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BACKGROUND: The prevalence of autoimmune conditions is two-fold higher in women than in men, especially during the reproductive years. Autoimmune conditions have been associated with a greater risk of adverse pregnancy outcomes, and some conditions have been studied more than others with inconsistent findings. The objective of this umbrella review was to identify, appraise, synthesise, and consolidate findings from published systematic reviews of autoimmune conditions and adverse pregnancy outcomes. METHODS: In this umbrella review, we searched Medline, Embase, and Cochrane databases for systematic reviews from inception to Sept 30, 2022, without language restrictions. We used the Medical Subject Headings and free text search for autoimmune conditions and pregnancy outcomes. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data was extracted using a standardised form, which was piloted before use. Data were synthesised narratively and quantitatively. Odds ratios (ORs) with 95% CIs were reported. The protocol has been registered to PROSPERO (CRD42022334992). FINDINGS: We selected 33 reviews, which included 709 primary studies. Pregnant women with autoimmune conditions were at high risk of both adverse maternal and fetal outcomes. The risk of miscarriage was increased in pregnant women with Sjögren's syndrome (relative risk [RR] 8·85, 95% CI 3·10-25·26), systemic lupus erythematosus (SLE; OR 4·90, 95% CI 3·10-7·69), thyroid autoimmunity (OR 2·77, 2·10-3·65), systemic sclerosis (OR 1·60, 1·29-2·22), and coeliac disease (OR 1·38, 1·12-1·69). The risk of pre-eclampsia was increased in pregnant women with type 1 diabetes (T1DM; OR 4·19, 3·08-5·71) and SLE (OR 3·20, 2·54 - 4·20). The risk of gestational diabetes was increased in pregnant women with inflammatory bowel disease (IBD; OR 2·96, 1·47-5·98) and thyroid autoimmunity (OR 1·49, 1·07-2·07). The risk of intrauterine growth restriction (IUGR) was increased in pregnant women with systemic sclerosis (OR 3·20, 2·21-4·53) and coeliac disease (OR 1·71, 1·36-2·14). The risk of delivering a small-for-gestational age baby was increased in pregnant women with SLE (OR 2·49, 1·88-3·31) and rheumatoid arthritis (OR 1·49, 1·22-1·82). The risks of other fetal outcomes such as stillbirth, preterm birth, and low birthweight were also increased in pregnant women with autoimmune disorders. T1DM in women was associated with lower odds of small-for-gestational-age outcome (OR 0·68, 0·56-0·83). INTERPRETATION: Pregnant women with autoimmune conditions are at greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to post-natal care for women with autoimmune conditions. FUNDING: Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR).
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Doença Celíaca , Diabetes Mellitus Tipo 1 , Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Nascimento Prematuro , Escleroderma Sistêmico , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. METHODS: Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. RESULTS: Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren's syndrome RR 8.85 (95% CI 3.10-25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10-7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08-5.71) and SLE OR 3.20 (2.54-4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47-5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21-4.53) and coeliac disease OR 1.71 (1.36-2.14). Preterm birth was associated with T1DM OR 4.36 (3.72-5.12) and SLE OR 2.79 (2.07-3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54-7.80) and OR 3.80 (2.16-6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44-4.58), IBD OR 1.57 (1.03-2.38), and coeliac disease OR 1.57 (1.17-2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56-0.83). CONCLUSIONS: Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.
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Doenças Autoimunes , Doença Celíaca , Doença de Crohn , Diabetes Mellitus Tipo 1 , Doenças Inflamatórias Intestinais , Lúpus Eritematoso Sistêmico , Nascimento Prematuro , Escleroderma Sistêmico , Recém-Nascido , Gravidez , Lactente , Feminino , Humanos , Nascimento Prematuro/epidemiologia , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Escleroderma Sistêmico/epidemiologiaRESUMO
Accurate source localization of the epileptogenic zone (EZ) is the primary condition of surgical removal of EZ. The traditional localization results based on three-dimensional ball model or standard head model may cause errors. This study intended to localize the EZ by using the patient-specific head model and multi-dipole algorithms using spikes during sleep. Then the current density distribution on the cortex was computed and used to construct the phase transfer entropy functional connectivity network between different brain areas to obtain the localization of EZ. The experiment result showed that our improved methods could reach the accuracy of 89.27% and the number of implanted electrodes could be reduced by (19.34 ± 7.15)%. This work can not only improve the accuracy of EZ localization, but also reduce the additional injury and potential risk caused by preoperative examination and surgical operation, and provide a more intuitive and effective reference for neurosurgeons to make surgical plans.
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Epilepsia , Couro Cabeludo , Humanos , Mapeamento Encefálico/métodos , Epilepsia/diagnóstico , Eletroencefalografia/métodos , EncéfaloRESUMO
Osteoarthritis (OA) is a disease characterized by cartilage damage and abnormal remodeling of subchondral bone. Our previous study showed that in the early stage of OA, knee loading exerts protective effects by suppressing osteoclastogenesis through Wnt signaling, but little is known about loading effects at the late OA stage. Endoplasmic reticulum (ER) stress and autophagy are known to be involved in the late OA stage. We determined the effects of mechanical loading on ER stress and autophagy in OA mice. One hundred seventy-four mice were used for a surgery-induced OA model. In the first set of experiments, 60 mice were devoted to evaluation of the role of ER stress and autophagy in the development of OA. In the second set, 114 mice were used to assess the effect of knee loading on OA. Histologic, cellular, microcomputed tomography, and electron microscopic analyses were performed to evaluate morphologic changes, ER stress, and autophagy. Mechanical loading increased phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) and regulated expressions of autophagy markers LC3II/I and p62. Osteoarthritic mice also exhibited an elevated ratio of calcified cartilage to total articular cartilage (CC/TAC), and synovial hyperplasia with increased lining cells was found. At the early disease stage, subchondral bone plate thinning and reduced subchondral bone volume fraction (B.Ar/T.Ar) were observed. At the late disease stages, subchondral bone plate thickened concomitant with increased B.Ar/T.Ar. Mice subjected to mechanical loading exhibited resilience to cartilage destruction and a correspondingly reduced Osteoarthritis Research Society International score at 4 and 8 wk, as well as a decrease in synovitis and CC/TAC. While chondrocyte numbers in the OA group was notably decreased, mechanical loading restored chondrogenic differentiation. These results demonstrate that mechanical loading can retard the pathologic progression of OA at its early and late stages. The observed effects of loading are associated with the regulations of ER stress and autophagy.-Zheng, W., Li, X., Liu, D., Li, J., Yang, S., Gao, Z., Wang, Z., Yokota, H., Zhang, P. Mechanical loading mitigates osteoarthritis symptoms by regulating endoplasmic reticulum stress and autophagy.
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Autofagia , Estresse do Retículo Endoplasmático , Osteoartrite/metabolismo , Estresse Mecânico , Animais , Cartilagem Articular/metabolismo , Células Cultivadas , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Sequestossoma-1/metabolismoRESUMO
This study evaluated the effects of topical use of caffeine hydrogel on hypertrophic scar in a rabbit ear wound model. Nine rabbits were randomly divided into three groups: control group, caffeine hydrogel group, and matrix group. Punched defects were established on each rabbit's ear which resulted in a hypertrophic scar. When the wound epithelialization and scar hyperplasia could be seen, control group did not do any treatment, while caffeine hydrogel group and matrix group were treated with caffeine hydrogel and hydrogel matrix, respectively. After 3 weeks of administration, the general morphological changes of scar were observed, and the scar tissue of rabbit ears was stained with HE and Masson. The relative expressions of TGF ß-1, α-SMA, type I collagen, and type III collagen in scar tissue were detected by Western blot. In all three groups, findings showed that caffeine hydrogel can inhibit scar growth by reducing the expression of TGF ß-1, reducing the proliferation of fibroblasts, improving collagen arrangement and reducing collagen deposition. The overall study shows efficacy and mechanism of caffeine. It concluded that caffeine could be an effective therapeutic agent for hypertrophicscars.
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Queimaduras , Cicatriz Hipertrófica , Animais , Coelhos , Cicatriz Hipertrófica/patologia , Cafeína/farmacologia , Cafeína/metabolismo , Cafeína/uso terapêutico , Hidrogéis/uso terapêutico , Queimaduras/metabolismo , Colágeno/metabolismo , Fibroblastos/metabolismoRESUMO
Diabetic wound is one of the serious complications of diabetes, and the wound is persistent and easily recurring, which seriously endangers the health and life of patients. How to effectively promote the healing of diabetic wounds has been a hot spot and difficult area of clinical research. Some previous studies have shown that dihydromyricetin has the effects of regulating blood glucose, controlling the severity, and inhibiting scarring. In the present study, we used polylactic-co-glycolic acid nanoparticles as a carrier to load dihydromyricetin to make drug-loaded nanoparticles and applied them dropwise (200 µL) to diabetic mice wounds by topical application to observe the healing and scar formation of diabetic wounds. We found that the healing rate of the diabetic mice was faster and the scar formation was less obvious. In addition, the elevated blood glucose level and weight loss of the mice in the treatment group were also reduced. Therefore, nanoparticle-mediated dihydromyricetin may be an effective treatment for diabetic wounds.
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Diabetes Mellitus Experimental , Flavonóis , Nanopartículas , Cicatrização , Animais , Flavonóis/farmacologia , Flavonóis/uso terapêutico , Cicatrização/efeitos dos fármacos , Camundongos , Diabetes Mellitus Experimental/complicações , Masculino , Glicemia/metabolismo , Ácido Láctico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/químicaRESUMO
BACKGROUND: Bariatric surgery leads to considerable weight loss and improved glycaemic control and seems to have a favourable impact on diabetes related foot complications (DFC). OBJECTIVES: To assess the effect of bariatric surgery on diabetes related foot complications in patients with type 2 diabetes and determine whether DFC symptoms are improved after bariatric surgery. METHODS: We searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials. The primary outcome was the presence of DFC after bariatric surgery. The secondary outcome was the improvement of DFC after bariatric surgery among patients who already had DFC before surgery. RESULTS: There were nine studies showing the presence of DFC post bariatric surgery and six detailing the changes in DFC post bariatric surgery. Bariatric surgery was not associated with a lower risk of developing or worsening DFC compared to conventional medical treatment based on 4 randomised control trials (IR 0.87, 95 % CI, 0.26, 2.98), while from observational studies was associated with 51 % lower risk of DFC (IR 0.49, 95 % CI, 0.31, 0.77). Bariatric surgery was associated with improvement in diabetic neuropathy assessment parameters including toe tuning fork score, self-reported neuropathy symptoms, neuropathy symptom score, and neuropathy symptom profile. CONCLUSION: Bariatric surgery led to a greater reduction in developing or worsening DFC among patients with type 2 diabetes compared to medical treatment in observational studies, but not among RCTs. Bariatric surgery was associated with improvements in diabetic neuropathy related assessment parameters and symptoms. Bariatric surgery could be a promising treatment for patients with type 2 diabetes who are at high risk of DFC.
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Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Pé Diabético , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Pé Diabético/cirurgia , Pé Diabético/epidemiologia , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/etiologia , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Obesidade/complicações , Obesidade/cirurgia , Redução de Peso/fisiologiaRESUMO
BACKGROUND: Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. METHODS: All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. DISCUSSION: With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021272686.
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Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metanálise em Rede , Revisões Sistemáticas como Assunto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Idoso , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Projetos de PesquisaRESUMO
To investigate the distortion process of thin-walled box girders, three commonly used methods based on energy variational calculus and static balance analysis are optimized. A generalized analytical formula for box-girder distortion research is derived, and a fourth-order distortion control differential equation is obtained. Typical numerical examples are used to verify and compare the three methods. The results show that the value of distortional warping normal stress calculated by the optimized methods is slightly different from the literature values and that the maximum error between methods does not exceed 5.39%. The calculation results of Method 2 and Method 3 are similar. The values of the geometric distortion characteristics calculated by the three methods are related to the cross-sectional form of the box girder and the distortion analysis process, and the calculated values are not unique. The absolute value of the peak normal stress of distortion on the top plate of a thin-walled box girder with a cantilever plate is smaller than that on the bottom plate. Under a concentrated distortion load, the distribution of the distortion deformation along the length of a simply supported box girder with only end diaphragm is not consistent, and there is reverse deformation near the beam end.
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Epilepsy is a chronic brain disease with recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is the most common pathological cause of epilepsy. With the development of computer-aided diagnosis technology, there are many auxiliary diagnostic approaches based on deep learning algorithms. However, the causes of epilepsy are complex, and distinguishing different types of epilepsy accurately is challenging with a single mode of examination. In this study, our aim is to assess the combination of multi-modal epilepsy medical information from structural MRI, PET image, typical clinical symptoms and personal demographic and cognitive data (PDC) by adopting a multi-channel 3D deep convolutional neural network and pre-training PET images. The results show better diagnosis accuracy than using one single type of medical data alone. These findings reveal the potential of a deep neural network in multi-modal medical data fusion.
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Background: Diabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes. Methods: A systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052). Results: With trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99). Conclusion: Our results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Hipoglicemiantes/farmacologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Acarbose/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Insulina/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/uso terapêuticoRESUMO
OBJECTIVES: The use of medications among pregnant women has been rising over the past few decades but the reporting of polypharmacy has been sporadic. The objective of this review is to identify literature reporting the prevalence of polypharmacy among pregnant women, the prevalence of multimorbidity in women taking multiple medications in pregnancy and associated effects on maternal and offspring outcomes. DESIGN: MEDLINE and Embase were searched from their inception to 14 September 2021 for interventional trials, observational studies and systematic reviews reporting on the prevalence of polypharmacy or the use of multiple medications in pregnancy were included.Data on prevalence of polypharmacy, prevalence of multimorbidity, combinations of medications and pregnancy and offspring outcomes were extracted. A descriptive analysis was performed. RESULTS: Fourteen studies met the review criteria. The prevalence of women being prescribed two or more medications during pregnancy ranged from 4.9% (4.3%-5.5%) to 62.4% (61.3%-63.5%), with a median of 22.5%. For the first trimester, prevalence ranged from 4.9% (4.7%-5.14%) to 33.7% (32.2%-35.1%). No study reported on the prevalence of multimorbidity, or associated pregnancy outcomes in women exposed to polypharmacy. CONCLUSION: There is a significant burden of polypharmacy among pregnant women. There is a need for evidence on the combinations of medications prescribed in pregnancy, how this specifically affects women with multiple long-term conditions and the associated benefits and harms. TWEETABLE ABSTRACT: Our systematic review shows significant burden of polypharmacy in pregnancy but outcomes for women and offspring are unknown. PROSPERO REGISTRATION NUMBER: CRD42021223966.
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Família , Polimedicação , Gravidez , Humanos , Feminino , Masculino , Prevalência , MEDLINE , MultimorbidadeRESUMO
Aim: We aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem. Methods: This was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination. Results: Of 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30). Conclusion: Individuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.
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Diabetes Mellitus Tipo 2 , Pé Diabético , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Pé Diabético/diagnóstico , Pé Diabético/epidemiologia , Pé , Humanos , Modelos de Riscos Proporcionais , Medição de RiscoRESUMO
Cardiac catheterization procedures are performed on about 20,000 children with congenital heart disease (CHD) annually in China. The procedure, which involves exposure to ionizing radiation, causes DNA damage and may lead to increased cancer risk. We have studied chromosomal aberrations (CA) in peripheral lymphocytes of CHD children. CA frequencies were assessed in an interventional group of 70 children who underwent cardiac catheterization and a control group of 51 children receiving open-heart surgery. Total CA and all chromosome-type aberrations were higher in the exposed children than in the control group. With respect to the type of septal defect, the translocation frequency was higher in patients with ventricular rather than atrial defects. Cardiac catheterization procedures increase CA frequencies and may also increase the risk of cancer.
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Cateterismo Cardíaco/efeitos adversos , Aberrações Cromossômicas/efeitos da radiação , Cardiopatias Congênitas/cirurgia , Linfócitos/efeitos da radiação , Radiação Ionizante , Adolescente , Cateterismo Cardíaco/métodos , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Cardiopatias Congênitas/patologia , Humanos , Linfócitos/imunologia , Masculino , Duração da Cirurgia , Cultura Primária de Células , RiscoRESUMO
In this study, the effect of ionizing radiation on 8-hydroxy-2'-deoxyguanosine (8-OHdG) in human peripheral blood was investigated. Blood samples were collected from 230 radiation workers and 8 patients who underwent radiotherapy for population study. Blood samples from 2 healthy individuals were irradiated with different X-ray doses for in vitro experiment, and levels of 8-OHdG in serum and cell culture supernatants were assessed by enzyme-linked immunosorbent assay. Observations demonstrated the positive relationships between serum 8-OHdG level and radiation dose and working period were observed, and serum 8-OHdG levels were higher among interventional radiation workers than among other hospital radiation workers. In addition, 8-OHdG yields in supernatants increased, peaked at 3 Gy of radiation dose, and then decreased with further increases in radiation; the dose-response curve obtained fitted a polynomial function. By contrast, a similar trend was not found in radiotherapy patients. The present study suggests that 8-OHdG may be a useful biomarker reflecting oxidative damage among workers occupationally exposed to low-dose radiation.
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Osteoporosis is a major skeletal disease with low bone mineral density, which leads to an increased risk of bone fracture. Salubrinal is a synthetic chemical that inhibits dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α) in response to endoplasmic reticulum (ER) stress. To understand possible linkage of osteoporosis to ER stress, we employed an unloading mouse model and examined the effects of salubrinal in the pathogenesis of disuse osteoporosis. The results presented several lines of evidence that osteoclastogenesis in the development of osteoporosis was associated with ER stress, and salubrinal suppressed unloading-induced bone loss. Compared to the age-matched control, unloaded mice reduced the trabecular bone area/total area (B.Ar/T.Ar) as well as the number of osteoblasts, and they increased the osteoclasts number on the trabecular bone surface in a time-dependent way. Unloading-induced disuse osteoporosis significantly increased the expression of Bip, p-eIF2α and ATF4 in short-term within 6h of tail suspension, but time-dependent decreased in HU2d to HU14d. Furthermore, a significant correlation of ER stress with the differentiation of osteoblasts and osteoclasts was observed. Administration of salubrinal suppressed the unloading-induced decrease in bone mineral density, B.Ar/T.Ar and mature osteoclast formation. Salubrinal also increased the colony-forming unit-fibroblasts and colony-forming unit-osteoblasts. It reduced the formation of mature osteoclasts, suppressed their migration and adhesion, and increased the expression of Bip, p-eIF2α and ATF4. Electron microscopy showed that rough endoplasmic reticulum expansion and a decreased number of ribosomes on ER membrane were observed in osteoblast of unloading mice, and the abnormal ER expansion was significantly improved by salubrinal treatment. A TUNEL assay together with CCAAT/enhancer binding protein homologous protein (CHOP) expression indicated that ER stress-induced osteoblast apoptosis was rescued by salubrinal. Collectively, the results support the notion that ER stress plays a key role in the pathogenesis of disuse osteoporosis, and salubrinal attenuates unloading-induced bone loss by altering proliferation and differentiation of osteoblasts and osteoclasts via eIF2α signaling.
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Estresse do Retículo Endoplasmático , Transtornos Musculares Atróficos/complicações , Transtornos Musculares Atróficos/patologia , Osteoporose/complicações , Osteoporose/patologia , Animais , Apoptose/efeitos dos fármacos , Peso Corporal , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/patologia , Contagem de Células , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cinamatos/farmacologia , Cinamatos/uso terapêutico , Ensaio de Unidades Formadoras de Colônias , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Fêmur/diagnóstico por imagem , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Elevação dos Membros Posteriores , Camundongos Endogâmicos C57BL , Transtornos Musculares Atróficos/tratamento farmacológico , Fatores de Transcrição NFATC/metabolismo , Osteoblastos/patologia , Osteoblastos/ultraestrutura , Osteoclastos/patologia , Osteogênese/efeitos dos fármacos , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Tioureia/análogos & derivados , Tioureia/farmacologia , Tioureia/uso terapêutico , Microtomografia por Raio-XRESUMO
OBJECTIVE: A new simple RT-LAMP method was applied to detect measles virus nucleic acid and compared with nest-RT-PCR. METHODS: Compare the detection rate of the RT-LAMP method with that of nest-RT-PCR by detecting measles virus nucleic acid from measles virus and clinical samples. RESULTS: The nucleic acid positive rates of all 23 strains of measles virus are all 100% by the two methods. But to the detection of 18 clinical samples which are negative in measles isolation, the nest-RT-LAMP showed 56.52% positive rate of nucleic acid of measles virus and nest-RT-PCR showed 47.83%. CONCLUSION: RT-LAMP is more sensitive than nest-RT-PCR.