Category: Nevin Manimala

Pain Ther. 2025 Oct 3. doi: 10.1007/s40122-025-00781-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Long-term use (≥ 3 months) of opioids for chronic noncancer pain (CNCP) shows limited benefit and often leads to dependence, especially when tapered too quickly. Standard opioid discontinuation typically involves gradual dose reduction, yet many patients fail to complete it. Meta-analyses show buprenorphine reduces withdrawal severity, increases treatment retention and completion rates, and facilitates analgesia and smoother transitions in patients with chronic pain, with low adverse effects and high initiation success.

METHODS: This single-center, prospective, nonrandomized proof-of-concept study assessed the efficacy of an outpatient buprenorphine-based discontinuation strategy in patients with CNCP and opioid dependence who had failed standard tapering. Participants first attempted gradual tapering; those unsuccessful transitioned to buprenorphine: 4-8 mg/day for 1 month, followed by tapering over up to 9 months. Success was defined as complete opioid cessation at 9 months, confirmed by urine analysis (including buprenorphine). The primary outcome was the success rate of the buprenorphine strategy, with ≥ 60% considered effective. A secondary outcome compared success rates between strategies.

RESULTS: Of 20 patients, six (30.0%) successfully withdrew using standard tapering. Fourteen failed; 11 of them transitioned to buprenorphine. Of these, seven (63.6%) achieved full discontinuation. While not statistically significant, the buprenorphine group showed a higher success rate than standard tapering (p = 0.076; OR = 4.08 [0.90-21.23]).

CONCLUSIONS: Buprenorphine substitution appears at least as effective as conventional tapering and may benefit patients unable to succeed with tapering alone. These preliminary results support further investigation in larger trials.

TRIAL REGISTRATION: ClinicalTrials. gov identifier, NCT03156907.

PMID:41042438 | DOI:10.1007/s40122-025-00781-z

Anal Chem. 2025 Oct 3. doi: 10.1021/acs.analchem.5c02192. Online ahead of print.

ABSTRACT

The assignment of bioactivity to compounds within complex natural product (NPs) mixtures remains a significant challenge in NPs research. The present research introduces a comprehensive protocol, named “PLANTA (PhytochemicaL Analysis for NaTural bioActives)” protocol, for the detection and identification of bioactive compounds in complex natural extracts prior to isolation combining the NMR–HeteroCovariance Approach (NMR-HetCA), high-performance thin-layer chromatography (HPTLC), and chemometric techniques. This study emphasizes two novel components: STOCSY-guided targeted spectral depletion, adapted to resolve overlapping NMR signals in complex matrices, improve minor component detection, and facilitate identification through NMR databases, as well as a new SHY variant termed SH-SCY (Statistical Heterocovariance – SpectroChromatographY), a new cross-correlation method linking orthogonal datasets by identifying the corresponding HPTLC spot from a single NMR peak and reconstructing of the ¹H NMR spectrum from a specific HPTLC spot, enhancing dereplication confidence. In this proof-of-concept study, an artificial extract (ArtExtr) composed of 59 standard compounds was evaluated for the detection of compounds active against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). Statistical approaches were applied to the spectral, chromatographic, and bioactivity data to identify the highly correlated bioactive compounds. The PLANTA protocol achieved an 89.5% detection rate of active metabolites and 73.7% correct identification of them. The integration of NMR and HPTLC with HetCA provides a robust and sensitive strategy for preisolation identification of bioactive constituents. This methodology addresses core challenges in metabolite profiling of complex mixtures and offers a streamlined, reproducible workflow for natural product dereplication and discovery.

PMID:41041709 | DOI:10.1021/acs.analchem.5c02192

Front Neurol. 2025 Sep 17;16:1630103. doi: 10.3389/fneur.2025.1630103. eCollection 2025.

ABSTRACT

BACKGROUND: Word retrieval deficits are the most prominent symptoms reported in primary progressive aphasia (PPA) and related syndromes. Current treatments, such as speech and language therapy, have shown limited success, highlighting the need for alternative non-pharmacological interventions with high-definition transcranial direct current stimulation (HD-tDCS) emerging as a promising tool.

OBJECTIVE: This study aimed to evaluate the effects of HD-tDCS on word retrieval function in individuals with PPA by comparing two stimulation sites: the pre-supplementary motor area (pre-SMA) and the left inferior frontal gyrus (LIFG), and to assess the relative benefits of each site.

METHODS: Eight individuals with PPA underwent 10 sessions of open-label HD-tDCS targeting either the LIFG (n = 4) or pre-SMA (n = 4). Word retrieval was assessed at baseline, immediately post-stimulation, and at 8-week follow-up. Electrophysiological measures, including event-related potentials during a non-verbal Go-NoGo task, were also collected to explore neural mechanisms.

RESULTS: LIFG stimulation yielded statistically significant improvements in phonemic fluency at immediate post testing compared to baseline, with 25-50% showing clinically meaningful improvement. Clinically meaningful improvement was observed in category fluency in 25-50% of the patients receiving stimulation at either site. Lastly, electrophysiological measures indicated HD-tDCS targeting LIFG differentially modulated event-related potential effects during non-verbal Go-NoGo tasks.

CONCLUSION: This research provides preliminary evidence supporting the use of both traditional (LIFG) and alternative (pre-SMA) stimulation sites for treating word retrieval deficits in individuals with PPA. The findings also suggest potential neural mechanisms of HD-tDCS intervention, which can inform future designs of non-invasive brain stimulation for cognitive symptoms in PPA.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT05368350.

PMID:41041680 | PMC:PMC12484069 | DOI:10.3389/fneur.2025.1630103

Front Neurol. 2025 Sep 17;16:1680268. doi: 10.3389/fneur.2025.1680268. eCollection 2025.

ABSTRACT

BACKGROUND: Cerebral hyperperfusion syndrome (CHS) is a serious complication that can follow intravascular mechanical thrombectomy for acute ischemic stroke (AIS). Dexmedetomidine (Dex), a selective α₂-adrenoceptor agonist used as a sedative, has known neuroprotective effects in ischemic cerebral injury. This double-blind, randomized, placebo-controlled clinical trial (ChiCTR 2500105088) aimed to evaluate the preventive impact of low-dose Dex on CHS after AIS.

METHODS: Patients with AIS and anterior circulation occlusion scheduled for endovascular mechanical thrombectomy from August 2023 to October 2024 were included. The occluded vessels were the internal carotid artery intracranial portion, M1, or M2 segments of the middle cerebral artery. After obtaining informed consent, patients were randomly allocated to two groups: one group (n = 70) received intravenous Dex with a 10-min preoperative loading dose of 0.5 μg/kg, followed by postoperative maintenance infusion at 0.1 μg/kg/h until 72 h postoperatively. The other group (n = 71) received an equal volume of placebo (normal saline) via the same intravenous route and schedule. The principal outcome was the occurrence of CHS evaluated through the seventh day post-operation. Subsidiary outcomes comprised the National Institutes of Health Stroke Scale (NIHSS) score within 24 h post-operation, Modified Rankin Scale (mRS) scores at discharge, within 30 days and 90 days post-operation, the duration of ICU stay, total hospital stay length, and the 30-day all-cause mortality rate.

RESULTS: A statistically significant reduction in the occurrence of CHS was observed in the Dex group relative to the placebo group: among 70 patients in the Dex group, only 2 cases of CHS were identified (2.9%), whereas 10 cases occurred in the placebo group (14.1%) from a total of 71 patients. This difference was confirmed by both odds ratio (OR: 0.203; 95% confidence interval [CI]: 0.046-0.893; p = 0.017) and hazard ratio (HR: 0.194; 95% CI: 0.043-0.887; p = 0.018) analyses. Additionally, the Dex group showed significantly lower postoperative pain scores assessed via the Numeric Rating Scale (NRS) on postoperative day 1 and day 3 compared with the placebo group (p < 0.0001).

CONCLUSION: Dex significantly reduced 7-day CHS occurrence after mechanical thrombectomy in AIS patients and lowered postoperative pain scores.

CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR 2500105088.

PMID:41041673 | PMC:PMC12483894 | DOI:10.3389/fneur.2025.1680268

Front Neurol. 2025 Sep 17;16:1622941. doi: 10.3389/fneur.2025.1622941. eCollection 2025.

ABSTRACT

BACKGROUND: Carotid plaque thickness and BRI are each associated with an increased risk of stroke. However, the value of their interaction in predicting stroke remains unclear. This study aimed to investigate the predictive performance of maximum carotid plaque thickness, BRI, and their interaction for the occurrence of stroke or TIA.

METHODS: In this prospective cohort study, 230 elderly Chinese adults were enrolled. Baseline measurements included maximum carotid plaque thickness and BRI, and an interaction term was calculated. Participants were followed for 1 year, during which the incidence of stroke or TIA was recorded. Multivariable logistic regression was used to assess the predictive value of each variable. Receiver operating characteristic curve analysis with 95% confidence intervals was conducted to determine the area under the curve (AUC) for model performance, and internal validation using bootstrap resampling (B = 1,000) was performed to correct for potential optimism.

RESULTS: Both maximum plaque thickness (3.305 ± 0.515 mm vs. 2.245 ± 0.820 mm, p < 0.001) and BRI (4.872 ± 1.240 vs. 3.751 ± 0.916, p < 0.001) were significantly higher in the stroke group than in the non-stroke group. Logistic regression analysis showed that maximum plaque thickness (Full multivariable adjustment: OR = 3.619, 95%CI: 1.781-7.355, p = 0.00038) and BRI (Full multivariable adjustment: OR = 3.116, 95% CI: 1.784-5.444, p = 0.00006) were both independent predictors. ROC analysis revealed that the interaction term yielded the highest AUC (0.9192, 95% CI: 0.8772-0.9612), compared with maximum plaque thickness (0.8819, 95% CI: 0.8353-0.9285) and BRI (0.7632, 95% CI: 0.6266-0.8997). Statistical comparisons indicated that the interaction model significantly outperformed BRI, while its advantage over maximum plaque thickness was numerically higher but did not reach statistical significance, likely due to the limited number of events. After bootstrap correction (B = 1,000), the optimism-corrected AUC of the interaction model was 0.897 (95% CI: 0.788-0.954).

CONCLUSION: Both maximum carotid plaque thickness and BRI independently predict the risk of stroke and TIA after adjusting for confounders. Their interaction further improves predictive performance. Combined assessment of these indicators may optimize early stroke risk stratification and warrants further validation in clinical practice.

PMID:41041669 | PMC:PMC12483859 | DOI:10.3389/fneur.2025.1622941

Front Neurol. 2025 Sep 17;16:1641820. doi: 10.3389/fneur.2025.1641820. eCollection 2025.

ABSTRACT

OBJECTIVES: This study aims to investigate gray matter (GM) and white matter (WM) changes in early Parkinson’s disease (PD) patients with mild cognitive impairment (PD-MCI) using high-resolution T1-weighted and diffusion-weighted MR images.

METHODS: We recruited 40 PD-MCI patients, 26 PD patients with normal cognition (PD-NC), and 40 healthy controls (HC). Voxel-based morphometry (VBM) and surface-based morphometry (SBM) were performed to assess the relationship between gray matter volume, cortical thickness, and cognitive ability. Microstructural white matter changes were evaluated using tract-based spatial statistics (TBSS) with diffusion tensor imaging measures.

RESULTS: White matter structural abnormalities were widespread in PD-MCI patients (corpus callosum, corona radiata, superior longitudinal fasciculus, left cerebral peduncle, and left corticospinal tract), with more pronounced involvement in the left cerebral hemisphere compared to healthy controls. Additionally, PD-MCI patients exhibited localized cortical atrophy in the left parieto-occipital region (calcarine, lingual gyrus, and precuneus), left parahippocampal gyrus, fusiform gyrus and entorhinal cortex. A significant positive correlation was observed between reduced gray matter volume (GMV) in the left parieto-occipital region and lower MoCA scores in the PD-MCI group (p < 0.001, R = 0.565).

CONCLUSION: Even in early-stage disease, our study demonstrates widespread WM microstructural damage but only subtle GM atrophy in PD-MCI, particularly in the left hemisphere. These findings provide new evidence to enhance our understanding of the pathogenic mechanisms and pathological basis underlying cognitive impairment in Parkinson’s disease.

PMID:41041668 | PMC:PMC12483916 | DOI:10.3389/fneur.2025.1641820

Transbound Emerg Dis. 2025 Sep 24;2025:5542740. doi: 10.1155/tbed/5542740. eCollection 2025.

ABSTRACT

Autochthonous cases of dengue in Europe are increasing. In 2023 (Lodi province) and 2024 (Fano, Pesaro and Urbino province), Italy saw the largest modern dengue outbreaks to date. Public health measures were adopted to mitigate transmission. The efficacy of these measures is unknown. We model the 2023 and 2024 dengue outbreaks to estimate the likely date of introduction of the primary case and efficacy of control measures, exploring explanations for the patterns of dengue cases for the two outbreaks. We apply a climate-driven mathematical model for Aedes albopictus and dengue virus transmission to the 2023 and 2024 outbreaks, comparing outputs to case data. The model accurately predicts the initial timeline of the Lodi dengue outbreak (R ² = 0.83), with a peak in cases in late August 2023, after which the control efforts reduced transmission. The model also accurately predicts the Fano dengue outbreak (R ² = 0.65), showing an increase in cases, peaking in mid-September 2024, after which there was an abrupt fall in cases. Our results suggest this can be attributed to substantial rainfall, and that public health measures may have latterly prevented a second peak in cases. The high predictive and explanatory ability of the model when applied to the Lodi and Fano outbreaks indicates that this framework may be of high value for public health decision-making for predicting the frequency and magnitude of future dengue outbreaks when coupled with real-time case data.

PMID:41041651 | PMC:PMC12488316 | DOI:10.1155/tbed/5542740

Front Pharmacol. 2025 Sep 17;16:1644029. doi: 10.3389/fphar.2025.1644029. eCollection 2025.

ABSTRACT

BACKGROUND: Opioid-induced respiratory depression (OIRD) is a critical safety concern during ambulatory percutaneous liver tumor thermal ablation. Esketamine has been shown to offer a promising opioid-sparing alternative with the potential to provide respiratory stability benefits. We hypothesize that hepatic hilar nerve block (HHNB) combined with esketamine will reduce the incidence of respiratory depression when compared to HHNB in conjunction with fentanyl in this particular context.

METHODS: This single-center, prospective, double-blind, randomized controlled trial (RCT) will enroll patients undergoing ambulatory ultrasound-guided percutaneous liver thermal ablation. Patients will be randomly assigned to receive either intravenous esketamine 0.37 mg kg^-1 (Intervention group) or intravenous fentanyl 1 μg·kg^– (Control group). All subjects will receive a standardized premedication consisting of midazolam 0.03 mg kg^-1 IV, followed by ultrasound-guided HHNB.

RESULTS AND ANALYSIS: The primary outcome is the incidence of respiratory depression, defined as SpO₂ <90% or EtCO₂ >55 mmHg. Secondary outcomes include the rate of anesthesia success, postoperative pain scores, and the consumption of remedial analgesia at 2, 6, and 24 h post-surgery. Additionally, satisfaction scores from both the sonographer and the patient are considered, along with any adverse events that may occur. The statistical analysis will utilize appropriate parametric/non-parametric tests for continuous data and chi-square/Fisher’s exact tests for categorical data (significance p < 0.05), using SPSS (v20.0) and R (v4.4.3; R Foundation) within the RStudio environment (v2024.12.1 + 563).

CONCLUSION AND DISCUSSION: This trial aims to provide Level I evidence comparing the respiratory depression risk between esketamine-based and fentanyl-based analgesia during HHNB-guided liver ablation. Should esketamine prove to be demonstrably superior in terms of respiratory safety, HHNB-esketamine has the potential to be a viable treatment option.

PMID:41041639 | PMC:PMC12487020 | DOI:10.3389/fphar.2025.1644029

Interv Pain Med. 2025 Jul 24;4(3):100618. doi: 10.1016/j.inpm.2025.100618. eCollection 2025 Sep.

ABSTRACT

SUMMARY OF BACKGROUND DATA: The risk of a symptomatic epidural bleed in patients continuing anticoagulation during most types of spinal injection procedures is extremely low. Cervical epidural steroid injections involve a unique risk of a catastrophic complication if an epidural hematoma is to occur secondary to spinal cord compression due to the anatomic confines of the cervical spinal canal. There is minimal research on the risk of cervical transforaminal epidural steroid injections (CTFESI) with anticoagulation.

OBJECTIVE: Evaluate the risk of performing CTFESI with patients continuing prescribed anticoagulation medication.

METHODS: A retrospective review was performed at two practice settings, a community-based outpatient practice and an academic practice, to identify all CTFESI performed between June 2018 through November 2023. Patient medical records were reviewed for the presence of anticoagulation and NSAID medication the day of the CTFESI. Data analysis used descriptive statistics to summarize the distribution of anticoagulants, NSAIDs, and cervical levels across practices, along with medication frequencies and percentages.

RESULTS: A total of 2792 CTFESIs were performed across both settings between June 2018 and November 2023. Of those, 1040 CTFESIs (37.2 %) were performed on patients taking some form of anticoagulant medication. 277 CTFESI were performed on patients taking anticoagulants or aspirin or a combination of anticoagulants and ASA. 763 were performed on patients taking NSAIDs. There were no reported cases of symptomatic epidural hematomas or other bleeding complications in the immediate post-procedural period or up to 1 week following the procedure.

CONCLUSION: It is likely that CTFESI can be safely performed in patients continuing anticoagulation, aspirin (ASA), or NSAIDs. Discontinuing anticoagulants or NSAIDs for CTFESIs may not be necessary. Further studies are warranted to confirm these results.

PMID:41041612 | PMC:PMC12486170 | DOI:10.1016/j.inpm.2025.100618

Res Sq [Preprint]. 2025 Sep 23:rs.3.rs-7665795. doi: 10.21203/rs.3.rs-7665795/v1.

ABSTRACT

Multi-omics integration faces several challenges, including heterogeneity across platforms, high dimensionality, and reduced effective sample size when all omics types are not available for every participant. We propose the AI-based Network Integration approach, which models connectivity within each omics layer as shaped by the broader biological system, including structured influences from other omics layers.We conducted a cross-sectional multi-omics study of genetic, glycomic, and lipidomic profiles related to immune and inflammatory pathways. We integrated N-glycans of immunoglobulin G (glycans) and specialized pro-resolving lipid mediators (SPMs) to advance the understanding of immune regulation and inflammation resolution, analyzing 24 glycans and 14 SPMs. The sample size decreased from N = 456 (with glycomics) to 368 (with both lipidomics and glycomics), and further to 266 (with genetic data, lipidomics, and glycomics). Pairwise association analysis revealed 10 statistically significant glycan-SPM associations (FDR < 0.05). Using the AI-based Network Integration, we found that these associations disappeared when conditioned on two bridging molecules, 5-Hydroxyeicosapentaenoic acid (5-HEPE) SPM and a glycan peak (GP 21) corresponding to disialylation, suggesting they may be mediated or confounded by a subset of these two molecules.Principal component analysis was applied to the previously identified associated genetic variants within each omics layer to derive polygenic factors, composite components summarizing shared genetic variation across variants. These polygenic factors were used in the Granularity Directed Acyclic Graph (G-DAG) algorithm to identify valid instrumental variables for the identification of molecular causal networks based on the principles of Mendelian randomization. This approach improved robustness and also identified polygenic molecules. Both bridging molecules, 5-HEPE and the GP21 glycan, were under polygenic control. 5-HEPE acted as a receiver (influenced by other SPMs), while GP21 acted as a broadcaster (influencing other glycans). The results suggest that variations in SPM lipidomics are linked to changes in glycosylation. These findings highlight a potential biological link between lipid mediators and glycan-mediated immune regulation and inflammation resolution.The AI-based Network Integration approach turns noisy associations into a small, interpretable, and biologically meaningful connectivity that cannot be explained by any other component in the study.

PMID:41041566 | PMC:PMC12486090 | DOI:10.21203/rs.3.rs-7665795/v1