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Department of Pharmacology

 

Surface Science Discussions: Bringing the community together

Recent Publications - 11 hours 40 min ago

J Phys Condens Matter. 2025 Aug 27;37(35). doi: 10.1088/1361-648X/adf024.

ABSTRACT

Surface Science Discussions (SSD) is an online seminar series aimed at bringing together worldwide experts and early-career researchers from the surface science community and exchanging knowledge on the recent progress in the field at the international level. The event took place for the first time during the COVID-19 pandemic and continues its mission to this day. In 2024, a Special Issue (SI) featuring articles authored by the Speakers of the first two editions of SSD-2022 and 2023-was published in the Journal of Physics: Condensed Matter. Experimental and theoretical reports constituting the issue reflect current trends in surface science studies, such as the growth, structure and physicochemical properties of supported 2D layers and molecules at surfaces,in operandomodel catalytic studies, application of machine learning to the studies of surface phenomena, and the development of novel surface investigation methods. The editorial provides a brief introduction to surface science, presents the idea behind SSD and the history of the event, and describes the articles comprising the SI, thus constituting a valuable source of information on the actual topics in the field.

PMID:40859653 | DOI:10.1088/1361-648X/adf024

Factors shaping physical activity engagement in patients with moderate to advanced stage of chronic kidney disease from a hospital-based cross-sectional study, Bangladesh

Recent Publications - Fri, 22/08/2025 - 11:00

BMC Nephrol. 2025 Aug 22;26(1):481. doi: 10.1186/s12882-025-04409-4.

ABSTRACT

BACKGROUND: Patients with chronic kidney disease (CKD) may experience better health outcomes when they engage in physical activity (PA). The aim of the study was to assess the physical activity level of chronic kidney disease (CKD) patients and its potentials risk factor for health.

METHODS: A cross-sectional study was carried out at Mymensingh Medical College Hospital, Mymensingh, Bangladesh from October 2023 to January 2024. A total of 253 CKD patients aged 18 years and older at moderate to advanced stages were enrolled in the study. The global physical activity questionnaire (GPAQ) was used to measure the physical activity for health of CKD patients. Physical component summary (PCS) and mental component summary (MCS) scores were measured by Short-Form Health Survey (SF-12) questionnaire. Socio-demographic and medical records were also collected. Both logistic regression and descriptive statistics were used for data.

RESULTS: Of 253 participants (62.8% male, mean age 60.1 years), 41.1% did not meet PA recommendations. Median PA durations were 28.57 min/day for moderate PA (MPA), 8.57 min/day for transport, and 11.43 min/day for recreation. Poor physical function (PCS ≤ 41.04) was observed in 85.8% of participants, and 51.0% had depressive disorders (MCS ≤ 45.6). Logistic regression identified younger age [adjusted OR (AOR) 3.29], moderate stage of CKD (AOR 2.39), good physical function (AOR 3.01), absence of depression (AOR 4.87), and family history of CKD (AOR 2.65) were significant predictors of meeting PA recommendations (p < 0.05).

CONCLUSIONS: A substantial proportion of Bangladeshi CKD patients do not meet PA recommendations, with younger age, moderate CKD, better physical function, absence of depression, and family history of CKD predicting higher PA engagement. Targeted interventions addressing these factors, particularly early in CKD progression, are needed to promote PA and improve health outcomes in this population.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40846909 | DOI:10.1186/s12882-025-04409-4

Knowledge, attitude and practices of primary livestock raisers regarding anthrax and anthrax vaccination of livestock in outbreak and non-outbreak areas of Bangladesh

Recent Publications - Thu, 21/08/2025 - 11:00

Prev Vet Med. 2025 Aug 14;245:106657. doi: 10.1016/j.prevetmed.2025.106657. Online ahead of print.

ABSTRACT

Anthrax is a zoonotic disease caused by the spore-forming bacterium Bacillus anthracis. Outbreaks are periodically reported among people and livestock in Bangladesh. From 2009-2020, approximately 4000 suspected human cutaneous anthrax cases were reported. Although annual livestock vaccination against anthrax is one of the primary control methods, we do not know the livestock vaccination practices in Bangladesh. We aimed to determine the knowledge, attitude, and practices of livestock raisers regarding the use of anthrax vaccination. We conducted a cross-sectional survey in four districts with the highest number of suspected human anthrax cases and four districts having no reported cases from October 2017 to March 2018. We randomly selected 81 villages in total; 10-11 villages per district. From each village, 20 households with at least one domestic animal (cattle/buffalo/goat/sheep) were randomly enrolled and the primary livestock raisers were interviewed. Among the 1620 livestock raisers, 36 % had heard of the livestock disease "anthrax" or "Torka" (the local name); 48 % from outbreak districts and 24 % from non-outbreak districts (p < 0.001). Only 11 % of total respondents were aware that anthrax caused human disease. Overall, 25 % of respondents reported vaccinating their livestock for any disease. Among those, only 18 % reported vaccinating against anthrax. Most (73 %) of the livestock raisers who did not vaccinate their animals reported they were unaware of the vaccine against anthrax. Livestock raisers reported being willing to pay an average of 0.12 USD per vaccine for cattle/buffalo, and 0.06 USD for goats/sheep. Although the reported use of livestock vaccination was low in outbreak districts, respondents were more likely to be aware of anthrax. These findings highlight a need for community engagement with targeted education, and risk communication for livestock raisers regarding knowledge of anthrax, the importance of vaccination, and increasing the accessibility of anthrax vaccine in endemic villages.

PMID:40840200 | DOI:10.1016/j.prevetmed.2025.106657

Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion

Pharmacology Cambridge RSS Paper feed - Wed, 20/08/2025 - 11:00

J Biol Chem. 2025 Aug 18:110604. doi: 10.1016/j.jbc.2025.110604. Online ahead of print.

ABSTRACT

The targeting of the Glucagon-like peptide-1 receptor (GLP-1R) for diabetes and obesity is not a novel strategy, with recent therapeutics showing efficacy in weight loss and glycaemic control. However, they are also associated with side effects, including gastrointestinal disruptions and pancreatitis. Developing agonists with different signalling profiles, or that exert some tissue selectivity can circumvent these on-target, unwanted effects. Receptor activity-modifying proteins (RAMPs) offer the potential to do both, through modulation of agonist binding and signalling, as well as surface expression. The GLP-1R was found to interact with RAMP3, with the heterodimer able to bind agonist at the cell surface. RAMP3 expression biased the receptor towards Ca2+ mobilisation, away from the canonical cAMP-driven signalling. When examining G protein coupling, the interaction with RAMP3 reduced activation of the cognate Gαs but increased secondary couplings to Gαq and Gαi. These increased couplings led to an elevation in glucose-stimulated insulin secretion when cells overexpressing RAMP3 were stimulated with GLP-1. A reciprocal effect was observed when looking at reduced expression of endogenous RAMP3, with a loss of sensitivity to GLP-1 in both glucose and insulin tolerance tests in a Ramp3 knockout mouse. The effects of this interaction can then inform selection of models and peptide design when targeting this receptor for therapeutic intervention.

PMID:40835007 | DOI:10.1016/j.jbc.2025.110604

Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion

Recent Publications - Wed, 20/08/2025 - 11:00

J Biol Chem. 2025 Aug 18:110604. doi: 10.1016/j.jbc.2025.110604. Online ahead of print.

ABSTRACT

The targeting of the Glucagon-like peptide-1 receptor (GLP-1R) for diabetes and obesity is not a novel strategy, with recent therapeutics showing efficacy in weight loss and glycaemic control. However, they are also associated with side effects, including gastrointestinal disruptions and pancreatitis. Developing agonists with different signalling profiles, or that exert some tissue selectivity can circumvent these on-target, unwanted effects. Receptor activity-modifying proteins (RAMPs) offer the potential to do both, through modulation of agonist binding and signalling, as well as surface expression. The GLP-1R was found to interact with RAMP3, with the heterodimer able to bind agonist at the cell surface. RAMP3 expression biased the receptor towards Ca2+ mobilisation, away from the canonical cAMP-driven signalling. When examining G protein coupling, the interaction with RAMP3 reduced activation of the cognate Gαs but increased secondary couplings to Gαq and Gαi. These increased couplings led to an elevation in glucose-stimulated insulin secretion when cells overexpressing RAMP3 were stimulated with GLP-1. A reciprocal effect was observed when looking at reduced expression of endogenous RAMP3, with a loss of sensitivity to GLP-1 in both glucose and insulin tolerance tests in a Ramp3 knockout mouse. The effects of this interaction can then inform selection of models and peptide design when targeting this receptor for therapeutic intervention.

PMID:40835007 | DOI:10.1016/j.jbc.2025.110604

Cancer Incidence and Mortality Across 43 Cancer Registries in India

Recent Publications - Wed, 20/08/2025 - 11:00

JAMA Netw Open. 2025 Aug 1;8(8):e2527805. doi: 10.1001/jamanetworkopen.2025.27805.

ABSTRACT

IMPORTANCE: Cancer is a significant global health concern, with India ranking second in Asia and third in the world in terms of cancer incidence. Regular monitoring and updates on cancer statistics are vital for assessing the impact and burden of the disease and the effectiveness of cancer control measures.

OBJECTIVE: To measure the recent patterns and trends in cancer incidence and mortality across 43 geographic regions in India from 2015 to 2019 and to provide estimates for 2024.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from 43 population-based cancer registries across India, covering varying periods between January 1, 2015, and December 31, 2019. Population at-risk data were obtained from the Census of India, and findings were assessed by registry area. Data were analyzed from May 1 to December 20, 2024.

MAIN OUTCOMES AND MEASURES: Number of cases, crude rates, and age-adjusted rates (per 100 000 population) for cancer incidence and mortality, estimated average annual percent change (AAPC) from time trends, and estimated cancer cases in India for 2024.

RESULTS: Incidence of 708 223 cases with 206 457 deaths from 43 population-based cancer registries were included. The lifetime risk of developing cancer in India was 11.0%, while Mizoram in the Northeastern region reported lifetime risks of 21.1% in males and 18.9% in females. The district of Aizawl reported the highest age-adjusted incidence rate (AAIR) in both males (256.1; 95% CI, 245.2-267.0) and females (217.2; 95% CI, 207.6-226.7). The most common cancers were oral, lung, and prostate in males and breast, cervical, and ovarian in females. Among metropolitan cities (defined as an urban agglomeration with a population of over 1 million), Delhi had the highest overall cancer AAIR for males (146.7; 95% CI, 145.1-148.3), while Srinagar recorded the highest AAIR for lung cancer (39.5; 95% CI, 35.8-43.2). Oral cancer showed significant increases in 14 population-based cancer registries (PBCRs) among males and 4 PBCRs among females; Ahmedabad Urban had an increase of 4.7% (95% CI, 2.9% to 6.6%) in males and 6.9% (95% CI, 4.1% to 9.7%) in females. The estimated AAPC in AAIR (all sites) showed a significant increase over time in Kamrup Urban in males (3.3%; 95% CI, 2.3%-4.3%) and Thiruvananthapuram Taluk in females (3.4%; 95% CI, 3.1%-3.8%). The estimated cancer incidence for 2024 was 1 562 099 cases; estimated cancer mortality, 874 404 cases.

CONCLUSIONS AND RELEVANCE: This cross-sectional study highlighted significant regional disparities in cancer incidence across India and the increasing cancer burden. The findings provide key insights for policymakers to enhance resource allocation and strengthen cancer control strategies nationwide.

PMID:40833697 | DOI:10.1001/jamanetworkopen.2025.27805

Receptor Activity-Modifying Protein 3 enhances GLP-1-mediated Insulin Secretion

Recent Publications - Wed, 20/08/2025 - 11:00

bioRxiv [Preprint]. 2025 Aug 13:2025.01.24.634724. doi: 10.1101/2025.01.24.634724.

ABSTRACT

The targeting of the Glucagon-like peptide-1 receptor (GLP-1R) for diabetes and obesity is not a novel strategy, with recent therapeutics showing efficacy in weight loss and glycaemic control. However, they are also associated with side effects, including gastrointestinal disruptions and pancreatitis. Developing agonists with different signalling profiles, or that exert some tissue selectivity can circumvent these on-target, unwanted effects. Receptor activity-modifying proteins (RAMPs) offer the potential to do both, through modulation of agonist binding and signalling, as well as surface expression. The GLP-1R was found to interact with RAMP3, with the heterodimer able to bind agonist at the cell surface. RAMP3 expression biased the receptor towards Ca 2+ mobilisation, away from the canonical cAMP-driven signalling. When examining G protein coupling, the interaction with RAMP3 reduced activation of the cognate Gα s but increased secondary couplings to Gα q and Gα i . These increased couplings led to an elevation in glucose-stimulated insulin secretion when cells overexpressing RAMP3 were stimulated with GLP-1. A reciprocal effect was observed when looking at reduced expression of endogenous RAMP3, with a loss of sensitivity to GLP-1 in both glucose and insulin tolerance tests in a Ramp3 knockout mouse. The effects of this interaction can then inform selection of models and peptide design when targeting this receptor for therapeutic intervention.

SIGNIFICANCE STATEMENT: G Protein-Coupled Receptors, such as the Glucagon-Like Peptide-1 (GLP-1) Receptor are common drug targets, although not without side effects due to on-target, unwanted signalling outputs. This study identifies an interacting protein which alters its signalling to promote insulin secretion. This may improve the therapeutic potential of GLP-1 mimetics, enhancing effectual signalling over that associated with unwanted effects by directly targeting this receptor complex.

PMID:40832355 | PMC:PMC12363685 | DOI:10.1101/2025.01.24.634724

Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain

Pharmacology Cambridge RSS Paper feed - Tue, 19/08/2025 - 11:00

Nat Metab. 2025 Aug 19. doi: 10.1038/s42255-025-01342-6. Online ahead of print.

ABSTRACT

Dual agonists targeting glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are breakthrough treatments for patients with type 2 diabetes and obesity. Compared to GLP1R agonists, dual agonists show superior efficacy for glucose lowering and weight reduction. However, delineation of dual agonist cell targets remains challenging. Here, we develop and test daLUXendin and daLUXendin+, non-lipidated and lipidated fluorescent GLP1R/GIPR dual agonist probes, and use them to visualize cellular targets. daLUXendins are potent GLP1R/GIPR dual agonists that advantageously show less functional selectivity for mouse GLP1R over mouse GIPR. daLUXendins label rodent and human pancreatic islet cells, with a signal intensity of β cells > α cells = δ cells. Systemic administration of daLUXendin strongly labels GLP1R+ and GIPR+ neurons in circumventricular organs characterized by an incomplete blood-brain barrier but does not penetrate the brain beyond labelling seen with single (ant)agonists. At the single-molecule level, daLUXendin targets endogenous GLP1R-GIPR nanodomains, which differ in organization and composition from those targeted by a single agonist. daLUXendins reveal dual agonist targets in the pancreas and brain and exclude a role for brain penetration in determining the superior efficacy of dual agonists, shedding new light on different modes of action of dual agonists versus single agonists.

PMID:40830598 | DOI:10.1038/s42255-025-01342-6

Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain

Recent Publications - Tue, 19/08/2025 - 11:00

Nat Metab. 2025 Aug 19. doi: 10.1038/s42255-025-01342-6. Online ahead of print.

ABSTRACT

Dual agonists targeting glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are breakthrough treatments for patients with type 2 diabetes and obesity. Compared to GLP1R agonists, dual agonists show superior efficacy for glucose lowering and weight reduction. However, delineation of dual agonist cell targets remains challenging. Here, we develop and test daLUXendin and daLUXendin+, non-lipidated and lipidated fluorescent GLP1R/GIPR dual agonist probes, and use them to visualize cellular targets. daLUXendins are potent GLP1R/GIPR dual agonists that advantageously show less functional selectivity for mouse GLP1R over mouse GIPR. daLUXendins label rodent and human pancreatic islet cells, with a signal intensity of β cells > α cells = δ cells. Systemic administration of daLUXendin strongly labels GLP1R+ and GIPR+ neurons in circumventricular organs characterized by an incomplete blood-brain barrier but does not penetrate the brain beyond labelling seen with single (ant)agonists. At the single-molecule level, daLUXendin targets endogenous GLP1R-GIPR nanodomains, which differ in organization and composition from those targeted by a single agonist. daLUXendins reveal dual agonist targets in the pancreas and brain and exclude a role for brain penetration in determining the superior efficacy of dual agonists, shedding new light on different modes of action of dual agonists versus single agonists.

PMID:40830598 | DOI:10.1038/s42255-025-01342-6

IL-17 Stimulates Sensory Neurons and Sensitises Colonic Afferents to Noxious Stimuli in a PI3K Dependent Manner in Male Mice

Pharmacology Cambridge RSS Paper feed - Tue, 19/08/2025 - 11:00

J Neurochem. 2025 Aug;169(8):e70191. doi: 10.1111/jnc.70191.

ABSTRACT

Managing visceral pain associated with gastrointestinal (GI) disease remains a significant challenge due to the gut-related side effects and contraindicated use of many commonly used painkillers in people with inflammatory bowel disease (IBD). Consequently, it is crucial to deepen our understanding of the mediators and mechanisms underlying inflammatory pain in people with IBD. To do this, we compared bulk RNA sequencing data from colonic biopsy samples from people with IBD with single-cell RNA sequencing data from colon-projecting dorsal root ganglion (DRG) neurons in mice to generate an interactome of putative pro-nociceptive cytokine signalling pathways. This in silico analysis revealed a 10-fold increase in IL17A expression in samples from people with ulcerative colitis (UC) alongside marked co-expression of Il17ra with Trpv1 in colon-projecting DRG neurons in mice, highlighting a likely role for interleukin-17 (IL-17) in colonic nociceptor signalling in people with UC. In support of this, Ca2+ imaging studies demonstrated that IL-17 stimulates DRG sensory neurons co-sensitive to capsaicin in male and female mice, with a similar proportion responding in neuron-enriched cultures generated by magnetic-activated cell sorting, thus confirming that IL-17 directly activates DRG neurons. IL-17-evoked Ca2+ signals were attenuated by TRPV1 inhibition, consistent with nociceptor activation, and blocked by inhibition of phosphoinositide 3-kinase (PI3K) activity, consistent with the known role for PI3K as a downstream effector of IL-17 receptor signalling. In keeping with these observations, IL-17 enhanced colonic afferent responses to colorectal distension at noxious distension pressures in male mice, an effect also blocked by PI3K inhibition. Overall, these findings demonstrate a pro-nociceptive effect of IL-17 in the GI tract, thus highlighting the potential utility of IL-17-targeting therapies to reduce pain in people with UC.

PMID:40827457 | DOI:10.1111/jnc.70191

IL-17 Stimulates Sensory Neurons and Sensitises Colonic Afferents to Noxious Stimuli in a PI3K Dependent Manner in Male Mice

Recent Publications - Tue, 19/08/2025 - 11:00

J Neurochem. 2025 Aug;169(8):e70191. doi: 10.1111/jnc.70191.

ABSTRACT

Managing visceral pain associated with gastrointestinal (GI) disease remains a significant challenge due to the gut-related side effects and contraindicated use of many commonly used painkillers in people with inflammatory bowel disease (IBD). Consequently, it is crucial to deepen our understanding of the mediators and mechanisms underlying inflammatory pain in people with IBD. To do this, we compared bulk RNA sequencing data from colonic biopsy samples from people with IBD with single-cell RNA sequencing data from colon-projecting dorsal root ganglion (DRG) neurons in mice to generate an interactome of putative pro-nociceptive cytokine signalling pathways. This in silico analysis revealed a 10-fold increase in IL17A expression in samples from people with ulcerative colitis (UC) alongside marked co-expression of Il17ra with Trpv1 in colon-projecting DRG neurons in mice, highlighting a likely role for interleukin-17 (IL-17) in colonic nociceptor signalling in people with UC. In support of this, Ca2+ imaging studies demonstrated that IL-17 stimulates DRG sensory neurons co-sensitive to capsaicin in male and female mice, with a similar proportion responding in neuron-enriched cultures generated by magnetic-activated cell sorting, thus confirming that IL-17 directly activates DRG neurons. IL-17-evoked Ca2+ signals were attenuated by TRPV1 inhibition, consistent with nociceptor activation, and blocked by inhibition of phosphoinositide 3-kinase (PI3K) activity, consistent with the known role for PI3K as a downstream effector of IL-17 receptor signalling. In keeping with these observations, IL-17 enhanced colonic afferent responses to colorectal distension at noxious distension pressures in male mice, an effect also blocked by PI3K inhibition. Overall, these findings demonstrate a pro-nociceptive effect of IL-17 in the GI tract, thus highlighting the potential utility of IL-17-targeting therapies to reduce pain in people with UC.

PMID:40827457 | DOI:10.1111/jnc.70191

Precision oncology informatics for anticancer drug combination responses: A systematic review

Recent Publications - Sun, 17/08/2025 - 11:00

Comput Biol Med. 2025 Aug 16;196(Pt C):110788. doi: 10.1016/j.compbiomed.2025.110788. Online ahead of print.

ABSTRACT

Drug combination therapy against cancer has been a promising approach in precision oncology. In recent literature, most anticancer drug combinations (ADC) are estimated and derived from their independent drug response efficacy. Synergistic drug combination response is the most effective drug therapy for various cancer treatments. However, the ADC identification problem is challenging and practically infeasible to exhaustively screen out experimentally from the extensive ADCs. Therefore, computational approaches can be efficiently used to measure and identify drug combination responses in precision oncology. In recent decades, numerous computational approaches have been applied and proposed to predict the responses of clinical ADC using different pharmacological and multi-omics cancer data. Effective computational tools and approaches are needed to predict and measure ADC, address its challenges, and reduce complexity. We have reviewed state-of-the-art computational methods for ADC prediction in the recent decade. This review paper has provided an overview of synergistic ADC response and computational machine-learning approaches for ADC. A critical discussion of the advantages and limitations is also provided. Moreover, we have reviewed the recent existing drug combination resources for ADC response prediction and found the most influential computational method for anticancer drug combination response. Finally, we have compared different computational approaches using benchmark data for ADC responses and discussed the experimental results, limitations, and future direction of ADC responses in precision oncology.

PMID:40819493 | DOI:10.1016/j.compbiomed.2025.110788

An Efficient Parallel Sketch-Based Algorithmic Workflow for Mapping Long Reads

Recent Publications - Thu, 14/08/2025 - 11:00

IEEE Trans Comput Biol Bioinform. 2025 Jan-Feb;22(1):13-26. doi: 10.1109/TCBB.2024.3489478.

ABSTRACT

Long read technologies are continuing to evolve at a rapid pace, with the latest of the high fidelity technologies delivering reads over 10 Kbp with high accuracy. Classical long read assemblers produce assemblies directly from long reads. Hybrid assembly workflows provide ways to combine partially constructed assemblies (or contigs) with newly sequenced long reads in order to generate genomic scaffolds. Under either setting, the main computational bottleneck is the step of mapping the long reads. While many tools implement the mapping step through overlap computations, designing alignment-free approaches is necessary for large-scale computations. In this paper, we visit the problem of mapping long reads to a database of subject sequences, in a fast and accurate manner. We present an efficient parallel algorithmic workflow, called JEM-mapper, that uses a new minimizer-based Jaccard estimator (or JEM) sketch to perform alignment-free mapping of long reads. For implementation and evaluation, we consider two application settings: (i) the hybrid scaffolding setting, which aims to map long reads to partial assemblies; and (ii) the classical long read assembly setting, which aims to map long reads to one another. We implemented an MPI+OpenMP version of JEM-mapper to enable parallelism at both distributed- and shared-memory layers. Experimental evaluation shows that JEM-mapper produces high-quality mapping while significantly improving the time to solution compared to state-of-the-art tools; e.g., in the hybrid setting for a large genome with 429 K HiFi long reads and 98K contigs, JEM-mapper produces a mapping with 99.41% precision and 97.91% recall, and 6.9x speedup over a state-of-the-art mapper.

PMID:40811229 | DOI:10.1109/TCBB.2024.3489478

Improving shoulder balance in lenke type 2 and 4 adolescent idiopathic scoliosis: clinical advantages of a proximal thoracic concave rod technique

Recent Publications - Thu, 14/08/2025 - 11:00

Spine Deform. 2025 Aug 14. doi: 10.1007/s43390-025-01157-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate a novel proximal thoracic concave rod (PTCR) technique for improving postoperative shoulder imbalance (SI) in adolescent idiopathic scoliosis (AIS) patients with Lenke types 2 and 4 curves, compared to conventional methods.

METHODS: A retrospective study of 30 AIS patients (10 with PTCR, 20 without) from a multicentric European database was conducted. Patients aged ≤ 18 years undergoing surgery for Lenke types 2 or 4 curves with ≥ 2 years of follow-up were included. Radiographic parameters, including Clavicle Angle (CA) and T1 Coronal Tilt (T1CT), were assessed preoperatively, immediately postoperatively, and at 2 years. Demographic, surgical, radiological parameters, and patient-reported outcomes measures (PROMs) were compared between groups.

RESULTS: PTCR significantly improved SI, achieving optimal CA in 80% of cases versus 35% in the non-PTCR group (p = 0.02). CA correction was superior in the PTCR group (-1.66° ± 1.34° vs. 1.06 ± 2.59°, p < 0.001). While T1CT correction showed greater improvement in the PTCR group (-3.62° ± 5.56° vs. -0.31° ± 8.13°) it was not statistically significant (p = 0.258). PTCR did not increase surgical time, blood loss, or complications.

CONCLUSIONS: PTCR is a promising approach for managing shoulder imbalance in AIS patients with Lenke types 2 or 4 curves. Larger prospective studies are necessary to validate these findings.

LEVEL OF EVIDENCE: Level of Evidence: III.

PMID:40810779 | DOI:10.1007/s43390-025-01157-1

Adenovirus Disease and Ocular Symptoms in Children: Diagnosis and Prognostic Considerations

Recent Publications - Thu, 14/08/2025 - 11:00

Case Rep Infect Dis. 2025 Aug 6;2025:2621782. doi: 10.1155/crdi/2621782. eCollection 2025.

ABSTRACT

Adenoviral infections significantly impact pediatric health, manifesting as respiratory, gastrointestinal, and ocular disorders. We report a 14-year-old male with adenoviral pharyngoconjunctival fever (PCF) complicated by subconjunctival hemorrhage and enlarged adenoids. The patient presented with high-grade fever, sore throat, bilateral conjunctivitis, and gastrointestinal symptoms, including vomiting and diarrhea. Initial laboratory findings suggested septicemia; however, an extended respiratory panel confirmed adenoviral infection. Notably, the patient also had left-sided undescended testes and scoliosis, raising questions about potential associations. This case underscores the complexity of adenoviral infections in children, highlighting the interplay of respiratory, gastrointestinal, and ocular symptoms. The presence of additional conditions warrants further investigation into possible correlations with adenoviral infection. Comprehensive evaluation is crucial for accurate diagnosis and management of adenoviral infections in pediatric patients, and future research should explore long-term implications and associations with cryptorchidism and scoliosis.

PMID:40810057 | PMC:PMC12349980 | DOI:10.1155/crdi/2621782

Trends in e-cigarette flavour use and demographic correlates among US youth from 2020 to 2023

Recent Publications - Wed, 13/08/2025 - 11:00

Tob Control. 2025 Aug 12:tc-2024-059186. doi: 10.1136/tc-2024-059186. Online ahead of print.

ABSTRACT

BACKGROUND: As US electronic cigarette (e-cigarette) flavour policies became increasingly restrictive during 2020-2023, flavoured e-cigarette use by the youth might have shifted.

METHODS: US eighth, 10th and 12th graders in the Monitoring the Future study assessed the past 12-month nicotine vaping by flavour, in annual cross-sectional surveys over 2020-2023 (n=91 220). Among the past 12-month users (n=17 761), the e-cigarette flavour youth reported using most often was analysed by year, demographic/vaping pattern and year × demographic/vaping interaction using log-binomial regression.

RESULTS: Among all respondents, past 12-month vaping of non-tobacco flavoured and tobacco/unflavoured products both declined over 2020-2023. Among past 12-month users, the proportion of youth who vaped a non-tobacco flavour remained unchanged from 2020 to 2023 (95.1-95.6%); fruit/ice-fruit (60.2-78.1%) and unflavoured (2.0-3.6%) product use rose and mint (24.7-6.8%), sweet/dessert (3.6-2.0%) and tobacco (2.8-0.8%) flavour use declined. Menthol flavour use increased non-linearly (6.7% in 2020, 15.9% in 2021, 8.7% in 2023). Collapsed across years, male, 12th grade, rural and frequent vaping statuses were associated with higher menthol use, and female, eighth and 10th grade, non-frequent vaping and suburban/town statuses were associated with higher fruit/ice-fruit use. Cross-year fruit/ice-fruit use increases were heightened in eighth graders (relative risk (RR)year= 1.13). Youth menthol use declined in cities (RRyear=0.87) but increased in rural areas (RRyear=1.33).

CONCLUSION: During 2020-2023, most US youth vaped non-tobacco flavours. Reducing the availability of: (1) fruit/ice-fruit flavoured e-cigarettes might impact most US youth, especially younger teens and (2) menthol-flavoured e-cigarettes might especially impact youth vulnerable to frequent vaping and rural youth.

PMID:40803830 | DOI:10.1136/tc-2024-059186

National root-cause analysis of 1724 post-colonoscopy colorectal cancers demonstrates avoidable harm

Recent Publications - Mon, 11/08/2025 - 11:00

Endoscopy. 2025 Aug 11. doi: 10.1055/a-2681-5642. Online ahead of print.

ABSTRACT

Background and study aims Post-colonoscopy colorectal cancer (PCCRC) represents a potential missed opportunity to diagnose or prevent colorectal cancer. This study aimed to create a standardised, nationwide audit system to determine why PCCRCs occur and to generate evidence to prevent them. Patients and methods PCCRCs occurring 6-48 months after a colonoscopy were identified from English national datasets and uploaded to a secure portal. The portal contained case review form based on World Endoscopy Organisation (WEO) recommendations for PCCRC review. 126 NHS colonoscopy providers were asked to review up to 25 PCCRCs. The data were analysed to investigate the characteristics of and reasons for PCCRC. Results Of 2,859 PCCRCs, 1,724 (60%) were reviewed. Colonoscopies were mostly performed for symptoms (59%) or surveillance (26%). PCCRCs were more common at the hepatic and splenic flexures and transverse colon than in the detected CRCs. PCCRC WEO categorisations were: possible missed lesion, examination adequate 68%; possible missed lesion, examination inadequate 18%; detected lesion, not resected 9%; and likely incompletely resected lesion 5%. 69% of PCCRCs were avoidable and 44% led to harm, including premature death in 8%. Non-procedural reasons contributed to 27% of PCCRCs: patient factors, 10%; clinical decision-making, 10%; and administrative factors, 7%. Conclusions This is the largest detailed PCCRC review to date. The majority of PCCRCs were avoidable and caused significant harm. This study clarifies the causes of diagnostic delays and highlights high-risk areas of the colon and high-risk patients, and what needs to be done to reduce PCCRC in the future.

PMID:40789323 | DOI:10.1055/a-2681-5642

Microgravity-induced alterations in the molecular and cellular characteristics of brain tumors: a systematic review

Recent Publications - Mon, 11/08/2025 - 11:00

Ann Med Surg (Lond). 2025 May 30;87(8):4982-4987. doi: 10.1097/MS9.0000000000003453. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Microgravity profoundly impacts various biological functions, including those crucial to tumorigenesis. Investigating the effects of microgravity on brain tumors is pivotal for understanding tumor biology and developing novel therapeutic strategies. This delineates the molecular and cellular characteristics of brain tumor cells under microgravity conditions.

METHODOLOGY: The authors systematically reviewed the literature to identify relevant studies.

RESULTS: Microgravity has been shown to (i) induce morphological changes, where cultured glioma cells showed inhibited invasion through formation of multicellular aggregates, and ANGM5 glioblastoma multiforme (GBM) cell line showed 3D multicellular spheroid formation and loss of adhesion; (ii) inhibit cellular proliferation generally, as well as reduce invasion and migration in U87 GBM cells, however, cell viability remained high in A-172 GBM cells and human umbilical vein endothelial cells; (iii) increase DNA damage, evidenced by increased comet tail length and expression of phosphorylated γ-H2A.X, and activate apoptotic pathways in GBM and microglial cells; (iv) alter signaling pathways and protein expression through activation of ERK1/2 and AKT, altering the expression of GSK3β, Bax, and Bcl-2 in microglial and GBM cells, and through decreasing expression of vinculin and active Yap1 in GBM cells, and that of of Yap1 and ZO-1 in endothelial cells; and (v) increase chemosensitivity of GBM cells to cisplatin.

CONCLUSION: Studies have shown that, across several rotary cell culture systems (RCCSs), random-position machines (RPMs), and 3D bioprinted GBM on-a-chip models, microgravity has consistently been proven to have profound effects on GBM cells. This further drills the potential role offered by microgravity as a promising anti-cancer agent in brain tumors, especially GBM.

PMID:40787566 | PMC:PMC12333833 | DOI:10.1097/MS9.0000000000003453

Machine perfusion for deceased donor kidney transplantation: network meta-analysis of the Cochrane review

Recent Publications - Fri, 08/08/2025 - 11:00

Am J Transplant. 2025 Aug 6:S1600-6135(25)02880-1. doi: 10.1016/j.ajt.2025.07.2489. Online ahead of print.

NO ABSTRACT

PMID:40780564 | DOI:10.1016/j.ajt.2025.07.2489

Sounding out Dysphagia: Using a Digital Stethoscope to Assess Audiometric Differences in Swallowing

Recent Publications - Fri, 08/08/2025 - 11:00

Laryngoscope. 2025 Aug 8. doi: 10.1002/lary.70012. Online ahead of print.

ABSTRACT

OBJECTIVES: A clinical swallow evaluation (CSE) is a subjective exam with limited diagnostic accuracy. We hypothesize that audiometric data collected superficially can enhance the detection of swallowing dysfunction. This study examines audiometric differences between normal and dysfunctional swallows on Flexible Endoscopic Evaluation of Swallowing (FEES) using a digital stethoscope.

METHODS: In this single-center prospective study, adult patients undergoing FEES for dysphagia had a digital stethoscope placed on the left neck. Audiometric data were analyzed by consistency and compared to Penetration-Aspiration Scale (PAS) and Yale Pharyngeal Residue Severity Rating Scale (YPS) scores.

RESULTS: Forty-nine patients with a total of 617 individual swallow events were included. Twenty-two patients (45%) had a PAS score of 1-2, 20 (41%) had a PAS score of 3-5, and 7 (14%) had a score of PAS 6-8. Multivariable analysis revealed significant differences in swallow duration (F = 4.65; p = 0.01), peak amplitude (F = 10.6; p < 0.0001), area under the curve (F = 6.13; p = 0.002), and median frequency (F = 8.52; p = 0.0002). Patients with PAS ≥ 3 had prolonged swallow (5.4 s versus 3.3 s, p < 0.0001), lower peak amplitudes (0.25 dB versus 0.32 dB; p < 0.001), and a lower median frequency (169.4 Hz versus 214.8 Hz; p < 0.0001) compared to those with PAS 1-2. Higher YPS scores (III-V) were associated with a longer swallow duration (5.5 s versus 3.5 s, p < 0.0001) and lower median frequency (158.1 Hz versus 221.1 Hz; p = 0.0005).

CONCLUSION: Audiometric data reveals significant differences in swallow duration, amplitude, and frequency in patients with swallow dysfunction. These findings suggest that audiometric analysis may serve as a valuable adjunct to the standard CSE.

PMID:40776676 | DOI:10.1002/lary.70012