Category: Nevin Manimala

Circulation. 2026 Feb 11. doi: 10.1161/CIR.0000000000001401. Online ahead of print.

ABSTRACT

Risk prediction has been used in the primary prevention of cardiovascular disease for >3 decades. Contemporary cardiovascular risk assessment relies on multivariable models, which integrate established cardiovascular risk factors and have evolved over time from the Framingham Risk Model to the pooled cohort equations to the PREVENT (Predicting Risk of CVD Events) equations. Recent scientific (ie, genomics, proteomics, metabolomics) and methodologic (ie, artificial intelligence) advances have led to a proliferation of novel models, biomarkers, and tools for potential use in risk prediction. In parallel, the growing armamentarium of preventive therapies, some with considerable cost, underscores the need for more accurate and precise risk assessment to prioritize those at highest risk who will derive the greatest absolute benefit. Accompanying the considerable enthusiasm for the potential of newer approaches to improve risk prediction is the need for rigorous evaluation and assessment of their performance (ie, accuracy, precision, incremental performance when added to contemporary multivariable risk models or established risk factors) and clinical utility (ie, actionability, scalability, generalizability) before adoption in clinical practice. Additional considerations in risk tool evaluation include reproducibility, cost-value considerations (including impact on downstream health care costs), and implications for health equity. This scientific statement defines a standardized framework for general considerations in risk prediction, statistical assessment of predictive utility, and critical appraisal of clinical utility and readiness. This scientific statement is intended to support clinicians, researchers, and policymakers in how best to evaluate current and emerging risk prediction tools and ultimately improve the prevention of cardiovascular disease in diverse populations.

PMID:41669831 | DOI:10.1161/CIR.0000000000001401

Stroke. 2026 Feb 11. doi: 10.1161/STROKEAHA.125.054876. Online ahead of print.

ABSTRACT

The CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trials) comprised 2 parallel randomized trials in asymptomatic carotid stenosis comparing medical management alone with medical management plus carotid artery stenting or carotid endarterectomy. Carotid stenting achieved a modest but statistically significant 4-year reduction in primary events, whereas carotid endarterectomy did not. This commentary examines methodological features that may have favored the revascularization arms, including omission of peri-procedural myocardial infarction and major hemorrhage as end points; allowing operator-team members to perform neurological assessments; highly selective credentialing of carotid stenting operators; and a primary analysis that weighted early and late events equally. Taken together, these methodological features and ongoing advances in contemporary medical therapy suggest that carotid stenting, carotid endarterectomy, and medical management may yield similar outcomes in clinical practice.

PMID:41669830 | DOI:10.1161/STROKEAHA.125.054876

J Cosmet Dermatol. 2026 Feb;25(2):e70716. doi: 10.1111/jocd.70716.

ABSTRACT

BACKGROUND: Calcium hydroxyapatite (CaHA) is a well-established biostimulatory filler approved for hand rejuvenation. Recent approaches have explored dilution with polymicronutrient (PMN) solutions to enhance cellular metabolism and extracellular matrix (ECM) regeneration.

AIMS: To evaluate the biological and clinical effects of CaHA diluted in a PMN solution (CaHA + PMN) compared with the conventional CaHA diluted in saline solution (CaHA + SS) for hand rejuvenation.

METHODS: An in vitro study was conducted to assess fibroblast proliferation and gene expression of ECM components (COL1A1, COL3A1, and ELN) after exposure to CaHA diluted with PMN or SS. A prospective, split-hand, double-blind clinical trial (n = 22) compared both formulations regarding Hand Grading Scale (HGS), Global Aesthetic Improvement Scale (GAIS), skin hydration (corneometry), and dermal thickness (ultrasound imaging) at baseline, 15 and 90 days after treatment.

RESULTS: In vitro, CaHA + PMN induced greater fibroblast proliferation and upregulated COL1A1 and ELN gene expression compared to CaHA + SS. Clinically, both treatments led to significant improvement from baseline in HGS (p < 0.001), skin hydration and dermal/hypodermal thickness, with no statistically significant differences between-group. Investigator-assessed GAIS and patient-reported satisfaction on a 5-point Likert scale also showed improvement in both groups.

CONCLUSION: Both treatments demonstrated comparable clinical outcomes, suggesting that the strong biostimulating effect of CaHA may have overshadowed potential additive effects of PMN. Nonetheless, in vitro findings confirmed enhanced biological activity with CaHA + PMN, supporting its investigation as a complementary strategy in future studies.

PMID:41669823 | DOI:10.1111/jocd.70716

Anal Methods. 2026 Feb 11. doi: 10.1039/d5ay02096d. Online ahead of print.

ABSTRACT

Saracatinib (AZD-0530; SRB) is a pharmaceutical agent produced by AstraZeneca and is currently undergoing clinical studies. It is classified as a dual-kinase inhibitor, exhibiting selective activity both as an Src inhibitor and a Bcr-Abl tyrosine kinase inhibitor. No metabolic stability study for SRB has been reported; hence, so the goal of the present study was to establish an ultra-fast, green, sensitive, and validated UPLC-MS/MS method for the quantification of SRB levels in human liver microsomes (HLMs) using different in silico software to support the practical outcomes. The validated approach was used to estimate the SRB metabolic stability in HLMs. In silico software tools were employed to predict the potential sites of metabolic lability and toxicity within the SRB structure. SRB and baricitinib, used as an internal standard (IS), were isolated from HLMs using protein precipitation with acetonitrile (ACN) as the extracting agent. Chromatographic separation was conducted utilizing a Luna 3 µm HILIC column (200 Å: 50 × 2 mm, Ea), with the mobile phase comprising 0.1% formic acid in ACN (85%) and 10 mM ammonium formate in water (15% at pH 3.2), and the total run time was 1.0 min. SRB and IS were analyzed utilizing the MRM mass analyzer mode. The approach was validated according to the latest FDA guidelines for bioanalytical method validation. The SRB calibration curve demonstrated significant sensitivity, with a range of statistical linearity from 1 to 4000 ng mL^-1. The intraday and interday accuracies of the four quality controls varied from -4.17% to 12.25% and -3.92% to 13.50%, respectively. The metabolic stability parameters, including the in vitro half-life (t_1/2) and intrinsic clearance (Cl_int) of SRB, were assessed at 17.24 min and 47.02 mL min^-1 kg^-1, respectively. In silico research indicated that slight structural modifications to the N-methyl piperazine ring in the drug design may enhance metabolic stability and safety compared with those of SRB.

PMID:41669815 | DOI:10.1039/d5ay02096d

Yi Chuan. 2026 Feb 20;48(2):158-176. doi: 10.16288/j.yczz.25-214.

ABSTRACT

Codon usage bias (CUB) refers to the non-random usage of synonymous codons during protein translation. It holds significant value for understanding species evolution, environmental adaptation, gene expression regulation, and population genetic diversity. In this review, we summarize the biological significance of codon usage bias, outline commonly used statistical approaches for its analysis, and provide a comprehensive overview of recent advances in codon usage research within the field of entomology. This work aims to offer new perspective and methodologies insights to support further in-depth studies of codon usage patterns in insects.

PMID:41669808 | DOI:10.16288/j.yczz.25-214

Ann Neurol. 2026 Feb 11. doi: 10.1002/ana.78135. Online ahead of print.

ABSTRACT

OBJECTIVE: Sleep-predominant network hyperexcitability is increasingly recognized as a potential disease-accelerating comorbidity in Alzheimer’s disease (AD). However, its prevalence and risk-factors remain debated, largely due to cohort-specific and methodological differences across studies. In this prospective case-control study, we investigated potential ways of improving detection, from translational approaches focusing on rapid eye movement (REM)-sleep to refined electroencephalogram (EEG) setups and added clinical questionnaires.

METHODS: We recruited 30 patients with early-stage AD without a history of epilepsy and 30 age-matched controls. Participants underwent overnight polysomnography with video-EEG. Interictal epileptic discharges (IEDs) were identified through a structured 3-step review by multiple independent experts using recommended criteria. Neuroanatomic patterns and sleep-related abnormalities were investigated as potential risk factors. Clinical symptoms in favor of epileptic seizures were evaluated through a tailored questionnaire at follow-up.

RESULTS: IEDs were detected in 3 patients (10%) and 1 control (3.33%), a difference not reaching statistical significance (p = 0.612). Most events occurred during non-REM (NREM) sleep. Eight patients (26.67%) reported symptoms compatible with epileptic seizures-one of whom also presented with IEDs. Patients with IEDs or reported symptoms suggestive of potential seizures exhibited more severe sleep-disordered breathing and reduced precuneus volume compared with those without.

INTERPRETATION: Despite efforts to optimize detection accuracy, our findings reveal a lower-than-expected percentage of patients with AD with IEDs, yet support previous findings suggesting that sleep-disordered breathing and specific atrophy patterns could flag at-risk patients, guiding screening in clinical settings. Our findings also favor validation efforts of questionnaires to support the diagnostic process. Finally, we highlight methodological issues in IED detection and call for the re-evaluation and standardization of diagnostic methods and criteria in this population to improve patient care. ANN NEUROL 2026.

PMID:41669802 | DOI:10.1002/ana.78135

Indian J Ophthalmol. 2026 Feb 11. doi: 10.4103/IJO.IJO_1029_25. Online ahead of print.

ABSTRACT

PURPOSE: Comparative evaluation of the corneal biomechanical parameters by the dynamic corneal response imaging with CORVIS-ST ST in normal and post-keratoplasty eyes.

METHODS: Cross-sectional observational study of CORVIS-ST imaging of 150 normal corneas and 150 post-keratoplasty corneas was done to evaluate corneal biomechanics of normal Asian-Indian corneas and post-keratoplasty corneas. Data on demographic details, postoperative period, visual acuity (UCVA, BCVA) (logmar units), refraction, axial length (D), corneal topography Scheimpflug’s imaging with Pentacam [Anterior-K1(AK1), Anterior-K2 (AK2), Posterior-K1(PK1), PosteriorK2(PK2), Mean keratometry (Kmean), Keratometry maximum (Kmax), Q-value, D-value, Thinnest pachymetry (TP), Corneal elevation [anterior (CE ant) and posterior (CE post)], CORVIS-ST imaging (bIOP, 1st and 2nd Appl time HCT, 1st Appl length, DA, TBI, CBI, HC rad, Vel in and out, DA ratio, IR, Inv CR, SSI, SPA1, ARTh) were recorded.

RESULTS: Comparative evaluation of CORVIS-ST in 150 normal corneas [mean age 32.54 ± 10 (9-68) years] and 150 post-keratoplasty corneas [mean age 35.14 ± 16.96 (8-72) years; PK (58), DSAEK (29), DALK (58), HALK (8), and SALK (3)] noted 18 parameters (bIOP, 1st and 2nd Appl time HCT, 1st Appl length, DA, TBI, CBI, HC rad, Vel in and out, DA ratio, IR, Inv CR, SSI, SPA1, ARTh) and showed that 12 of these were statistically different in post-keratoplasty corneas. Parameters of DA, TBI, CBI, IR, and Inv CR were higher, whereas HC rad, SSI, SPA1, and ARTh showed significantly lesser values in post-keratoplasty corneas as compared to normal corneas. Subgroup analysis (PK, DSAEK, DALK, HALK) showed eyes that underwent DSAEK had biomechanical values closest to that of normal corneas. Post-DALK in comparison to post-PK corneas showed significantly higher values in CBI and IR, and lower values in HC rad, SSI, and ARTh (0.87 ± 0.17, 9.9 ± 3.5, 0.85 ± 0.25, 190.92 ± 119.06 and 0.71 ± 0.25, 8.19 ± 1.92, 1.02 ± 0.38, and 340.90 ± 178.37, respectively). Correlational analysis showed significant mild positive correlation of CBI with corneal curvature in normal and post-PK corneas (P = 0.004 and 0.040, respectively).

CONCLUSION: Post-keratoplasty corneas were seen to have lesser biomechanical strength as compared to normal corneas. Post-DSAEK corneas had a better biomechanical strength than other groups and closest biomechanics to normal corneas. Post-DALK in comparison to post-PK corneas showed a lower biomechanical strength in our study.

PMID:41669797 | DOI:10.4103/IJO.IJO_1029_25

Indian J Ophthalmol. 2026 Feb 11. doi: 10.4103/IJO.IJO_1929_25. Online ahead of print.

ABSTRACT

This experiment was designed to study the effect of mitomycin C (MMC) on conjunctival lymphatics and the lymphangiogenesis potential of synthetic retinoic acid (ec23) in rat eyes. This prospective animal experimental study included 30 Sprague-Dawley rats, and they were allocated into five groups. The right eye underwent localized subconjunctival surgical trauma with a 31-G needle, along with subconjunctival injection of either balanced salt solution, 0.01% MMC, 100 nM ec23, 0.01% MMC with 100 nM ec23, or 0.1% dimethyl sulfoxide in the right eye. The left eyes were control. Enucleation was done on post-operative day 14, and each conjunctival specimen was stained with Masson trichome, CD 31, and D2-40 to study fibrosis, vascular and lymphatic density, respectively. The main outcome measured was the density of conjunctival lymphatic vessels at the surgical site. It was noted that MMC resulted in a significant reduction in conjunctival lymphatic and vascular density in comparison with the control eyes (179 ± 21.33 vs 85 ± 30.82 and 190 ± 18.71 vs 85 ± 30.82 P = .009), whereas 100 nM ec23 caused significant increase in lymphatic vessel density in comparison with control eyes (310 ± 82.16 Vs 134 ± 32.09, P = .008). Similarly, 100 nM ec23 significantly increased conjunctival lymphatic density in 0.01% MMC-treated eyes (1000 ± 374.17 vs 388 ± 121.53, P = .016). Inter-group analysis showed that combined use of 100 nM ec23 caused the highest lymphatic (1000 ± 374.17, P = .001) and blood vessels (596 ± 294.67, P = .014) density. Masson trichome score (fibrosis) between intervention and control eyes was compared across different groups, and it was statistically insignificant. To conclude, MMC caused a significant reduction in lymphatic vessel density, and application of 100 nM ec23 resulted in significant lymphangiogenesis in both MMC-exposed and non-MMC-exposed eyes.

PMID:41669796 | DOI:10.4103/IJO.IJO_1929_25

Indian J Ophthalmol. 2026 Feb 11. doi: 10.4103/IJO.IJO_897_25. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to analyze the genetic polymorphisms of specific genes- VEGF +936T/C, ACE ID, TNF 308G/A, and GSTP1-on the progression or regression of retinopathy of prematurity (ROP) in premature infants. The goal is to determine how these genetic variations influence the development of ROP and assess their potential as biomarkers for the disease.

METHODS: This study is a genetic association study focused on identifying the relationship between genetic polymorphisms and ROP progression in a cohort of premature infants. The study involves genotyping 12 polymorphisms in four genes (VEGF, ACE, TNF, and GSTP1) in a sample of 100 premature infants diagnosed with ROP. A total of 100 premature infants diagnosed with ROP, without any other ophthalmologic disease, were included in the study. Twelve genetic polymorphisms in the genes VEGF (+936T/C), ACE (Insertion/ Deletion), TNF (308G/A), and GSTP1 were genotyped using standard molecular techniques. The frequencies of these polymorphisms in the ROP-positive group were compared, and their association with ROP progression or regression was evaluated using statistical tests such as Chi-square or Fisher’s exact test. P values less than 0.05 were considered statistically significant.

RESULTS: Out of the 12 polymorphisms studied, only two showed statistically significant associations with ROP progression or regression.The ACE insertion allele was associated with ROP regression and VEGF +936T/C polymorphism was found to increase the risk of ROP, with the C allele being a potential risk factor for the progression of the disease. The other polymorphisms in the TNF 308G/A and GSTP1 genes did not show a statistically significant influence on ROP progression or regression.

CONCLUSION: The ACE ID polymorphism appears to provide a protective effect against the development of ROP. Premature infants with the insertion allele of the ACE gene may be at lower risk for ROP progression,suggesting a potential role for ACE gene variation in influencing disease outcomes. The VEGF +936T/C polymorphism seems to increase the risk of ROP development, with the C allele possibly contributing to the progression of the disease.This study emphasizes the potential genetic factors involved in ROP, which could pave the way for personalized approaches in monitoring and managing ROP in premature infants,particularly in resource-limited settings. Further research with larger sample sizes is needed to confirm these findings and explore the underlying mechanisms of these genetic polymorphisms in ROP.

PMID:41669786 | DOI:10.4103/IJO.IJO_897_25

Indian J Ophthalmol. 2026 Feb 11. doi: 10.4103/IJO.IJO_2328_25. Online ahead of print.

ABSTRACT

PURPOSE: To assess the one-year visual, refractive, and tomographic outcomes of corneal collagen cross-linking (CXL) performed at diagnosis in Indian children with keratoconus and to evaluate its safety in eyes with controlled vernal keratoconjunctivitis (VKC).

METHODS: Thirty-eight eyes of 30 children (9-18 years) diagnosed with keratoconus underwent standard epithelium-off CXL (Dresden protocol). “At diagnosis” was defined as treatment within four weeks of first topographic confirmation. Outcome measures included uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), keratometric indices (flat K, steep K, apical K), pachymetry, and endothelial cell density. Statistical analysis included paired and adjusted comparisons with 95% confidence intervals (CIs).

RESULTS: UCVA improved from 0.72 ± 0.46 to 0.45 ± 0.42 logMAR (P < 0.001) and BCVA from 0.37 ± 0.30 to 0.21 ± 0.28 logMAR (P < 0.001). MRSE improved by 1.72 D (P < 0.001). Steep K and apical K flattened by 2.02 D and 2.26 D respectively (P < 0.001). Endothelial cell counts were stable. Subgroup analysis showed no difference between VKC and non-VKC eyes. Three patients developed transient sterile infiltrates that resolved with medical therapy.

CONCLUSION: Performing CXL at diagnosis is safe and effective in halting pediatric keratoconus progression while improving visual and refractive outcomes. Early treatment is particularly relevant for high-risk ethnic groups such as Indian children, where keratoconus is aggressive and rapidly progressive.

PMID:41669774 | DOI:10.4103/IJO.IJO_2328_25