’s primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.

by Xiaofeng Zhu, Yi Zhang, Haoru Ying, Huanning Chi, Guanqun Sun, Lingxia Zeng The COVID-19 pandemic and influenza outbreaks have underscored the critical need for predictive models that can effectively integrate spatial and temporal dynamics to enable accurate epidemic forecasting. Traditional time-series analysis approaches have fallen short in capturing the intricate interplay between these factors. Recent advancements have witnessed the incorporation of graph neural networks and machine learning techniques to bridge this gap, enhancing predictive accuracy and providing novel insights into disease spread mechanisms. Notable endeavors include leveraging human mobility data, employing transfer learning, and integrating advanced models such as Transformers and Graph Convolutional Networks (GCNs) to improve forecasting performance across diverse geographies for both influenza and COVID-19. However, these models often face challenges related to data quality, model transferability, and potential overfitting, highlighting the necessity for more adaptable and robust approaches. This paper introduces the Graph Attention-based Spatial Temporal (GAST) model, which employs graph attention networks (GATs) to overcome these limitations by providing a nuanced understanding of epidemic dynamics through a sophisticated spatio-temporal analysis framework. Our contributions include the development and validation of the GAST model, demonstrating its superior forecasting capabilities for influenza and COVID-19 spread, with a particular focus on short-term, daily predictions. The model’s application to both influenza and COVID-19 datasets showcases its versatility and potential to inform public health interventions across a range of infectious diseases.

by Jotham Josephat Kimondo, Ramadhan Rashid Said, Jun Wu, Chao Tian, Zhe Wu Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies.

by Alexandre Méloux, Geoffrey Dogon, Eve Rigal, Luc Rochette, Yannick Bejot, Catherine Vergely Background and purpose Growth differentiation factor 15 (GDF15) has emerged as a promising biomarker in cerebro-cardiovascular disease, particularly in acute and chronic inflammatory stress situations. However, understanding the origins, targets and functions of GDF15 in clinical situations, such as ischemic stroke, remains a complex challenge. This study aims to assess the sources of GDF15 production following an experimental ischemic stroke. Methods Adult male Wistar rats underwent cerebral embolization through microspheres injection into the left or right internal carotid artery. Two hours post-surgery, GDF15 expression was analyzed in the brain, blood, lungs, liver and heart using quantitative RT-PCR and Western blotting. Results Stroke model induced large cerebral infarcts accompanied by severe neurological deficits. GDF15 gene expression exhibited a substantial increase in the ipsilateral cortex and cerebellum, with a lesser extent in the contralateral cortex. Regarding GDF15 protein expression, proGDF15 levels were elevated in the 3 aforementioned organs mentioned and the heart. However, the mature form of GDF15 was exclusively present and increased in the heart. Finally, the expression of GDF15 expression was correlated with the neurological deficit score. Conclusions Our findings suggest that both the GDF15 gene and pro-protein are expressed in the ischemic brain after a stroke, while only its mature form is expressed remotely in in the heart. The impact of increased GDF15 in the heart following a stroke remains to be established. This is particularly relevant in understanding its relationships with poor neurological outcomes, determining whether it may contribute to stroke-induced cardiac dysfunction. …

by Carolina Sousa de Sá Leitão, Carlos Henrique dos Anjos dos Santos, Jefferson Valente, Bernardo Maia, Rogério Santos Pereira, Larissa Matos Batista, Felipe Guedes Amorim, Luciana Mara Fé-Gonçalves, Marcus Lacerda, Fernando Almeida-Val, Adalberto Luis Val Background Amazonas was one of the most impacted Brazilian states by the COVID-19 pandemic. Mortality rates were high, and the health systems collapsed. It is important to identify possible intermediate reservoirs to avoid animal-to-human contamination. Several tropical fish are of commercial interest and are sold in large open-air markets in the region, representing a large economic and dietary importance. Objectives This study aimed to verify if fish species of commercial importance, aerosols, and fish wastewater in local open-air markets, at a major capital city in the western Brazilian Amazon, are contaminated by SARS-CoV-2. Methods 488 fish, 50 aerosol, and 45 wastewater samples were analyzed for the presence of SARS-CoV-2. The samples were subjected to extraction using the BIOGENE Viral DNA/RNA Extraction kit, and the molecular diagnosis was tested for SARS-CoV-2 using the Bio-Manguinhos SARS-CoV-2 (EDx) Molecular Kit. Results It was not possible to detect the virus (Ct≤40, for Gene E) in these samples, however, in 181 samples of fish it was possible to detect the human RP gene (Ct≤35, for the RP Gene), indicating human contact. There was a high number of COVID-19 diagnoses in all city districts in which the samples were collected, showing that SARS-CoV-2 was circulating. Conclusion This study indicates that fish of local commercial importance do not carry SARS-CoV-2 viral particles, despite circulation of SARS-CoV-2, and are not an important source of animal-to-human contamination. Despite these results, the human RP gene was found detectable in fish, air, and fish wastewater, showing that such places may carry human pathogens. …

by Jessica Bates, Nicky Milner, Chantal Conneller, Aimée Little This paper explores tool-using activities undertaken in and around the earliest known evidence of post-built structures in Britain. Microwear results associated with at least three structures identified at the Early Mesolithic site of Star Carr, North Yorkshire, are examined as a means of identifying activity zones associated with the diverse stone tools used to process a variety of materials (e.g. wood, bone, antler, plant, hide, meat, fish). With 341 lithic artefacts analysed, this research represents the first microwear study focused on the post-built structures at Star Carr. A combination of spatial and microwear data has provided different scales of interpretation: from individual tool use to patterns of activity across the three structures. Different types of tool use observed have aided interpretations of possible activity areas where objects were produced and materials were processed. Zones of activity within one of the structures suggest that the working of some materials was more spatially restricted than others; even where there are high densities of flint deposition, spatial patterns in tool-using activity were observed. From this, it is interpreted that social norms and behaviours influenced the spatial organisation of different spaces. Our results demonstrate the importance of combining microwear analysis with GIS to explore function and variability in the use of Mesolithic structures—providing new insights into their role as social spaces.

by Ève-Marie Lavallée-Bourget, Christopher Fernandez-Prada, Ariane Massé, Patricia Turgeon, Julie Arsenault Echinococcus spp. is an emerging zoonotic parasite of high concern. In Canada, an increase in the number of human and animal cases diagnosed has been reported, but information regarding the parasite’s distribution in wildlife reservoir remains limited. A cross-sectional study was conducted to estimate the prevalence of wild canids infected with Echinococcus spp. and Echinococcus multilocularis in areas surrounding populated zones in Québec (Canada); to investigate the presence of areas at higher risk of infection; to evaluate potential risk factors of the infection; and as a secondary objective, to compare coproscopy and RT-PCR diagnostic tests for Taenia spp. and Echinococcus identification. From October 2020 to March 2021, fecal samples were collected from 423 coyotes (Canis latrans) and 284 red foxes (Vulpes vulpes) trapped in 12 administrative regions. Real-time PCR for molecular detection of genus Echinococcus spp. and species-specific Echinococcus multilocularis were performed. A total of 38 positive cases of Echinococcus spp., of which 25 were identified as E. multilocularis, were detected. Two high-risk areas of infection were identified. The prevalence of Echinococcus spp. was 22.7% (95% CI 11.5–37.8%) in the Montérégie centered high-risk area, 26.5% (95% CI 12.9–44.4%) in the Bas-St-Laurent high-risk area, and 3.0% (95%CI 1.8–4.7%) outside those areas. For E. multilocularis, a prevalence of 20.5% (95% CI 9.8–35.3%) was estimated in the high-risk area centered in Montérégie compared to 2.4% (95% CI 1.4–3.9%) outside. Logistic regression did not show any association of infection status with species, sex, or geolocation of capture (p > 0.05). This study shows the circulation of Echinococcus in a wildlife cycle in 9/12 administrative regions of Québec.

by Mélodie A. Nasr, Annette Aldous, Jason Daniels, Christopher Joy, Eleanor Capozzi, Michelle Yang, Patricia Moriarty, Vanessa Emmanuel-Baker, Sharyn Malcolm, Stefan J. Green, Veronica Gomez-Lobo, Mimi Ghosh Adolescent girls bear a disproportionate burden of both the HIV epidemic and unintended pregnancies; yet important questions remain unanswered regarding the effects of hormonal contraceptives on the vaginal immune microenvironment, which can impact HIV susceptibility in this group. Multiple studies report genital immune alterations associated with the progestin-based contraceptive Depot medroxyprogesterone acetate (DMPA) in adult women, but there is little available data in adolescents. The objective of this longitudinal cohort study was to evaluate the effects of short-term use of three progestin-based contraceptives, levonorgestrel intrauterine device (LNG-IUD), subdermal etonogestrel (ETNG), and injectable DMPA, on HIV-associated vaginal immune biomarkers and microbiome in adolescent girls. Fifty-nine sexually active, HIV-uninfected girls aged 15-19, were recruited from the Washington DC metro area and self-selected into Control (condoms only), combined oral contraceptive pills, LNG-IUD, ETNG and DMPA groups. Vaginal swabs were collected at baseline prior to contraceptive use and at 3-month follow-up visit. Vaginal secretions were tested for pro-inflammatory (IL-1α, IL-1β, TNF-α, IL-6, IL-8, MIP-3α, IP-10, RANTES, MIP-1α, MIP-1β) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2, SLPI) immune biomarkers using ELISA and for anti-HIV activity using TZM-bl assay. Vaginal microbiome was evaluated using 16S rRNA gene sequencing. Data were analyzed using SAS Version 9. Among the 34 participants who completed both visits, no significant changes in median biomarker concentrations, HIV inhibition and microbiome composition were observed between baseline and follow-up visits for any of the contraceptive groups. IL-8 (p…

by Japan Huynh, Thi Minh Hue Phan This study explores the effects of banking uncertainty on firms’ debt financing. Employing data from 2007 to 2022 of Vietnam–a bank-based economy, we document that banking uncertainty negatively impacts corporate debt. The impact firmly holds across various debt maturities and sources, with the most predominant driver witnessed in bank debt. We also investigate the potential underlying mechanism linking banking uncertainty to debt financing, thereby validating the working of three crucial channels, including increased costs of debt, substitution of trade credit, and contractions in firm investment. Furthermore, conducting extended analysis, we find that debt financing exhibits more pronounced reactions to banking uncertainty for firms with closer ties to banks or during macroeconomic shocks, as captured by the financial crisis and the COVID-19 pandemic. Our findings survive after robustness checks by alternative measurement, static and dynamic econometric models, and endogeneity controls.

by Aina Astorch-Cardona, Lionel Bertaux, Yann Denis, Alain Dolla, Céline Rommevaux Autotrophic microaerophilic iron-oxidizing Zetaproteobacteria seem to play an important role in mineral weathering and metal corrosion in different environments. Here, we compare the bacterial and zetaproteobacterial communities of a mature iron-rich mat together with in situ incubations of different Fe-bearing materials at the EMSO-Ligure West seafloor observatory, which is located on the abyssal plain in the NW Mediterranean Sea. Our results on bacterial communities enable us to make a clear distinction between those growing on mild steel anthropic substrata and those developing on basaltic substrata. Moreover, on anthropic substrata we highlight an influence of mat age on the bacterial communities. Regarding zetaproteobacterial communities, our results point to an increase in ZetaOTUs abundance and diversification with the age of the mat. We corroborate the key role of the ZetaOTU 2 in mat construction, whatever the environment, the substrata on which they develop or the age of the mat. We also show that ZetaOTU 28 is specific to anthropogenic substrata. Finally, we demonstrate the advantage of using dPCR to precisely quantify very low abundant targets, as Zetaproteobacteria on our colonizers. Our study, also, allows to enrich our knowledge on the biogeography of Zetaproteobacteria, by adding new information on this class and their role in the Mediterranean Sea.

by Sheela B. Abraham, Farah Al-Marzooq, Lakshman Samaranayake, Rifat Akram Hamoudi, Wan Harun Himratul-Aznita, Hany Mohamed Aly Ahmed Objective Endodontic microbiota appears to undergo evolutionary changes during disease progression from inflammation to necrosis and post-treatment. The aim of this study was to compare microbiome composition and diversity in primary and post-treatment endodontic infections from a cohort of patients from the UAE. Design Intracanal samples were collected from primarily infected (n = 10) and post-treatment infected (n = 10) root canals of human teeth using sterile paper points. Bacterial DNA was amplified from seven hypervariable regions (V2–V4 and V6–V9) of the 16S rRNA gene, then sequenced using next-generation sequencing technology. The data was analyzed using appropriate bioinformatic tools. Results Analyses of all the samples revealed eight major bacterial phyla, 112 genera and 260 species. Firmicutes was the most representative phylum in both groups and was significantly more abundant in the post-treatment (54.4%) than in primary (32.2%) infections (p>0.05). A total of 260 operational taxonomic units (OTUs) were identified, of which 126 (48.5%) were shared between the groups, while 83 (31.9%) and 51 (19.6%) disparate species were isolated from primary and post-treatment infections, respectively. A significant difference in beta, but not alpha diversity was noted using several different indices (p< 0.05). Differential abundance analysis indicated that, Prevotella maculosa, Streptococcus constellatus, Novosphigobium sediminicola and Anaerococcus octavius were more abundant in primary infections while Enterrococcus faecalis, Bifidobacterium dentium, Olsenella profusa and Actinomyces dentalis were more abundant in post-treatment infections (p…

Survival after hematopoietic stem cell transplant (SCT) has been improving over the years due to multifactorial reasons including changes in condition regimens, infection prevention and supportive care [1]. However, graft-versus-host disease (GVHD) and infections remain one of the major causes of non-relapse mortality (NRM). Hence, guidelines like the National Comprehensive Cancer Network [2] and Infectious Diseases Society of America [3] recommend prophylaxis in patients with high risks for infections.

Abstract Background This case report presents a unique instance of abscesses with an uncommon pathogen isolated from blood cultures. Case presentation We present the case of a perianal abscess in a 50-year-old man with a history of cocaine abuse and bilateral hip replacements. The rapid progression led to septic shock and multi-organ failure, requiring intensive care unit admission, surgery including protective transversostomy. Blood cultures showed growth of Butyricimonas spp. with resistance to penicillin and piperacillin-tazobactam. The immediate switch to meropenem led to a significant improvement in the patient’s condition. The patient was discharged after 40 days of hospitalization in good general condition and the reversal of the transversostomy was performed six months later. Conclusion The identification of Butyricimonas faecihominis, a rarely reported pathogen, emphasizes the challenges of diagnosing and treating unusual infections. This case emphasizes the importance of rapid microbiological diagnosis, interdisciplinary collaboration, and targeted antibiotic therapy in the treatment of abscesses and sepsis. …

New England Journal of Medicine, Ahead of Print.

Abstract Background Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden.Methods We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens.Results Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59).Conclusions The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.

Abstract Background Approximately 296 million people suffer from chronic hepatitis B (CHB) caused by hepatitis B virus (HBV). Current standard treatment, nucleos(t)ide analogs, are not efficient enough to eradicate HBV from the hepatocytes. Thus, developing new drugs for CHB is desired to achieve complete cure.Methods Here we established a novel HBV reporter system, HBV-HiBiT-PS2, to screen new drugs for CHB. HBV-HiBiT-PS2 was constructed by introducing a HiBiT-tag at the 5’-end of PreS2 and introduced into HepG2-NTCP cells. Culture supernatant containing HBV-HiBiT-PS2 virions was fractionated by a sucrose density gradient ultracentrifugation to characterize their components. Replication kinetics and reporter function of HBV-HiBiT-PS2 were determined by analyzing the parameters for HBV replication in the presence or absence of HBV inhibitors.Results HBV-HiBiT-PS2 could be used for monitoring most of the replication cycle of HBV. The effects of well-characterized HBV inhibitors could be evaluated by the HiBiT activity. HBV-HiBiT-PS2 could be specialized for screening secretion inhibitors for hepatitis B surface antigen (HBsAg) because most of the HiBiT activity was derived from subviral particles which are the multimers of HBsAg.Conclusions We demonstrated that HBV-HiBiT-PS2 would be a robust tool for screening novel drugs, especially HBsAg secretion inhibitors, targeted for CHB.

Abstract Background Paracoccidioidomycosis (PCM), a systemic mycosis in Latin America, is regulated by suppressive mechanisms mediated by tolerogenic plasmacytoid-dendritic-cells and regulatory T-cells. Our recent studies revealed that myeloid-derived suppressor cells (MDSCs), are important mediators in PCM. Their suppressive activity on Th1/Th17 immunity was shown to be mediated by inhibitory effect of IL-10, IDO-1 and PD-L1. Studies revealed the chemotherapeutic drug 5-Fluorouracil (5-FU) as a selective MDSC apoptosis-inducing agent, but its in vivo effect on infectious processes remains poorly investigated.Methods MDSCs and other leukocytes were evaluated in the lungs of 5-FU-treated mice after four, six, and eight weeks of P. brasiliensis infection. Disease severity and immunological response were evaluated in MDSCs-depleted.Results 5-FU treatment caused a significant reduction of pulmonary MDSCs and fungal loads. The specific depletion of MDSCs by 5-FU reduced all pulmonary CD4+ T-cell populations (Th1, Th2, Th17, and Treg) resulting in improved tissue pathology and increased survival rates. Importantly, this reduction was concomitant with increased frequencies of Th1/Th17 cells and the increased levels of Th1/Th2/Th17 cytokines in the lungs and liver of treated mice suggesting an early and efficient protective effect of these cells. Furthermore, the immuneprotection conferred by the specific depletion of MDSCs by 5FU treatment could be reversed by the adoptive transfer of MDSCs.Conclusions 5-FU treatment depletes lung-MDSCs of P. brasiliensis-infected mice resulting in enhanced immunity. The protective effect of 5-FU treatment in pulmonary PCM suggests that the specific depletion of MDSCs can be viewed as a potential immunotherapeutic tool for PCM.

Abstract Follow-up of previously healthy patients surviving cryptococcal meningitis found that cryptococcal antigen could be detected for more than one year in serum from 38 of 44 (86%) patients and in CSF from 20 of 31 patients (67%), far beyond the time of culture conversion. The speed of titer decline, measured as the number of days for a two fold drop in titer to occur, was slower in serum than in CSF. Speed of decline of antigen titers was much slower in serum and CSF for patients infected with C. gattii than C. neoformans. The speed of decline in CSF and serum titers was also much slower in patients who had received a ventriculoperitoneal shunt for increased intracranial pressure. The variable and extraordinarily slow rate of clearance in our patients did not appear to reflect differences in disease control but rather differences in species and shunting for increased intracranial pressure.