International Scholars Journal of Medical Advances and Discoveries | Vol. 16, No. 7, July 2025 | pp. 41–48

DOI: 10.46882/2025/IJMAD/000106

Original Research Article

Title: Efficacy of Low-Level Laser Therapy in Accelerating Orthodontic Tooth Movement and Reducing Pain Intensity

Names of Authors: A. A. Al-Hassan¹, B. C. Dubois²

Authors’ Affiliations: ¹Department of Orthodontics, Faculty of Dentistry, Cairo University, Cairo, Egypt; ²Department of Restorative Dentistry, University of Geneva, Geneva, Switzerland

Abstract: Prolonged treatment duration and mechanical discomfort remain major deterrents for patients undergoing fixed orthodontic therapy. This split-mouth clinical trial investigated the efficacy of low-level laser therapy (LLLT) using an 810 nm gallium-aluminum-arsenide diode laser in accelerating canine retraction velocity and mitigating associated pain. Twenty-four adult patients requiring bilateral maxillary first premolar extractions and subsequent canine distalization were enrolled. Each patient's maxillary canines were randomly assigned to either the LLLT irradiation group (energy density of 4 J/cm² applied at 4 distinct points on days 0, 3, 7, and every 14 days thereafter) or the placebo control group. Dental cast measurements at 30, 60, and 90 days demonstrated that canine retraction rate in the LLLT-irradiated side was significantly accelerated, showing a mean total movement of 2.64 ± 0.31 mm compared to 1.82 ± 0.24 mm on the control side (P < 0.001). Pain perception evaluated via a 10-point visual analog scale (VAS) revealed significantly lower pain scores in the laser-treated quadrants at 24 h (1.8 vs 5.4, P < 0.001) and 48 h post-activation. Histological markers of root resorption evaluated via cone-beam computed tomography indicated no statistically significant difference in root length reduction between the two sides. These findings confirm that LLLT is a safe, non-invasive adjuvant that successfully curtails overall orthodontic treatment duration while enhancing patient comfort through localized biomodulation and pain reduction.

Keywords: Low-level laser therapy; Orthodontic tooth movement; Canine retraction; Pain reduction; Biomodulation

Manuscript Timeline: Received: 02 March 2025; Revised: 02 June 2025; Accepted: 18 June 2025; Published: 05 July 2025

Citation: Al-Hassan, A. A., & Dubois, B. C. (2025). Efficacy of Low-Level Laser Therapy in Accelerating Orthodontic Tooth Movement and Reducing Pain Intensity. International Journal of Medical Advances and Discoveries, 16(7), 41–48.

International Journal of Medical Advances and Discoveries | Vol. 16, No. 9, September 2025 | pp. 60–67

DOI: 10.46882/2025/IJMAD/000108

Original Research Article

Title: A Multicenter Evaluation of High-Sensitivity Troponin I Decision Thresholds for Accelerating Myocardial Infarction Rule-Out Protocols

Names of Authors: Patricia K. Thorne¹, Mateo Fernandes², Oliver Vance³

Authors’ Affiliations: ¹Emergency Medicine Clinical Trials Consortium, University of Edinburgh, Edinburgh, UK; ²Department of Cardiology, Hospital de Clínicas, São Paulo, Brazil; ³Division of Emergency Medicine, Monash University, Melbourne, Australia

Abstract: Early diagnostic safety for patients presenting to the emergency department (ED) with suspected acute myocardial infarction (AMI) is a vital metric for preventing hospital overcrowding. High-sensitivity cardiac troponin I (hs-cTnI) assays permit rapid evaluation, but consensus on optimal rapid rule-out cutoffs varies across clinical settings. This prospective, observational validation study assessed the safety and efficacy of a 0/1-hour rapid rule-out protocol using a novel hs-cTnI decision threshold (<3 ng/L) in 1850 consecutive patients presenting with acute chest pain. The primary safety endpoint was a missed index AMI or a major adverse cardiac event (MACE) within 30 days. At presentation, 42.1% of patients (n = 779) were eligible for immediate rule-out based on a baseline hs-cTnI <3 ng/L and a non-ischemic electrocardiogram. An additional 18.4% (n = 340) were ruled out after a 1-hour delta change of <2 ng/L. The combined 0/1-hour protocol achieved a diagnostic sensitivity of 99.6% (95% Confidence Interval [98.9%, 99.9%]) and a negative predictive value (NPV) of 99.8% (95% CI [99.4%, 100%]) for AMI. The 30-day MACE rate among ruled-out patients was exceptionally low at 0.16%. Implementation of this protocol effectively reduced the median ED length of stay by 78 minutes compared to traditional 0/3-hour diagnostic protocols (p < 0.001).

Keywords: High-sensitivity troponin, Myocardial infarction, Emergency department, Rule-out protocol, Chest pain, Diagnostic safety

Manuscript Timeline: Received: June 15, 2025; Revised: July 28, 2025; Accepted: August 14, 2025; Published: September 19, 2025

Citation: Thorne, K. P., Fernandes, M., & Vance, O. (2025). A Multicenter Evaluation of High-Sensitivity Troponin I Decision Thresholds for Accelerating Myocardial Infarction Rule-Out Protocols. International Journal of Medical Advances and Discoveries, 16(9), 60–67. doi.org

International Journal of Medical Advances and Discoveries | Vol. 16, No. 10, October 2025 | pp. 68–76

DOI: 10.46882/2025/IJMAD/000109

Original Research Article

Title: Neuroprotective Effects of Intranasally Delivered Exosomes Doped with Curcumin in a Murine Model of Alzheimer’s Disease

Names of Authors: Yukihiro Tanaka¹, Alia M. Al-Shami², Richard P. Gallagher¹

Authors’ Affiliations: ¹Department of Neurosciences, Kyoto University Graduate School of Medicine, Kyoto, Japan; ²Department of Pharmaceutics, American University of Beirut, Beirut, Lebanon

Abstract: Efficient drug delivery across the blood-brain barrier (BBB) presents a critical hurdle in therapeutic drug development for Alzheimer’s disease (AD). This study investigated the neuroprotective, anti-inflammatory, and amyloid-clearing capabilities of mesenchymal stem cell-derived exosomes engineered to encapsulate curcumin (Exo-Cur) administered via a non-invasive intranasal pathway. Transgenic APP/PS1 mice (age: 6 months, n = 80) were treated intranasally with Exo-Cur (5 mg/kg), free curcumin, empty exosomes, or a vehicle control daily for 8 consecutive weeks. Spatial learning and memory evaluations via the Morris Water Maze demonstrated that Exo-Cur treated mice had significantly shorter escape latencies (22.4 ± 3.1 seconds) compared to the free curcumin (41.2 ± 4.5 seconds) and vehicle cohorts (55.8 ± 5.2 seconds; p < 0.001). Immunohistochemical analysis revealed a 48% reduction in cortical and hippocampal beta-amyloid (A-beta) plaque burden within the Exo-Cur group (p < 0.001). Enzyme-linked immunosorbent assays (ELISA) demonstrated a profound attenuation of pro-inflammatory cytokines, specifically IL-1-beta (-56%) and TNF-alpha (-62%), alongside a marked reduction in microglial activation (Iba1 immunoreactivity, p = 0.002). Western blot tracking confirmed the up-regulation of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein-95 (PSD-95) in treated brain tissues. Intranasal delivery of Exo-Cur effectively bypasses the BBB, producing substantial anti-amyloid and anti-inflammatory neuroprotective benefits in AD models.

Keywords: Exosomes, Curcumin, Alzheimer’s disease, Blood-brain barrier, Intranasal delivery, Neuroinflammation

Manuscript Timeline: Received: July 11, 2025; Revised: August 20, 2025; Accepted: September 10, 2025; Published: October 24, 2025

Citation: Tanaka, Y., Al-Shami, M. A., & Gallagher, P. R. (2025). Neuroprotective Effects of Intranasally Delivered Exosomes Doped with Curcumin in a Murine Model of Alzheimer’s Disease. International Journal of Medical Advances and Discoveries, 16(10), 68–76. doi.org

International Scholars Journal of Medical Advances and Discoveries | Vol. 16, No. 2, February 2025 | pp. 1–8

DOI: 10.46882/2025/IJMAD/000101

Original Research Article

Title: Evaluation of Myocardial Infarction Outcomes Using High-Sensitivity Troponin T Thresholds in Emergency Settings

Names of Authors: A. B. Mensah¹, C. D. Okoye², E. F. Smith³

Authors’ Affiliations: ¹Department of Cardiology, University Teaching Hospital, Lagos, Nigeria; ²Department of Emergency Medicine, National Medical Center, Abuja, Nigeria; ³Biostatistics Unit, Global Health Research Institute, London, UK

Abstract: The rapid evaluation of acute chest pain remains a central challenge in emergency cardiovascular care. This prospective multi-center study assessed the diagnostic performance and prognostic utility of optimized high-sensitivity troponin T (hs-TnT) thresholds in triaging patients presenting with suspected acute myocardial infarction. Over a twelve-month surveillance period, clinical data and serial blood samples were collected from 1,240 adult participants within a mean time of 1.5 h from admission. Patients were categorized using a baseline cutoff of 14 ng/L versus an accelerated 0/1-hour algorithm incorporating a delta change of > 5 ng/L. Results demonstrated that the accelerated protocol achieved a diagnostic sensitivity of 96.4% (95% CI, 94.2% - 98.1%) and a negative predictive value of 99.1%, effectively ruling out non-ST-elevation myocardial infarction earlier than standard 3-hour testing. Mean length of stay in the emergency department decreased by 2.4 ± 0.8 h (P < 0.001) without any elevation in 30-day major adverse cardiac events among early discharges. Subgroup analysis revealed consistent efficacy across diverse demographic profiles, though specificity was moderately lower in patients with chronic renal impairment (eGFR < 60 mL/min/1.73 m²). Cost-utility estimation further indicated a 15% reduction in overall inpatient bed utilization costs per episode. These findings support the widespread adoption of accelerated hs-TnT protocols to streamline acute coronary syndrome management pathways, reduce overcrowding in emergency departments, and maintain high safety margins for early patient disposition in resource-limited or high-volume clinical environments.

Keywords: Acute coronary syndrome; High-sensitivity troponin T; Emergency triage; Diagnostic accuracy; Myocardial infarction

Manuscript Timeline: Received: 12 October 2024; Revised: 04 January 2025; Accepted: 18 January 2025; Published: 05 February 2025

Citation: Mensah, A. B., Okoye, C. D., & Smith, E. F. (2025). Evaluation of Myocardial Infarction Outcomes Using High-Sensitivity Troponin T Thresholds in Emergency Settings. International Journal of Medical Advances and Discoveries, 16(2), 1–8.

International Journal of Medical Advances and Discoveries | Vol. 16, No. 12, December 2025 | pp. 86–94

DOI: 10.46882/2025/IJMAD/000111

Original Research Article

Title: Long-Term Neurodevelopmental Outcomes of Preterm Infants Managed with Early Prophylactic Hydrocortisone Infusion

Names of Authors: Mariam O. Bello¹, William J. Sterling², Chidi E. Okafor¹

Authors’ Affiliations: ¹Department of Pediatrics, College of Medicine, University of Ibadan, Ibadan, Nigeria; ²Division of Neonatal-Perinatal Medicine, Boston Children's Hospital, Boston, USA

Abstract: Bronchopulmonary dysplasia (BPD) is a critical driver of mortality in extremely preterm infants. While systemic corticosteroids effectively decrease BPD incidence, widespread clinical concern persists regarding adverse neurodevelopmental outcomes, particularly cerebral palsy. This multi-center prospective cohort study investigated the 24-month corrected age neurodevelopmental outcomes of extremely low birth weight (ELBW) infants (birth weight <1000 g, gestational age <28 weeks; n = 210) who received early low-dose prophylactic hydrocortisone (0.5 mg/kg twice daily for 12 days) compared to an untreated matched control cohort. The primary outcome was neurodevelopmental impairment (NDI), defined via the Cognitive, Language, and Motor composite scores of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). At 24 months of corrected age, no significant differences in mean cognitive composite scores (94.2 ± 11.5 vs. 93.8 ± 12.1, p = 0.81) or motor composite scores (91.6 ± 10.8 vs. 92.1 ± 11.3, p = 0.74) were observed between the hydrocortisone and control cohorts. The overall incidence of cerebral palsy remained statistically identical between groups (4.8% vs. 5.7%, p = 0.76). Conversely, the hydrocortisone-treated infants demonstrated a significant reduction in BPD severity and post-discharge oxygen supplementation needs (p = 0.01). Early prophylactic hydrocortisone administration in ELBW infants provides valuable pulmonary protection without increasing the long-term risk of neurodevelopmental impairment at two years of corrected age.

Keywords: Preterm infants, Hydrocortisone prophylaxis, Neurodevelopmental outcome, Bronchopulmonary dysplasia, Cerebral palsy, Bayley scales

Manuscript Timeline: Received: September 05, 2025; Revised: October 18, 2025; Accepted: November 11, 2025; Published: December 16, 2025

Citation: Bello, M. O., Sterling, J. W., & Okafor, C. E. (2025). Long-Term Neurodevelopmental Outcomes of Preterm Infants Managed with Early Prophylactic Hydrocortisone Infusion. International Journal of Medical Advances and Discoveries, 16(12), 86–94. doi.org

International Scholars Journal of Medical Advances and Discoveries | Vol. 16, No. 3, March 2025 | pp. 9–16

DOI: 10.46882/2025/IJMAD/000102

Clinical Review

Title: Mechanisms of Insulin Resistance in Gestational Diabetes Mellitus and Therapeutic Implications for Fetal Outcomes

Names of Authors: G. H. Patel¹, I. J. Van Der Merwe²

Authors’ Affiliations: ¹Division of Endocrinology, Metro Health Sciences Center, Mumbai, India; ²Department of Obstetrics and Gynecology, Stellenbosch University, Cape Town, South Africa

Abstract: Gestational diabetes mellitus (GDM) represents a complex metabolic disturbance characterized by progressive maternal insulin resistance coupled with inadequate pancreatic beta-cell compensation during pregnancy. This comprehensive review synthesizes recent insights into the molecular signaling pathways—specifically alterations in the IRS-1/PI3K/AKT cascade—triggered by placental hormones, systemic low-grade inflammation, and elevated circulating free fatty acids (mean increase of 35% compared to normoglycemic pregnancies). We examine how maternal hyperglycemia drives fetal hyperinsulinemia, leading to macrosomia, neonatal hypoglycemia, and long-term metabolic risks for the offspring. The therapeutic efficacy of lifestyle modifications, traditional insulin regimens, and emerging second-line oral hypoglycemic agents such as metformin and glyburide is critically appraised. Particular emphasis is placed on maintaining target fasting blood glucose levels below 5.3 mmol/L and 1-hour postprandial levels below 7.8 mmol/L to mitigate perinatal morbidity. Furthermore, we explore the potential of novel biomarkers, including adiponectin and microRNA profiles (e.g., miR-16 and miR-20a), for early first-trimester risk stratification before standard 24-28 week oral glucose tolerance testing occurs. Integrating these pathogenetic mechanisms with individualized glycemic control strategies offers clinicians an optimized framework for reducing both immediate obstetric complications and the transgenerational cycle of metabolic syndrome. Continued research into targeted placental drug delivery systems remains paramount for minimizing transplacental transfer of pharmacological agents while preserving maternal metabolic equilibrium throughout gestation.

Keywords: Gestational diabetes; Insulin resistance; Fetal macrosomia; Placental signaling; Glycemic control

Manuscript Timeline: Received: 02 November 2024; Revised: 10 February 2025; Accepted: 22 February 2025; Published: 05 March 2025

Citation: Patel, G. H., & Van Der Merwe, I. J. (2025). Mechanisms of Insulin Resistance in Gestational Diabetes Mellitus and Therapeutic Implications for Fetal Outcomes. International Journal of Medical Advances and Discoveries, 16(3), 9–16.

International Scholars Journal of Medical Advances and Discoveries | Vol. 16, No. 5, May 2025 | pp. 25–32

DOI: 10.46882/2025/IJMAD/000104

Original Research Article

Title: Impact of Continuous Glucose Monitoring on Glycemic Variability and Hypoglycemia in Type 1 Diabetes Mellitus

Names of Authors: O. P. Chen¹, Q. R. Johansson², S. T. Weber³

Authors’ Affiliations: ¹Department of Internal Medicine, Pacific Health Center, Vancouver, Canada; ²Department of Endocrinology, Karolinska Institute, Stockholm, Sweden; ³Center for Digital Health Diagnostics, Berlin, Germany

Abstract: Glycemic variability and unpredictable nocturnal hypoglycemia remain persistent clinical hurdles in the optimization of type 1 diabetes mellitus (T1DM) management. This open-label randomized controlled trial investigated the longitudinal impact of real-time continuous glucose monitoring (rt-CGM) versus conventional self-monitoring of blood glucose (SMBG) utilizing capillary blood tests at least 4 times daily. A total of 210 adult subjects with baseline HbA1c levels between 8.0% and 10.5% were monitored over 6 months. Primary endpoints included changes in time-in-range (TIR, defined as 3.9 - 10.0 mmol/L) and time-below-range (TBR < 3.9 mmol/L). The rt-CGM cohort demonstrated an absolute increase in TIR of 18.5% (corresponding to an increase of 4.4 h/day, P < 0.001) alongside a significant contraction in TBR from a baseline median of 6.2% to 1.8% of readings. Mean HbA1c in the CGM group dropped by 0.9 ± 0.3%, whereas the SMBG control arm experienced a reduction of only 0.3 ± 0.2%. Furthermore, episodes of severe nocturnal hypoglycemia requiring external assistance declined by 74% in the intervention group. Psychometric evaluation via the Diabetes Distress Scale indicated marked improvements in emotional burden and fear of hypoglycemia. These robust empirical outcomes reinforce clinical practice guidelines advocating for real-time sensor technology as a standard of care in T1DM, highlighting its capacity to transform behavioral self-management and curtail acute metabolic emergencies.

Keywords: Type 1 diabetes; Continuous glucose monitoring; Glycemic variability; Hypoglycemia; HbA1c reduction

Manuscript Timeline: Received: 10 January 2025; Revised: 08 April 2025; Accepted: 20 April 2025; Published: 05 May 2025

Citation: Chen, O. P., Johansson, Q. R., & Weber, S. T. (2025). Impact of Continuous Glucose Monitoring on Glycemic Variability and Hypoglycemia in Type 1 Diabetes Mellitus. International Journal of Medical Advances and Discoveries, 16(5), 25–32.

International Scholars Journal of Medical Advances and Discoveries | Vol. 16, No. 8, August 2025 | pp. 49–56

DOI: 10.46882/2025/IJMAD/000107

Original Research Article

Title: Diagnostic Accuracy of Artificial Intelligence Algorithms in Detecting Early Diabetic Retinopathy from Fundus Photographs

Names of Authors: C. D. Garcia¹, D. E. Martinez², E. F. Kalu³

Authors’ Affiliations: ¹Department of Ophthalmology, San Jose Medical Center, Manila, Philippines; ²Department of Data Science, National Autonomous University, Mexico City, Mexico; ³Ophthalmology Unit, Lagos State University, Lagos, Nigeria

Abstract: Diabetic retinopathy (DR) is a leading cause of preventable blindness globally, yet screening programs are frequently hindered by a shortage of trained ophthalmologists. This diagnostic validation study assessed the performance of a deep convolutional neural network (CNN) in detecting referable DR (moderate non-proliferative DR or worse) and diabetic macular edema from un-mydriatic digital fundus photographs. A retrospective dataset of 12,500 retinal images obtained from diverse primary care screening sites was analyzed by the algorithm and benchmarked against a consensus reference standard established by three senior retinal specialists. The CNN achieved an overall sensitivity of 94.8% (95% CI, 93.1% - 96.2%) and a specificity of 91.5% (95% CI, 89.8% - 93.0%) for referable DR. Area under the receiver operating characteristic curve (AUC-ROC) reached 0.978. Processing time averaged 2.4 seconds per image. Subgroup analysis showed robust performance even in low-illumination or partially degraded image qualities, with sensitivity dropping by only 3.2% for images graded as suboptimal by human operators. Integration of this AI screening tool in community health centers demonstrated a 40% increase in throughput and earlier referral for sight-saving laser photocoagulation. These findings substantiate the clinical viability of automated deep learning systems as frontline triage mechanisms to expand screening coverage and prevent irreversible visual loss in high-risk diabetic populations.

Keywords: Artificial intelligence; Diabetic retinopathy; Deep learning; Fundus photography; Screening triage

Manuscript Timeline: Received: 10 April 2025; Revised: 05 July 2025; Accepted: 22 July 2025; Published: 05 August 2025

Citation: Garcia, C. D., Martinez, D. E., & Kalu, E. F. (2025). Diagnostic Accuracy of Artificial Intelligence Algorithms in Detecting Early Diabetic Retinopathy from Fundus Photographs. International Journal of Medical Advances and Discoveries, 16(8), 49–56.

International Journal of Medical Advances and Discoveries | Vol. 16, No. 11, November 2025 | pp. 77–85

DOI: 10.46882/2025/IJMAD/000110

Original Research Article

Title: Comparative Efficacy and Safety of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin in Cancer-Associated Thrombosis

Names of Authors: Helena S. Vance¹, Klaus M. Brand², Jonathan R. Cross¹

Authors’ Affiliations: ¹Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; ²Department of Internal Medicine, Ludwig-Maximilians-Universität, Munich, Germany

Abstract: Cancer-associated thrombosis (CAT) increases the risk of mortality and recurrent venous thromboembolism (VTE). Low-molecular-weight heparin (LMWH) has long served as standard first-line management, but direct oral anticoagulants (DOACs) offer an attractive oral option. This multi-center, open-label, randomized non-inferiority trial evaluated the clinical outcomes of a next-generation DOAC, apixaban, compared to dalteparin (LMWH) over a 6-month treatment phase in 540 cancer patients presenting with acute symptomatic or incidental VTE. The primary efficacy endpoint was recurrent VTE, while safety endpoints measured major bleeding and clinically relevant non-major bleeding (CRNMB). Recurrent VTE occurred in 3.7% (10 of 270) of patients in the apixaban arm compared to 6.3% (17 of 270) in the dalteparin arm, satisfying the non-inferiority criteria (Hazard Ratio = 0.58, 95% Confidence Interval [0.31, 1.07], p < 0.001 for non-inferiority). Major bleeding events were comparable between groups, occurring in 2.2% of the apixaban cohort and 2.6% of the dalteparin cohort (p = 0.78). However, CRNMB rates were slightly higher in the apixaban treatment arm (6.7% vs 4.1%, p = 0.12), predominantly localized within patients presenting with unresected gastrointestinal malignancies. Patient-reported treatment satisfaction scales were significantly higher for oral apixaban (p < 0.001). Apixaban is an effective and safe oral alternative to dalteparin for CAT treatment.

Keywords: Cancer-associated thrombosis, Venous thromboembolism, Direct oral anticoagulants, Apixaban, Dalteparin, Major bleeding

Manuscript Timeline: Received: August 18, 2025; Revised: September 29, 2025; Accepted: October 15, 2025; Published: November 20, 2025

Citation: Vance, S. H., Brand, M. K., & Cross, R. J. (2025). Comparative Efficacy and Safety of Direct Oral Anticoagulants Versus Low-Molecular-Weight Heparin in Cancer-Associated Thrombosis. International Journal of Medical Advances and Discoveries, 16(11), 77–85. doi.org