Irish Journal of Medical Science最新文献

Background: Glioblastoma (GBM) is an aggressive brain tumor, necessitating the identification of new therapeutic targets. Toll-like receptor 7 (TLR7), a key component of innate immunity, influences oncological processes, but its role in GBM is unclear. This study investigates the impact of TLR7 overexpression on GBM and its underlying mechanisms.

Methods: Glioblastoma cell lines (U87 and U251) were transfected with a pcDNA-TLR7 plasmid to induce overexpression, verified by qRT-PCR. Proliferation was assessed using CCK-8 and colony formation assays. Migration and invasion were evaluated via Transwell and wound healing assays. Activation of the PI3K/AKT/mTOR signaling pathway was analyzed by Western blotting. Macrophage polarization was studied by exposing M0 macrophages to the TLR7 agonist R837, followed by qRT-PCR and cytokine quantification.

Results: TLR7 was successfully overexpressed in U87 and U251 cells. TLR7 overexpression significantly reduced GBM cell proliferation, colony formation, migration, and invasion. It suppressed the PI3K/AKT/mTOR signaling pathway. In the tumor microenvironment, TLR7 promoted M1 macrophage polarization, increasing M1 markers and pro-inflammatory cytokines while suppressing M2 markers.

Conclusion: TLR7 suppresses glioblastoma by inhibiting cell progression via the PI3K/AKT/mTOR signaling pathway and promoting an anti-tumoral immune microenvironment. These findings suggest the potential of TLR7 as a promising therapeutic target for GBM.

Background: Total knee arthroplasty (TKA) is a widely performed surgery with high satisfaction rates; however, only a minority of patients reported being able to kneel postoperatively. Kneeling is essential in various daily and cultural activities, yet its determinants remain unclear.

Aim: This study aimed to compare functional outcomes, patient-reported outcome measures (PROMs), self-perceived knee condition, and fear of damaging the prosthesis between patients who can and cannot kneel after TKA.

Methods: A prospective cross-sectional study was conducted with 59 TKA patients aged 50-75 years. Participants were grouped based on their self-reported kneeling ability. Outcomes included isometric flexor and extensor knee strength, range of motion (ROM), 2-minute walk test, 5-times sit-to-stand test, and PROMs including the Oxford Knee Score (OKS), Forgotten Joint Score (FJS), and Tampa Scale for Kinesiophobia (TSK). Perceptions of knee condition and fear of prosthesis damage were assessed via a custom survey.

Results: Patients able to kneel had significantly greater knee flexion ROM (p=0.013), higher flexor muscle strength (p=0.027), better performance in sit-to-stand (p=0.031), and higher OKS scores (p<0.01). No differences were found in extensor strength, FJS, TSK, or perception of knee condition and fear of prosthesis damage (p>0.05).

Conclusion: Kneeling ability after TKA is associated with better functional outcomes, yet perceptions of the knee and fear of damage remain similar across groups. Tailored rehabilitation and education addressing both physical and psychological barriers may improve postoperative kneeling outcomes.

Acute myeloid leukaemia (AML) is a clonal disorder of the bone marrow, attributable to genetic alterations leading to clonal stem cell overproduction. Tazi et al., have developed a unified molecular and risk stratification tool for AML, based on the correlation between clinical presentation, cytogenetics and a 32-gene variant signature. This classification proposes an integrated risk score based on 16 molecular classes defined by favourable, intermediate and adverse risks groups. The aim of this retrospective study was to investigate the utility of the AML online calculator to stratify real-world data relating to 159 patients diagnosed with AML in Northern Ireland (NI) between 2017 and 2023 into the appropriate classification and risk group in comparison to their classification under European LeukaemiaNet 2017 guidelines. 15% of patients were reclassified, showing the benefit of incorporating clinical and molecular data into classification and risk stratification models.

Background: Opioids such as morphine and fentanyl are widely used for pain management and in cardiovascular conditions; however, their misuse has become a significant public health concern. Non-cardiogenic pulmonary edema is a hallmark of opioid intoxication, often associated with impaired alveolar fluid clearance (AFC), a sodium transport-driven process that removes excess fluid from the alveoli.

Aims: This study aimed to elucidate the potential mechanisms of morphine-induced pulmonary edema by investigating the effects of μ-, δ-, and κ-opioid receptor (MOR, DOR, and KOR) modulation on AFC in rat lungs and determining whether receptor-specific blockade alters sodium transport across the alveolar epithelium.

Methods: Adult male Wistar rats were anesthetized, and a 5% BSA solution was instilled intratracheally to quantify alveolar fluid clearance (AFC) using bronchoalveolar lavage (BAL). A dose-response analysis (0.1-10 µM morphine) identified 10 µM as the concentration that significantly impaired AFC. Immunohistochemistry was performed to identify MOR, DOR, and KOR localization in lung tissue. To assess receptor-specific involvement, rats received intratracheal co-administration of morphine with selective antagonists (10 µM)-β-Funaltrexamine (μ), Naltrindole (δ), or Nor-binaltorphimine (κ)-and/or the ENaC inhibitor amiloride (1 mM).

Results: All receptor subtypes were expressed in type II alveolar cells and macrophages. Morphine (10 µM) reduced AFC significantly. DOR antagonism produced the most marked impairment, whereas μ- and κ-blockade caused ENaC-dependent reductions comparable to amiloride.

Conclusions: Opioid-induced AFC impairment involves receptor-specific alterations in alveolar fluid regulation, with the DOR playing a dominant inhibitory role, suggesting its involvement in the development of pulmonary edema.

Background: Vitamin D deficiency is common in obesity and has been linked to depression. However, the specific relationship between vitamin D status and depression in overweight or obese adults remains unclear.

Objective: This study aimed to evaluate the association between serum vitamin D levels and depression among obese adults using data from NHANES 2009-2018.

Methods: Cross-sectional analysis of NHANES 2009-2018, a nationally representative survey with a multistage, stratified, cluster design; analyses incorporated survey weights. Of 49,693 participants, we excluded those aged < 18 or > 60 years (n = 28,464), those with BMI < 30 kg/m² (n = 13,582), and records missing serum 25(OH)D (n = 371) or PHQ-9 (n = 2,454), yielding a final analytic sample of 4,822. Depression was assessed with the PHQ-9 (scores ≥ 10). Associations between serum 25(OH)D and depression were estimated using survey-weighted multivariable logistic regression, with exploratory subgroup analyses. NHANES protocols were approved by the National Center for Health Statistics (NCHS) with written informed consent.

Results: A total of 4,822 subjects (mean age 41 years; 44% male) were included in this study, in which the prevalence of depression was 20%. The results of the study showed that the detection rate of vitamin D insufficiency/deficiency was 16% in the depressed group, which was significantly higher than the 12% in the non-depressed group (P = 0.002). After adjusting for age, gender, race, education level, marital status, poverty-to-income ratio, smoking, alcohol consumption, hours of sleep, diabetes, hypertension, and number of hyperlipidemia, there remained a significant positive association between depression and serum vitamin D insufficiency/deficiency (adjusted OR = 1.41, 95%CI 1.06, 1.88).

Conclusion: In this cross-sectional analysis of NHANES 2009-2018 obese adults, vitamin D insufficiency/deficiency was associated with higher odds of depression; causality cannot be inferred.

Background: Timely electrocardiograms (ECGs) are essential for identifying acute coronary syndrome (ACS), with international guidelines - including those from the European Society of Cardiology (ECS) and American Heart Association (AHA) guidelines recommending a time to ECG (TTE) of less than 10 minutes. However, achieving this in busy emergency departments (ED) is challenging, particularly for ambulatory patients who are not conveyed via ambulance to ED. A baseline audit at Galway University Hospital (GUH) identified prolonged TTE in this group, prompting a quality improvement project (QIP).

Methods: Using ESC, and AHA guidelines standard of ECG within 10 minutes, we implemented a QIP comprising three Plan-Do-Study-Act (PDSA) cycles. The UK Care Quality Commission's (CQC) threshold of ECG within 30 minutes was also measured. Prospective data were collected via rapid-cycle audits from June to September 2024, capturing real-time performance. Educational and workflow measures were introduced to improve TTE.

Results: Across the three cycles (n=10, n=19, n=16), only 6% of patients achieved TTE within 10 minutes in the final cycle. However, the median TTE improved from 42 minutes at baseline to 14 minutes in the final cycle. Performance against the CQC's 30-minute benchmark improved from 50% in Cycle 1 to 100% in the final cycle.

Conclusions: This QIP demonstrates that meaningful improvement in TTE is achievable despite persistent difficulty meeting the 10-minute target. Context-aware quality metrics may better reflect progress in busy EDs. Future efforts will focus on earlier ECG acquisition in the patient journey, including an exploration of triage redesign and front door ECG capability.

Background: This study investigates gender-based differences among individuals alleging kleptomania during forensic psychiatric evaluations in Türkiye, with attention to diagnostic inflation and potential legal misuse.

Methods: A total of 158 cases evaluated between 1 January 2019 and 31 December 2023 were retrospectively analyzed using standardized forensic psychiatric reports. Sociodemographic variables, offense characteristics, clinical features, and diagnostic outcomes were compared by sex.

Results: Age and education levels did not significantly differ between sexes. Women were more likely to be widowed, steal from commercial settings, target luxury or low/high-value items, and confess to the offense. Men displayed higher rates of alcohol/substance use, mood stabilizer prescription, nighttime offending, and thefts directed at individuals. Kleptomania diagnoses were disproportionately frequent in forensic settings compared with clinical prevalence, suggesting possible strategic invocation for legal advantage. Moreover, behavioral patterns frequently deviated from DSM-5 criteria, raising concerns about malingering.

Conclusions: The findings highlight the need for standardized, multidimensional forensic psychiatric evaluation protocols integrating psychometric assessment and contextual analysis to enhance diagnostic accuracy and ensure reliability in criminal responsibility judgments.