Nevin Manimala

Chaos. 2025 Apr 1;35(4):043106. doi: 10.1063/5.0233640.

ABSTRACT

In neuroscience, delayed synaptic activity plays a pivotal and pervasive role in influencing synchronization, oscillation, and information-processing properties of neural networks. In small rhythm-generating networks, such as central pattern generators (CPGs), time-delays may regulate and determine the stability and variability of rhythmic activity, enabling organisms to adapt to environmental changes, and coordinate diverse locomotion patterns in both function and dysfunction. Here, we examine the dynamics of a three-cell CPG model in which time-delays are introduced into reciprocally inhibitory synapses between constituent neurons. We employ computational analysis to investigate the multiplicity and robustness of various rhythms observed in such multi-modal neural networks. Our approach involves deriving exhaustive two-dimensional Poincaré return maps for phase-lags between constituent neurons, where stable fixed points and invariant curves correspond to various phase-locked and phase-slipping/jitter rhythms. These rhythms emerge and disappear through various local (saddle-node, torus) and non-local (homoclinic) bifurcations, highlighting the multi-functionality (modality) observed in such small neural networks with fast inhibitory synapses.

PMID:40168609 | DOI:10.1063/5.0233640

Ocul Immunol Inflamm. 2025 Apr 1:1-6. doi: 10.1080/09273948.2025.2487164. Online ahead of print.

ABSTRACT

PURPOSE: Adalimumab (ADA) is the only biologic agent approved for treating non-infectious uveitis (NIU). Anti-drug antibodies (AAA) may be an essential factor associated with treatment failure. We conducted a study to determine the clinical response to ADA treatment in patients with NIU. We also aimed to determine AAA’s frequency and clinical importance in these patients.

METHODS: This cross-sectional study included 60 NIU patients who used ADA therapy every other week or weekly for at least three months. The clinical findings recorded before starting ADA and on the day included in the study were compared. Serum AAA formation was evaluated. AAA-positive and AAA-negative patients were compared in terms of etiology, duration, and localization of uveitis, duration of ADA treatment, and additional IMT.

RESULTS: The increase in visual acuity, decrease in central macular thickness, improvement in the number of attacks/year, and decrease in need for CS were statistically significant with ADA treatment. AAA was positive in 15 (25%) patients. The improvement in median visual acuity, CMT, and number of attacks/year was statistically significant in both ADA-positive and negative patients. The effect of disease etiology, disease duration, uveitis localization, ADA treatment duration, and additional IMT use on serum AAA formation could not be demonstrated.

CONCLUSION: ADA is mostly associated with favorable clinical response in treating NIU. In insufficient clinical response, the dose escalation method may increase treatment success. AAA formation may not be the only factor in the ineffectiveness of treatment.

PMID:40168605 | DOI:10.1080/09273948.2025.2487164

NCHS Data Brief. 2025 Mar;(525).

ABSTRACT

OBJECTIVES: This report examines trends in neonatal intensive care unit (NICU) admission in the United States overall and by maternal age, race and Hispanic origin, gestational age and birthweight of the newborn, and state of residence of the mother from 2016 to 2023.

METHODS: Data are from the National Vital Statistics System birth files. The percentage of total NICU admissions in the United States from 2016 to 2023 are presented. Also presented are percentages of NICU admissions by maternal age, race and Hispanic origin, gestational age and birthweight of the newborn, and state of residence of the mother from 2016 to 2023.

KEY FINDINGS: The percentage of infants admitted to a neonatal intensive care unit (NICU) in the United States rose 13% from 2016 to 2023, from 8.7% to 9.8%. Increases from 2016 to 2023 were seen for all maternal age, race and Hispanic origin groups, gestational age and birthweight categories and in 40 states.

PMID:40168594

Pain Physician. 2025 Mar;28(2):E183-E189.

ABSTRACT

BACKGROUND: Lumbar epidural steroid injections (ESIs) are commonly used to alleviate pain associated with lumbar disorders. However, administering steroids to patients with osteoporosis may lead to a decline in bone mineral density (BMD) and increase fracture risk. While various steroids are utilized in ESIs, limited research exists on their effect on BMD.

OBJECTIVES: This study aimed to analyze the effect of dexamethasone-based ESI therapy on osteoporosis in patients receiving or not receiving denosumab, utilizing real-world clinical data.

STUDY DESIGN: Retrospective analysis.

SETTING: A university hospital orthopedic department.

METHODS: A retrospective review was conducted, incorporating patients who underwent denosumab therapy alongside ESIs for pain alleviation from January 2018 through April 2022. Eligibility criteria included patients with a minimum follow-up period of 12 months. Forty patients who had received an ESI and denosumab treatment were enrolled in Group One. Similarly, 35 patients who had only received an ESI (Group 2) and 33 patients who underwent denosumab treatment alone (Group 3) were enrolled and analyzed. Statistical analysis was performed using analysis of variance (ANOVA) to compare patient age, gender, lumbar and hip BMD, difference in lumbar and hip BMD at postinjection one year, serum vitamin D, calcium, phosphorus levels, and one-year cumulative steroid dosage.

RESULTS: In terms of patient demographics, the mean age of Group One was 71.73 (± 9.59) years, Group 2 was 70.00 (± 9.82) years, and Group 3 was 71.18 (± 5.64) years. The ANOVA analysis revealed no significant differences among groups. The BMD analysis showed that the lumbar BMD in Group One was 0.811 g/cm2, Group 2 was 0.831 g/cm2, and Group 3 was 0.822 g/cm2. Hip BMD in Group One was 0.696 g/cm2, Group 2 was 0.711 g/cm2, and Group 3 was 0.668 g/cm2. The change in BMD values showed that in Group One, lumbar BMD increased by 0.0411 g/cm2 compared to baseline, a 5.06% increase, while hip BMD increased by 0.0047 g/cm2, a 0.68% increase. In Group 2, lumbar BMD decreased by -0.0307 g/cm2, a 3.7% decrease, and hip BMD decreased by -0.036 g/cm2, a 5.02% decrease. In Group 3, lumbar BMD increased by 0.056 g/cm2, a 6.77% increase, while hip BMD increased by 0.005 g/cm2, a 0.69% increase.

LIMITATIONS: The number of patients recruited was relatively small and limited to specific age groups. Study design was retrospective.

CONCLUSION: Lumbar ESIs with dexamethasone reduce BMD in elderly patients with osteoporosis. However, when denosumab is administered alongside dexamethasone-based ESIs, the steroid does not significantly affect the decline of BMD.

PMID:40168571

Pain Physician. 2025 Mar;28(2):E157-E164.

ABSTRACT

BACKGROUND: Despite the availability of clinical practice guidelines, suboptimal adherence among general practitioners (GPs) in pain management remains a concern. The French Pain Society issued revised guidelines for pain management in 2020.

OBJECTIVES: This study aimed to evaluate the current adherence of French doctors to the updated guidelines for pain management.

STUDY DESIGN: A non-interventional, cross-sectional study.

SETTING: A panel of doctors from France, participated in an online questionnaire.

METHODS: Two selected vignettes describing patients with chronic neuropathic pain (central and peripheral) were completed. The ability to correctly prescribe appropriate first- and second-line treatments according to the 2020 French Pain Society guidelines was assessed.

RESULTS: A total of 191 physicians were recruited from a database of 3,380, representing a response rate of 5.7%. Of the participants, 182 (95.3%) completed the survey correctly and were included in the final analysis. Among those participants, 64% were general practitioners (GPs). Adherence to the guidelines for the management of l ocalized peripheral neuropathic pain was reported by 15.38% of participants, while 21% reported adherence for central neuropathic pain. A significant disparity was observed in the prescription of medications, with pregabalin being prescribed by 32.9% of participants and gabapentin by 22.5% for localized neuropathic pain. For central neuropathic pain, pregabalin use was reported by 30.7% of respondents and gabapentin by 26.3%. Following the failure of a second-line therapy, 66% of participants considered reorientation to be a viable treatment option for localized peripheral neuropathic pain, compared to 45% for central neuropathic pain.

LIMITATIONS: The number of participants is one of the main limitations in this study.

CONCLUSIONS: Despite the participants’ low adherence to guidelines, substantial variation in medication use, and limited support for reorientation after failed treatment, this study offers insight into management practices for neuropathic pain among French GPs in Burgundy.

PMID:40168568

Pain Physician. 2025 Mar;28(2):147-154.

ABSTRACT

BACKGROUND: The optimal dosing and delivery strategies for intrathecal ziconotide are debated. Previous research suggests that high volume, low concentration dosing techniques may decrease side effects and enhance analgesic effect. Previous studies that have investigated the effects of diluting ziconotide have examined continuous infusions of the medication through an intrathecal pump.

OBJECTIVES: This study investigates the trial phase to determine if diluting the bolus dose leads to improved outcomes. The hypothesis of the authors is that the dilution of ziconotide will improve the trial outcomes.

STUDY DESIGN: This single-center, retrospective, case-control study included 62 patients with chronic pain refractory to conservative therapy who received a one-time intrathecal bolus dose of ziconotide.

METHODS: The study included 62 patients who received a single outpatient trial dose of ziconotide. The study was approved by an institutional review board. Data were collected from electronic medical records. Doses ranged from a total of 2.5 µg-5 µg in a volume of 0.5 mL-5 mL. The primary endpoints were the number of patients that achieved significant pain relief (>= 50%) and the presence or absence of side effects. Statistical analysis was performed using a c2 test to evaluate side effects and meaningful pain relief and an unpaired, 2-tailed t test to evaluate pain relief percentage.

RESULTS: There were no differences in side effects experienced by the patients in the Undiluted Group compared to the patients in the Diluted Group (21% vs 25%; P = 0.679). There were no differences in pain relief in the Undiluted Group compared to the Diluted Group (59% vs 61%; P = 0.880). The mean (SD) pain relief in the Undiluted Group was 46% (± 40%) compared to 51% (± 41%) in the Diluted Group (P = 0.645). A power analysis revealed a 68% power to detect a difference between the groups.

LIMITATIONS: These results are limited by the accuracy of the chart review and sample size; therefore, additional investigation may be warranted.

CONCLUSION: This study demonstrates there is no substantial difference between diluted and undiluted bolus doses of intrathecal ziconotide in regard to analgesic effect or side effects.

PMID:40168566

Pain Physician. 2025 Mar;28(2):E147-E156.

ABSTRACT

BACKGROUND: Opioid medications are widely used for pain management, but their impact on obstructive sleep apnea (OSA) remains controversial. Given the high prevalence of OSA and the increasing use of opioids, understanding the causal relationship between the condition and this type of medication is critical.

OBJECTIVES: This study aims to investigate the causal relationship between opioid use and OSA using a bidirectional 2-sample Mendelian randomization (MR) analysis. Specifically, the study seeks to determine whether exposure to opioid use increases the risk of developing OSA and whether OSA influences the likelihood of opioid use.

STUDY DESIGN: The study employed a bidirectional 2-sample MR analysis to explore the causal relationship between opioid use and OSA. Genetic variants from large-scale genome-wide association studies (GWAS) were used as instrumental variables to ensure robust causal inference.

SETTING: The study utilized data from 2 large-scale GWAS datasets. Opioid use data were obtained from the UK Biobank, while OSA data were sourced from the FinnGen study. Both datasets predominantly included patients of European ancestry with similar demographic characteristics.

METHODS: This study employed a 2-sample bidirectional Mendelian randomization (MR) approach to investigate the causal relationship between opioid use and obstructive sleep apnea (OSA). Genetic instruments for opioid use and OSA were selected from large-scale genome-wide association studies (GWAS) conducted in European populations, ensuring consistency in genetic backgrounds. The inverse variance-weighting (IVW) method was used as the primary analysis to estimate causal effects, supplemented by the weighted median, MR-Egger, simple mode, and weighted mode methods to ensure robustness. Sensitivity analyses, including MR-Egger regression, leave-one-out analysis, and MR-PRESSO, were conducted to assess pleiotropy, heterogeneity, and the influence of individual SNPs on the results.

RESULTS: The IVW method demonstrated a significant causal effect of opioid use on the risk of developing OSA, with a causal effect size of 0.28 (OR = 1.32, 95% CI = 0.09 to 0.46, P-value = 0.004). This association was supported by the weighted median method, though the MR-Egger, simple mode, and weighted mode methods did not achieve statistical significance but showed a consistent direction of effect. Conversely, no significant causal relationship was observed between OSA and opioid use across all methods, suggesting that OSA did not significantly influence opioid use.

LIMITATIONS: The primary limitations of this study include the use of binary phenotypes for opioid use and OSA, which precludes the assessment of dose-response relationships. Additionally, the genetic data were derived predominantly from European populations, limiting the generalizability of the findings to other ethnic groups. Potential pleiotropy and unmeasured confounders, although addressed through various sensitivity analyses, may still introduce bias into the results.

CONCLUSION: This study provides strong evidence of a unidirectional causal relationship in which opioid use increases the risk of developing OSA. These findings underscore the importance of monitoring patients who use opioids for potential respiratory complications, particularly OSA.

PMID:40168564

Pain Physician. 2025 Mar;28(2):71-81.

ABSTRACT

BACKGROUND: Lumbar spinal stenosis is the most common cause for spinal surgery of older adults. It is associated with pain in the legs and back as well as impaired ambulation. Minimally Invasive Lumbar Decompression (MILD®, Vertos Medical) is a percutaneous, image-guided lumbar decompression technique for central canal stenosis secondary to a hypertrophied ligamentum flavum. However, whether MILD can achieve adequate beneficial results in patients with lumbar spinal stenosis remains undetermined.

OBJECTIVE: To assess the efficacy and complications of MILD for lumbar spinal stenosis.

STUDY DESIGN: A systematic review and meta-analysis.

METHODS: Electronic databases were searched to identify all clinical trials of patients undergoing MILD surgery. Primary outcomes included Visual Analog Scale scores (VAS) or Oswestry Disability Index scores (ODI) at baseline, < 6 months posttreatment, = one year posttreatment. Secondary outcomes included postoperative complications. For continuous variables, the treatment effects were calculated by weighted mean difference and 95% CI. The statistical significance was defined as P < 0.05.

RESULTS: There were 334 trials identified; 12 of them, with data from 500 patients, were included in our analysis. MILD treatment resulted in a significant decrease in the mean pain score compared to the baseline (P < 0.01). There is a consistent pattern of decreased mean ODI scores following MILD compared to the baseline (P < 0.01).

LIMITATIONS: The included MILD clinical trials did not have the same exclusion and inclusion criteria. While all clinical trials in this study adopted conservative treatments prior to MILD, there were no standardized treatment modalities and length of time. All of the studies employed subjective outcome tools including VAS and ODI. However, these self-reported outcome tools are subject to bias.

CONCLUSIONS: Our study suggests MILD is an effective and safe surgical technique for patients with stenosis from ligamentum flavum hypertrophy. This technique resulted in significant clinical improvement, as indicated by changes in pain scores and ODI scores. In addition, adverse events were low compared to other surgical decompression techniques. To further confirm this, more well designed and powered randomized trials are needed.

PMID:40168556

J Cataract Refract Surg. 2025 Mar 31. doi: 10.1097/j.jcrs.0000000000001661. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this project is to compare the accuracy, safety, and consistency of near-square and asymmetric trapezoid side-port incisions in cataract surgery.

SETTING: Aier Eye Hospital of Wuhan University, Wuhan Hubei Province, China.

DESIGN: Prospective pilot study.

METHODS: The patients were divided into Groups A and B using the random number table method. Group A received a near-square side-port incision (SPI) with a 22G needle, and Group B received an asymmetric trapezoid SPI with a 15-degree blade. We contrasted the differences in incision length, width, and shape; surgical time; and postoperative intraocular pressure (IOP) between the two groups.

RESULTS: Eighty eyes from 80 patients were included. The mean external width of incision in Group A was much smaller than that in Group B (p < .01), while the internal width in Group A was significantly larger (p < .01). In Group A, there is no statistically significant difference between the external and internal incision diameters (p = .081). In Group B, the external diameter is obviously larger than the internal diameter (p < .01). The incision diameter consistency in Group A was higher than that in Group B. There was no statistically significant difference in incision length between the two groups (p = 0.67). One day after surgery, there were no significant differences in incision morphology (p = 1.0; .723) or operating time between the two groups (p = .89). There was no obvious incision leakage in either group after surgery (p =.337).

CONCLUSIONS: The present study suggests that a near-square side-port with a 22G needle is smaller and results in better incision consistency. Moreover, the 22G needle is inexpensive and can be easily obtained.

PMID:40168526 | DOI:10.1097/j.jcrs.0000000000001661

J Glob Health. 2025 Apr 2;15:04070. doi: 10.7189/jogh.15.04070.

ABSTRACT

BACKGROUND: The outbreak of Mpox in China has rendered the promotion of effective preventive measures among susceptible populations particularly crucial. We aimed to explore the correlates and develop a model for Mpox vaccination intention.

METHODS: We distributed a questionnaire to a sample of 2403 men who have sex with men to investigate whether they would get a Mpox vaccine. The participants were randomly split into a training set and a testing set in a ratio of 3:1. We screened relevant variables by the least absolute shrinkage and selection operator (LASSO) regression analysis and included them into a Mpox vaccination intention model, which used a multivariate logistic regression analysis and presented the findings as a nomogram. We used the receiver operating characteristic curve, calibration curve, Kolmogorov-Smirnov test, lift test, and population stability index to test the validity and stability of the model.

RESULTS: Of the 2403 participants in our sample, 87.1% intended to get an Mpox vaccine. Five of the thirty-one screened variables, i.e. Mpox knowledge, social support, vaccination internal rewards, vaccination external rewards, and vaccination response efficacy, were included in the vaccination intention model. The model demonstrated strong risk differentiation (Kolmogorov-Smirnov value = 0.46), moderate predictive power (training area under the curve = 0.7709), and good calibration fit, indicating robust performance.

CONCLUSIONS: Our proposed model has a good performance and is highly stable, while our findings suggest that governments should design targeted public health strategies, integrating social engagement and leveraging peer and community education to promote Mpox vaccination.

PMID:40168515 | DOI:10.7189/jogh.15.04070