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J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2025 Jul 24. doi: 10.1007/s00359-025-01752-7. Online ahead of print.

ABSTRACT

The naked mole-rat (NMR, Heterocephalus glaber) is a subterranean rodent that exhibits a range of unusual physiological traits, including diminished inflammatory pain. For example, nerve growth factor (NGF), a key inflammatory mediator, fails to induce sensitization of sensory neurons and thermal hyperalgesia in NMRs. This lack of NGF-induced neuronal sensitization and thermal hyperalgesia results from hypofunctional signaling of the NGF receptor, tropomyosin receptor kinase A (TrkA). Like NGF-TrkA signaling, the neurotrophic factor artemin, a member of the glial cell line-derived neurotrophic factor (GDNF) family, is implicated in mediating inflammatory pain through its receptor, GDNF family receptor α3 (GFRα3), which is expressed by a subset of dorsal root ganglia (DRG) sensory neurons. Here we investigated GFRα3 expression in DRG neurons of mice and NMRs, as well as measuring the impact of artemin on DRG sensory neuron function in both species in vitro. Using immunohistochemistry, we observed a similar abundance of GFRα3 in mouse and NMR DRG sensory neurons, high coexpression with the transient receptor potential vanilloid 1 (TRPV1) ion channel suggesting that these neurons are nociceptive neurons. Using in vitro electrophysiology to record from cultured DRG sensory neurons, we observed that artemin induced depolarization of the resting membrane potential and decreased the rheobase in both species, as well as diminishing the degree of TRPV1 desensitization to multiple capsaicin stimuli. Overall, results indicate that artemin similarly sensitizes sensory neurons in both mice and NMRs, future in vivo studies being required to confirm if the conserved in vitro sensitization also occurs in vivo.

PMID:40705105 | DOI:10.1007/s00359-025-01752-7

J Clin Tuberc Other Mycobact Dis. 2025 Jul 14;40:100552. doi: 10.1016/j.jctube.2025.100552. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Performance of OMNIgene.SPUTUM (OM-S) for transporting sputum was evaluated.

METHODS: This exploratory study was conducted during January-December 2019 at four near and one distant healthcare-facilities of Dhaka. Smear-positive pulmonary TB patients' sputa were collected, divided into 'OM-S untreated' and 'OM-S treated' portions, and transported to testing laboratory, Dhaka, on same-day from near-sites, and through courier from distant-site for smear-microscopy, culture, and Xpert MTB/RIF (Xpert) testing. Subset of 'OM-S treated' sample was tested with Xpert without centrifugation. Test results of all portions were compared in between.

RESULTS: Total 444 participants were enrolled (near-sites:198, distant-site: 246). All test results were comparable in both portions for near-sites. For distant-site, smear-microscopy's positivity was reduced by 4.1 % in 'OM-S treated', Xpert showed 100 % concordance in both portions, and culture was higher in 'OM-S treated' than 'OM-S untreated' (92.3 % vs 89.4 %; p = 0.288). Primary contamination rate in 'OM-S treated' was lower than 'OM-S untreated' (2.0 % vs 9.8 %; p < 0.05). For all sites, median (IQR) time-to-culture positivity was 35 (28, 42) days in both portions. Xpert positivity was 99 % concordant in 'OM-S treated' regardless of centrifugation.

CONCLUSIONS: OM-S is safe for sputum transportation. OM-S mixed sputum can be tested with Xpert and culture. Further studies can validate findings and assess cost-effectiveness.

PMID:40697678 | PMC:PMC12281178 | DOI:10.1016/j.jctube.2025.100552

Osteoarthritis Cartilage. 2025 Jul 19:S1063-4584(25)01091-X. doi: 10.1016/j.joca.2025.07.011. Online ahead of print.

ABSTRACT

OBJECTIVE: Osteoarthritis (OA) has a multifactorial pathogenesis, pain being the main symptom driving clinical decision making. Dysregulation of multiple mediators occurs in OA, the roles of many remaining to be identified. In dogs and humans with OA, synovial fluid lipidome dysregulation occurs, some findings being replicated in the plasma lipidome in a mouse OA model. One upregulated lipid is the sphingomyelin N-palmitoyl-D-erythro-sphingosylphosphorylcholine (d18:1/16:0), referred to here as SM. This study aimed to determine if SM causes joint pain and neuronal hyperexcitability in mice.

DESIGN: The effects of SM or a structurally related ceramide (CM) on mouse sensory neuron excitability were measured using patch-clamp electrophysiology, as well as the ability of intraarticular SM and CM to induce inflammatory pain in mice.

RESULTS: Incubation of sensory neurons with 1 µM SM decreased rheobase, compared to incubation with vehicle (p-adj = 0.0000146, 95% confidence interval (CI): 50.20, 76.73 pA) or CM (p-adj = 0.138, CI: 103.45, 171.55 pA). Similarly, SM induced mechanical hypersensitivity in mice compared to mice receiving vehicle (p-adj = 0.000003, 95% confidence interval (CI): 166.82, 251.63 g) or CM (p-adj = 0.055, 95% CI: 218.28, 268.12 g), which was coupled with a significant decrease in rheobase of knee-innervating neurons isolated from SM-injected mice compared to those receiving vehicle (p-adj = 0.0138, CI: 50.19, 76.73 pA) or CM (p-adj = 1.0, CI: 103.45, 171.55 pA).

CONCLUSIONS: The results generated demonstrate that a dysregulated lipidome can contribute to inflammatory OA pain, further work being necessary to determine the mechanism by which SM exerts its activity.

PMID:40691970 | DOI:10.1016/j.joca.2025.07.011

Osteoarthritis Cartilage. 2025 Jul 19:S1063-4584(25)01091-X. doi: 10.1016/j.joca.2025.07.011. Online ahead of print.

ABSTRACT

OBJECTIVE: Osteoarthritis (OA) has a multifactorial pathogenesis, pain being the main symptom driving clinical decision making. Dysregulation of multiple mediators occurs in OA, the roles of many remaining to be identified. In dogs and humans with OA, synovial fluid lipidome dysregulation occurs, some findings being replicated in the plasma lipidome in a mouse OA model. One upregulated lipid is the sphingomyelin N-palmitoyl-D-erythro-sphingosylphosphorylcholine (d18:1/16:0), referred to here as SM. This study aimed to determine if SM causes joint pain and neuronal hyperexcitability in mice.

DESIGN: The effects of SM or a structurally related ceramide (CM) on mouse sensory neuron excitability were measured using patch-clamp electrophysiology, as well as the ability of intraarticular SM and CM to induce inflammatory pain in mice.

RESULTS: Incubation of sensory neurons with 1 µM SM decreased rheobase, compared to incubation with vehicle (p-adj = 0.0000146, 95% confidence interval (CI): 50.20, 76.73 pA) or CM (p-adj = 0.138, CI: 103.45, 171.55 pA). Similarly, SM induced mechanical hypersensitivity in mice compared to mice receiving vehicle (p-adj = 0.000003, 95% confidence interval (CI): 166.82, 251.63 g) or CM (p-adj = 0.055, 95% CI: 218.28, 268.12 g), which was coupled with a significant decrease in rheobase of knee-innervating neurons isolated from SM-injected mice compared to those receiving vehicle (p-adj = 0.0138, CI: 50.19, 76.73 pA) or CM (p-adj = 1.0, CI: 103.45, 171.55 pA).

CONCLUSIONS: The results generated demonstrate that a dysregulated lipidome can contribute to inflammatory OA pain, further work being necessary to determine the mechanism by which SM exerts its activity.

PMID:40691970 | DOI:10.1016/j.joca.2025.07.011

Am J Cardiovasc Dis. 2025 Jun 15;15(3):175-180. doi: 10.62347/GLVD7571. eCollection 2025.

ABSTRACT

A coronary artery calcium (CAC) score of 0 is generally indicative of a low risk for both all-cause mortality and cardiovascular events, often serving as a basis for excluding obstructive coronary artery disease (CAD). Although isolated cases of coronary involvement have been reported in patients with a CAC score of 0, the incidence of extensive multivessel disease under these circumstances is exceedingly rare. A 48-year-old man with diabetes and hypercholesterolemia presented with atypical non-exertional left-sided chest pain. Despite a nonspecific ECG, a HEART score of 3, and a zero CAC score on echocardiography, coronary computed tomography angiography (CCTA) revealed multiple non-calcified plaques in the right coronary artery (RCA), right posterior descending coronary artery (RPDA), and left circumflex artery (LCX). The patient underwent staged percutaneous coronary intervention with drug-eluting stents, resulting in complete resolution of the stenosis. At the one-month follow-up, he remained symptom-free and tolerated the medication regimen well. This case report demonstrates that a zero CAC score should not preclude further evaluation in high-risk symptomatic patients. Extensive non-calcified plaques causing significant luminal obstruction underscore the limitations of CAC scoring, highlighting the need for additional imaging modalities, such as CCTA, to achieve timely and accurate diagnoses and appropriate therapeutic interventions.

PMID:40689064 | PMC:PMC12267082 | DOI:10.62347/GLVD7571

Drug Alcohol Depend. 2025 Jul 8;274:112774. doi: 10.1016/j.drugalcdep.2025.112774. Online ahead of print.

ABSTRACT

INTRODUCTION: Machine learning may enable detection of opioid misuse to prevent opioid-related risks including overdose and opioid use disorder.

METHODS: Here, we collected 9238 datapoints from on-body sensors and cognitive tasks in a sample of 169 patients who were prescribed opioid analgesics to manage chronic pain. We categorized patients into one of two groups using the Current Opioid Misuse Measure (COMM): those showing signs of opioid misuse (MISUSE+, n = 116) and those without signs of opioid misuse (MISUSE-, n = 53). Heart rate variability and respiration rate were assessed while participants completed a Dot Probe task involving shifting attention towards and away from opioid-related and emotional cues, and a Go/No-Go task involving inhibition of automatic responses. Cross-sectional data (e.g., physiological responses, task reaction times, task accuracy) were analyzed with a temporal fusion transformer machine learning (ML) model to predict COMM opioid misuse status. We employed Leave-One-Group-Out (LOGO) cross-validation with the participants divided into 10 groups. Each cycle, one group was held out for testing, ensuring robust, unbiased model validation across different subsets of participants.

RESULTS: The ML model showed good predictive performance for identifying opioid misuse (AUC, 0.81; specificity, 0.78; sensitivity, 0.78). Behavioral responses were stronger predictors of misuse status than physiological signals.

CONCLUSIONS: ML models using data from cognitive tasks and on-body sensors detected opioid misuse with an accuracy comparable to gold-standard self-reported opioid misuse assessments. Wearable sensors may provide only incremental predictive power over behavioral responses. Our ML model should be benchmarked against objective measures of opioid misuse.

PMID:40684523 | DOI:10.1016/j.drugalcdep.2025.112774

Br J Cancer. 2025 Jul 17. doi: 10.1038/s41416-025-03117-y. Online ahead of print.

ABSTRACT

BACKGROUND: BOADICEA is a widely used algorithm for predicting breast and ovarian cancer risks, using a combination of genetic and lifestyle, hormonal and reproductive risk factors. However, it has largely been developed using data from White/European individuals, limiting its applicability to other ethnicities. Here, we updated BOADICEA to provide ethnicity-specific risk estimates.

METHODS: We utilised data from multiple sources to derive estimates for the distributions and effect sizes of risk factors in major UK ethnic groups (White, Black, South Asian, East Asian, and Mixed), along with ethnicity-specific population cancer incidences. We also developed a method for deriving adjusted polygenic scores for individuals of mixed genetic ancestry.

RESULTS: The predicted average absolute risks were smaller in all non-White ethnic groups than in Whites, and the risk distributions were narrower. The proportion of women classified as at moderate or high risk of breast or ovarian cancer, according to national guidelines, was considerably smaller in non-Whites.

DISCUSSION: The updated BOADICEA, available in the CanRisk tool ( www.canrisk.org ), is based on more appropriate estimates for non-White women in the UK. Further validation of the model in prospective studies is required. Considering these findings, risk classification guidelines for non-White women may need to be revised.

PMID:40676226 | DOI:10.1038/s41416-025-03117-y

Spine (Phila Pa 1976). 2025 Jul 16. doi: 10.1097/BRS.0000000000005453. Online ahead of print.

ABSTRACT

STUDY DESIGN: retrospective analysis of prospectively collected data.

OBJECTIVE: to investigate whether two clustering approaches applied to the same database would lead to differences in the minimal clinical important difference (MCID) for health-related quality of life parameters (HRQoL).

SUMMARY OF BACKGROUND DATA: Machine learning approaches are being increasingly employed for the analysis of complex and heterogeneous settings such as that of adult spine deformity (ASD). However, it is not yet clear whether and how the choice of number and type of variables impacts the outcomes of a study.

METHODS: Two previously published clustering approaches (C12 and C16) were applied to a multicentric database of ASD patients who underwent surgery and had a minimum follow-up of one year. After clustering, the MCID for the Oswestry Disability Index, SRS-22, and SF-36 PCS were calculated for all clusters using the ROC method.

RESULTS: Data from 516 patients were available. Both algorithms led to a division of the database in three clusters, which presented similar characteristics both for C12 and C16. In particular, patients in clusters 1 to 3 presented an increasing level of imbalance and disability. The MCID for ODI, SRS-22, and SF-36 for each cluster differed between C12 and C16, but a similar pattern of increase of the MCID from Cluster 1 to Cluster 3 was observed for all HRQoL parameters and in both C12 and C16. The error rate, however, was smaller for C16.

CONCLUSION: Different clustering algorithms applied to the same database allowed to obtain similar clusters of ASD patients. However, the obtained MCIDs for the evaluated HRQoL parameters were different, highlighting the relevance of the choice of variables for the investigation of these parameters. The results suggest that clinically-driven clusters should be used when investigating clinical outcomes, as they allow for a smaller error rate.

PMID:40667701 | DOI:10.1097/BRS.0000000000005453

AoB Plants. 2025 Jun 26;17(4):plaf036. doi: 10.1093/aobpla/plaf036. eCollection 2025 Aug.

ABSTRACT

Legume introduction is effective for boosting primary productivity in C4-grass-dominated subtropical and tropical grasslands by overcoming nitrogen (N) limitation and consequently improving radiation-use efficiency (RUE), a key metric underlying plant production. However, an excessive proportion of C3 legumes may negatively affect RUE, especially in warm climates. We assessed the relationship between aboveground RUE and legume proportion of Paspalum notatum Flügge (C4 grass) mixtures with a tropical legume (Arachis glabrata Benth.; 0%-80%) under different defoliation and N fertilizer treatments in two studies over 3 years in Florida, USA. Linking the field data to a conceptual model, RUE was optimized at 26%-30% legume proportion across studies and years. When pastures were N-fertilized, RUE plateaued at 26% legume (0.60 g MJ-1) and linearly decreased with higher legume proportions. When pastures were unfertilized, RUE showed a quadratic relationship with legume proportion, being maximized at 30% legume (1.10 g MJ-1), overyielding the RUE in only-grass and legume-dominated sites by 110% and 86%, respectively. These responses suggest that RUE is N-limited when legume is below 30% in unfertilized canopies and is physiologically limited when legume is above 30% due to replacement of the C4 grass with a C3 legume. These findings provide a robust rationale to target low-to-moderate legume proportions in tropical grasslands for optimizing production and other ecosystem services. We empirically demonstrated that optimum legume proportion is ∼30% in a C4-grass-based tropical grassland compared with previous observations of ≥40% in C3-grass-based temperate grasslands, relevant insights for the design and maintenance of grassland ecosystems.

PMID:40667455 | PMC:PMC12260219 | DOI:10.1093/aobpla/plaf036

RSC Chem Biol. 2025 Jun 23. doi: 10.1039/d5cb00079c. Online ahead of print.

ABSTRACT

Accurate measurements of binding kinetics, encompassing equilibrium dissociation constant (K D), association rate (k on), and dissociation rate (k off), are critical for the development and optimisation of high-affinity binding proteins. However, such measurements require highly purified material and precise ligand immobilisation, limiting the number of binders that can be characterised within a reasonable timescale and budget. Here, we present the SpyBLI method, a rapid and cost-effective biolayer interferometry (BLI) pipeline that leverages the SpyCatcher003-SpyTag003 covalent association, eliminating the need for both binder purification and concentration determination. This approach allows for accurate binding-kinetic measurements to be performed directly from crude mammalian-cell supernatants or cell-free expression blends. We also introduce a linear gene fragment design that enables reliable expression in cell-free systems without any PCR or cloning steps, allowing binding kinetics data to be collected in under 24 hours from receiving inexpensive DNA fragments, with minimal hands-on time. We demonstrate the method's broad applicability using a range of nanobodies and single-chain antibody variable fragments (scFvs), with affinity values spanning six orders of magnitude. By minimising sample preparation and employing highly controlled, ordered sensor immobilisation, our workflow delivers reliable kinetic measurements from crude mixtures without sacrificing precision. We expect that the opportunity to carry out rapid and accurate binding measurements in good throughput should prove especially valuable for binder engineering, the screening of next-generation sequencing-derived libraries, and computational protein design, where large numbers of potential binders for the same target must be rapidly and accurately characterised to enable iterative refinement and candidate selection.

PMID:40655043 | PMC:PMC12247212 | DOI:10.1039/d5cb00079c

RSC Chem Biol. 2025 Jun 23. doi: 10.1039/d5cb00079c. Online ahead of print.

ABSTRACT

Accurate measurements of binding kinetics, encompassing equilibrium dissociation constant (K D), association rate (k on), and dissociation rate (k off), are critical for the development and optimisation of high-affinity binding proteins. However, such measurements require highly purified material and precise ligand immobilisation, limiting the number of binders that can be characterised within a reasonable timescale and budget. Here, we present the SpyBLI method, a rapid and cost-effective biolayer interferometry (BLI) pipeline that leverages the SpyCatcher003-SpyTag003 covalent association, eliminating the need for both binder purification and concentration determination. This approach allows for accurate binding-kinetic measurements to be performed directly from crude mammalian-cell supernatants or cell-free expression blends. We also introduce a linear gene fragment design that enables reliable expression in cell-free systems without any PCR or cloning steps, allowing binding kinetics data to be collected in under 24 hours from receiving inexpensive DNA fragments, with minimal hands-on time. We demonstrate the method's broad applicability using a range of nanobodies and single-chain antibody variable fragments (scFvs), with affinity values spanning six orders of magnitude. By minimising sample preparation and employing highly controlled, ordered sensor immobilisation, our workflow delivers reliable kinetic measurements from crude mixtures without sacrificing precision. We expect that the opportunity to carry out rapid and accurate binding measurements in good throughput should prove especially valuable for binder engineering, the screening of next-generation sequencing-derived libraries, and computational protein design, where large numbers of potential binders for the same target must be rapidly and accurately characterised to enable iterative refinement and candidate selection.

PMID:40655043 | PMC:PMC12247212 | DOI:10.1039/d5cb00079c

Org Lett. 2025 Jul 14. doi: 10.1021/acs.orglett.5c02795. Online ahead of print.

NO ABSTRACT

PMID:40653978 | DOI:10.1021/acs.orglett.5c02795

Chem Commun (Camb). 2025 Jul 11. doi: 10.1039/d5cc03483c. Online ahead of print.

ABSTRACT

Nb-polyoxometalates (Nb-POMs) and Zr-metal organic frameworks (Zr-MOFs) are two of the most proven metal-oxide based materials for nerve gas degradation, purported for base and acid hydrolysis mechanisms respectively. We compare nerve-agent simulant degradation between several Nb-POMs plus a Zr-oxyhydroxide cluster, as a soluble surrogate for Zr-MOFs. We conclude that lability of the metal-oxo species and re-hydrolysis of metal fluoride or metal phosphonate bonds is as important, if not more important than acid/base catalysis of the metal-cation.

PMID:40641320 | DOI:10.1039/d5cc03483c

Sage Open Aging. 2025 Jun 9;11:30495334251345091. doi: 10.1177/30495334251345091. eCollection 2025 Jan-Dec.

ABSTRACT

Polypharmacy is the concurrent use of many drugs increasingly prevalent in elderly populations worldwide, with over 50% of older adults taking more than five drugs. The rise in chronic conditions such as diabetes, hypertension, and dementia largely drives this trend. However, polypharmacy poses significant risks, including adverse drug events, falls, cognitive decline, and hospitalizations, particularly due to age-related physiological changes that alter drug metabolism and clearance. Vulnerable populations, especially those with comorbidities, face heightened risks of complications associated with polypharmacy, underscoring the need for effective management strategies. Despite extensive literature on polypharmacy, gaps remain in practical, evidence-based approaches to safely reduce medication burdens. Structured deprescribing protocols are emerging as a critical intervention for reducing inappropriate medication use, improving patient outcomes, and lowering healthcare costs. These protocols involve stepwise algorithms and tools for screening to find potentially inappropriate medications and clinical decision-making frameworks to prioritize deprescribing as it can reduce fall risk, hospitalizations, and healthcare costs while enhancing quality of life. This narrative review examines evidence from trials, cohort studies, and meta-analyses on deprescribing protocols, highlighting challenges like patient resistance and withdrawal effects. It emphasizes tailored approaches, patient engagement, and shared decision-making for safe, effective, patient-centered deprescribing across healthcare settings.

PMID:40611862 | PMC:PMC12220885 | DOI:10.1177/30495334251345091

Sci Rep. 2025 Jul 2;15(1):23673. doi: 10.1038/s41598-025-07436-1.

ABSTRACT

Integrating artificial intelligence (AI) into sustainable urban development presents an innovative pathway for addressing global environmental and socio-economic challenges. This study examines how AI technologies-such as machine learning, the Internet of Things (IoT), and big data analytics-can advance the three zeros method, a sustainability framework proposed by Nobel laureate Muhammad Yunus, which focuses on zero carbon emissions, zero poverty, and zero waste. By analyzing panel data across 50 countries and incorporating case studies, the research highlights AI's role in promoting carbon neutrality, economic inclusivity, and waste reduction. The findings reveal that AI-driven R&D innovation exerts the most decisive influence on sustainability, followed by AI-powered infrastructure, while market advantage plays a comparatively more minor role. Additionally, the study uncovers regional disparities in AI's impact, with the most significant benefits observed in countries at upper-middle levels of sustainable development. Moreover, urbanization serves as a threshold factor, altering AI's effects on sustainability. When urbanization is below a critical level, AI-driven innovation and infrastructure support sustainability, whereas the AI market advantage inhibits it. However, infrastructure may hinder sustainable development beyond this threshold while AI market mechanisms become more influential. These insights underscore the need for policymakers to tailor AI-driven sustainability strategies based on urbanization dynamics and regional development levels.

PMID:40603460 | DOI:10.1038/s41598-025-07436-1

PLoS One. 2025 Jul 1;20(7):e0327348. doi: 10.1371/journal.pone.0327348. eCollection 2025.

ABSTRACT

BACKGROUND: Tuberculosis (TB) regained its position as the leading cause of death globally from a single infectious disease agent in 2024. Delayed diagnosis and treatment hamper effective TB control. We investigated the duration of diagnostic and treatment delay along with the associated factors among people with pulmonary TB in Bangladesh.

METHODS: A mixed-method study was conducted between December'19 and March'21, at icddr,b TB Screening and Treatment Centres (TBSTCs), Dhaka. We interviewed people with TB (PWTB) seeking care at these TBSTCs using a structured questionnaire to collect data on socio-demographic, clinical and healthcare seeking behaviors. We used established frameworks to define stages of delay and associated factors. Qualitative interviews were conducted among a subset of participants to gain further insight into the factors associated with delay.

RESULTS: We enrolled 895 PWTB with mean (±SD) age 36.6 (±16.1) years; majority of participants were males (69.9%) and living in urban areas (82.3%). The median (IQR) patient delay estimated was 47 (29-72) days, with diagnostic delay 45 (30-70) days and treatment delay 2 (2-4) days. The predictors of delay were those with diabetes (OR 2.0, 95% CI - 1.11, 3.42), who initially self-treated (OR 2.1, 95% CI - 1.09, 3.88), and were bacteriologically diagnosed (OR 3.7, 95% CI - 1.31, 10.46). Qualitative approach supported the quantitative findings and revealed the practice of visiting formal physicians during worsening illness, neglecting to acknowledge signs or symptoms consistent with TB, lack of TB related knowledge, and financial insolvency as major reasons for delay.

CONCLUSION: Our findings showed that improper health-seeking behavior is one of the major drivers of patient delay. Thus, targeted programmatic intervention to raise community awareness on TB and its care services with a special focus on informal providers can help reduce this delay.

PMID:40591627 | DOI:10.1371/journal.pone.0327348

J Cardiothorac Vasc Anesth. 2025 May 8:S1053-0770(25)00363-5. doi: 10.1053/j.jvca.2025.05.006. Online ahead of print.

ABSTRACT

Genetic polymorphisms within the β1-adrenoceptor are common within the population. Although not directly causative of disease, accumulating evidence supports that they have significant molecular and clinical effects, including altering the response to inotropes and β-blockers, as well as altering exercise capacity. Here, we summarize current evidence as relevant to anesthetists who treat patients with heart failure.

PMID:40581538 | DOI:10.1053/j.jvca.2025.05.006

J Cardiothorac Vasc Anesth. 2025 May 8:S1053-0770(25)00363-5. doi: 10.1053/j.jvca.2025.05.006. Online ahead of print.

ABSTRACT

Genetic polymorphisms within the β1-adrenoceptor are common within the population. Although not directly causative of disease, accumulating evidence supports that they have significant molecular and clinical effects, including altering the response to inotropes and β-blockers, as well as altering exercise capacity. Here, we summarize current evidence as relevant to anesthetists who treat patients with heart failure.

PMID:40581538 | DOI:10.1053/j.jvca.2025.05.006

J Adv Vet Anim Res. 2025 Mar 24;12(1):80-89. doi: 10.5455/javar.2025.l874. eCollection 2025 Mar.

ABSTRACT

OBJECTIVE: The goal of this study is to describe the genome of Streptococcus agalactiae that was found in clinical mastitis in cattle in Bangladesh. This work will show how strong the bacteria are and how important they are for public health.

MATERIALS AND METHODS: Whole genome sequencing (WGS) was performed using the Illumina MiSeq platform, followed by comprehensive analysis with various bioinformatic tools to identify key genomic features.

RESULTS: WGS revealed that the isolates are closely related, belonging to sequence type ST4, a rare type previously identified in both human and animal hosts. The isolates possess 44 virulence-related genes linked to adherence, capsule biogenesis, enzyme production, immunoreactive antigens, protease, and cytolysin production. They also carry two pilus islands (PIs), PI-1 and PI-2b, which are often associated with invasive diseases. PI-2b proteins are key targets for vaccine development against Group B Streptococcus (GBS). The isolates belong to serotype Ia and carry the gbs2018-2 variant, indicating their adaptability to a wide range of hosts, including humans and animals. These virulence factors are critical for understanding S. agalactiae's pathogenicity and developing vaccines against its infections. Additionally, the isolates harbor antimicrobial resistance genes conferring resistance to glycopeptides (vanT, vanY), macrolides (mreA), peptides (mprF), penicillins and β-lactams (pbp), and aminoglycosides. Source tracking via the BacWGSTdb website identified these isolates as closely related to human pathogens, indicating their zoonotic potential.

CONCLUSION: These results suggest that S. agalactiae could be a zoonotic pathogen. This highlights the need for ongoing genomic surveillance to fully understand how it causes disease and come up with effective ways to control it.

PMID:40568491 | PMC:PMC12186781 | DOI:10.5455/javar.2025.l874

Adv Sci (Weinh). 2025 Jun 25:e03957. doi: 10.1002/advs.202503957. Online ahead of print.

ABSTRACT

Mutational variants of human lysozyme cause a rare but fatal hereditary systemic amyloidosis by populating an intermediate state that self-assembles into amyloid fibrils. However, this intermediate state is recalcitrant to detailed structural investigation, as it is only transiently and sparsely populated. Here, this work investigates the intermediate state of an amyloid-forming human lysozyme variant (I59T) using CEST and CPMG RD NMR at low pH. 15N CEST profiles probe the thermal unfolding of the native state into the denatured ensemble and reveal a distinct intermediate state. Global fitting of 15N CEST and CPMG data provides kinetic and thermodynamic parameters, characterizing the intermediate state populated at 0.6%. 1H CEST data further confirm the presence of the intermediate state displaying unusually high or low 1HN chemical shifts. To investigate the structural details of this intermediate state, this work uses molecular dynamics (MD) simulations, which recapitulate the experimentally observed folding pathway and free energy landscape. This work observes a high-energy intermediate state with a locally disordered β-domain and C-helix, stabilized by non-native hydrogen bonding and amide-π interactions, accounting for its anomalous 1H chemical shifts. Together, these NMR and MD data provide the first direct structural information on the intermediate state, offering insights into targeting lysozyme amyloidosis.

PMID:40557600 | DOI:10.1002/advs.202503957