Search Results (2,920)

Background: Male infertility is evaluated using standard semen parameters. However, these criteria offer limited insight into sperm functionality and poorly predict natural fertility or assisted reproductive technology (ART) outcomes. Methods: In this study, the expression levels of three genes (AURKA, HDAC4, and CARHSP1) involved in mitosis regulation, epigenetic modulation and early embryonic development, were measured by RT-qPCR in sperm samples (training dataset). For each gene, thresholds of normal and reduced expression were established by biostatistical modeling and combined with the number of motile spermatozoa to develop the Spermatozoa Function Index (SFI). Results: The ROC analysis was used to interpret the SFI values: SFI > 320 (normal), 290–320 (intermediate), and <290 (low). Then, this index was validated using 627 fresh semen samples from 25- to 60-year-old men at our ART center. Based on the World Health Organization criteria, 54.5% of the 627 sperm samples were normospermic, 8.8% showed oligo-astheno-teratospermia, and 36.6% had one or two abnormal parameters. According to the SFI values, 41% of sperm samples displayed normal expression, 55.9% low expression, and 4.1% intermediate expression. Only 57% of the 342 normospermic samples had normal SFI values and 37% had low SFI values. Among the 81 samples with stringent normal criteria (≥50 million/mL, ≥50% total motility, ≥14% normal morphology), 67.9% displayed normal SFI and 22.2% low SFI values. These findings suggest that even sperm with normal parameters may harbor dysfunctions. Conclusions: Our data highlight a gene signature with strong discriminatory power and promising diagnostic value for detecting subclinical sperm defects and improving male infertility assessment. Full article

Hemodynamics significantly impact the biology of endothelial cells (ECs) lining the blood vessels. ECs are exposed to various hemodynamic forces, particularly frictional shear stress from flowing blood. While physiological flows are critical for the normal functioning of ECs, abnormal flow dynamics, known as disturbed flows, may trigger endothelial dysfunction leading to atherosclerosis and other vascular conditions. Such flows can occur due to sudden geometrical variations and vascular abnormalities in the cardiovascular system. In the current study, a microfluidic system was used to investigate the impact of different flow conditions (i.e, normal vs. disturbed) on ECs in vitro. We particularly explored the relationship between specific flow patterns and cellular pathways linked to oxidative stress and inflammation related to atherosclerosis. Here, we utilized a 2D cell culture perfusion system featuring an immortalized human vascular endothelial cell line (EA.hy926) connected to a modified peristaltic pump system to generate either steady laminar flows, representing healthy conditions, or disturbed oscillatory flows, representing diseased conditions. EA.hy926 were exposed to an oscillatory flow shear stress of 0.5 dynes/cm² or a laminar flow shear stress of 2 dynes/cm² up to 24 h. Following flow exposure, cells were harvested from the perfusion chamber for quantitative PCR analysis of gene expression. Reactive oxygen species (ROS) generation under various shear stress conditions was also measured using DCFDA/H2DCFDA fluorescent assays. Under oscillatory shear stress flow conditions (0.5 dynes/cm²), EA.hy926 ECs showed a 3.5-fold increase in the transcription factor nuclear factor (NFκ-B) and a remarkable 28.6-fold increase in cyclooxygenase-2 (COX-2) mRNA expression, which are both proinflammatory markers, compared to static culture. Transforming growth factor-beta (TGFβ) mRNA expression was downregulated in oscillatory and laminar flow conditions compared to the static culture. Apoptosis marker transcription factor Jun (C-Jun) mRNA expression increased in both flow conditions. Apoptosis marker C/EBP homologous protein (CHOP) mRNA levels increased significantly in oscillatory flow, with no difference in laminar flow. Endothelial nitric oxide synthase (eNOS) mRNA expression was significantly decreased in cells exposed to oscillatory flow, whereas there was no change in laminar flow. Endothelin-1 (ET-1) mRNA expression levels dropped significantly by 0.5- and 0.8-fold in cells exposed to oscillatory and laminar flow, respectively. ECs subjected to oscillatory flow exhibited a significant increase in ROS at both 4 and 24 h compared to the control and laminar flow. Laminar flow-treated cells exhibited a ROS generation pattern similar to that of static culture, but at a significantly lower level. Overall, by exposing ECs to disturbed and normal flows with varying shear stresses, significant changes in gene expression related to inflammation, endothelial function, and oxidative stress were observed. In this study, we present a practical, optimized system as an in vitro model that can be employed to investigate flow-associated diseases, such as atherosclerosis and aortic aneurysm, thereby supporting the understanding of the underlying molecular mechanisms. Full article

Background/Objectives: This study aims to investigate the development of oculomotor behavior in children born preterm using a DIVE device (Device for an Integral Visual Examination) equipped with eye-tracking technology. Visual and visuo-cognitive measures obtained through eye-tracking technology provide quantitative and sensitive indicators of early neural development, as visual function is one of the earliest cerebral processes to develop postnatally. Design: This is a cross-sectional study. Participants: The study included 428 children aged 0.5 to 14 years. Of these, 214 were born preterm (78 late preterm, born at 32–36 weeks’ gestation, and 136 early preterm, born at less than 32 weeks’ gestation) and 214 were full-term controls, matched by age and gender. Methods: All participants underwent a comprehensive ophthalmological assessment. Oculomotor behavior was analyzed using a DIVE device, focusing on fixation duration, saccadic performance and fixation stability. Fixation stability was quantified by the bivariate contour ellipse area for short tasks (BCEA), which measures (in deg²) the area of the ellipse enclosing a specified percentage of fixation positions—smaller BCEA values indicate greater fixation stability. We performed a cluster analysis on these oculomotor metrics to identify distinct oculomotor control patterns. Results: Preterm children exhibited significantly poorer fixation stability than controls (mean BCEA 0.21 vs. 0.09 logdeg², p = 0.004), alongside shorter fixation durations and longer saccadic reaction times. Early preterm children showed more unstable fixations compared to late-preterm and control groups (0.26 vs. 0.12 and 0.09 logdeg², respectively, p = 0.001). Cluster analysis revealed three distinct OMC (oculomotor control) patterns: “good,” “impulsive,” and “poor.” Children classified in the “good OMC” cluster demonstrated stable fixations and appropriate saccadic reaction times. In contrast, those in the “impulsive OMC” and “poor OMC” clusters exhibited more unstable fixations and abnormal saccadic times, with the “poor” cluster being significantly associated with extreme prematurity, lower birth weights, and a higher incidence of intraventricular hemorrhage (IVH). Conclusions: Preterm birth is associated with measurable oculomotor deficits, most pronounced in early preterm infants, affecting their fixation and saccadic abilities. The findings emphasize the need for targeted interventions to support the development of preterm children, particularly those with “poor” oculomotor control behavior. Full article

This study aimed to characterize the computed tomographic (CT) dimensions and contrast attenuation properties of the equine eye. CT scans from 21 horses without ocular abnormalities were analyzed to obtain detailed ocular measurements and attenuation values. In addition, cranial measurements, such as nasal–occipital length and zygomatic width, were incorporated to explore potential anatomical relationships between the skull and intraocular structures. Although most correlations between cranial and ocular parameters were weak, statistically significant associations—particularly those involving lens dimensions and anterior chamber measurements—suggest that skull morphology may exert a subtle influence on ocular anatomy. Full article

Background: Obesity and gestational diabetes mellitus (GDM) are the most common metabolic conditions that have an unfavorable impact on maternal and fetal health. Maternal obesity and GDM are often associated with placental dysfunction and structural alterations. The apelin receptor (APLNR), vascular endothelial growth factor (VEGF), leptin, and DNA methylation play crucial roles in placental function. We aimed to investigate the placental volume and vascularization, and to determine the changes in these markers in obese and GDM mothers. Material and Methods: In our study, we investigated the human placenta (n = 48) at term. The placental structural analyses on volume and vascularization were conducted using three-dimensional ultrasound before labor. Placental APLNR expression was determined using RT-PCR, and leptin and VEGF concentrations using ELISA in placental tissues. Global DNA methylation was measured using colometric assay. Results: The age of GDM mothers was significantly higher than that of normal and obese mothers. The gestation length of GDM mothers was significantly shorter than that of normal and obese mothers. The placental volume was significantly higher in obese and GDM cases compared with normal cases. Vascularization indices (VI, FI, VFI) were significantly depressed in GDM and obesity. In the case of biomarker studies, APLNR, leptin, and VEGF showed similar decreases in obese and GDM placentas. Based on our results, the effect of GDM, not obesity, was more pronounced for these biomarkers. VEGF reduction correlates with three-dimensional placental vascularity studies. The DNA methylation was significantly elevated in both GDM and obese placental samples, while the GDM effect was more pronounced. Conclusions: This study is the first to demonstrate structural alterations of the placenta using placental tissue biomarkers in obesity and gestational diabetes mellitus (GDM). We found that both GDM and obesity affect placental volume and vascularity, as indicated by reduced leptin and VEGF levels, presumably mediated by epigenetic effects. Our findings may provide a novel therapeutic target for improving abnormal placental function caused by GDM and obesity. Full article

Background/Objectives: Chorionic villus sampling (CVS) is a pivotal diagnostic tool for early prenatal detection of chromosomal and genetic abnormalities; however, the safety and diagnostic efficacy of different CVS approaches remain a subject of clinical interest. This monocentric study compares transcervical (TC-CVS), transabdominal (TA-CVS) and transvaginal (TV-CVS) techniques, focusing on procedure-related fetal loss and diagnostic yield. Methods: In this 15-year, single-operator prospective study, a total of 5500 women underwent CVS between 10 and 14 weeks of gestation at a single center. Sampling was performed via TA-CVS (n = 4500), TC-CVS (n = 850), or TV-CVS (n = 150). Outcomes assessed included fetal loss rates, sample adequacy, early complications and hemodynamic changes measured by Doppler ultrasound. A p-value < 0.05 (two-tailed) was considered statistically significant. Results: Spontaneous abortion rates were significantly lower following TA-CVS (0.18%; 8/4500) compared to TC-CVS (0.6%; 5/850) and TV-CVS (1.3%; 2/150) (χ² = 24.56, p < 0.001). Post hoc pairwise analysis showed significantly lower fetal loss in TA-CVS compared to TC-CVS, but not between TA-CVS and TV-CVS. Cytogenetic abnormalities were detected in 220 cases (4.0%), and clinically significant copy number variants (CNVs) were confirmed in fetuses with major structural malformations. Five-year follow-up showed no diagnosed intellectual disability among assessed children. Optimal tissue weight (10–20 mg) was more frequent with TA-CVS (66.7%) than TC-CVS (35.3%) or TV-CVS (36.7%) (χ² = 350.92, p < 0.001). In a Doppler subset (n = 400), uterine, spiral, and interplacental artery PI changes were non-significant; the umbilical (p = 0.032) and middle cerebral arteries (p < 0.001) showed transient PI reductions after sampling. Conclusions: Transabdominal CVS demonstrated the most favorable balance of safety and diagnostic quality, suggesting it should be the preferred first-line technique in early prenatal diagnosis. Standardized technique and operator training remain critical to optimize outcomes. Full article

(1) Background: Resting heart rate (RHR) is an easily measurable cardiovascular risk indicator, yet its relationship with cardiometabolic risk factors remains understudied in rural African populations. This study investigated the association between RHR and cardiovascular risk factors among adults in the rural Ellisras community, South Africa. (2) Methods: A cross-sectional analysis was conducted among 629 participants (306 males, 323 females) aged 18 years and above from the Ellisras Longitudinal Study. Anthropometric measurements, blood pressure, biochemical parameters, and lifestyle factors were assessed. RHR was categorized as normal (60–100 bpm), bradycardia (<60 bpm), or tachycardia (>100 bpm). Statistical analysis included descriptive statistics, chi-square tests, Pearson correlations, and logistic regression to identify predictors of abnormal RHR. (3) Results: The mean age was 25.55 ± 1.97 years, with significant gender differences in cardiovascular parameters. Females had higher RHR (81.78 ± 11.73 vs. 70.36 ± 12.89 bpm, p < 0.001), body mass index (BMI) (24.62 vs. 20.67 kg/m², p < 0.001), and waist circumference (WC) (81.00 vs. 73.50 cm, p < 0.001). Resting heart rate (RHR) distribution varied significantly by gender (p < 0.001), with bradycardia more prevalent in males (91.3% vs. 8.7%) and tachycardia in females (75.0% vs. 25.0%). Significant positive correlations were observed between RHR and age (r = 0.105, p = 0.009), diastolic blood pressure (DBP) (r = 0.135, p < 0.001), fasting blood glucose (FBG) (r = 0.098, p = 0.016), total cholesterol (TCHOL) (r = 0.168, p < 0.001), LDL-C (r = 0.201, p < 0.001), WC (r = 0.169, p < 0.001), and sum of 4 skinfolds (bicep, tricep, subscapular and supraspinale) and (r = 0.184, p < 0.001). A negative correlation was found with systolic blood pressure (SBP) (r = −0.105, p < 0.001). In the logistic regression analysis, participants aged >25 years had significantly lower odds of abnormal RHR (OR = 0.50, 95% CI: 0.26–0.97, p = 0.039), after adjusting for confounders. In the fully adjusted model, RHR remained significantly associated with DBP (β = 0.59, p < 0.001), LDL-C (β = 2.76, p = 0.008), WC (β = 0.10, p = 0.012), and triglycerides (TG) (β = 2.78, p = 0.002). (4) Conclusions: RHR demonstrates significant associations with multiple cardiovascular risk factors in this rural South African population, with distinct gender-specific patterns. Age emerged as the primary independent predictor of abnormal RHR. These findings suggest that RHR could serve as a valuable, cost-effective screening tool for cardiovascular risk assessment in resource-limited rural settings. Full article

Background: During adolescence, the brain is undergoing anatomical and physiological maturation processes with changes to cognitive development. However, in adolescents with phenylketonuria (PKU), executive function and mental health are adversely affected by high blood phenylalanine (Phe) levels. Objectives: We aim to describe clinical outcomes in adolescents with PKU. Methods: Cross-sectional questionnaires were performed on quality of life (EuroQol “EQ-5D-5L” questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale- HADS) and food neophobia in a single PKU centre. Retrospective data on metabolic control (previous 12 months) and medical history, and current data on anthropometry, dietary treatment, and comorbidities were collected. Results: In total, 33 adolescents with PKU participated with a mean age of 13.5 ± 1.3 y (16 boys, 17 girls). All were on a Phe restricted diet, with 3 also prescribed sapropterin. Questionnaires were self-completed by n = 25/33 (76%) adolescents. A mean of 36 ± 26 blood Phe spots were performed over 12 months. There was a mean of 83% of blood Phe < 600 µmol/L and 49% < 360 µmol/L. In total, 39% (n = 13/33) of adolescents were overweight/obese, 18% (n = 6/33) overweight and 21% (n = 7/33) obese. Medical history documented mental health disorders (anxiety/depression) in 7 cases, low mood, suicidal thoughts and self-harming in 5, and neuro diversity in 4 (autism and/or attention-deficit hyperactivity disorder (ADHD). In the HADS questionnaire, 12% (n = 3/25) of adolescents scored borderline abnormal for anxiety and 12% (n = 3/25) abnormal for depression. Mean anxiety scores for females were almost twice as high compared to males. No significant correlation was found between blood Phe and anxiety/depression scores. However, higher Phe levels showed a trend towards reduced enjoyment and emotional responsiveness, including lower scores on measures of pleasure, cheerfulness, and emotional reactivity. Although not statistically significant, these findings suggest a potential subtle association between poorer metabolic control and mood disturbances in adolescents with PKU. No food neophobia was identified in our study. Conclusions: Adolescents with PKU presented with high levels of depression and anxiety. Long term studies focusing on quality of life and neurocognition even when achieving the PKU European guidelines are necessary. Different therapeutic options are needed to improve the outcome of patients with PKU. Full article

Background/Objectives: Heart rate variability (HRV) is associated with the risk of vascular events. However, the predictive value of HRV for the presence of intracranial atherosclerosis (ICAS) is unclear. This study aimed to investigate the relationship between daytime HRV measured by 3 min ECG monitoring and ICAS identified by high-resolution magnetic resonance imaging (HR-MRI). Methods: A total of 272 adults (mean age, 63.4 ± 6.8; 43% male) were recruited from November 2022 to December 2024. A series of cardiac function parameters is automatically generated through a 3 min analysis by the electrocardiographic dispersion mapping (ECG-DM) software, including heart rate variability and myocardial ischemic metabolic impairment. HRV was assessed as the standard deviation of normal-to-normal intervals (SDNN), which was categorized into tertiles for data analysis. Myocardial micro-alteration index (MMI, %) was used as an indicator of ischemia, reflecting myocardial abnormalities at the metabolic level. Atrial and ventricular myocardial oxygenation deficits were directly visualized in a color-coded scatter plot, with different colors indicating the severity of pathological changes. On HR-MRI intracranial artery wall scanning, the prevalence of ICAS was assessed in middle cerebral arteries (MCAs), vertebral arteries (VAs), and basilar arteries (BAs), and the associated plaque characteristics (eccentricity, thickening patterns, remodeling index, and surface morphology) were evaluated. Results: Among the subjects, 209 arterial lesions caused by ICAS were detected in 152 subjects (56%), including MCAs (105/544), VAs (68/526), and BAs (36/272). Ninety-four subjects (94/272) with significant HRV deviation had ICAS (p = 0.040). Furthermore, subjects with ICAS were more likely to present with atrial hypoxia (p = 0.030) compared to those without ICAS. In multivariate analyses, lower standard deviation of normal-to-normal intervals (SDNN, odds ratio, OR = 1.55, 95% CI 1.10–2.18, p = 0.012) and atrial deviation (OR = 1.85, 95% CI 1.10–3.14, p = 0.022) were independently associated with the presence of ICAS. Conclusions: Among middle-aged or older adults in a local community, our study suggested that lower HRV and significant atrial hypoxia were independently associated with the presence of ICAS. Full article

Objective: To identify distinct subtypes of ICU patients with Acute Kidney Injury (AKI) using serum electrolyte data and assess their associations with in-hospital mortality risk. Methods: This study used the eICU Collaborative Research Database (eICU-CRD) as its primary data source. AKI patients were identified according to the KDIGO clinical practice guidelines. Using K-Medoids clustering, we identified distinct AKI subtypes based on the first serum electrolyte measurements taken within 24 h of AKI diagnosis in the ICU. Logistic regression analysis was then employed to assess associations between these subtypes and in-hospital mortality risk. Within each subtype, we further examined the relationship between two AKI-related treatments, diuretics and renal replacement therapy (RRT), and mortality risk. Finally, to validate the identified subtypes, we replicated the entire analysis using a critical care dataset from a grade A tertiary hospital in Beijing, China. Results: We identified three distinct AKI subtypes from 15,838 eligible patients in the eICU-CRD. Subtype 1 (6364 patients, 40.2%) showed the lowest risk of in-hospital death and had all serum electrolyte levels within normal ranges. Subtype 2 (6624 patients, 41.8%) carried a moderate death risk and was characterized by abnormally high chloride levels. Subtype 3 (2850 patients, 18.0%) had the highest death risk, presenting with high serum phosphate and low bicarbonate levels. Importantly, the associations between treatments and mortality risk differed significantly by subtype. In the high-risk Subtype 3, both diuretics (OR = 0.71, p = 0.010) and RRT (OR = 0.78, p = 0.045) were associated with a lower risk of in-hospital death. However, in Subtype 2, both diuretics (OR = 1.30, p = 0.044) and RRT (OR = 1.56, p = 0.003) were associated with an increased risk. Neither treatment showed a significant association with death risk in Subtype 1. These findings were validated in the critical care database (431 AKI patients) from a Chinese local hospital, where the same three subtypes emerged with consistent electrolyte patterns, death risk profiles, and associations between treatments and mortality risks, validating the stability of the identified subtypes. Conclusions: Serum electrolyte data can help identify ICU AKI subtypes with different mortality risks. Additionally, associations between treatments (diuretics and RRT) and mortality risk vary significantly across these subtypes. These results generate the hypothesis that AKI subtyping could potentially inform personalized management strategies. Full article

Objective: Allergic rhinitis (AR) continues to adversely affect the life quality of a substantial patient population, highlighting the necessity for enhanced treatment modalities. Our research utilized licorice extract (LE) in nasal irrigation for managing this condition, with its therapeutic efficacy gauged against traditional saline nasal irrigation (SNI) through clinical trials. Additionally, the study incorporated traditional Chinese medicine (TCM) principles, measuring not just subjective symptom relief but also the objective shifts in lung meridian electrical conductance (MEC), to provide a comprehensive evaluation of the treatment’s effectiveness. Methods: Based on our previous laboratory and animal studies, we developed an LE solution and applied it through nasal irrigation to treat AR. In a one-month controlled trial, 60 patients with AR received either licorice nasal irrigation (LNI) or SNI daily. We assessed treatment efficacy by subjective questionnaire scores (Total Nasal Symptom Score [TNSS] and 22-item Sino-Nasal Outcome Test [SNOT-22]) and objective lung MEC analysis. Result: In the trial, 30 participants were randomly allocated to each group, and 28 individuals in the LNI group and 24 in the SNI group finished the study without any side effects. The LNI group had better improvements in sneezing, nasal itchiness, and rhinorrhea, along with a greater overall TNSS reduction. On the SNOT-22, the LNI group scored better across most nasal and extra-nasal symptoms, sleep, and physiological and psychosocial well-being. Participants were sorted into low, normal, and high lung MEC subgroups. After treatment, those in the LNI group normalized their lung MEC levels in both the low and high subgroups, which was not observed in the SNI group. Conclusions: LNI markedly improves symptoms in patients with AR, enhancing their quality of life. This treatment method, integrating Western and TCM practices, also normalizes abnormal lung MEC values following therapy. It offers a method of objectively validating the effectiveness of treatments based on TCM theories. Full article

Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are forms of primary large vessel vasculitis (LVV) affecting the aorta and its major branches. Timely diagnosis and accurate monitoring are essential to prevent irreversible damage. Current assessment strategies rely heavily on symptoms, physical examination, and inflammatory markers, which lack sensitivity and specificity, particularly in patients treated with IL-6 inhibitors. This narrative review provides a comprehensive overview of the role of imaging in monitoring LVV. Ultrasound, magnetic resonance imaging, and positron emission tomography better reflect disease activity and treatment response compared to conventional clinical and laboratory measures. Notably, emerging imaging-based tools such as the OMERACT GCA Ultrasound Score, the Takayasu Ultrasound Index, and the TAK Integrated Disease Activity Index (TAIDAI) are promising treat-to-target instruments. While computed tomography is primarily used to assess structural damage, conventional angiography now plays a more limited role, mainly reserved for procedural planning and haemodynamic evaluation. A key challenge remains: interpreting persistent vascular abnormalities, which may indicate active disease, vascular remodelling, or irreversible damage. Standardisation of imaging protocols and interpretation is needed, alongside further research on the prognostic value of imaging for relapse risk. This review supports a multimodal, patient-tailored approach in which imaging is central to the long-term management of LVV. Full article

Intrusion detection aims to identify the unauthorized activities within computer networks or systems by classifying events into normal or abnormal categories. As modern scenarios often involve multi-source data, multi-view fusion deep learning methods are employed to leverage diverse viewpoints for enhancing security threat detection. This paper introduces a novel intrusion detection approach using multi-view fusion within a federated learning framework, proposing an integrated AE Neural SVM (AE-NSVM) model that combines auto-encoder (AE) multi-view feature extraction and Support Vector Machine (SVM) classification. This approach simultaneously learns representative features from multiple views and classifies network samples into normal or seven attack categories while employing federated learning across clients to ensure adaptability and robustness in diverse network environments. The experimental results obtained from two benchmark datasets validate its superiority: on TON_IoT, the CAE-NSVM model achieves a highest F1-measure of 0.792 (1.4% higher than traditional pipeline systems); on UNSW-NB15, it delivers an F1-score of 0.829 with a 73% reduced training time and an 89% faster inference compared to baseline models. These results demonstrate the advantages of multi-view fusion in federated learning for balancing accuracy and efficiency in distributed intrusion detection systems. Full article

This white paper, prepared by a consortium of Canadian national and provincial organizations and experts, outlines urgent strategies to curb the rising incidence of HPV-related cancers, of which, cervical cancer is currently the fastest-growing cancer in Canada. Despite school-based vaccination programs, the national HPV vaccine uptake remains suboptimal at about 64%, far below the 90% coverage target by 2025 necessary to eliminate cervical cancer by 2040. The report emphasizes a multi-pronged approach: support access to HPV vaccination with expanded funding policies and education around school-based programs while addressing inequities in underserved populations. HPV testing is highlighted as the preferred method for cervical cancer screening, offering higher sensitivity than Pap smears. Self-collection is presented as an innovative strategy to reduce barriers, particularly for marginalized groups, with promising evidence from Canadian pilots and international models. Crucially, we call for investment in comprehensive, population-based databases to track vaccination, screening participation, and follow-up care. Robust registries would allow targeted outreach to under- or never-screened individuals, ensure timely follow-up of abnormal results, and measure the impact of prevention programs across Canada. With vaccination, equitable access to HPV testing, integration of self-collection, and strong data systems, Canada can achieve its goal of eliminating cervical cancer within two decades. Full article

Background/Objectives: Polymyxin B (PMB) was incorporated into a sodium deoxycholate sulfate (SDCS) micelle formulation to mitigate polymyxin-induced nephrotoxicity. This study examined the effect of the formulation on nephrotoxicity and biodistribution in a rat model. Methods: Four groups of rats were subcutaneously administered one of the following: normal saline, SDCS, PMB, or a PMB-SDCS formulation. After treatment, the weight changes were recorded, and the rats were euthanized to collect blood for serum biochemistry measurements. The histopathological damage to organs was examined. Two additional groups of rats received the same dose of PMB and the PMB-SDCS formulation subcutaneously; however, their serum PMB was measured at predetermined time points, and the PMB concentrations in the organs were measured. Molecular docking for PMB and formulation with human serum albumin was also performed. Results: The PMB-SDCS formulations showed improvement in serum biomarker measurements. Several abnormalities were observed in the kidney, liver, lung, and spleen tissues following PMB treatment, which indicated evidence of toxicity. The docking showed SDCS reduces PMB binding affinity on HSA. The PMB-SDCS formulations were associated with less acute toxicity and less nephrotoxic damage compared with the PMB group. The results were supported by less PMB accumulation in the kidneys in the formulation group. Conclusions: The study indicates that SDCS has the potential to mitigate PMB-induced nephrotoxicity in rat models, suggesting a promising strategy for safer use that warrants further investigation. Full article