RESUMEN
Objective: To investigate the effects of preoperative quetiapine on postoperative delirium (POD) and sleep quality in elderly orthopedic patients. Methods: Prospectively, 111 elderly patients, American Society of Anesthesiologists (ASA) grade â ¡-â ¢, scheduled to undergo knee or hip surgery in the Affiliated Huangyan Hospital of Wenzhou Medical University under continuous spinal anesthesia from August 2021 to March 2023, were selected and randomly divided into two groups by random number table: control group (group C, 1 h preoperative placebo) and quetiapine group (group Q, 1 h preoperative quetiapine 12.5 mg). In group C, 54 cases were enrolled, including 25 males and 29 females, with an average age of (73.5±4.9) years. In group Q, 57 cases were enrolled, including 26 males and 31 females, with an average age of (74.8±5.0) years. The primary outcome measures were the incidence of POD evaluated by using confusion assessment method (CAM) at 24, 48, and 72 hours after surgery, and the secondary outcome measures included Pittsburgh sleep quality index (PSQI) scores at 24 and 48 hours after surgery and satisfaction of pain management within 24 hours after surgery. Results: The incidence of POD at 24, 48, and 72 h after surgery in group Q was 5.4% (3/57), 12.5% (7/57), 14.3% (8/57), respectively, while that in group C was 18.2% (10/54), 21.8% (12/54), 21.8% (12/54), respectively. The incidence of POD at 24 h after surgery in group Q was lower than that in group C (P=0.036). There was no significant difference in the incidence of POD at 48 and 72 h after surgery between two groups (all P>0.05). The PSQI score of patients in group Q at 24 and 48 h after surgery were (3.8±1.2) and (6.9±1.1) scores, respectively, which in group C were (10.5±2.8) and (7.3±1.3) scores, respectively. Compared with group C, the PSQI score of patients in group Q at 24 h after surgery was significantly higher (P<0.001), but there was no significant difference at 48 h after surgery (P=0.068). The satisfaction scores of pain management at 24 h after surgery in group Q was (91±7) scores, which was higher than that in group C of (81±6) scores (P<0.001). Conclusion: Oral intake of low-dose quetiapine 1 h preoperatively can reduce the incidence of POD, improve postoperative sleep quality and enhance postoperative satisfaction of pain management at 24 hours after surgery in elderly orthopedic patients undergoing knee or hip surgery.
Asunto(s)
Delirio del Despertar , Ortopedia , Anciano , Femenino , Humanos , Masculino , Fumarato de Quetiapina/uso terapéutico , Calidad del SueñoRESUMEN
Objective: To analyze the phenotypic and genotypic characteristics of Escherichia coli causing bloodstream and abdominal co-infection (CoECO), and provide clues for empirical antibiotics treatment. Methods: The strains of Escherichia coli isolated from blood and abdominal samples in the Department of Laboratory Medicine of the First Medical Center of the PLA General Hospital from 2010 to 2020 were retrospectively analyzed. Mass spectrometer was used to identify all of the strains and the minimum inhibitory concentration (MIC) were detected by VITEK 2 Compact. All isolates were sequenced by 2×150 bp double terminal sequencing strategy on the HiSeq X Ten sequencer (Illumina). After the genome sequence was spliced, the single nucleotide polymorphism (SNP) analysis of the strain sequence was performed using kSNP3 software to clarify the homologous relationship between strains. If the strains isolated from two different parts had high homology, they were regarded as the same strain and the case was with CoECO infection. Meanwhile, the multilocus sequence type (MLST) was determined using PubMLST website and resistant genes were screened by CARD website. Results: A total of 70 cases of CoECO infection were screened, including 45 males and 25 females, and aged (59.2±16.3) years old. The 70 CoECO isolates belonged to 35 sequence types (STs). The most prevalent STs included ST38 (n=6), ST 405 (n=6), ST 1193 (n=6) and ST131 (n=5), and other ST types contained less than 5 strains. The homologous relationship among strains was relatively scattered, presenting a sporadic trend as a whole, and only a few strains had a small-scale outbreak. The CoECO isolates showed significantly resistance to ampicillin (91.4%, 64/70), ampicillin/sulbactam (74.3%, 5 2/70), ceftriaxone (72.9%, 51/70), ciprofloxacin (71.4%, 50/70) and levofloxacin (71.4%, 50/70), and high-sensitivity to piperacillin/tazobactam, carbapenems and amikacin. The most prevalent resistant gene was tet (A/B) (70%, 49/70), followed by blaTEM (58.6%, 41/70), sul1 (55.7%, 40/70), sul2 (54.3%, 38/70), blaCTX-M-14(25.7%, 18/70), blaCTX-M-15(17.1%, 13/70), blaCTX-M-55(15.7%, 11/70), blaCTX-M-64/65(5.7%, 4/70), blaCTX-M-27(4.3%, 3/70), mcr-1 (4.3%, 3/70), blaNDM-5(2.9%, 2/70). Conclusions: CoECO is distributed dispersedly and has no obvious advantage clone. No genotype with obvious advantages was found. Although the strain has a high resistance rate to some antibacterial drugs, the proportion of carrying resistant genes is low, and it has a high sensitivity to some first-line antibacterial drugs.
Asunto(s)
Coinfección , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Masculino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Escherichia coli/genética , Tipificación de Secuencias Multilocus , Estudios Retrospectivos , Antibacterianos/farmacología , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Ampicilina , beta-Lactamasas/genética , Pruebas de Sensibilidad Microbiana , Proteínas de Escherichia coli/genéticaRESUMEN
Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).
Asunto(s)
Variaciones en el Número de Copia de ADN , ADN Mitocondrial , Megacariocitos/fisiología , Mitocondrias/genética , Activación Plaquetaria , Polimorfismo de Nucleótido Simple , Anciano , Proliferación Celular , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Nucleótidos/metabolismo , FenotipoRESUMEN
Panax notoginseng round spot disease (PRSD), caused by Mycocentrospora acerina, is the main leaf disease occurring in cultured P. notoginseng. Aiming to find a safe and efficient control method for PRSD, we studied the disease characteristics of PRSD and the optimal growth conditions of M. acerina and evaluated the efficacy of rain-shelter cultivation in PRSD control. Moreover, we described M. acerina based on morphological characterization and molecular analyses (ITS, ACT, LSU, and TEF-1α). The optimum temperature for M. acerina conidial germination was found to be 14 to 22°C. Furthermore, leaf surface wetness for at least 4 h is required for conidial germination, and conidia can successfully infect P. notoginseng when the leaf wetness lasts for more than 8 h. Additionally, rainwater splashing determines the conidial transfection distance, which is less than 2 m. Finally, our study revealed that rain-shelter cultivation is an effective and simple physical prevention strategy to control PRSD, with an average efficacy of up to 100%.
Asunto(s)
Ascomicetos , Panax notoginseng , Hojas de la PlantaRESUMEN
Objective: To explore the changes of γ-GCS mRNA expression and GSH-PX in serum of workers exposed to manganese in order to provide scientific basis for early diagnosis of manganese poisoning. Methods: In June 2017, a total of 180 workers from a motorcycle manufacturer were selected by stratified random sampling, including 115 welders as the exposure group and 65 administrative office workers as the Control Group, the exposure group was divided into high exposure group (43 persons) and low exposure group (72 persons) according to whether the exposure group exceeded the standard limit. The levels of γ-gcs Mrna expression and GSH-Px activity in serum were determined by Occupational Health Survey, and the differences of γ-gcs Mrna expression and GSH-Px activity among different groups were analyzed. Results: Compared with the control group, the serum GSH-Px activity was lower and the serum γ-GCS mRNA expression level was higher in the exposed group (F=370.52, 275.95, P<0.01) . Compared with the control group, there was significant difference in γ-GCS mRNA expression level and GSH-Px activity (F=0.475ã1.06, P<0.01; F=48.53ã111.70, P<0.01) . The concentrations of manganese in air, welding dust and urine were positively correlated with the level of γ-GCS mRNA (r=0.71, 0.50, 0.31, P<0.01) The serum GSH-Px activity was negatively correlated with the concentrations of manganese in air, welding dust and urine (r=-0.80, -0.52, -0.30, P< 0.01) , There was no correlation between Serum γ-GSH-Px activity and age and years of exposure (P>0.05) . Conclusion: Serum γ-GCS mRNA expression level and GSH-Px activity level can be used as early biomarkers of manganese poisoning. The concentrations of manganese in workplace air, welding dust and urine manganese in workers are the influencing factors.
Asunto(s)
Contaminantes Ocupacionales del Aire , Intoxicación por Manganeso , Exposición Profesional , Soldadura , Polvo , Humanos , Iones , Manganeso , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , ARN Mensajero/genéticaRESUMEN
Mammograms contain information that predicts breast cancer risk. We developed two novel mammogram-based breast cancer risk measures based on image brightness (Cirrocumulus) and texture (Cirrus). Their risk prediction when fitted together, and with an established measure of conventional mammographic density (Cumulus), is not known. We used three studies consisting of: 168 interval cases and 498 matched controls; 422 screen-detected cases and 1197 matched controls; and 354 younger-diagnosis cases and 944 controls frequency-matched for age at mammogram. We conducted conditional and unconditional logistic regression analyses of individually- and frequency-matched studies, respectively. We estimated measure-specific risk gradients as the change in odds per standard deviation of controls after adjusting for age and body mass index (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). For interval, screen-detected and younger-diagnosis cancer risks, the best fitting models (OPERAs [95% confidence intervals]) involved: Cumulus (1.81 [1.41-2.31]) and Cirrus (1.72 [1.38-2.14]); Cirrus (1.49 [1.32-1.67]) and Cirrocumulus (1.16 [1.03 to 1.31]); and Cirrus (1.70 [1.48 to 1.94]) and Cirrocumulus (1.46 [1.27-1.68]), respectively. The AUCs were: 0.73 [0.68-0.77], 0.63 [0.60-0.66], and 0.72 [0.69-0.75], respectively. Combined, our new mammogram-based measures have twice the risk gradient for screen-detected and younger-diagnosis breast cancer (P ≤ 10-12 ), have at least the same discriminatory power as the current polygenic risk score, and are more correlated with causal factors than conventional mammographic density. Discovering more information about breast cancer risk from mammograms could help enable risk-based personalised breast screening.
Asunto(s)
Mamografía/métodos , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity and disability globally. This study aims to investigate the causal effects of varying blood levels of five minerals -- iron, zinc, copper, calcium, and magnesium, on OA and RA. DESIGN: We performed two-sample Mendelian randomization (MR) analyses to assess the associations of five circulating minerals with OA and RA. Single nucleotide polymorphisms (SNPs) serving as genetic instruments for the circulating mineral levels were selected from large genome-wide association studies of European-descent individuals. The associations of these SNPs with OA and RA were evaluated in UK Biobank participants. Multiple sensitivity analyses were applied to detect and correct for the presence of pleiotropy. RESULTS: Genetically determined copper and zinc status were associated with OA, but not with RA. Per standard deviation (SD) increment in copper increases the risk of OA (OR = 1.07, 95% CI: 1.02-1.13) and one of its subtypes, localized OA (OR = 1.08, 95% CI: 1.03-1.15). Per SD increment in zinc is positively associated with risks of OA (OR = 1.07, 95% CI: 1.01-1.13), generalized OA (OR = 1.18, 95% CI: 1.05-1.31), and unspecified OA (OR = 1.21, 95% CI: 1.11-1.31). Additionally, per SD increment in calcium decreases the risk of localized OA (OR = 0.83, 95% CI: 0.69-0.98). CONCLUSIONS: Genetically high zinc and copper status were positively associated with OA, but not with RA. Given the modifiable nature of circulating mineral status, these findings warrant further investigation for OA prevention strategies.
Asunto(s)
Artritis Reumatoide/sangre , Cobre/sangre , Osteoartritis/sangre , Zinc/sangre , Calcio/sangre , Femenino , Humanos , Hierro/sangre , Magnesio/sangre , Masculino , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido SimpleRESUMEN
AIM: To evaluate the accuracy of ultra-low-dose computed tomography (ULDCT) with ASiR-V using a noise index (SmartmA) for pulmonary nodule detection and Lung CT Screening Reporting And Data System (Lung-RADS) classifications compared with low-dose CT (LDCT). MATERIALS AND METHODS: Two-hundred and ten patients referred for lung cancer screening underwent conventional chest LDCT (0.80 ± 0.28 mSv) followed immediately by ULDCT (0.16 ± 0.03 mSv). ULDCT was scanned using 120 kV/SmartmA with a noise index of 28 HU and reconstructed with ASiR-V70%. The types and diameters of all nodules were recorded. The attenuation of pure ground-glass nodules (pGGNs) was measured on LDCT. All nodules were further classified using Lung-RADS. Sensitivities of nodule detection on ULDCT were analysed using LDCT as the reference standard. Logistic regression was used to establish a prediction model for the sensitivity of nodules. RESULTS: LDCT revealed 362 nodules and the overall sensitivity on ULDCT was 90.1%. The sensitivity for solid nodules (SNs) of ≥1 mm diameter was 96.6% (228/236) and 100% (26/26) for SNs of ≥6 mm diameter. For pGGNs of ≥6 mm, the overall sensitivity was 93% (40/43) and 100% (29/29) for nodules with a attenuation value -700 HU or more. The agreement of Lung-RADS classification between two scans was good. On logistic regression, diameter was the only independent predictor for sensitivity of SNs (p<0.05). Diameter and attenuation value were predictors for pGGNs (p<0.05). CONCLUSION: ULDCT with ASiR-V using SmartmA is suitable for lung-cancer screening in people with a BMI ≤35 kg/m2 as it has a low radiation dose of 0.16 mSv, high sensitivity for nodule detection and good performance of Lung-RADS classifications.
Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Sistemas de Información Radiológica , Tomografía Computarizada por Rayos X/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosis de Radiación , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Objective: To investigate the feasibility, efficacy and safety of semiconductor laser in situ fenestration of type A aortic dissection during thoracic endovascular aortic repair. Methods: The clinical data of 68 patients with type A aortic dissection treated by semiconductor laser in situ fenestration from June 2016 to January 2020 in Department of Vascular Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University were analyzed retrospectively. Of the patients, 45 were male, 23 were female, the mean age was (52±14) years. The technical success rate and complication rates were assessed. Results: The technical success rate of 68 patients was 92.6% (63/68), only 5 patients failed due to the complex aortic arch type, 3 patients underwent chimney stent implantation, 2 patients underwent artificial vessel bypass. During the perioperative period, 1 patient died due to severe pulmonary infection, 4 patients developed neurological symptoms such as cerebral infarction after surgery, and the remaining patients had no related complications. Postoperative CTA follow-up indicated that the primary intercalation rupture was completely closed, and the main and branch stents were patency, 8 (8.8%) type â leakage were occurred. Conclusion: It showed that in situ semiconductor laser fenestration is a feasible, effective and safe method to treat type A aortic dissection.
Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Adulto , Anciano , Disección Aórtica/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Prótesis Vascular , China , Femenino , Humanos , Láseres de Semiconductores , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case-control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69-0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts-an increased risk of developing an interval breast cancer.
Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Estrógenos/metabolismo , Mamografía/métodos , Anamnesis/métodos , Progesterona/metabolismo , Adulto , Anciano , Australia , Índice de Masa Corporal , Densidad de la Mama , Neoplasias de la Mama/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Curva ROC , Encuestas y CuestionariosRESUMEN
Objective: To analyze the effect of influenza vaccination intervention among key populations of chronic disease management in communities of Shanghai. Methods: A total of 50 787 patients aged ≥60 with diabetes, hypertension and chronic obstructive pulmonary disease (COPD) in Huangpu, Yangpu, Baoshan and Qingpu districts of Shanghai from January 2013 to August 2017 were selected as the intervention group, and 52 268 people from key populations with chronic disease management in Xuhui, Hongkou, Jiading and Fengxian districts were selected as the control group according to the geographical location and economic level. The intervention group accepted follow-up and health education of influenza vaccination via chronic disease outpatient based on information system. The implementation time of the intervention was from September 2017 to January 2018. The basic information and diagnosis information of two groups, and intervention completion of the intervention group were obtained from Shanghai chronic disease management information system and hospital record system. Results: The age of the intervention group and the control group were (76.76±8.33) and (77.97±8.51) years old, respectively (P<0.001); and there were statistical differences in gender, occupational and influenza vaccination rate between the two groups (P<0.001). A total of 28 644 (56.40%) subjects of the intervention group received intervention. There was no significant difference in age composition between finished and unfinished intervention groups (P=0.095), and there was significant difference in gender composition (P=0.044). Before the intervention, the vaccination rate of the intervention group was 0.75% (382 subjects) which was lower than that of the control group with 1.02% (533 subjects) (χ(2)=20.96, P<0.001). After the intervention, the vaccination rate of the intervention group was 1.73% (496 subjects) which was higher than that of the control group with 1.42% (744 subjects) (χ(2)=11.65, P=0.001). Subjects that were male, younger, uptake of influenza vaccine before the intervention, received intervention and professional and technical personnel were more likely to take influenza vaccine, with OR (95%CI) 1.29 (1.13-1.47), 0.97 (0.96-0.98), 260.30 (215.21-314.83), 1.85 (1.61-2.11) and 1.48 (1.10-1.99), respectively. Conclusion: Influenza vaccination intervetion raised the vaccination rate of key population of chronic disease management. Male, younger, those who had been vaccinated before the intervention, who received the intervention, and professional and technical personnel were more likely to be vaccinated.
Asunto(s)
Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vacunación/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , China , Enfermedad Crónica , Diabetes Mellitus , Femenino , Humanos , Hipertensión , Masculino , Educación del Paciente como Asunto , Enfermedad Pulmonar Obstructiva CrónicaRESUMEN
Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.
Asunto(s)
Hipocampo/citología , Memoria a Corto Plazo/fisiología , Células-Madre Neurales/citología , Neurogénesis/genética , Neuronas/citología , Animales , Trastorno del Espectro Autista/genética , Catecol O-Metiltransferasa/genética , Cromosomas Humanos Par 22 , Variaciones en el Número de Copia de ADN , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Células HEK293 , Hipocampo/metabolismo , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , Esquizofrenia/genética , Proteínas de Dominio T Box/genéticaRESUMEN
Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.
Asunto(s)
Trastorno del Espectro Autista/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/genética , Proteínas Tirosina Quinasas/metabolismo , Animales , Trastorno del Espectro Autista/metabolismo , Trastorno Autístico/genética , Niño , Preescolar , Dendritas/genética , Dendritas/metabolismo , Espinas Dendríticas/genética , Espinas Dendríticas/metabolismo , Femenino , Humanos , Masculino , Ratones , Neurogénesis/fisiología , Neuronas/metabolismo , Fosforilación , Quinasas DyrKRESUMEN
BACKGROUND: Case-control studies show that mammographic density is a better risk factor when defined at higher than conventional pixel-brightness thresholds. We asked if this applied to interval and/or screen-detected cancers. METHOD: We conducted a nested case-control study within the prospective Melbourne Collaborative Cohort Study including 168 women with interval and 422 with screen-detected breast cancers, and 498 and 1197 matched controls, respectively. We measured absolute and percent mammographic density using the Cumulus software at the conventional threshold (Cumulus) and two increasingly higher thresholds (Altocumulus and Cirrocumulus, respectively). Measures were transformed and adjusted for age and body mass index (BMI). Using conditional logistic regression and adjusting for BMI by age at mammogram, we estimated risk discrimination by the odds ratio per adjusted standard deviation (OPERA), calculated the area under the receiver operating characteristic curve (AUC) and compared nested models using the likelihood ratio criterion and models with the same number of parameters using the difference in Bayesian information criterion (ΔBIC). RESULTS: For interval cancer, there was very strong evidence that the association was best predicted by Cumulus as a percentage (OPERA = 2.33 (95% confidence interval (CI) 1.85-2.92); all ΔBIC > 14), and the association with BMI was independent of age at mammogram. After adjusting for percent Cumulus, no other measure was associated with risk (all P > 0.1). For screen-detected cancer, however, the associations were strongest for the absolute and percent Cirrocumulus measures (all ΔBIC > 6), and after adjusting for Cirrocumulus, no other measure was associated with risk (all P > 0.07). CONCLUSION: The amount of brighter areas is the best mammogram-based measure of screen-detected breast cancer risk, while the percentage of the breast covered by white or bright areas is the best mammogram-based measure of interval breast cancer risk, irrespective of BMI. Therefore, there are different features of mammographic images that give clinically important information about different outcomes.
Asunto(s)
Densidad de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Mamografía/métodos , Anciano , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Programas InformáticosRESUMEN
Purpose To compare three mammographic density measures defined by different pixel intensity thresholds as predictors of breast cancer risk for two different digital mammographic systems. Materials and Methods The Korean Breast Cancer Study included 398 women with invasive breast cancer and 737 control participants matched for age at mammography (±1 year), examination date, mammographic system, and menopausal status. Mammographic density was measured by using the automated Laboratory for Individualized Breast Radiodensity Assessment (LIBRA) software and the semiautomated Cumulus software at the conventional threshold (Cumulus) and at increasingly higher thresholds (Altocumulus and Cirrocumulus, respectively). Measures were Box-Cox-transformed and adjusted for age, body mass index, and menopausal status. Conditional logistic regression was used to estimate risk associations. For calculation of measures of predictive value, the change in odds per standard deviation (OPERA) and the area under the receiver operating characteristic curve (AUC) were used. Results For dense area, with use of the direct conversion system the OPERAs were 1.72 (95% confidence interval [CI]: 1.38, 2.15) for LIBRA, 1.58 (95% CI: 1.27, 1.97) for Cumulus, 2.04 (95% CI: 1.60, 2.59) for Altocumulus, and 3.48 (95% CI: 2.45, 4.47) for Cirrocumulus (P < .001). The corresponding AUCs were 0.70, 0.69, 0.76, and 0.89, respectively. With use of the indirect conversion system, the corresponding OPERAs were 1.50 (95% CI: 1.28, 1.76), 1.36 (95% CI: 1.16, 1.59), 1.40 (95% CI: 1.19, 1.64), and 1.47 (95% CI: 1.25, 1.73) (P < .001) and the AUCs were 0.64, 0.60, 0.61, and 0.63, respectively. Conclusion It is possible that mammographic density defined by higher pixel thresholds could capture more risk-predicting information with use of a direct conversion mammographic system; the mammographically bright, rather than white, regions are etiologically important. © RSNA, 2017.
Asunto(s)
Densidad de la Mama , Neoplasias de la Mama/patología , Área Bajo la Curva , Neoplasias de la Mama/diagnóstico por imagen , Estudios de Casos y Controles , Detección Precoz del Cáncer , Femenino , Humanos , Mamografía/métodos , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: To present a theoretical analysis of how the presence of bone in interstitial brachytherapy affects dose rate distributions with MCNP4C Monte Carlo code and to prepare for the next clinical study on the dose distribution of interstitial brachytherapy in head and neck neoplasm. METHODS: Type 6711,125I brachytherapy source was simulated with MCNP4C Monte Carlo code whose cross section library was DLC-200. The dose distribution along the transverse axis in water and dose constant were compared with the American Association of Physicists in Medicine (AAPM) TG43UI update dosimetry formalism and current literature. The validated computer code was then applied to simple homogeneous bone tissue model to determine the affected different bone tissue had on dose distribution from 125I interstitial implant. RESULTS: 125I brachytherapy source simulated with MCNP4C Monte Carlo code met the requirements of TG43UI report. Dose rate constant, 0.977 78 cGy/(h×U), was in agreement within 1.32% compared with the recommended value of TG43UI. There was a good agreement between TG43UI about the dosimetric parameters at distances of 1 to 10 cm along the transverse axis of the 125I source established by MCNP4C and current published data. And the dose distribution of 125I photon emitting source in different bone tissue was calculated. Dose-deposition capacity of photons was in decreasing order: cortical bone, spongy bone, cartilage, yellow bone marrow, red bone marrow in the same medium depth. Photons deposited significantly in traversal axis among the phantom material of cortical bone and sponge bone relevant to the dose to water. In the medium depth of 0.01 cm, 0.1 cm, and 1 cm, the dose in the cortical bone was 12.90 times, 9.72 times, and 0.30 times of water respectively. CONCLUSION: This study build a 125I source model with MCNP4C Monte Carlo code, which is validated, and could be used in subsequent study. Dose distribution of photons in different bone medium is not the same as water, and its main energy deposits in bone medium surface, so we should consider the effect of bone medium when we design the target area adjacent to the bone tissue in 125I sources implantation plan.
Asunto(s)
Braquiterapia , Método de Montecarlo , Radioisótopos de Yodo , Fotones , Dosificación RadioterapéuticaRESUMEN
With the continuous development of endovascular surgery, thoracic endovascular aortic repair (TEVAR) has gradually replaced traditional open surgery and has become the preferred treatment strategy for Stanford type B aortic dissection. However, the disadvantage of the short proximal landing zone greatly limited the indication of TEVAR surgery and affected the prognosis. In recent years, many strategies such as hybrid surgery, in vitro fenestrated and branched aortic endo-graft, chimney technique, in-situ fenestration technique, etc., have been developed, which greatly broadens the TEVAR indication and improved the prognosis.
Asunto(s)
Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Disección Aórtica/terapia , Aneurisma de la Aorta Torácica/terapia , Prótesis Vascular , Humanos , Pronóstico , Estudios Retrospectivos , Stents , Resultado del TratamientoRESUMEN
MOTIVATION: Dispersed duplications (DDs) such as transposon element insertions and copy number variations are ubiquitous in the human genome. They have attracted the interest of biologists as well as medical researchers due to their role in both evolution and disease. The efforts of discovering DDs in high-throughput sequencing data are currently dominated by database-oriented approaches that require pre-existing knowledge of the DD elements to be detected. RESULTS: We present DD_DETECTION, a database-free approach to finding DD events in high-throughput sequencing data. DD_DETECTION is able to detect DDs purely from paired-end read alignments. We show in a comparative study that this method is able to compete with database-oriented approaches in recovering validated transposon insertion events. We also experimentally validate the predictions of DD_DETECTION on a human DNA sample, showing that it can find not only duplicated elements present in common databases but also DDs of novel type. AVAILABILITY AND IMPLEMENTATION: The software presented in this article is open source and available from https://bitbucket.org/mkroon/dd_detection.
Asunto(s)
Variaciones en el Número de Copia de ADN/genética , Bases de Datos Factuales , Duplicación de Gen/genética , Genoma Humano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Biología Computacional/métodos , HumanosRESUMEN
A critical step toward understanding autism spectrum disorder (ASD) is to identify both genetic and environmental risk factors. A number of rare copy number variants (CNVs) have emerged as robust genetic risk factors for ASD, but not all CNV carriers exhibit ASD and the severity of ASD symptoms varies among CNV carriers. Although evidence exists that various environmental factors modulate symptomatic severity, the precise mechanisms by which these factors determine the ultimate severity of ASD are still poorly understood. Here, using a mouse heterozygous for Tbx1 (a gene encoded in 22q11.2 CNV), we demonstrate that a genetically triggered neonatal phenotype in vocalization generates a negative environmental loop in pup-mother social communication. Wild-type pups used individually diverse sequences of simple and complicated call types, but heterozygous pups used individually invariable call sequences with less complicated call types. When played back, representative wild-type call sequences elicited maternal approach, but heterozygous call sequences were ineffective. When the representative wild-type call sequences were randomized, they were ineffective in eliciting vigorous maternal approach behavior. These data demonstrate that an ASD risk gene alters the neonatal call sequence of its carriers and this pup phenotype in turn diminishes maternal care through atypical social communication. Thus, an ASD risk gene induces, through atypical neonatal call sequences, less than optimal maternal care as a negative neonatal environmental factor.
Asunto(s)
Trastorno Autístico/genética , Proteínas de Dominio T Box/fisiología , Animales , Trastorno del Espectro Autista/genética , Comunicación , Variaciones en el Número de Copia de ADN/genética , Modelos Animales de Enfermedad , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Heterocigoto , Masculino , Conducta Materna , Ratones , Fenotipo , Factores de Riesgo , Conducta Social , Relación Estructura-Actividad , Proteínas de Dominio T Box/genética , Vocalización AnimalRESUMEN
OBJECTIVE/BACKGROUND: The objective was to assess the mid-term results of pharmacomechanical catheter-directed thrombolysis (PCDT) for symptomatic acute and subacute inferior vena cava (IVC) thrombosis; the risk factors of early thrombosis recurrence and iliocaval patency were also evaluated. METHODS: From January 2010 to December 2015, 54 patients (33 men; mean age 47.1 years) with symptomatic acute and subacute IVC thrombosis were treated with PCDT. Primary technical success (clot lysis ≥ 50% after PCDT), stent-assisted technical success (residual stenosis < 30% after stenting), clinical success (freedom from thrombosis recurrence within 30 days), complications, frequency of post-thrombotic syndrome (PTS; Villalta score ≥ 5), and iliocaval patency were recorded at follow-up evaluation. A multivariate regression model was used to determine predictors of early thrombosis reoccurrence and iliocaval patency. RESULTS: The primary technical success and the stent-assisted technical success were 63% (n = 34/54) and 100% (n = 54/54) respectively. There were 11 patients (20%) with immediate recurrent thrombosis requiring repeat PCDT. Minor bleeding complications occurred in seven patients, and one patient with major bleeding needed a blood transfusion. The occurrence of PTS at a mean of 26 months (range 1-60 months) was 13% (7/54). The 3-year primary and secondary iliocaval patency was 63% and 81%, respectively. On multivariate analysis, active malignancy was predictive of immediate IVC thrombosis recurrence (hazard ratio [HR] 5.8, 95% confidence interval [CI] 1.7-19.8; p = .01), whereas the pre-existing filter played a protective role against iliocaval re-occlusion (HR 0.3, 95% CI 0.1-0.8; p = .01). CONCLUSIONS: PCDT is safe and effective in managing symptomatic acute and subacute IVC thrombosis. Active malignancy is predictor of thrombosis re-occurrence, whereas the presence of a filter is associated with a higher rate of iliocaval patency at mid-term follow-up.