Inflammation as a pathway for heavy metal-induced liver damage-Insights from a repeated-measures study in residents exposed to metals and bioinformatics analysis.

BACKGROUND: Epidemiological studies on heavy metal exposure and liver injury are predominantly cross-sectional, lacking longitudinal data and exploration of potential mechanisms. METHOD: We conducted a repeated-measures study in Northeast China from 2016 to 2019, involving 322 participants. Linear mixed models (LMM) and Bayesian kernel machine regression (BKMR) were employed to explore the associations between individual and mixed blood metal concentrations [chromium (Cr), cadmium (Cd), vanadium (V), manganese (Mn), lead (Pb)] and liver function biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), globulin (GLB), total protein (TP)]. Mediation and enrichment analyses were used to determine whether the inflammatory response is a critical pathway for heavy metal-induced liver damage. RESULT: We obtained a total of 958 observations. The results from LMM and BKMR indicated significant associations between individual and mixed heavy metals and liver function biomarkers. Longitudinal analysis revealed associations between Cd and the annual increase rate of ALT (ß = 2.61; 95% CI: 0.97, 4.26), the annual decrease rate of ALB (ß = -0.21; 95% CI: -0.39, -0.03), Mn and the annual increase rate of GLB (ß = 0.38; 95% CI: 0.05, 0.72), and V and the annual decrease rate of ALB/GLB (ß = -1.15; 95% CI: -2.00, -0.31). Mediation analysis showed that high-sensitivity C-reactive protein (hsCRP) mediated the associations between Cd and AST, TP, with mediation effects of 27.7% and 13.4%, respectively. Additionally, results from Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses supported the role of inflammatory response pathways. CONCLUSION: Our findings indicate that heavy metal exposure leads to liver damage, with the inflammatory response potentially serving as a crucial pathway in this process. This study offers a novel perspective on understanding heavy metal-induced liver injury and provides insights for preventive measures against the health damage caused by heavy metals.

Antitumor activity and transcriptome sequencing (RNA-seq) analyses of hepatocellular carcinoma cells in response to exposure triterpene-nucleoside conjugates.

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 µM), KYSE-150 (IC50 = 5.68 µM), and SW620 (IC50 = 4.61 µM) and along with lower toxicity (TC50 > 100 µM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 µg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 µg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.

The cross-sectional and longitudinal interconnectedness of physical, psychological and role functioning following physical trauma: A network analysis.

OBJECTIVE: Surviving physical trauma can have a large impact on one's daily life. Patients are at increased risk for poor physical health, psychological complaints, and problems in role functioning - which is often experienced simultaneously. The present study explores the interconnectedness of physical, psychological, and role functioning during the first two years post-injury, both cross-sectionally and longitudinally from a network perspective. METHODS: 3785 trauma patients (Mage = 64.2 years, SDage = 18.9 years, 50.5% female) completed questionnaires on physical, psychological, and role functioning across six measurement occasions during the first two years post-injury. The Injury Severity Score (ISS) was retrieved from the local trauma registry. Mixed graphical network models and cross-lagged network models were estimated to examine which items of recovery played a central role and were mostly related to other items in cross-sectional and longitudinal networks respectively. RESULTS: The cross-sectional networks showed especially strong interconnections between impairments of physical and role functioning and also within post-traumatic stress symptoms. The longitudinal networks extended these results by showing that pain, impaired mobility, limitations in self-care, anxiety/depressive symptoms, and several post-traumatic stress symptoms were strong predictors for impairments in functioning at later stages of recovery. CONCLUSION: Our findings showed that impairments in physical, psychological, and role functioning experienced by trauma patients are largely intertwined across the two years following injury. Monitoring physical impairments and psychological complaints early in recovery might help to more promptly provide the best fitting aftercare for trauma patients, which can improve recovery on the long-term.

Hepatic arterial infusion chemotherapy plus camrelizumab and apatinib for advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: There is limited information on combination of hepatic arterial infusion chemotherapy (HAIC) and systemic therapy for advanced hepatocellular carcinoma (Ad-HCC). We aim to compare the efficacy and safety of HAIC plus camrelizumab (a PD-1 inhibitor) and apatinib (an VEGFR-2 inhibitor) versus camrelizumab and apatinib for Ad-HCC. METHODS: From April 2019 to October 2022, 416 patients with Ad-HCC who received either HAIC plus camrelizumab and apatinib (TRIPLET protocol, n = 207) or camrelizumab and apatinib (C-A protocol, n = 209) were reviewed retrospectively. The propensity score matching (PSM) was used to reduce selective bias. Overall survival (OS) and progression-free survival (PFS) were compared using the Kaplan-Meier method with the log-rank test. Cox regression analyses of independent prognostic factors were evaluated. RESULTS: After PSM 1:1, 109 patients were assigned to two groups. The median OS of not reached in the TRIPLET group was significantly longer than that of 19.9 months in the C-A group (p < 0.001), while in the TRIPLET group, the median PFS of 11.5 months was significantly longer than that of 9.6 months in the C-A group (p < 0.001). Multivariate analyses showed that the factors significantly affected the OS were CTP grade, tumor number > 3, and TRIPLET treatment (p < 0.001). Grade 3/4 adverse events occurred at a rate of 82.1% vs. 71.3% in TRIPLET and C-A groups, respectively. CONCLUSION: The TRIPLET protocol has promising survival benefits in the management of patients with Ad-HCC, with acceptable safety. TRAIL REGISTRATION: The study has been retrospectively registered at Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ , ChiCTR2300075828).

Bacillus suppresses nitrogen efficiency of soybean-rhizobium symbiosis through regulation of nitrogen-related transcriptional and microbial patterns.

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.

PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis. METHODS: Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches. RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer. CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.

SERENE ER Analysis Part 1-SERENE CD: Exposure-Response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients With Moderately to Severely Active Crohn Disease.

SERENE CD (NCT02065570) evaluated whether a higher adalimumab induction dose would improve patients with Crohn disease response and suggested a flat dose-response relationship for efficacy in the induction study. We investigated exposure-response relationships in induction and maintenance studies considering patients' baseline characteristics. Adalimumab exposures were simulated using the established population pharmacokinetic model. Efficacy end points (clinical remission/endoscopic response) at Weeks 4, 12, and 56 were evaluated in exposure-response analyses using multivariable logistic regression. Analyses showed an increasing trend with heterogeneity between induction regimens, which suggested that average concentration has an impact on coprimary efficacy end points within each group, but data did not fit a single-response curve. Although higher concentrations within arms were associated with improved outcomes, increasing the concentration through a higher induction dose was not associated with increasing clinical remission/endoscopic response at Week 4/12. A model including inverse effective clearance eliminated heterogeneity and described trends across induction regimens with a single curve. In the maintenance study, the response rates at Week 56 showed no heterogeneity. In the induction study, patients with lower effective adalimumab clearance responded better, whereas in the maintenance study average concentration drove primary efficacy end points at Week 56. Research extending these findings to other indications is needed.

The bidirectional relationship between peer relationships and bullying: Evidence from cross-lagged analyses among Chinese children.

BACKGROUND: In the digital age, bullying manifests in two distinct forms: traditional bullying and cyberbullying. Children's peer relationships are important predictors of bullying, and bullying in turn predicts peer relationships. However, few researchers have noted the bidirectional relationship between peer relationships and bullying. METHODS: The present study used a two-wave cross-lagged longitudinal design to fill this gap. The potential sex differences were also examined in this relationship. The sample consisted of 527 Chinese children aged 8 to 12 years (M = 9.69, SD = .96; 53.5% female). Participants completed peer nominations for peer acceptance, peer rejection and social dominance, as well as self-reports of traditional bullying and cyberbullying. RESULTS: Results showed that peer rejection at the first time point (T1) significantly and positively predicted traditional bullying perpetration, cyberbullying perpetration and cyberbullying victimization at the second time point (T2). Traditional bullying victimization at T1 significantly and negatively predicted peer acceptance and social dominance at T2. The results also revealed significant male and female differences. For instance, among boys, peer acceptance at T1 significantly and negatively predicted cyberbullying victimization at T2. In contrast, this relationship was not observed among girls. The present findings have important implications for understanding the cyclical relationship between peer relationships and bullying and providing practical guidance for improving peer relationships and reducing bullying.

SERENE ER Analysis Part 2 SERENE-UC: Exposure-response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients with Moderately to Severely Active Ulcerative Colitis.

SERENE UC (NCT02065622) evaluated whether a higher adalimumab induction regimen improved patients with ulcerative colitis (UC) response, but a flat dose-response relationship was found in the induction study. We investigated exposure-response (ER) relationships in induction and maintenance studies considering patients' baseline characteristics. Adalimumab exposures were simulated using the established population pharmacokinetic model. Multivariable logistic regressions were used to assess the efficacy endpoints (clinical remission, endoscopic remission, endoscopic improvement) at weeks 8 and 52. In the induction study, an increasing ER trend with heterogeneity between induction regimens was shown, suggesting average concentration (Cavg) had a significant impact on primary efficacy endpoints within each group. However, data were not described by a single ER curve. Using inverse effective clearance as the exposure metric described trends across induction regimens with a single curve. Patients with inherently lower effective adalimumab clearance responded better. The patient response rates at week 52 showed no heterogeneity. A short-term increase in adalimumab dose did not drive better responses for induction, and apparent ER relationships were better explained by patient-inherent lower clearance. Conversely, during maintenance up to week 52, increasing the concentration via dose translated to better responses more robustly. The ER findings for SERENE UC were consistent with SERENE CD.

Status of Research on Dental Caries during Pregnancy: A Biometric Exploration.

AIM: To describe the bibliometric characteristics of the state of scientific production on dental caries during pregnancy. MATERIALS AND METHODS: A bibliometric study with a sample of 408 publications indexed in the Scopus database, which were selected based on a search strategy that included logical operators and the term MESH. The Scival tool was used to analyze the metadata. RESULTS: Jamieson Lisa Marie is positioned as the author with the most publications, and Schroth Robert as the one with the best-weighted impact (FWCI: 37.7). High-impact journals such as BMC Oral Health, Journal of Dental Research, and BMC Public Health stand out for their productivity and an average number of citations. The United States has a large number of publications and evidence of networks of scientific activity with Australia, Canada, and Brazil. The University of Adelaide leads the production and the work of two Latin American institutions (Universidade de São Paulo and Universidade Federal do Maranhão) stands out. International collaboration has improved during the study period. CONCLUSION: Scientific production on dental caries during pregnancy is increasingly published in high-impact journals, with growing international collaboration. The United States leads in publications, while Australian institutions are the most productive in this field. CLINICAL SIGNIFICANCE: Caries during pregnancy is a problem that has an important impact on maternal and perinatal health; thus, its timely management and prevention are important areas of research in the field of oral health. How to cite this article: Muñoz-Hidalgo M, Verastegui-Cabanillas Y, Barja-Ore J. Status of Research on Dental Caries during Pregnancy: A Biometric Exploration. J Contemp Dent Pract 2024;25(4):386-391.

Mapping and assessment of groundwater pollution risks in the main aquifer of the Mostaganem plateau (Northwest Algeria): utilizing the novel vulnerability index and decision tree model.

Water plays a pivotal role in socio-economic development in Algeria. However, the overexploitations of groundwater resources, water scarcity, and the proliferation of pollution sources (including industrial and urban effluents, untreated landfills, and chemical fertilizers, etc.) have resulted in substantial groundwater contamination. Preserving water irrigation quality has thus become a primary priority, capturing the attention of both scientists and local authorities. The current study introduces an innovative method to mapping contamination risks, integrating vulnerability assessments, land use patterns (as a sources of pollution), and groundwater overexploitation (represented by the waterhole density) through the implementation of a decision tree model. The resulting risk map illustrates the probability of contamination occurrence in the substantial aquifer on the plateau of Mostaganem. An agricultural region characterized by the intensive nutrients and pesticides use, the significant presence of septic tanks, widespread illegal dumping, and a technical landfill not compliant with environmental standards. The critical situation in the region is exacerbated by excessive groundwater pumping surpassing the aquifer's natural replenishment capacity (with 115 boreholes and 6345 operational wells), especially in a semi-arid climate featuring limited water resources and frequent drought. Vulnerability was evaluated using the DRFTID method, a derivative of the DRASTIC model, considering parameters such as depth to groundwater, recharge, fracture density, slope, nature of the unsaturated zone, and the drainage density. All these parameters are combined with analyses of inter-parameter relationship effects. The results show a spatial distribution into three risk levels (low, medium, and high), with 31.5% designated as high risk, and 56% as medium risk. The validation of this mapping relies on the assessment of physicochemical analyses in samples collected between 2010 and 2020. The results indicate elevated groundwater contamination levels in samples. Chloride exceeded acceptable levels by 100%, nitrate by 71%, calcium by 50%, and sodium by 42%. These elevated concentrations impact electrical conductivity, resulting in highly mineralized water attributed to anthropogenic agricultural pollution and septic tank discharges. High-risk zones align with areas exhibiting elevated nitrate and chloride concentrations. This model, deemed satisfactory, significantly enhances the sustainable management of water resources and irrigated land across various areas. In the long term, it would be beneficial to refine "vulnerability and risk" models by integrating detailed data on land use, groundwater exploitation, and hydrogeological and hydrochemical characteristics. This approach could improve vulnerability accuracy and pollution risk maps, particularly through detailed local data availability. It is also crucial that public authorities support these initiatives by adapting them to local geographical and climatic specificities on a regional and national scale. Finally, these studies have the potential to foster sustainable development at different geographical levels.

The predictive capability of several anthropometric indices for identifying the risk of metabolic syndrome and its components among industrial workers.

Metabolic syndrome (MetS) is closely associated with adverse cardiometabolic outcomes. The objective of this study was to identify practical methods that could enable the effective identification of MetS based on anthropometric indices. The basis of our study involved retrospective database obtained from routine medical prophylactic examinations. This was a cross-sectional study on the health status of male workers employed in hazardous working conditions at industrial enterprises in the Ural region conducted in 2019. A total of 347 male workers employed under hazardous working conditions were investigated. The presence of MetS was established by a healthcare professional in accordance with the guidelines of the International Diabetes Federation (IDF). Simple linear regression was used to evaluate the associations between anthropometric indices and MetS incidence. Logistic regression was used to determine the odds ratios of MetS in relation to increases in anthropometric indices. ROC curves were calculated to compare the ability of each anthropometric index to predict MetS and to determine the diagnostic thresholds of the indicators considered. According to the IDF criteria, 36.3% of the workers had MetS. A direct relationship was found between the individual components of MetS and the anthropometric indices studied. The highest OR was shown by the Body Roundness Index (BRI) of 2.235 (95% CI 1.796-2.781). For different age quartiles, the optimal cut-off values for predicting MetS were as follows: BRI, 4.1-4.4 r.u.; body shape index (ABSI), 0.080-0.083 m11/6 kg-2/3; and lipid accumulation product (LAP), 49.7-70.5 cm mmol/l. The most significant associations with MetS were observed where the values were greater than these cut-off points (Se = 97.4%). The results of this study demonstrated the rapid use of new anthropometric indicators, which have shown good predictive ability and are quite easy to use.

Development of Promising Interventions to Improve Human Papillomavirus Vaccination in a School-Based Program in Quebec, Canada: Results From a Formative Evaluation Using a Mixed Methods Design.

BACKGROUND: Despite the availability of school-based human papillomavirus (HPV) vaccination programs, disparities in vaccine coverage persist. Barriers to HPV vaccine acceptance and uptake include parental attitudes, knowledge, beliefs, and system-level barriers. A total of 3 interventions were developed to address these barriers: an in-person presentation by school nurses, an email reminder with a web-based information and decision aid tool, and a telephone reminder using motivational interviewing (MI) techniques. OBJECTIVE: Here we report on the development and formative evaluation of interventions to improve HPV vaccine acceptance and uptake among grade 4 students' parents in Quebec, Canada. METHODS: In the summer of 2019, we conducted a formative evaluation of the interventions to assess the interventions' relevance, content, and format and to identify any unmet needs. We conducted 3 focus group discussions with parents of grade 3 students and nurses. Interviews were recorded, transcribed, and analyzed for thematic content using NVivo software (Lumivero). Nurses received training on MI techniques and we evaluated the effect on nurses' knowledge and skills using a pre-post questionnaire. Descriptive quantitative analyses were carried out on data from questionnaires relating to the training. Comparisons were made using the proportions of the results. Finally, we developed a patient decision aid using an iterative, user-centered design process. The iterative refinement process involved feedback from parents, nurses, and experts to ensure the tool's relevance and effectiveness. The evaluation protocol and data collection tools were approved by the CHU (Centre Hospitalier Universitaire) de Québec Research Ethics Committee (MP-20-2019-4655, May 16, 2019). RESULTS: The data collection was conducted from April 2019 to March 2021. Following feedback (n=28) from the 3 focus group discussions in June 2019, several changes were made to the in-person presentation intervention. Experts (n=27) and school nurses (n=29) recruited for the project appreciated the visual and simplified information on vaccination in it. The results of the MI training for school nurses conducted in August 2019 demonstrated an increase in the skills and knowledge of nurses (n=29). School nurses who took the web-based course (n=24) filled out a pretest and posttest questionnaire to evaluate their learning. The rating increased by 19% between the pretest and posttest questionnaires. Several changes were made between the first draft of the web-based decision-aid tool and the final version during the summer of 2019 after an expert consultation of experts (n=3), focus group participants (n=28), and parents in the iterative process (n=5). More information about HPV and vaccines was added, and users could click if more detail is desired. CONCLUSIONS: We developed and pilot-tested 3 interventions using an iterative process. The interventions were perceived as potentially effective to increase parents' knowledge and positive attitudes toward HPV vaccination, and ultimately, vaccine acceptance. Future research will assess the effectiveness of these interventions on a larger scale.

Sodium valproate effects on the morphological and neurobehavioral phenotype of zebrafish.

The anticonvulsant sodium valproate (SV) is frequently administered as a medicament but bears several negative effects in case of exposure during development. We analyzed extensively these early development effects of using the zebrafish model. Zebrafish embryos were exposed as eggs to two sublethal concentrations of SV, 10 and 25mg/L. A general embryo toxicity analysis revealed extended anomalies in the cardiovascular system, and in the craniofacial and the spinal skeleton, as well as high mortality, in the embryos exposed to SV. The teratogenic potential of SV was confirmed in hacthed larvae by morphometric and cartilage profile analysis. Last, neurobehavioral impairments due to SV were highlighted in subjects' activity, anxiety, response to stimulations, habituation learning, and daily synchronization of locomotor activity, overall mirroring typical phenotypes associated with autistic spectrum disorders. In conclusion, our results confirmed the presence of extended and multifaced impacts of exposure to SV during development.

Clinical and patient-level predictors of procedure and tooth survival after direct pulp capping.

BACKGROUND: Historical reports of unpredictable outcomes associated with vital pulpal therapies, particularly direct pulp capping (DPC), have contributed to clinicians' skepticism of the procedure. Contemporary reports highlight more predictable outcomes of vital pulpal therapies, inclusive of DPC. There is a dearth of reported patient-centered outcomes of these procedures. METHODS: Insurance claims were used in an observational, retrospective cohort study to evaluate outcomes of DPC performed on permanent teeth. Statistical analyses included Kaplan-Meier survival estimates and Cox proportional hazards regression. Log-rank tests were used to evaluate unadjusted differences in survival. Cox proportional hazard regression was used to evaluate the adjusted hazard of adverse event occurrence. RESULTS: The analytic cohort included 4,136 teeth from 3,716 patients. DPC procedures were identified in public-payer (85.5%) and private-payer (13.4%) insurance claims databases. After DPC, procedure survival rate was 83% and tooth survival rate was 93% during a mean follow-up time of 52 months. Molar tooth type, same-day permanent restoration placement, and amalgam restoration type were significant positive predictors of procedure (DPC) survival. Age was not a statistically significant predictor of procedure survival after controlling for tooth type, gender, time to restoration, and restoration type. Nonmolar tooth type and younger age were significant positive predictors of tooth survival after DPC. Failures were most likely to occur within the first year. CONCLUSIONS: DPC has favorable patient-centered outcomes and contributes to long-term tooth survival. PRACTICAL IMPLICATIONS: The favorable patient-centered outcomes of DPC bolster calls to consider cost-effectiveness and access to care for endodontic procedures.

A pharmacovigilance study of chronic kidney disease in diabetes mellitus patients with statin treatment by using the US Food and Drug Administration adverse event reporting system.

Background: Statins were regarded as a main medication for managing hypercholesterolemia. Administration of statin therapy could reduce the incidence of cardiovascular disease in individuals diagnosed with type 2 diabetes mellitus (DM), which was recognized by multipal clinical guidelines. But previous studies had conflicting results on whether the long-term use of statins could benefit the renal function in diabetic patients. Aim: To evaluate the association between statin treatment and Chronic Kidney Disease in DM patients. Methods: This is a retrospective disproportionality analysis and cohort study based on real-world data. All DM cases reported in US Food and Drug Administration adverse event reporting system (FAERS) between the first quarter of 2004 and the fourth quarter of 2022 were included. Disproportionality analyses were conducted by estimating the reporting odds ratio (ROR) and the information component (IC). We further compared the CKD odds ratio (OR) between the statins group and the other primary suspected drug group among the included diabetes mellitus cases. Results: We finally included 593647 DM cases from FAERS, 5113 (5.31%) CKD cases in the statins group and 8810 (1.77%) CKD cases in the control group. Data analysis showed that the statins group showed a significant CKD signal (ROR: 3.11, 95% CI: 3.00-3.22; IC: 1.18, 95% CI: 1.07-1.29). In case group with two or more statins treatment history, the CKD signal was even stronger (ROR: 19.56, 95% CI: 18.10-21.13; IC: 3.70, 95% CI:3.44-3.93) compared with cases with one statin treatment history. Conclusion: The impact of statin therapy on the progression of renal disease in individuals diagnosed with type 2 diabetes mellitus (DM) remains inconclusive. After data mining on the current FAERS dataset, we discovered significant signals between statin treatment and CKD in diabetic patients. Furthermore, the incidence rate of CKD was higher among DM patients who used statins compared to those who did not.

Survival and pulmonary function in stage IA non-small cell lung cancer after sublobar resection versus lobectomy: An updated meta-analysis.

Traditionally, lobectomy was standard for stage IA non-small-cell lung cancer (NSCLC). Recent RCTs suggest sublobar resection's comparable outcomes. Our meta-analysis, incorporating 30 studies (including four RCTs), assessed sublobar resection's efficacy. Employing a random-effects model and I2 statistics for heterogeneity, we found sublobar resection reduced DFS (HR 1.31, p < 0.01) and OS (HR 1.27, p < 0.01) overall. However, RCT subgroup analysis showed no significant differences in DFS (p = 0.28) or OS (p = 0.62). Sublobar resection is a viable option for well-selected patients.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting over 300,000 people worldwide. It is characterized by the progressive decline of the nervous system that leads to the weakening of muscles which impacts physical function. Approximately, 15% of individuals diagnosed with ALS have a known genetic variant that contributes to their disease. As therapies that slow or prevent symptoms continue to develop, such as antisense oligonucleotides, it is important to discover novel genes that could be targets for treatment. Additionally, as cohorts continue to grow, performing analyses in ALS subtypes, such as primary lateral sclerosis (PLS), becomes possible due to an increase in power. These analyses could highlight novel pathways in disease manifestation. METHODS: Building on our previous discoveries using rare variant association analyses, we conducted rare variant burden testing on a substantially larger multi-ethnic cohort of 6,970 ALS patients, 166 PLS patients, and 22,524 controls. We used intolerant domain percentiles based on sub-region Residual Variation Intolerance Score (subRVIS) that have been described previously in conjunction with gene based collapsing approaches to conduct burden testing to identify genes that associate with ALS and PLS. RESULTS: A gene based collapsing model showed significant associations with SOD1, TARDBP, and TBK1 (OR = 19.18, p = 3.67 × 10-39; OR = 4.73, p = 2 × 10-10; OR = 2.3, p = 7.49 × 10-9, respectively). These genes have been previously associated with ALS. Additionally, a significant novel control enriched gene, ALKBH3 (p = 4.88 × 10-7), was protective for ALS in this model. An intolerant domain-based collapsing model showed a significant improvement in identifying regions in TARDBP that associated with ALS (OR = 10.08, p = 3.62 × 10-16). Our PLS protein truncating variant collapsing analysis demonstrated significant case enrichment in ANTXR2 (p = 8.38 × 10-6). CONCLUSIONS: In a large multi-ethnic cohort of 6,970 ALS patients, collapsing analyses validated known ALS genes and identified a novel potentially protective gene, ALKBH3. A first-ever analysis in 166 patients with PLS found a candidate association with loss-of-function mutations in ANTXR2.

Identification and functional analysis of a deduced geraniol synthase from Camphora officinarum.

The market demand for essential oil containing citral is increasing. Our research group identified a rare chemotype of Camphora officinarum whose leaves are high in citral content by examining over 1000 wild trees across the entire native distribution area of C. officinarum in China. Because C. officinarum is suitable for large-scale cultivation, it is therefore seen as a promising source of natural citral. However, the molecular mechanism of citral biosynthesis in C. officinarum is poorly understood. In this study, transcriptomic analyses of C. officinarum with different citral contents revealed a strong positive correlation between the expression of a putative geraniol synthase gene (CoGES) and citral content. The CoGES cDNA was cloned, and the CoGES protein shared high similarity with other monoterpene synthases. Enzymatic assays of CoGES with geranyl diphosphate (GPP) as substrate yielded geraniol as the single product, which is the precursor of citral. Further transient expression of CoGES in Nicotiana benthamiana resulted in a higher relative content of geranial and the appearance of a new substance, neral. These findings indicate that CoGES is a geraniol synthase-encoding gene, and the encoded protein can catalyze the transformation of GPP into geraniol, which is further converted into geranial and neral through an unknown mechanism in vivo. These findings expand our understanding of citral biosynthesis in Lauraceae plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01463-4.

Significant increase in the number of occupational exposures reported to the Dutch Poisons Information Centre (2016-2022): the importance of poison centre data in health surveillance.

INTRODUCTION: Exposure to hazardous substances in the workplace can result in injuries and fatalities. This study aimed to investigate the characteristics and trend of occupational exposures reported to the Dutch Poisons Information Centre and to investigate whether the COVID-19 pandemic had an impact on the trend. METHODS: A retrospective analysis of all acute occupational exposures reported to the Dutch Poisons Information Centre between 1 January 2016 and 31 December 2022 was performed. Data on patient and exposure characteristics, symptoms and treatment recommendations were analyzed. RESULTS: Between 2016 and 2022, the Dutch Poisons Information Centre received 5,508 calls regarding acute occupational exposures. The annual number of calls on acute occupational exposures almost doubled over the years studied (from 475 in 2016 to 936 in 2022). During and after the COVID-19 pandemic (March 2020-December 2022), the number of calls stabilized, but the upward trend was not significantly affected. There were an estimated 0.20 calls per 1,000 human exposure calls per month (95 per cent confidence interval: -0.14; 0.53). Victims were often exposed through multiple routes, with inhalation being the most common route (44 per cent), followed by ocular (32 per cent) and dermal contact (30 per cent). Acids (1,138 exposures) and alkalis (912 exposures) were often involved. The Dutch Poisons Information Centre had information on 6,334 patients, although the total number of exposed patients was not known as some victims did not seek medical assistance, or were treated by healthcare professionals who did not consult our Centre. At the time of contact, 13 per cent (n = 795) of the patients reported no symptoms, 76 per cent (n = 4,805) reported mild to moderate symptoms and 3 per cent (n = 183) reported potentially severe symptoms. Information on symptoms was missing for 9 per cent (n = 551) of the patients. Hospital observation and treatment were recommended for 5 per cent (n = 325) of the patients. DISCUSSION: This study highlights the necessity for poisoning prevention strategies to reduce the number of work-related incidents involving hazardous substances. CONCLUSION: The continuing increase in the number of workplace incidents involving hazardous substances is of concern. A comprehensive and multidisciplinary approach should be taken to gain a full understanding of occupational exposure to hazardous substances and to identify risk factors.