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The Journal of Infectious Diseases Jun 2024Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune...
Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.
PubMed: 38942608
DOI: 10.1093/infdis/jiae330 -
European Journal of Public Health Jun 2024The role of the social environment can facilitate positive health outcomes through active community engagement, normalization of healthy behaviors, and stress buffering....
The role of the social environment can facilitate positive health outcomes through active community engagement, normalization of healthy behaviors, and stress buffering. We aim to examine the associations of neighborhood social cohesion with changes in BMI over time. A total of 7641 participants from The Maastricht Study between the ages of 40 and 75 years were analyzed. Weight and height were measured at baseline, and weight was self-reported annually up to 10 years of follow-up (median = 4.7 years). Perceived social cohesion was obtained by questionnaire. Home addresses for each participant were linked to geographic information system data from the Geoscience and Health Cohort Consortium to create neighborhood exposure variables including area level social cohesion, neighborhood walkability, and food environment within a 1000 m Euclidian buffer. Linear regression analyses were performed with BMI adjusted for socioeconomic variables. A mixed model analysis was carried out to examine changes in BMI. Living in the highest quartile area of individually perceived social cohesion was associated with lower BMI (Q4 B: -.53; 95% CI = -.79, -.28) compared to the lowest quartile. Similar findings were discovered using the area level measure (Q4 B: -.97; 95% CI = -1.29, -.65). There was no longitudinal association between social cohesion and BMI. Neighborhood social cohesion was associated with lower BMI classifying it as an obesogenic area characteristic that influences weight, independent of conventional built environment features.
PubMed: 38942603
DOI: 10.1093/eurpub/ckae109 -
Respiratory Care Jun 2024
Topics: Humans; Nebulizers and Vaporizers; Ventilators, Mechanical; Equipment Design; Administration, Inhalation; High-Frequency Jet Ventilation
PubMed: 38942599
DOI: 10.4187/respcare.12218 -
RMD Open Jun 2024To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.
OBJECTIVES
To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS
In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS
53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS
Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
TRIAL REGISTRATION NUMBER
NCT04991753.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Treatment Outcome; Antirheumatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Aged; Adult; Tumor Necrosis Factor-alpha; Double-Blind Method; Patient Reported Outcome Measures; Anti-Citrullinated Protein Antibodies
PubMed: 38942592
DOI: 10.1136/rmdopen-2024-004278 -
RMD Open Jun 2024Discontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Discontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable clinical and biological markers are lacking. The WIN-IgE study assesses the value of serum anti-dsDNA IgE autoantibodies as a biomarker for the prediction of relapse in severe LN.
METHODS
WIN-IgE is an ancillary study of the WIN-Lupus study (NCT01284725), a prospective controlled clinical trial which evaluated the discontinuation of MIST after 2-3 years in class III or IV±V LN with active lesions. WIN-IgE included all patients with available serum collected at randomisation for continuation or discontinuation of MIST. In these sera, anti-dsDNA antibodies, IgE and IgG, were quantified by ELISA and compared between patients who experienced LN relapse and those who did not during the 24 months of follow-up.
RESULTS
52 patients were included, 25 in the MIST continuation group and 27 in the MIST discontinuation group, 12 experienced a biopsy-proven relapse of LN. Initial anti-dsDNA IgE antibodies levels were higher in patients with subsequent LN relapse. Anti-dsDNA IgG was not associated with relapse. Survival without LN relapse was lower in patients with anti-dsDNA IgE levels above vs below a threshold of 1.9 arbitrary units (p=0.019), particularly in the subgroup of patients randomised to discontinue MIST (p=0.002). In all patients, anti-dsDNA IgE above 1.9 arbitrary units had a positive predictive value of 0.8 for severe LN relapse.
CONCLUSIONS
These results suggest blood anti-dsDNA IgE as a non-invasive predictive marker of LN relapse.
Topics: Humans; Lupus Nephritis; Female; Male; Recurrence; Adult; Biomarkers; Immunoglobulin E; Antibodies, Antinuclear; Middle Aged; Prognosis; Prospective Studies; DNA; Immunosuppressive Agents
PubMed: 38942591
DOI: 10.1136/rmdopen-2024-004255 -
BMJ Paediatrics Open Jun 2024Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic...
BACKGROUND
Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic medical conditions in Japan and explore factors leading to increased use of these devices.
METHODS
This retrospective cohort study was conducted using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Children receiving HHD aged ≤18 years between April 2011 and March 2019 were included. Children newly administered HHD between 2011 and 2013 were followed up for 5 years, and logistic regression analysis was performed to assess the relationship between increased HHD use and each selected risk factor (comorbidity or types of HHD). The models were adjusted for age category at home device introduction, sex and region.
RESULTS
Overall, 52 375 children receiving HHD were identified. The number (proportion) of children receiving HHD increased during the study period (11 556 [0.05%] in 2010 and 25 593 [0.13%] in 2018). The most commonly administered HHD was oxygen (51.0% in 2018). Among the 12 205 children receiving HHD followed up for 5 years, 70.4% and 68.3% who used oxygen or continuous positive airway pressure, respectively, were released from the devices, while only 25.8% who used mechanical ventilation were released from the device. The following diagnosis/comorbidities were associated with increased HHD use: other neurological diseases (OR): 2.85, 95% CI): 2.54-3.19), cerebral palsy (OR: 2.16, 95% CI: 1.87 to 2.49), congenital malformations of the nervous system (OR: 1.70, 95% CI: 1.34 to 2.13) and low birth weight (OR: 1.68, 95% CI: 1.41 to 2.00).
CONCLUSIONS
This study provides nationwide population-based empirical data to clarify the detailed information regarding children receiving HHD in Japan. This information could assist healthcare professionals in improving the quality of life of these children and their families and help health policymakers consider measures.
Topics: Humans; Japan; Retrospective Studies; Female; Male; Child; Home Care Services; Child, Preschool; Infant; Adolescent; Chronic Disease; Infant, Newborn
PubMed: 38942589
DOI: 10.1136/bmjpo-2024-002685 -
BMJ Paediatrics Open Jun 2024Raised intracranial pressure (ICP) contributes to approximately 20% of the admissions in the paediatric intensive care unit (PICU) in our setting. Timely identification... (Observational Study)
Observational Study
BACKGROUND
Raised intracranial pressure (ICP) contributes to approximately 20% of the admissions in the paediatric intensive care unit (PICU) in our setting. Timely identification and treatment of raised ICP is important to prevent brain herniation and death in such cases. The objective of this study was to examine the role of optic nerve sheath diameter (ONSD) in detecting clinically relevant raised ICP in children.
METHODS
A hospital-based observational analytical study in a PICU of a tertiary care institute in India on children aged 2-14 years. ONSD was measured in all children on three time points that is, day 1, day 2 and between day 4 and 7 of admission. ONSD values were compared between children with and without clinical signs of raised ICP.
RESULTS
Out of 137 paediatric patients recruited, 34 had signs of raised ICP. Mean ONSD on day 1 was higher in children with signs of raised ICP (4.99±0.57 vs 4.06±0.40; p<0.01). Mean ONSD on day 2 also was higher in raised ICP patients (4.94±0.55 vs 4.04±0.40; p<0.01). The third reading between days 4 and 7 of admission was less than the first 2 values but still higher in raised ICP patients (4.48±1.26 vs 3.99±0.57; p<0.001). The cut-off ONSD value for detecting raised ICP was 4.46 mm on the ROC curve with an area under curve 0.906 (95% CI 0.844 to 0.968), 85.3% sensitivity and 86.4% specificity. There was no difference in ONSD between the right and the left eyes at any time point irrespective of signs of raised ICP.
CONCLUSION
We found that measurement of ONSD by transorbital ultrasound was able to detect clinically relevant raised ICP with an excellent discriminatory performance at the cut-off value of 4.46 mm.
Topics: Humans; Child; Optic Nerve; Intracranial Hypertension; Child, Preschool; Female; Male; Adolescent; Intensive Care Units, Pediatric; India; Ultrasonography; Intracranial Pressure; ROC Curve; Sensitivity and Specificity
PubMed: 38942587
DOI: 10.1136/bmjpo-2023-002353 -
RNA (New York, N.Y.) Jun 2024Direct methods for determining the fidelity of DNA polymerases are robust, with relatively little sample manipulation before sequencing. In contrast, methods for...
Direct methods for determining the fidelity of DNA polymerases are robust, with relatively little sample manipulation before sequencing. In contrast, methods for measuring RNA polymerase and reverse transcriptase fidelities are complicated by additional preparation steps that introduce ambiguity and error. Here, we describe a sequencing method, termed Roll-Seq, for simultaneously determining the individual fidelities of RNA polymerases and reverse transcriptases (RT) using Pacific Biosciences Single Molecule Real-Time sequencing. By employing reverse transcriptases with high rolling-circle activity, Roll-Seq generates long concatemeric cDNA from a circular RNA template. To discern the origin of a mutation, errors are recorded and determined to occur within a single concatemer (reverse transcriptase error) or all concatemers (RNA polymerase error) over the cDNA strand. We used Roll-Seq to measure the fidelities of T7 RNA polymerases, a Group II intron-encoded RT (Induro), and two LINE RTs (Fasciolopsis buski R2-RT and human LINE-1). Substitution rates for Induro and R2-RT are the same for cDNA and second strand synthesis while LINE-1 has 2.5-fold lower fidelity when performing second strand synthesis. Deletion and insertion rates increase for all RTs during second strand synthesis. In addition, we find that a structured RNA template impacts fidelity for both RNA polymerase and RT. The accuracy and precision of Roll-Seq enable this method to be applied as a complementary analysis to structural and mechanistic characterization of RNA polymerases and reverse transcriptases or as a screening method for RNAP and RT fidelity.
PubMed: 38942481
DOI: 10.1261/rna.080002.124 -
Letters in Applied Microbiology Jun 2024Neocosmospora solani causes Fusarium wilt disease and root rot, which are serious problems worldwide. To determine the growth inhibition of Neocosmospora solani by...
Neocosmospora solani causes Fusarium wilt disease and root rot, which are serious problems worldwide. To determine the growth inhibition of Neocosmospora solani by Trichoderma hamatum volatile organic compounds (VOCs), the major chemical components of Trichoderma hamatum VOCs and the differences in their contents at different times were analysed, and the activity of these components was evaluated. The antifungal activity of Trichoderma hamatum was measured by a screening test, as Trichoderma hamatum exhibited strong antagonism against Neocosmospora solani in vitro. The double plate technique was used to verify the activity of Trichoderma hamatum VOCs, and the inhibition rate was 63.77%. Neocosmospora solani mycelia were uneven and expanded, the contents of the cells leaked, and the mycelia shrank and presented a diaphragm in the hyphae upon Trichoderma hamatum VOCs treatment. Trichoderma hamatum VOCs and their contents at different times were analysed by using GC-MS. 6-Pentyl-2H-pyran-2-one clearly presented in greater amounts than the other components on Day 3, 4, 5, and 6. VOCs from Trichoderma hamatum exhibited evident effects on the percentage of healthy fruit after Day 3. Moreover, Trichoderma hamatum can improve the biological control of diseases caused by soilborne pathogens, and can be applied in biocontrol fields.
PubMed: 38942473
DOI: 10.1093/lambio/ovae063 -
Integrative and Comparative Biology Jun 2024Peak metabolic rate reflects maximal performance and may have direct fitness consequences, whereas resting metabolic rate (RMR) represents the maintenance cost of the...
Peak metabolic rate reflects maximal performance and may have direct fitness consequences, whereas resting metabolic rate (RMR) represents the maintenance cost of the whole animal. These traits may be linked, which has significant implications for the evolution of both traits. In vertebrates, a positive correlation between resting metabolic rate and aerobic capacity has been proposed to explain the origin of endothermy. However, as studies on the relationship between resting metabolic rate and aerobic capacity have focused on vertebrates, we know much less about these traits in ectothermic insects. I measured RMR in the Glanville fritillary butterfly (Melitaea cinxia) using two configurations: one optimized for measuring flight metabolic rate, the other optimized for resting metabolic rate. The relationship between RMR and body mass was similar for the two configurations. Body mass explained 82% of the variation in RMR when it was measured using the "flight" configuration at 32°C, and 91% when using the "rest" configuration at 23°C. The Q10 coefficient calculated based on the two RMR measurements was 2.8. Mass-independent RMR was positively correlated between measurements obtained using the two instrument configurations. However, neither measure of RMR was correlated with peak metabolic rate, which indicates that RMR cannot be used as a surrogate measure for aerobic capacity in the Glanville fritillary. Ectothermic insects may be able to combine high metabolic capacity with no apparent increase in maintenance cost. Even though RMR is among the most frequently measured physiological variables, it may have limited predictive power when it comes to questions related to activity or aerobic capacity, or in the case of butterflies, flight performance.
PubMed: 38942463
DOI: 10.1093/icb/icae085