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Carcinogenic effects of long-term exposure from prenatal life to glyphosate and glyphosate-based herbicides in Sprague-Dawley rats

Environ Health. 2025 Jun 10;24(1):36. doi: 10.1186/s12940-025-01187-2.

ABSTRACT

BACKGROUND: Glyphosate-based herbicides (GBHs) are the world’s most widely used weed control agents. Public health concerns have increased since the International Agency for Research on Cancer (IARC) classified glyphosate as a probable human carcinogen in 2015. To further investigate the health effects of glyphosate and GBHs, the Ramazzini Institute launched the Global Glyphosate Study (GGS), which is designed to test a wide range of toxicological outcomes. Reported here are the results of the carcinogenicity arm of the GGS.

METHODS: Glyphosate and two GBHs, Roundup Bioflow used in the European Union (EU) and RangerPro used in the U.S., were administered to male and female Sprague-Dawley (SD) rats, beginning at gestational day 6 (via maternal exposure) through 104 weeks of age. Glyphosate was administered through drinking water at three doses: the EU acceptable daily intake (ADI) of 0.5 mg/kg body weight/day, 5 mg/kg body weight/day and the EU no-observed adverse effect level (NOAEL) of 50 mg/kg body weight/day. The two GBH formulations were administered at the same glyphosate-equivalent doses.

RESULTS: In all 3 treatment groups, statistically significant dose-related increased trends or increased incidences of benign and malignant tumors at multiple anatomic sites were observed compared to historical and concurrent controls. These tumors arose in haemolymphoreticular tissues (leukemia), skin, liver, thyroid, nervous system, ovary, mammary gland, adrenal glands, kidney, urinary bladder, bone, endocrine pancreas, uterus and spleen (hemangiosarcoma). Increased incidences occurred in both sexes. Most of these involved tumors that are rare in SD rats (background incidence < 1%) with 40% of leukemias deaths in the treated groups occurring before 52 weeks of age and increased early deaths were also observed for other solid tumors.

CONCLUSIONS: Glyphosate and GBHs at exposure levels corresponding to the EU ADI and the EU NOAEL caused dose-related increases in incidence of multiple benign and malignant tumors in SD rats of both sexes. Early-life onset and mortality were observed for multiple tumors. These results provide robust evidence supporting IARC’s conclusion that there is “sufficient evidence of carcinogenicity [of glyphosate] in experimental animals”. Furthermore, our data are consistent with epidemiological evidence on the carcinogenicity of glyphosate and GBHs.

PMID:40490737 | DOI:10.1186/s12940-025-01187-2

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Traditional contraceptive practices: survey of medicinal plants used to control birth in four states in Nigeria

BMC Complement Med Ther. 2025 Jun 9;25(1):210. doi: 10.1186/s12906-025-04935-6.

ABSTRACT

Although modern contraceptive practices are actively advocated, many individuals continue to rely on traditional medicines for contraception due to their perceived safety. The open-ended questionnaire used in this study sought to gain insights into contraceptive practices from traditional providers’ perspectives. Herb sellers and herbal practitioners from four yoruba-speaking states in Nigeria-Kwara, Lagos, Oyo, and Osun-were interviewed. Data from questionnaires were analyzed via descriptive and inferential statistics. Quantitative analysis was done using the informant consensus factor (ICF) and relative frequency of citation (RFC) indices. A total of 31 species were recorded across the study areas. Kwara had the highest diversity, with 20 plant species, followed by Lagos (16), Oyo (10) and Osun (4). The ICF value recorded across the study areas was 0.7, with the most frequently cited species for female and male contraception varying by location. Carica papaya had RFC values of 0.58 in Oyo and 0.44 in Osun, while Mucuna pruriens recorded 0.30 in Lagos and Jatropha gossypiifolia had 0.27 in Kwara. The plant species were mostly prepared in combination forms, with seeds and leaves being the most used parts. These were administered as herbal contraceptive decoctions, powders, or worn as contraceptive rings or waist beads. A statistically significant difference existed between the plant form, the education level of participants, and having patients seeking contraception. In conclusion, this survey underscores the diverse range of medicinal plant species used for contraception. Further research is essential to validate their efficacy and understand the mechanisms of herbal contraceptives.

PMID:40490736 | DOI:10.1186/s12906-025-04935-6

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Application of 3D-Printed Artificial Vertebrae in the Reconstruction After Resection of Complex Malignant Spinal Tumors

Clin Spine Surg. 2025 Jun 9. doi: 10.1097/BSD.0000000000001847. Online ahead of print.

ABSTRACT

STUDY DESIGN: The reconstruction of the anterior vertebral body using 3D-printed artificial vertebrae after total en bloc spondylectomy for spinal tumors restores spinal stability.

OBJECTIVE: To investigate the feasibility of using 3D-printed artificial vertebrae for spinal reconstruction after tumor resection.

SUMMARY OF BACKGROUND DATA: Total en bloc spondylectomy is an effective surgical method for treating spinal tumors. However, reconstructing the vertebral body after tumor resection is challenging. 3D-printed artificial vertebrae offer a novel solution to this issue.

METHODS: From December 2016 to September 2023, 43 patients with malignant spinal tumors underwent vertebrectomy followed by reconstruction using 3D-printed artificial vertebrae. The cohort included 30 males and 13 females, aged 15-76 years, with a mean age of 58.0 years. Tumor types included 12 primary malignant tumors and 36 metastatic tumors. Clinical outcomes were assessed using preoperative and postoperative VAS scores at 24 hours and 3 months, Frankel grades, and radiologic evaluation of local tumor control and prosthesis subsidence.

RESULTS: Follow-up ranged from 3 to 31 months, with a mean of 10.9 months. There was a statistically significant improvement in VAS scores at 24 hours and 3 months postoperatively compared with preoperative scores (P<0.01). Of the 43 patients, 42 (97.7%) showed at least one grade improvement in Frankel grade at the last follow-up. During the follow-up period, there were no cases of prosthesis subsidence among the patients who underwent reconstruction with 3D-printed artificial vertebrae.

CONCLUSION: Porous titanium artificial vertebrae produced by 3D printing technology exhibit good biocompatibility and mechanical stability, making them suitable for reconstruction after vertebrectomy.

PMID:40489897 | DOI:10.1097/BSD.0000000000001847

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Impact of Cage Material (PEEK vs. Titanium) on Subsidence, Fusion, and Patient-reported Outcomes After Transforaminal Lumbar Interbody Fusion

Clin Spine Surg. 2025 Jun 9. doi: 10.1097/BSD.0000000000001837. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective cohort study.

OBJECTIVE: To assess potential risk factors for cage subsidence after transforaminal lumbar interbody fusion (TLIF), specifically comparing polyetheretherketone (PEEK) versus titanium cages.

SUMMARY OF BACKGROUND DATA: PEEK and titanium cages are commonly used for arthrodesis in TLIF. Titanium may demonstrate osseointegration superior to PEEK, but there is little evidence comparing the risk-stratified subsidence rate between the 2 cage types.

METHODS: We identified adult patients who underwent 1-level TLIF over a 5-year period at our institution. We recorded patient demographics, cage subsidence, fusion status, and average Hounsfield unit (HU) measurements of the target endplates. Univariate analysis evaluated cage subsidence and clinical and patient-reported outcomes. Risk stratification was based on subsidence grades. Potential risk factors for subsidence were identified by multivariate analysis.

RESULTS: The 130 TLIF patients received 74 PEEK and 56 titanium cages. Demographics, clinical characteristics, and average HU did not differ between the cage types, and no statistically significant correlation was observed between these measures and subsidence grade. PEEK (86.5%) and titanium (89.3%) groups demonstrated similar fusion rates (P=0.630). The titanium group had a higher subsidence rate than the PEEK group (55.4% vs. 39.2%, P=0.067) and overall more higher-grade (25%-100%) subsidence (51.5% vs. 45.5%, P=0.186). Patients who demonstrated evidence of subsidence within 1 month of surgery were more likely to experience high-grade subsidence at 1-year follow-up (odds ratio=30.178, P<0.001). Although high-grade subsidence was associated with pseudarthrosis, early subsidence did not necessarily lead to pseudarthrosis.

CONCLUSIONS: The rate and severity of cage subsidence may be multifactorial and warrant further high-powered, risk-adjusted studies.

LEVEL OF EVIDENCE: Level III.

PMID:40489896 | DOI:10.1097/BSD.0000000000001837

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Etiology and pattern of maxillofacial fractures among patients who visited Jimma Medical Center Dental Clinic, Jimma, Southwest Ethiopia

Medicine (Baltimore). 2025 Jun 6;104(23):e42569. doi: 10.1097/MD.0000000000042569.

ABSTRACT

The maxillofacial region consists of soft and hard tissues that form the face and extend from the frontal bone superiorly to the mandible inferiorly. Because the face is the most exposed part of the body, it is especially vulnerable to trauma. Trauma to the maxillofacial regions is a major public health problem worldwide. Nearly 5% to 10% of trauma patients have facial fractures. Thus, the aim of this study was to assess the etiology and pattern of maxillofacial fractures among patients who visited Jimma Medical Center (JMC) dental clinic, Southwest Ethiopia. Institutional based retrospective cross-sectional study was conducted on 331 patients (279 males and 52 females with a mean age of 26.23 ± 13.51 years) with maxillofacial fractures who visited JMC dental clinic from January 2018 to December 2020. To collect data first charts of the patients were found using their medical record numbers. Then information like socio-demographic characteristics, patterns of fractures, and causes of fractures, was collected using a structured and pretested checklist from the chart. Data was entered into the Epi-data version 3.1 and exported to SPSS version 25 for analysis. Descriptive analysis was done and presented by the use of tables, bar graphs and pie chart. The leading cause of fracture was road traffic accidents (45%), followed by assault (33.2%) and accidental fall (11.8%). Head (51.6%) injuries were the most common associated injuries. Surgical site infection (52.2%) was the most common posttreatment complication. The study’s findings can be used to guide public health activities, healthcare professional training, and resource allocation in Ethiopia in order to enhance maxillofacial fracture prevention, management, and outcomes.

PMID:40489882 | DOI:10.1097/MD.0000000000042569

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The causal relationship between enlarged perivascular spaces and intracerebral hemorrhage: A 2-sample Mendelian randomization study

Medicine (Baltimore). 2025 Jun 6;104(23):e42658. doi: 10.1097/MD.0000000000042658.

ABSTRACT

The genetic prediction of the causal relationship between enlarged perivascular spaces (PVS) and intracerebral hemorrhage (ICH). We performed a 2-sample Mendelian randomization (MR) study that used published data from genome-wide association studies on ICH and PVS. We primarily utilized the inverse variance weighted (IVW), MR-Egger, weighted median and weighted mode method. Sensitivity analyses included Cochran Q test, MR-Egger regression, MR-PRESSO global test and leave-one-out analysis. IVW analysis showed no statistical association between genetically predicted enlargement of hippocampal PVS (OR = 0.74, 95% CI = 0.23-2.35, P = .605), basal ganglia PVS (OR = 1.59, 95% CI = 0.64-3.95, P = .318), or white matter PVS (OR = 1.59, 95% CI = 0.64-3.95, P = .318) with the risk of ICH. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. The sensitivity analyses did not reveal any pleiotropy or heterogeneity. The leave-one-out plots did not found any single mutation that might influence the results. Our findings indicate that there is no causal relationship between PVS enlargement and the development of ICH at the genetic level. Using PVS as a diagnostic marker might lack specificity, needed for the planning of timely diagnostic procedures in the risk populations.

PMID:40489879 | DOI:10.1097/MD.0000000000042658

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Causal effects of childhood obesity on venous thromboembolism in adulthood: A bidirectional Mendelian randomization study

Medicine (Baltimore). 2025 Jun 6;104(23):e42591. doi: 10.1097/MD.0000000000042591.

ABSTRACT

Obesity is a recognized risk factor for VTE in both children and adults. However, the causal relationship between childhood obesity and the risk of VTE in adulthood remains unclear. This study conducted a bidirectional 2-sample Mendelian randomization (MR) analysis using genome-wide association study data to explore this association. The inverse-variance weighting (IVW) method, along with weighted median and MR-Egger approaches, was employed to assess causality, while linkage disequilibrium score regression (LDSC) evaluated genetic correlations. Sensitivity analyses, including Cochran Q statistics, the MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis, ensured the robustness of the findings. In the forward MR analysis, the IVW analysis identified a significant causal association between childhood body mass index (BMI) and UBK_VTE (OR: 1.005, 95% CI: 1.000-1.008, P = .002), FinnGen_VTE (OR: 1.303, 95% CI: 1.175-1.446, P < .001), FinnGen_pulmonary embolism (PE) (OR: 1.265, 95% CI: 1.079-1.484, P = .004) and FinnGen_deep vein thrombosis (DVT) (OR: 1.345, 95% CI: 1.145-1.58, P < .001). The results remained consistent across different MR methods, with no evidence of pleiotropy or heterogeneity. Reverse MR analysis showed that VTE, including PE and DVT, had no causal effect on childhood obesity. LDSC analysis further confirmed significant genetic correlations between childhood BMI and VTE outcomes (FinnGen_VTE [rg = 0.28, P = 2.21 × 10-7], FinnGen_PE [rg = 0.24, P = 8.62 × 10-5], and FinnGen_DVT [rg = 0.27, P = 1.79 × 10-5]). In conclusion, these findings provide genetic evidence that childhood obesity increases the risk of developing VTE in adulthood, emphasizing the need for early prevention and weight management strategies. Further studies are required to explore underlying biological mechanisms and assess the impact of obesity interventions on VTE risk reduction.

PMID:40489873 | DOI:10.1097/MD.0000000000042591

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Comparison of hypnosis plus sedoanalgesia and sedoanalgesia alone methods used in the ERCP procedure: A prospective randomized study

Medicine (Baltimore). 2025 Jun 6;104(23):e42641. doi: 10.1097/MD.0000000000042641.

ABSTRACT

Endoscopic retrograde cholangiopancreatography (ERCP) is an interventional procedure that is often performed under sedation anesthesia and that is used in the diagnosis and treatment of hepatopancreaticobiliary diseases. The objective of this study was to compare the efficacy of hypnosis in conjunction with sedoanalgesia and sedoanalgesia alone in the context of outpatient anesthesia prior to ERCP. Patients undergoing ERCP in the endoscopy unit between March and May 2021 were randomly assigned to 1 of 2 groups: group 1 received hypnosis and sedoanalgesia, and group 2 received sedoanalgesia alone. Both groups were administered 0.5 to 0.6 mg/kg intravenous pethidine hydrochloride (HCl), 1 to 3 mg intravenous midazolam, and 1 to 2 mg/kg intravenous propofol. The first group also received hypnotic induction before the procedure and anesthetic agents. In the event of patients exhibiting movement during the procedure, an anesthesiologist was unaware of the patient’s allocation and administered additional propofol and/or pethidine HCl. A statistical comparison was conducted between the 2 groups regarding demographic data, vital parameters, medication requirements, and satisfaction scales. Thirty patients were included in both groups. Following the procedure, the administration of propofol and pethidine HCl was reduced in group 1 (P = .031 and P = .009, respectively). The 5-minute heart rate, baseline peripheral oxygen saturation at 3 and 10 minutes were lower in group 2 (P = .008, P = .011, P = .017, and P = .031, respectively). Although the dose of anesthetic drugs were lower, no significant difference was observed neither in the patient satisfaction scores, nor in patient movements. The use of hypnosis during ERCP enhances the efficacy of sedoanalgesia. Hypnotic anesthesia may be employed as an alternative method in cases where high-dose administration of these agents is contraindicated.

PMID:40489869 | DOI:10.1097/MD.0000000000042641

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Cytokines and oral cancer risk: Genetic evidence from a bidirectional Mendelian randomization study

Medicine (Baltimore). 2025 Jun 6;104(23):e42642. doi: 10.1097/MD.0000000000042642.

ABSTRACT

This study aimed to elucidate the causal relationship between cytokines and oral cancer using Mendelian randomization (MR) analysis. Utilizing genetic data from genome-wide association studies (GWAS) and publicly available datasets, we conducted a bidirectional 2-sample MR analysis. The study design employed single nucleotide polymorphisms as genetic instruments to investigate the link between cytokines and oral cancer. The analysis was based on data from 2 cohorts with total 132 cytokines: 41 cytokines from comprehensive GWAS meta-analysis data, 91 cytokines from GWAS summary statistics for circulating inflammatory cytokines. Oral cancer genetic association data was sourced from the FinGen R10 datasets. To discern the causal relationship between cytokines and oral cancer, 5 MR methodologies, including inverse variance weighted and MR-Egger regression, weighted median, weighted mode, and simple mode were applied. The MR analysis revealed nominal associations between certain cytokines and the risk of oral cancer. Specifically, increased levels of C-X-C motif chemokine ligand 9 (odd ratios [OR] = 0.760, 0.600-0.962, 95% confidence interval [CI] 0.600-0.962, P = .023), monocyte chemoattractant protein 1 (OR = 0.78, 95% CI 0.32-0.99, P = .046), and TNF related activation induced cytokine (OR = 0.792, 95% CI 0.630-0.994, P = .044) were associated with a reduced risk of oral cancer, while higher levels of monocyte chemoattractant protein 2 (OR = 1.164, 95% CI 1.001-1.353, P = .048) and CC motif chemokine 25 (OR = 1.434, 95% CI 1.106-1.858, P = .006) were linked to an increased risk. The reverse analysis suggested a possible effect of oral cancer on the level of circulating cytokines, particularly Fractalkine (OR = 0.942, 95% CI 0.897-0.990, P = .019). No evidence of heterogeneity or significant pleiotropy was detected, validating the instrumental variables used. The findings support a causal relationship between specific cytokines and the risk of oral cancer, highlighting the complex interplay between inflammatory mediators and cancer development. These results underscore the importance of individualized immune profiling in treating oral cancer patients and pave the way for future research into targeted therapies based on cytokine profiles.

PMID:40489865 | DOI:10.1097/MD.0000000000042642

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The correlation study between post-surgery oxygen partial pressure level and prognosis of patients with sepsis during hospitalization

Medicine (Baltimore). 2025 Jun 6;104(23):e42449. doi: 10.1097/MD.0000000000042449.

ABSTRACT

Sepsis remains a leading cause of mortality and healthcare burden, necessitating improved diagnostic and therapeutic strategies. Observational studies suggest that hyperoxemia may improve postoperative sepsis outcomes, but evidence remains limited. This study aims to explore the optimal range of oxygen partial pressure (PaO2) in postsurgical sepsis patients and its impact on prognosis. Clinical data of adult sepsis patients were extracted from the medical information mart for intensive care-IV database. Patients were categorized into control (PaO2 ≤ 100 mm Hg) and hyperoxemia (PaO2 > 100 mm Hg) groups. Primary outcome was 90-day mortality, while secondary outcomes included 1-year mortality, intensive care unit (ICU)/hospital length of stay, and invasive ventilation duration. Restricted cubic spline analysis stratified postsurgical PaO2 into normal (≤128.7 mm Hg), mild hyperoxemia (128.7-162.1 mm Hg), and severe hyperoxemia (≥162.1 mm Hg). Kaplan-Meier survival analysis and multivariate regression were conducted. Among 1220 patients, hyperoxemia patients were younger, had lower disease severity, and received more aggressive treatment. They had lower rates of acute respiratory failure and acute kidney injury. After cubic spline-based classification, mild hyperoxemia was associated with lower 90-day mortality (OR: 0.54, 95% CI: 0.34-0.86, P = .010), while severe hyperoxemia showed no significant effect (OR: 0.60, 95% CI: 0.30-1.20, P = .147). Kaplan-Meier curves demonstrated significantly improved long-term survival for mild hyperoxemia patients. Mild hyperoxemia in postsurgical sepsis patients is associated with reduced 90-day mortality, suggesting a potential optimal oxygenation range for better outcomes.

PMID:40489846 | DOI:10.1097/MD.0000000000042449