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1.
Artigo em Inglês | MEDLINE | ID: mdl-39256069

RESUMO

The aim of this study was to assess the prognostic value of the weight loss percentage (WLP) over the 2 years pre-treatment for operated patients with advanced oral squamous cell carcinoma (OSCC). This cohort study included 506 operated patients who were diagnosed with advanced primary OSCC between October 2001 and March 2022, and who were followed up until July 2022. Fine-Gray models, marginal structural models with stabilized inverse probability of treatment weighting, and Cox proportional hazards models were utilized to evaluate the prognostic significance of pre-treatment WLP for disease-specific survival (DSS). The median follow-up time was 32.6 months (interquartile range 13.0-71.6 months). A high pre-treatment WLP (>9.23%) was significantly associated with worse DSS (multivariate Fine-Gray model: hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.29-3.22, P = 0.002; multivariate Cox: HR 2.01, 95% CI 1.28-3.16, P = 0.002). In the weighted cohort, a similar association pattern was observed (marginal structural model: HR 2.26, 95% CI 1.28-3.98, P = 0.005; multivariate Cox: HR 2.28, 95% CI 1.38-3.76, P = 0.001). In subgroup analyses, high WLP could predict worse DSS among patients with buccal mucosa/other cancer sites (not including the oral tongue), moderate tumor differentiation, and larger cancer size (>1.8 cm) (all P < 0.05). Pre-treatment WLP over 2 years might be a useful tool to predict the prognosis of operated patients with advanced OSCC.

4.
Zhonghua Yi Xue Za Zhi ; 104(34): 3171-3174, 2024 Sep 03.
Artigo em Chinês | MEDLINE | ID: mdl-39193604

RESUMO

Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.


Assuntos
Colecistectomia , Doenças da Vesícula Biliar , Pólipos , Humanos , Pólipos/cirurgia , Doenças da Vesícula Biliar/cirurgia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/cirurgia
5.
Zhonghua Yi Shi Za Zhi ; 54(3): 184-187, 2024 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-38987011

RESUMO

In 1934-1945, Guangxi Provincial Medical College continued to actively conducting scientific research and achieved fruitful results The research areas included medicine and pharmacy, with at least 43 research projects implemented and at least 130 research outputs. These achievements were made in a variety of ways, such as papers, monographs, compilations, anthologies, pharmaceutical products, diagnostic techniques, and instruments for therapy. Some of the achievements were awarded, and some others were widely applied clinically, contributing to the prevention and treatment of war injuries and the protection of people's health.


Assuntos
Faculdades de Medicina , História do Século XX , China , Faculdades de Medicina/história
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(2): 213-219, 2024 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-38413059

RESUMO

Objective: To analyze the spatial-temporal epidemiological characteristics of pertussis from 2013 to 2022 in Hebei Province and to provide a reference for improving prevention and control measures. Methods: Based on the data of pertussis reported in Hebei Province during 2013-2022 to analyze the popular characteristic, the ArcGIS 10.8 software was used to construct a ring map and to perform spatial autocorrelation analysis; the SaTScan 10.1 software was used for spatial-temporal scan statistics. Results: There were 6 715 cases of the cumulative report in Hebei Province from 2013 to 2022 without death. The annual report incidence was 0.90/100 000. The overall incidence rate showed an upward trend from 2013 to 2019, and during 2020-2021, it showed a sharp decline, but in 2022, it showed a sharp increase. Summer and autumn are the peak seasons of the epidemic. The incidence was highest in age group <1 year (48.67%), and the lowest age group in age group ≥15 years (0.45%) and mainly scattered children (78.03%); the incidence about men is higher than women. Spatial autocorrelation analysis showed that the onset of pertussis has spatial clustering, and high-high clusters were found in Langfang, Baoding, and Cangzhou, the top three countries with reported incidence. The area covered by a low-low cluster was consistent with the distribution of the corresponding low-incidence areas in this study. Space-time scan detects five statistically significant areas, and three zones were concentrated in 2022. Conclusions: The incidence of pertussis in Hebei had obvious season, population, and area-specific differences. There was obvious spatiotemporal and clustering, so the control of key areas should target the characteristics of time and space.


Assuntos
Coqueluche , Criança , Masculino , Humanos , Feminino , Adolescente , Análise Espaço-Temporal , Coqueluche/epidemiologia , Análise Espacial , Incidência , Análise por Conglomerados , China/epidemiologia
9.
Zhonghua Yi Xue Za Zhi ; 104(1): 5-9, 2024 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-38178761

RESUMO

With the further understanding of the concept of three-dimensional correction by spinal surgeons, the progress of internal fixation instruments, de-rotation tools and the improvement of surgical techniques, the scientific formulation of surgical strategies for Lenke 5 adolescent idiopathic scoliosis has gradually become the focus of controversy. The formulation of preoperative surgical strategy not only directly affects the correction of deformity and balance reconstruction, but also is directly related to the activity function of spine and the quality of life of patients after operation. Therefore, this paper will discuss from three aspects: the method of surgical fixation, the surgical approach and the selection of fixed vertebrae. The author believes that Risser sign should be taken as an important consideration to judge the method of surgical fixation. The choice of surgical approach must refer to the operator's familiarity and experience with the approach, grasp the adaptive signs and consider the risks and benefits of the operation, and choose the appropriate surgical approach according to the needs of different patients. The choice of fixed vertebrae, choosing upper end vertebra (UEV) as upper instrumented vertebra (UIV), is safer than the more radical upper end vertebra-1 (UEV-1), and five factors need to be combined in the specific selection of lower instrumented vertebra (LIV).


Assuntos
Cifose , Escoliose , Fusão Vertebral , Humanos , Adolescente , Escoliose/cirurgia , Qualidade de Vida , Vértebras Torácicas/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos , Radiografia , Cifose/cirurgia , Vértebras Lombares/cirurgia , Resultado do Tratamento , Seguimentos
10.
Hernia ; 28(2): 301-319, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37715026

RESUMO

PURPOSE: Incisional hernia (IH) post renal transplant (RT) is relatively uncommon and can be challenging to manage clinically due to the presence of the kidney graft and patient immunosuppression. This systematic review and meta-analysis synthesises the current literature in relation to IH rates, risk factors and outcomes post RT. METHODS: PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials (CENTRAL) were searched up to July 2023. The most up to date Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines were followed. Pertinent clinical information was synthesised. A meta-analysis of the pooled proportions of IH rates, the rates of patients requiring surgical repair and the rates of recurrence post RT are reported. RESULTS: Twenty studies comprising 16,018 patients were included in this analysis. The pooled rate of IH occurrence post RT was 4% (CI 3-5%). The pooled rate of IH repair post RT was 61% (CI 14-100%). The pooled rate of IH recurrence after repair was 16% (CI 9-23%). Risk factors identified for IH development post RT are BMI, immunosuppression, age, smoking, incision type, reoperation, concurrent abdominal wall hernia, lymphocele formation and pulmonary disease. CONCLUSIONS: IH post RT is uncommon and the majority of IH post RT are repaired surgically on an elective basis.


Assuntos
Hérnia Ventral , Hérnia Incisional , Transplante de Rim , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Transplante de Rim/efeitos adversos , Herniorrafia/efeitos adversos , Hérnia Ventral/complicações , Rim
11.
J Dent Res ; 103(1): 51-61, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37950483

RESUMO

Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.


Assuntos
Proteínas do Esmalte Dentário , Proteína HMGN1 , Proteína HMGN2 , Animais , Camundongos , Ameloblastos/metabolismo , Proteína HMGN2/genética , Proteína HMGN2/metabolismo , Proteína HMGN1/genética , Proteína HMGN1/metabolismo , Epigênese Genética , Diferenciação Celular/genética , Proteínas HMGN/genética , Proteínas HMGN/metabolismo , Fatores de Transcrição/metabolismo , Proteínas do Esmalte Dentário/genética , Proteínas do Esmalte Dentário/metabolismo , Cromatina/metabolismo , Amelogenina/metabolismo
12.
Appl Biochem Biotechnol ; 196(1): 537-557, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37155003

RESUMO

The technological development for efficient nutrient removal from liquid dairy manure is critical to a sustainable dairy industry. A nutrient removal process using a two-step fed sequencing batch reactor (SBR) system was developed in this study to achieve the applicability of simultaneous removal of phosphorus, nitrogen, and chemical oxygen demand from anaerobically digested liquid dairy manure (ADLDM). Three operating parameters, namely anaerobic time:aerobic time (min), anaerobic DO:aerobic DO (mg L-1), and hydraulic retention time (days), were systematically investigated and optimized using the Taguchi method and grey relational analysis for maximum removal efficiencies of total phosphorus (TP), ortho-phosphate (OP), ammonia-nitrogen (NH3-N), total nitrogen (TN), and chemical oxygen demand (COD) simultaneously. The results demonstrated that the optimal mean removal efficiencies of 91.21%, 92.63%, 91.82%, 88.61%, and 90.21% were achieved for TP, OP, NH3-N, TN, and COD at operating conditions, i.e., anaerobic:aerobic time of 90:90 min, anaerobic DO:aerobic DO of 0.4:2.4 mg L-1, and HRT of 3 days. Based on analysis of variance, the percentage contributions of these operating parameters towards the mean removal efficiencies of TP and COD were ranked in the order of anaerobic DO:aerobic DO > HRT > anaerobic time:aerobic time, while HRT was the most influential parameter for the mean removal efficiencies of OP, NH3-N, and TN followed by anaerobic time:aerobic time and anaerobic DO:aerobic DO. The optimal conditions obtained in this study are beneficial to the development of pilot and full-scale systems for simultaneous biological removal of phosphorus, nitrogen, and COD from ADLDM.


Assuntos
Esterco , Eliminação de Resíduos Líquidos , Eliminação de Resíduos Líquidos/métodos , Esterco/análise , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos , Fósforo , Fosfatos , Nitrogênio
13.
Zhonghua Xin Xue Guan Bing Za Zhi ; 51(9): 951-957, 2023 Sep 24.
Artigo em Chinês | MEDLINE | ID: mdl-37709711

RESUMO

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ2=0.277, P=0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P=0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P=0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P=0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.


Assuntos
Fibrilação Atrial , Ablação por Cateter , AVC Isquêmico , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Fibrilação Atrial/cirurgia , Estudos Transversais , Seguimentos , Estudos Retrospectivos , Anticoagulantes/uso terapêutico
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 44(9): 1426-1433, 2023 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-37743277

RESUMO

Objective: To explore the association between internet use and healthy lifestyles in urban adults. Methods: From May to August, 2022, a face-to-face questionnaire survey was conducted in residents aged 18-64 years selected in the urban area of Hangzhou by integrated cluster stratified random sampling and Kish grid method. The information about internet use included the internet use time in the past 7 days and 12 kinds of internet use contents. Using factor analysis and K-means clustering, three types of internet use were summarized, i.e. general type, video game type and working/learning type. Healthy lifestyles were defined as active physical activity, healthy diet habit, non-smoking, non-drinking, healthy weight, and healthy waist circumference. The correlations between internet use and healthy lifestyles were evaluated by using binary logistic regression and multinomial logistic regression analyses. Results: A total of 1 624 participants were included. After adjusting for potential confounding factors, the longer internet use time group (≥8.5 h/d) was less likely to have healthy weight (OR=0.59, 95%CI:0.41-0.85) and 5-6 healthy lifestyles (OR=0.55, 95%CI: 0.32-0.96) compared with those with shorter internet use time group (<2.5 h/d). For different types of internet use, it was found that compared with working/learning type group, the general type group was less likely to have healthy diet habits (OR=0.63, 95%CI: 0.46-0.86), non-drinking (OR=0.68, 95%CI: 0.47-0.99), healthy waist circumference (OR=0.59, 95%CI: 0.42-0.84) and 5-6 healthy lifestyles (OR=0.40, 95%CI: 0.23-0.69), the video game type group was less likely to have active physical activity (OR=0.73, 95%CI: 0.55-0.97) and healthy diet habits (OR=0.79, 95%CI: 0.62-0.99). Conclusion: Too long internet use (≥8.5 h/d), general type and video game type of internet use were associated with unhealthy lifestyles.


Assuntos
Estilo de Vida Saudável , Uso da Internet , Humanos , Adulto , Dieta Saudável , China/epidemiologia , Estilo de Vida
15.
Zhonghua Nei Ke Za Zhi ; 62(9): 1085-1092, 2023 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-37650182

RESUMO

Objective: To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification. Methods: Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC). Results: A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95%CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions: There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Diabetes Mellitus Tipo 1/diagnóstico , Peptídeo C , Consenso , População do Leste Asiático , Estudos Retrospectivos , Autoanticorpos
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 57(8): 1164-1170, 2023 Aug 06.
Artigo em Chinês | MEDLINE | ID: mdl-37574307

RESUMO

Conventional wisdom holds that the onset of chronic obstructive pulmonary disease (COPD) is usually in older people. However, with extended follow-up in large cohort studies, the trajectory of lung function development has been gradually delineated, indicating that the decline of lung function may originate early in life. In addition, a large number of studies have shown that people with chronic respiratory symptoms, pulmonary imaging changes and abnormal lung physiology, but not in line with pulmonary function diagnosis of COPD, tend to develop COPD in the future and may have a worse prognosis, suggesting the necessity of early intervention. The GOLD 2022 report proposes a series of terms related to COPD, including COPD in young people and pre-COPD, opening up new opportunities for the prevention, early diagnosis and treatment of COPD. These concepts also guide the study design of the biological mechanism of COPD and the trajectory of disease progression. This article reviews the research progress of COPD in young people and pre-COPD to attract more attention in clinical practice.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Adolescente , Pulmão , Estudos de Coortes , Projetos de Pesquisa
18.
Zhonghua Yi Xue Za Zhi ; 103(29): 2239-2245, 2023 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-37544760

RESUMO

Objective: To investigate the risk factors associated with the development of proximal junctional kyphosis (PJK) after posterior spinal fusion for in children with Lenke type 5 adolescent idiopathic scoliosis (AIS). Methods: It was a retrospective case-control study that included medical records of 98 children with Lenke type 5 AIS who underwent posterior orthopedic surgery under general anesthesia at the Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2013 to December 2018. There were 23 males and 75 females with a mean age of (14.5±2.2) years (10-18 years). Patients were divided into PJK and non-PJK groups according to whether the posterior junctional angle (PJA) was greater than 10° and increased for more than 10° from the preoperative period at the the last follow-up. Univariate analysis was used to analyze the correlation of general data of the children with occurrence of PJK after the operation. Multivariate logistic regression analysis was used to analyze the risk factors of postoperative PJK. Results: There were 35 cases in the PJK group and 63 cases in the non-PJK group. The PJK and non-PJK groups were followed up for (35.6±7.3) months and (36.4±7.5) months, respectively, and the difference was not statistically significant (P=0.637). There was no statistically significant difference between the two groups in general data such as gender, age, and body mass index (all P>0.05), while there were statistically significant differences between the two groups in upper instrumented vertebrea (UIV) location and junctional area posterior ligamentous complex (PLC) injury (all P<0.05). The results of univariate analysis showed that UIV location at T10-T12, junctional area PLC injury, preoperative coronal thoracic curve (TC), preoperative and final follow-up PJA, and preoperative and final follow-up pelvic incidence-lumbarlordosis (PI-LL) were correlated with postoperative PJK (OR=2.50, 5.37, 0.92, 1.12, 1.32, 1.06, 3.35, all P<0.05). Multifactorial logistic regression analysis showed that UIV located at T10-T12 (OR=2.346, 95%CI: 1.582-3.481, P=0.001), junctional area PLC injury (OR=5.112, 95%CI: 1.283-20.418, P=0.023) and last follow-up PI-LL (OR=1.826, 95%CI: 1.558-24.745, P=0.012) were risk factors for the occurrence of postoperative PJK in children with Lenke type 5 AIS. Conclusions: Postoperative UIV fixation to the thoracolumbar segment, PLC injury in the junctional area and excessive postoperative PI-LL in children with Lenke type 5 AIS may be the risk factors for the occurrence of PJK after the operation. It is suggested that avoidance of UIV selection to the thoracolumbar segment, intraoperative protection of the PLC located near the UIV and restoration of a good PI-LL relationship may reduce the incidence of PJK.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Masculino , Criança , Feminino , Humanos , Adolescente , Escoliose/cirurgia , Estudos Retrospectivos , Estudos de Casos e Controles , Cifose/cirurgia , Fusão Vertebral/efeitos adversos , Fatores de Risco , Complicações Pós-Operatórias , Vértebras Torácicas/cirurgia , Vértebras Lombares/cirurgia
19.
bioRxiv ; 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37503220

RESUMO

Elevated manganese (Mn) exposure is associated with attentional deficits in children, and is an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn exposure causes lasting attention and sensorimotor deficits in a rat model of early childhood Mn exposure, and that these deficits are associated with a hypofunctioning catecholaminergic system in the prefrontal cortex (PFC), though the mechanistic basis for these deficits is not well understood. To address this, male Long-Evans rats were exposed orally to Mn (50 mg/kg/d) over PND 1-21 and attentional function was assessed in adulthood using the 5-Choice Serial Reaction Time Task. Targeted catecholaminergic system and epigenetic gene expression, followed by unbiased differential DNA methylation and gene regulation expression transcriptomics in the PFC, were performed in young adult littermates. Results show that developmental Mn exposure causes lasting focused attention deficits that are associated with reduced gene expression of tyrosine hydroxylase, dopamine transporter, and DNA methyltransferase 3a. Further, developmental Mn exposure causes broader lasting methylation and gene expression dysregulation associated with epigenetic regulation, inflammation, cell development, and hypofunctioning catecholaminergic neuronal systems. Pathway enrichment analyses uncovered mTOR and Wnt signaling pathway genes as significant transcriptomic regulators of the Mn altered transcriptome, and Western blot of total, C1 and C2 phospho-mTOR confirmed mTOR pathway dysregulation. Our findings deepen our understanding of the mechanistic basis of how developmental Mn exposure leads to lasting catecholaminergic dysfunction and attention deficits, which may aid future therapeutic interventions of environmental exposure associated disorders. Significance Statement: Attention deficit hyperactivity disorder (ADHD) is associated with environmental risk factors, including exposure to neurotoxic agents. Here we used a rodent model of developmental manganese (Mn) exposure producing lasting attention deficits to show broad epigenetic and gene expression changes in the prefrontal cortex, and to identify disrupted mTOR and Wnt signaling pathways as a novel mechanism for how developmental Mn exposure may induce lasting attention and catecholaminergic system impairments. Importantly, our findings establish early development as a critical period of susceptibility to lasting deficits in attentional function caused by elevated environmental toxicant exposure. Given that environmental health threats disproportionately impact communities of color and low socioeconomic status, our findings can aid future studies to assess therapeutic interventions for vulnerable populations.

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