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Mendelian randomization analysis of causal relationship between cheese intake and diabetic retinopathy

AIM: To assess whether there is a possible causal link between the intake of cheese and the risk of diabetic retinopathy (DR) utilizing a two-sample Mendelian randomization (MR) analysis. METHODS: The research data were obtained from summary statistics of genome-wide association studies (GWAS). Genetic loci closely related to cheese intake were extracted as instrumental variables (IVs), and DR was the outcome variable. The data were extracted from individuals of European ethnicity. The data of cheese intake consisted of 451 486 samples with 9 851 867 single nucleotide polymorphisms (SNPs), while the DR data consisted of 206 234 samples with 16 380 446 SNPs. Sixty-one genetic loci closely related to cheese intake were selected as IVs. MR analysis was performed by inverse-variance weighted (IVW) method and MR-Egger regression respectively. The causal relationship between cheese intake and DR was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Egger-intercept test was used to test horizontal pleiotropy and sensitivity analysis was performed by leave-one-out test. RESULTS: The P value of the IVW method was less than 0.05, indicating a significant negative correlation between cheese intake and DR. MR-Egger regression showed that the intercept was 0.01 with a standard error of 0.022, and a P-value of 0.634, indicating no evidence of horizontal pleiotropy affecting the IVs related to the exposure factors. Besides, heterogeneity tests confirmed the absence of heterogeneity, and the “leave-one-out” sensitivity analysis demonstrated that the results were stable. CONCLUSION: Cheese intake is causally negatively correlated with the occurrence of DR, and cheese intake could reduce the risk of DR.

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Corneal and intraocular pressure changes associated to the circadian rhythms: a narrative review

AIM: To synthesize the current body of research regarding the diurnal variations in intraocular pressure (IOP) and corneal biomechanical and morphological parameters, highlighting their significance in various eye conditions. METHODS: A comprehensive review of studies on the diurnal variations of IOP and corneal parameters was conducted. Tonometry findings from various studies were assessed, including the Goldmann applanation tonometry (GAT) and non-contact tonometers. Data on the variations in central corneal thickness (CCT), corneal curvature, and corneal biomechanics measured by the Ocular Response Analyzer system across different population groups was extracted and analyzed. RESULTS: In both healthy subjects and those with Fuchs dystrophy, IOP and CCT demonstrate marked diurnal declines. GAT remains the gold standard for tonometry, with the highest reliability. However, its measurements are influenced by CCT. Keratoconus patients and those with pseudoexfoliation showed significant diurnal variations in IOP. The biomechanical parameters, especially corneal hysteresis (CH) and the corneal resistance factor (CRF), largely remain stable throughout the day for most of eye conditions, with some exceptions. Notably, the corneal morphology diurnal variation, particularly curvature, yielded mixed conclusions across studies. CONCLUSION: Circadian rhythms significantly influence various corneal parameters, most notably IOP and CCT. Further studies should emphasize standardized approaches larger sample sizes, and delve deeper into less-explored areas, such as the effects of orthokeratology lenses on diurnal biomechanical shifts.

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Dexamethasone implant for refractory macular edema secondary to diabetic retinopathy and retinal vein occlusion

AIM: To evaluate the efficacy, timing of retreatment and safety of dexamethasone (DEX) implant on macular edema (ME) secondary to diabetic retinopathy (DME) and retinal vein occlusion (RVO-ME) patients who were refractory to anti-vascular endothelial growth factor (VEGF) treatment. METHODS: This retrospective study included 37 eyes received at least one DEX implant treatment for DME or RVO-ME between January 1, 2019, and January 1, 2023. These refractory DME and RVO-ME cases received at least 5 anti-VEGF injections and failure to gain more than 5 letters or a significant reduction in central retinal thickness (CRT). The best corrected visual acuity (BCVA) and CRT were measured at baseline, and at 1, 3, 4 and 6mo post-DEX implant injection. Adverse events such as elevated intraocular pressure (IOP) and cataract were recorded. RESULTS: For RVO cases (n=22), there was a significant increase in BCVA from 0.27±0.19 to 0.35±0.20 at 6mo post-DEX injection (P<0.05) and CRT decreased from 472.1±90.6 to 240.5±39.0 µm at 6mo (P<0.0001). DME cases (n=15) experienced an improvement in BCVA from 0.26±0.15 to 0.43±0.20 at 6mo post-DEX implant injection (P=0.0098), with CRT reducing from 445.7±55.7 to 271.7±34.1 µm at 6mo (P<0.0001). Elevated IOP occurred in 45.9% of patients but was well-controlled with topical medications. No cases of cataract or other adverse events were reported. CONCLUSION: DEX implants effectively improve BCVA and reduce CRT in refractory DME and RVO-ME. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and assess long-term outcomes.

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Research trends in exercise therapy for the treatment of pain in postmenopausal osteoporosis over the past decade: A bibliometric analysis

BACKGROUND Postmenopausal osteoporosis (PMOP) is the most common form of primary osteoporosis among women, and the associated pain often drives patients to seek clinical intervention. Numerous studies have highlighted the unique clinical benefits of exercise therapy (ET) in alleviating PMOP-related pain. However, bibliometric analyses examining collaboration, development trends, and research frontiers in the field of ET for PMOP pain remain scarce. AIM To explore the research trends in ET for pain treatment in PMOP patients over the past decade. METHODS All scholarly works were meticulously sourced from the Science Citation Index-Expanded within the prominent Web of Science Core Collection. Utilizing the capabilities of CiteSpace 6.2.R5, we conducted a thorough analysis of publications, authors, frequently cited scholars, contributing nations, institutions, journals of significant citation, comprehensive references, and pivotal keywords. Additionally, our examination explored keyword cooccurrences, detailed timelines, and periods of heightened citation activity. This comprehensive search, from 2014 through 2023, was completed within a single day, on October 11, 2023. RESULTS In total, 2914 articles were ultimately included in the analysis. There was a rapid increase in annual publication output in 2015, followed by stable growth in subsequent years. Boninger, Michael L, is the most prolific author, whereas Ware JE has the most citations. The United States’ global influence is significant, surpassing all other nations. The University of California System and Harvard University are the most influential academic institutions. J Bone Joint Surg Am is the most influential journal in this field. “Spinal cord injury” is the keyword that has garnered the most attention from researchers. The developmental pattern in this field is characterized by interdisciplinary fusion, with different disciplines converging to drive progress. CONCLUSION The academic development of the field of ET for pain in PMOP has matured and stabilized. Clinical management and rehabilitation strategies, along with the mechanisms underlying the relationship between ET and bone resorption analgesia, continue to be the current and future focal points of research in this field.

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Evidence-based orthobiologic practice: Current evidence review and future directions

The field of orthopedic and regenerative medicine is rapidly evolving with the increasing utilization of orthobiologic. These biologically derived therapies, including platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate, stromal vascular fraction (SVF), and autologous chondrocyte implantation, are gaining traction for their potential to enhance the body's natural healing processes. They offer a promising alternative to traditional surgical interventions for musculoskeletal injuries and degenerative conditions. Current evidence suggests significant benefits of orthobiologics in treating conditions like osteoarthritis, tendon injuries, and spinal disorders, yet inconsistencies in treatment protocols and outcomes persist. The global market for orthobiologics is projected to grow substantially, driven by advancements in biologic therapies such as adipose-derived stem cells and SVF, and the demand for minimally invasive treatments. Despite their promise, regulatory and ethical challenges, as well as the need for high-quality, standardized research, remain significant obstacles. Future directions in the field include advancements in delivery systems, personalized medicine approaches, and the exploration of novel sources like induced pluripotent stem cells, aiming for more targeted and effective treatments. Collaborative efforts are crucial to overcoming these challenges and ensuring the safe and effective application of orthobiologics in clinical practice.

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Spectrum of delayed post-hypoxic leukoencephalopathy syndrome: A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome (DPHLS), also known as Grinker’s myelinopathy, is a rare but significant neurological condition that manifests days to weeks after a hypoxic event. Characterized by delayed onset of neurological and cognitive deficits, DPHLS presents substantial diagnostic and therapeutic challenges. AIM To consolidate current knowledge on pathophysiology, clinical features, diagnostic approaches, and management strategies for DPHLS, providing a comprehensive overview and highlighting gaps for future research. METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines, we systematically searched PubMed, ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy. Inclusion criteria were original research articles, case reports, and case series involving human subjects with detailed clinical, neuroimaging, or pathological data on DPHLS. Data were extracted on study characteristics, participant demographics, clinical features, neuroimaging findings, pathological findings, treatment, and outcomes. The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist. RESULTS A total of 73 cases were reviewed. Common comorbidities included schizoaffective disorder, bipolar disorder, hypertension, and substance use disorder. The primary causes of hypoxia were benzodiazepine overdose, opioid overdose, polysubstance overdose, and carbon monoxide (CO) poisoning. Symptoms frequently include decreased level of consciousness, psychomotor agitation, cognitive decline, parkinsonism, and encephalopathy. Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter, sometimes involving the basal ganglia and the globus pallidus. Magnetic resonance spectroscopy often showed decreased N-acetylaspartate, elevated choline, choline-to-creatinine ratio, and normal or elevated lactate. Treatment is often supportive, including amantadine, an antioxidant cocktail, and steroids. Hyperbaric oxygen therapy may be beneficial in those with CO poisoning. Parkinsonism was often treated with levodopa. Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits. CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations. Early recognition and appropriate management are crucial to improving patient outcomes. Future research should focus on standardizing diagnostic criteria, using advanced imaging techniques, and exploring therapeutic interventions to improve understanding and treatment of DPHLS. Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

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Tumor Hypoxia and Radioresistance

Tumor hypoxia is a prevalent feature of solid tumors, significantly contributing to increased tumor aggressiveness, metastatic potential, and resistance to conventional therapies such as radiotherapy. This review explores the complex relationship between tumor hypoxia and radioresistance, highlighting the molecular mechanisms involved and potential therapeutic strategies to enhance radiotherapy efficacy in hypoxic tumors. Key mechanisms include the role of hypoxia-inducible factors (HIFs), particularly HIF-1α, which regulates numerous genes involved in tumor survival, proliferation, and resistance under hypoxic conditions. The review also discusses the oxygen enhancement ratio (OER) and its impact on radiotherapy outcomes, emphasizing how hypoxia leads to reduced radiosensitivity by limiting the formation of radiation-induced DNA damage. Despite the development of various strategies to counteract hypoxia-induced radioresistance, such as HIF inhibitors, hypoxia-targeted gene therapy, and hypoxia-activated prodrugs (HAPs), clinical results have been mixed, necessitating further research. Additionally, advances in imaging techniques for detecting tumor hypoxia are explored, which may allow for more personalized radiotherapy approaches, such as dose painting. The future of overcoming tumor hypoxia in radiotherapy lies in the integration of innovative therapeutic strategies, personalized medicine, and improved imaging technologies, offering hope for enhanced treatment outcomes in cancer patients.

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