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BACKGROUND: The male sterile lines are an important foundation for heterosis utilization in wheat (Triticum aestivum L.). Thereinto, pollen development is one of the indispensable processes of wheat reproductive development, and its fertility plays an important role in wheat heterosis utilization, and are usually influencing by genes. However, these key genes and their regulatory networks during pollen abortion are poorly understood in wheat. RESULTS: DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) is a member of the R2R3-MYB family and has been shown to be essential for early tapetal layer development and pollen grain fertility in rice (Oryza sativa L.) and Arabidopsis thaliana. In order to clarify the function of TDF1 in wheat anthers development, we used OsTDF1 gene as a reference sequence and homologous cloned wheat TaTDF1 gene. TaTDF1 is localized in the nucleus. The average bolting time of Arabidopsis thaliana overexpressed strain (TaTDF1-OE) was 33 d, and its anther could be colored normally by Alexander staining solution, showing red. The dominant Mosaic suppression silence-line (TaTDF1-EAR) was blue-green in color, and the anthers were shrimpy and thin. The TaTDF1 interacting protein (TaMAP65) was confirmed using Yeast Two-Hybrid Assay (Y2H) and Bimolecular-Fluorescence Complementation (BiFC) experiments. The results showed that downregulated expression of TaTDF1 and TaMAP65 could cause anthers to be smaller and shrunken, leading to pollen abortion in TaTDF1 wheat plants induced by virus-induced gene-silencing technology. The expression pattern of TaTDF1 was influenced by TaMAP65. CONCLUSIONS: Thus, systematically revealing the regulatory mechanism of wheat TaTDF1 during anther and pollen grain development may provide new information on the molecular mechanism of pollen abortion in wheat.
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Infertilidad Vegetal , Proteínas de Plantas , Polen , Triticum , Triticum/genética , Triticum/fisiología , Infertilidad Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polen/genética , Polen/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/fisiología , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/genética , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Genes de PlantasRESUMEN
AIMS: Although static abnormalities of functional brain networks have been observed in patients with social anxiety disorder (SAD), the brain connectome dynamics at the macroscale network level remain obscure. We therefore used a multivariate data-driven method to search for dynamic functional network connectivity (dFNC) alterations in SAD. METHODS: We conducted spatial independent component analysis, and used a sliding-window approach with a k-means clustering algorithm, to characterize the recurring states of brain resting-state networks; then state transition metrics and FNC strength in the different states were compared between SAD patients and healthy controls (HC), and the relationship to SAD clinical characteristics was explored. RESULTS: Four distinct recurring states were identified. Compared with HC, SAD patients demonstrated higher fractional windows and mean dwelling time in the highest-frequency State 3, representing "widely weaker" FNC, but lower in States 2 and 4, representing "locally stronger" and "widely stronger" FNC, respectively. In State 1, representing "widely moderate" FNC, SAD patients showed decreased FNC mainly between the default mode network and the attention and perceptual networks. Some aberrant dFNC signatures correlated with illness duration. CONCLUSION: These aberrant patterns of brain functional synchronization dynamics among large-scale resting-state networks may provide new insights into the neuro-functional underpinnings of SAD.
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Encéfalo , Conectoma , Imagen por Resonancia Magnética , Red Nerviosa , Fobia Social , Humanos , Masculino , Femenino , Adulto , Fobia Social/fisiopatología , Fobia Social/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Adulto JovenRESUMEN
Although numerous studies have emphasized the male predominance in autism spectrum disorder (ASD), how sex differences are related to the topological organization of functional networks remains unclear. This study utilized imaging data from 86 ASD (43 females, aged 7-18 years) and 86 typically developing controls (TCs) (43 females, aged 7-18 years) obtained from Autism Brain Imaging Data Exchange databases, constructed individual whole-brain functional networks, used a graph theory analysis to compute topological metrics, and assessed sex-related differences in topological metrics using a 2 × 2 factorial design. At the global level, females with ASD exhibited significantly higher cluster coefficient and local efficiency than female TCs, while no significant difference was observed between males with ASD and male TCs. Meanwhile, the neurotypical sex differences in cluster coefficient and local efficiency observed in TCs were not present in ASD. At the nodal level, ASD exhibited abnormal nodal centrality in the left middle temporal gyrus.
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Trastorno del Espectro Autista , Encéfalo , Imagen por Resonancia Magnética , Humanos , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/diagnóstico por imagen , Niño , Adolescente , Masculino , Femenino , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Caracteres Sexuales , Factores Sexuales , Mapeo Encefálico/métodosRESUMEN
Behavioral addiction (BA) is a conceptually new addictive phenotype characterized by compulsive reward-seeking behaviors despite adverse consequences. Currently, its underlying neurogenetic mechanism remains unclear. Here, this study aimed to investigate the association between cortical thickness (CTh) and genetic phenotypes in BA. We conducted a systematic search in five databases and extracted gene expression data from the Allen Human Brain Atlas. Meta-analysis of 10 studies (343 addicted individuals and 355 controls) revealed that the BA group showed thinner CTh in the precuneus, postcentral gyrus, orbital-frontal cortex, and dorsolateral prefrontal cortex (P < 0.005). Meta-regression showed that the CTh in the precuneus and postcentral gyrus were negatively associated with the addiction severity (P < 0.0005). More importantly, the CTh phenotype of BA was spatially correlated with the expression of 12 genes (false discovery rate [FDR] < 0.05), and the dopamine D2 receptor had the highest correlation (rho = 0.55). Gene enrichment analysis further revealed that the 12 genes were involved in the biological processes of behavior regulation and response to stimulus (FDR < 0.05). In conclusion, our findings demonstrated the thinner CTh in cognitive control-related brain areas in BA, which could be associated with the expression of genes involving dopamine metabolism and behavior regulation.
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Conducta Adictiva , Corteza Cerebral , Humanos , Conducta Adictiva/genética , Conducta Adictiva/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Masculino , Adulto , Femenino , Grosor de la Corteza Cerebral , Receptores de Dopamina D2/genética , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Self-body satisfaction is considered a psychological factor for exercise dependence (EXD). However, the potential neuropsychological mechanisms underlying this association remain unclear. PURPOSE: To investigate the role of white matter microstructure in the association between body satisfaction and EXD. STUDY TYPE: Prospective. POPULATION: One hundred eight regular exercisers (age 22.11 ± 2.62 years; 58 female). FIELD STRENGTH/SEQUENCE: 3.0 Tesla; diffusion-weighted echo planar imaging with 30 directions. ASSESSMENT: The Body Shape Satisfaction (BSS) and Exercise Dependence Scale (EDS); whole-brain tract-based spatial statistics (TBSS) and correlational tractography analyses; average fractional anisotropy (FA) and quantitative anisotropy (QA) values of obtained tracts. STATISTICAL TESTS: The whole-brain regression model, mediation analysis, and simple slope analysis. P values <0.05 were defined as statistically significant. RESULTS: The BSS and EDS scores were 37.33 ± 6.32 and 68.22 ± 13.88, respectively. TBSS showed negative correlations between EDS and FA values in the bilateral corticospinal tract (CST, r = -0.41), right cingulum (r = -0.41), and left superior thalamic radiation (STR, r = -0.50). Correlational tractography showed negative associations between EDS and QA values of the left inferior frontal occipital fasciculus (r = -0.35), STR (r = -0.42), CST (r = -0.31), and right cingulum (r = -0.28). The FA values, rather than QA values, mediated the BSS-EDS association (indirect effects = 0.30). The BSS was significantly associated with the EDS score at both low (ß = 1.02) and high (ß = 0.43) levels of FA value, while the association was significant only at the high level of QA value (ß = 1.26). DATA CONCLUSION: EXD was correlated with white matter in frontal-subcortical and sensorimotor networks, and these tracts mediated the body satisfaction-EXD association. White matter microstructure could be a promising neural signature for understanding the underlying neuropsychological mechanisms of EXD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.
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Rhabdomyosarcoma (RMS) is a common soft tissue malignant tumor, especially in young patients. Alveolar rhabdomyosarcoma (ARMS) is a subtype of RMS that is prevalent in adolescents. This malignant tumor usually develops in the extremities and can also involve the trunk, perineum, and pelvis. Now, we report a rare case of pelvic lymph node metastatic alveolar RMS in a young patient, which was determined by fine needle aspiration cytology (FNAC). To the best of our knowledge, this is the first case in which the definite diagnosis of ARMS was initially made by FNAC.
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Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received meditation-based therapy in two separate studies of mindfulness-based stress reduction (MBSR) and Transcendental Meditation (TM). The PTSD Checklist was administered to assess symptoms at baseline and after 9 weeks of meditation intervention. We examined the SLC6A4 promoter (5HTTLPR_L/S insertion/deletion + rs25531_A/G) polymorphisms according to previously defined gene expression groups, and the FKBP5 variant rs1360780 previously associated with PTSD disease risk. Methylation for CpG sites of SLC6A4 (28 sites) and FKBP5 (45 sites) genes was quantified in DNA samples collected before and after treatment. The 5HTTLPR LALA high expression genotype was associated with greater symptom improvement in participants exposed to early life trauma (p = 0.015). Separately, pre to post-treatment change of DNA methylation in a group of nine FKBP5 CpG sites was associated with greater symptom improvement (OR = 2.8, 95% CI 1.1-7.1, p = 0.027). These findings build on a wealth of existing knowledge regarding epigenetic and genetic relationships with PTSD disease risk to highlight the potential importance of SLC6A4 and FKBP5 for treatment mechanisms and as biomarkers of symptom improvement.
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African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n=58) and low (n=60) TAC troughs (N=515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12mg, respectively. Of 34,542 identified variants across 99 genes, 1,406 variants were suggestively associated with TAC troughs in univariate models (p-value <0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.
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PURPOSE: Major depressive disorder (MDD) tends to emerge during adolescence, but the neurobiology of adolescent MDD is still poorly understood. This study aimed to explore the topological organization of white matter structural networks and the relationship between structural and functional connectivity in adolescent MDD. METHODS: Structural and functional magnetic resonance imaging data were acquired from 94 first-episode drug-naïve adolescent MDD patients and 78 healthy adolescents. Whole brain structural and functional brain networks were constructed for each subject. Then, the topological organization of structural brain networks and the coupling strength between structural and functional connectivity were analyzed. RESULTS: Compared with controls, adolescent MDD patients showed disrupted small-world, rich-club, and modular organizations. Nodal centralities in the medial part of bilateral superior frontal gyrus, bilateral hippocampus, right superior occipital gyrus, right angular gyrus, bilateral precuneus, left caudate nucleus, bilateral putamen, right superior temporal gyrus, and right temporal pole part of superior temporal gyrus were significantly lower in adolescent MDD patients compared with controls. The coupling strength between structural and functional connectivity was significantly lower in adolescent MDD patients compared with controls. DISCUSSION: Our findings suggest widespread disruption of structural brain networks and structural-functional decoupling in adolescent MDD, potentially leading to reduced network communication capacity.
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Trastorno Depresivo Mayor , Humanos , Adolescente , Trastorno Depresivo Mayor/diagnóstico por imagen , Encéfalo/patología , Corteza Prefrontal , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Although brain structural covariance network (SCN) abnormalities have been associated with suicidal thoughts and behaviors (STBs) in individuals with major depressive disorder (MDD), previous studies have reported inconsistent findings based on small sample sizes, and underlying transcriptional patterns remain poorly understood. METHODS: Using a multicenter magnetic resonance imaging dataset including 218 MDD patients with STBs, 230 MDD patients without STBs, and 263 healthy control participants, we established individualized SCNs based on regional morphometric measures and assessed network topological metrics using graph theoretical analysis. Machine learning methods were applied to explore and compare the diagnostic value of morphometric and topological features in identifying MDD and STBs at the individual level. Brainwide relationships between STBs-related connectomic alterations and gene expression were examined using partial least squares regression. RESULTS: Group comparisons revealed that SCN topological deficits associated with STBs were identified in the prefrontal, anterior cingulate, and lateral temporal cortices. Combining morphometric and topological features allowed for individual-level characterization of MDD and STBs. Topological features made a greater contribution to distinguishing between patients with and without STBs. STBs-related connectomic alterations were spatially correlated with the expression of genes enriched for cellular metabolism and synaptic signaling. CONCLUSIONS: These findings revealed robust brain structural deficits at the network level, highlighting the importance of SCN topological measures in characterizing individual suicidality and demonstrating its linkage to molecular function and cell types, providing novel insights into the neurobiological underpinnings and potential markers for prediction and prevention of suicide.
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Genome-wide association studies (GWAS) have led to rapid growth in detecting genetic variants associated with various phenotypes. Owing to a great number of publicly accessible GWAS summary statistics, and the difficulty in obtaining individual-level genotype data, many existing gene-based association tests have been adapted to require only GWAS summary statistics rather than individual-level data. However, these association tests are restricted to unrelated individuals and thus do not apply to family samples directly. Moreover, due to its flexibility and effectiveness, the linear mixed model has been increasingly utilized in GWAS to handle correlated data, such as family samples. However, it remains unknown how to perform gene-based association tests in family samples using the GWAS summary statistics estimated from the linear mixed model. In this study, we show that, when family size is negligible compared to the total sample size, the diagonal block structure of the kinship matrix makes it possible to approximate the correlation matrix of marginal Z scores by linkage disequilibrium matrix. Based on this result, current methods utilizing summary statistics for unrelated individuals can be directly applied to family data without any modifications. Our simulation results demonstrate that this proposed strategy controls the type 1 error rate well in various situations. Finally, we exemplify the usefulness of the proposed approach with a dental caries GWAS data set.
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Caries Dental , Estudio de Asociación del Genoma Completo , Humanos , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Modelos Genéticos , FenotipoRESUMEN
Suicide is a major concern for health, and depression is an established proximal risk factor for suicide. This study aimed to investigate white matter features associated with suicide. We constructed white matter structural networks by deterministic tractography via diffusion tensor imaging in 51 healthy controls, 47 depressed patients without suicide plans or attempts and 56 depressed patients with suicide plans or attempts. Then, graph theory analysis was used to measure global and nodal network properties. We found that local efficiency was decreased and path length was increased in suicidal depressed patients compared to healthy controls and non-suicidal depressed patients; moreover, the clustering coefficient was decreased in depressed patients compared to healthy controls; and the global efficiency and normalized characteristic path length was increased in suicidal depressed patients compared to healthy controls. Similarly, compared with those in non-suicidal depressed patients, nodal efficiency in the thalamus, caudate, medial orbitofrontal cortex, hippocampus, olfactory cortex, supplementary motor area and Rolandic operculum was decreased. In summary, compared with those of non-suicidal depressed patients, the structural connectome of suicidal depressed patients exhibited weakened integration and segregation and decreased nodal efficiency in the fronto-limbic-basal ganglia-thalamic circuitry. These alterations in the structural networks of depressed suicidal brains provide insights into the underlying neurobiology of brain features associated with suicide.
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BACKGROUND: Alterations in brain functional connectivity (FC) have been frequently reported in adolescent major depressive disorder (MDD). However, there are few studies of dynamic FC analysis, which can provide information about fluctuations in neural activity related to cognition and behavior. The goal of the present study was therefore to investigate the dynamic aspects of FC in adolescent MDD patients. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 94 adolescents with MDD and 78 healthy controls. Independent component analysis, a sliding-window approach, and graph-theory methods were used to investigate the potential differences in dynamic FC properties between the adolescent MDD patients and controls. RESULTS: Three main FC states were identified, State 1 which was predominant, and State 2 and State 3 which occurred less frequently. Adolescent MDD patients spent significantly more time in the weakly-connected and relatively highly-modularized State 1, spent significantly less time in the strongly-connected and low-modularized State 2, and had significantly higher variability of both global and local efficiency, compared to the controls. Classification of patients with adolescent MDD was most readily performed based on State 1 which exhibited disrupted intra- and inter-network FC involving multiple functional networks. CONCLUSIONS: Our study suggests local segregation and global integration impairments and segregation-integration imbalance of functional networks in adolescent MDD patients from the perspectives of dynamic FC. These findings may provide new insights into the neurobiology of adolescent MDD.
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Encéfalo , Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Adolescente , Masculino , Femenino , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Estudios de Casos y Controles , Conectoma , Mapeo Encefálico/métodosRESUMEN
BACKGROUND: The neuroanatomical alteration in bipolar II depression (BDII-D) and its associations with inflammation, childhood adversity, and psychiatric symptoms are currently unclear. We hypothesize that neuroanatomical deficits will be related to higher inflammation, greater childhood adversity, and worse psychiatric symptoms in BDII-D. METHODS: Voxel- and surface-based morphometry was performed using the CAT toolbox in 150 BDII-D patients and 155 healthy controls (HCs). Partial Pearson correlations followed by multiple comparison correction was used to indicate significant relationships between neuroanatomy and inflammation, childhood adversity, and psychiatric symptoms. RESULTS: Compared with HCs, the BDII-D group demonstrated significantly smaller gray matter volumes (GMVs) in frontostriatal and fronto-cerebellar area, insula, rectus, and temporal gyrus, while significantly thinner cortices were found in frontal and temporal areas. In BDII-D, smaller GMV in the right middle frontal gyrus (MFG) was correlated with greater sexual abuse (r = -0.348, q < 0.001) while larger GMV in the right orbital MFG was correlated with greater physical neglect (r = 0.254, q = 0.03). Higher WBC count (r = -0.227, q = 0.015) and IL-6 levels (r = -0.266, q = 0.015) was associated with smaller GMVs in fronto-cerebellar area in BDII-D. Greater positive symptoms was correlated with larger GMVs of the left middle temporal pole (r = 0.245, q = 0.03). CONCLUSIONS: Neuroanatomical alterations in frontostriatal and fronto-cerebellar area, insula, rectus, temporal gyrus volumes, and frontal-temporal thickness may reflect a core pathophysiological mechanism of BDII-D, which are related to inflammation, trauma, and psychiatric symptoms in BDII-D.
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Experiencias Adversas de la Infancia , Trastorno Bipolar , Humanos , Trastorno Bipolar/diagnóstico por imagen , Depresión/diagnóstico por imagen , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Inflamación/diagnóstico por imagenRESUMEN
OBJECTIVE: Metabolic syndrome (MetS) is defined by clustering of cardiometabolic components, which may be present in different combinations. The authors evaluated clustering in individuals and extended families within and across ancestry groups. METHODS: The prevalence of different combinations of MetS components (high fasting glucose, low high-density lipoprotein cholesterol, high triglycerides, high blood pressure, and abdominal obesity) was estimated in 1651 individuals (340 families) self-reporting as European American (EA), Hispanic/Mexican American (MA), African American (AA), and Japanese American (JA). Odds ratios were estimated using logistic regression with generalized estimating equations comparing individual MetS components, number, and combinations of components for each ancestry group versus EA. RESULTS: Clustering of all five components (Combination #16) was more prevalent in EA (29.9%) and MA (25.2%) individuals than in AA (18.7%) and JA (15.5%) individuals. Compared with EA individuals, AA individuals were 64% and 66% less likely to have high triglycerides and low high-density lipoprotein cholesterol, whereas JA individuals were 85% and 56% less likely to have abdominal obesity and high blood pressure, respectively. Compared with EA individuals, the odds of having two, four, or five components were at least 77% lower in JA individuals, whereas the odds of having three, four, or five components were at least 3.79 times greater in MA individuals. CONCLUSIONS: Understanding heterogeneity in MetS clustering may identify factors important in reducing health disparities.
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Hipertensión , Síndrome Metabólico , Humanos , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Obesidad Abdominal/epidemiología , Triglicéridos , Obesidad , Hipertensión/epidemiología , Análisis por Conglomerados , Lipoproteínas HDL , Colesterol , Factores de RiesgoRESUMEN
BACKGROUND: Cytoplasmic male sterility (CMS) plays a crucial role in hybrid production. K-type CMS, a cytoplasmic male sterile line of wheat with the cytoplasms of Aegilops kotschyi, is widely used due to its excellent characteristics of agronomic performance, easy maintenance and easy restoration. However, the mechanism of its pollen abortion is not yet clear. RESULTS: In this study, wheat K-type CMS MS(KOTS)-90-110 (MS line) and it's fertile near-isogenic line MR (KOTS)-90-110 (MR line) were investigated. Cytological analysis indicated that the anthers of MS line microspore nucleus failed to divide normally into two sperm nucleus and lacked starch in mature pollen grains, and the key abortive period was the uninucleate stage to dinuclear stage. Then, we compared the transcriptome of MS line and MR line anthers at these two stages. 11,360 and 5182 differentially expressed genes (DEGs) were identified between the MS and MR lines in the early uninucleate and binucleate stages, respectively. Based on GO enrichment and KEGG pathways analysis, it was evident that significant transcriptomic differences were "plant hormone signal transduction", "MAPK signaling pathway" and "spliceosome". We identified 17 and 10 DEGs associated with the IAA and ABA signal transduction pathways, respectively. DEGs related to IAA signal transduction pathway were downregulated in the early uninucleate stage of MS line. The expression level of DEGs related to ABA pathway was significantly upregulated in MS line at the binucleate stage compared to MR line. The determination of plant hormone content and qRT-PCR further confirmed that hormone imbalance in MS lines. Meanwhile, 1 and 2 DEGs involved in ABA and Ethylene metabolism were also identified in the MAPK cascade pathway, respectively; the significant up regulation of spliceosome related genes in MS line may be another important factor leading to pollen abortion. CONCLUSIONS: We proposed a transcriptome-mediated pollen abortion network for K-type CMS in wheat. The main idea is hormone imbalance may be the primary factor, MAPK cascade pathway and alternative splicing (AS) may also play important regulatory roles in this process. These findings provided intriguing insights for the molecular mechanism of microspore abortion in K-type CMS, and also give useful clues to identify the crucial genes of CMS in wheat.
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Redes Reguladoras de Genes , Triticum , Triticum/metabolismo , Infertilidad Vegetal/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Semillas , Perfilación de la Expresión Génica , Transcriptoma , Citoplasma/genética , Hormonas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Although previous studies have demonstrated regional gray matter (GM) structural abnormalities in adolescents with major depressive disorder (MDD), how the topological organization of GM networks is affected in these patients is still unclear. Structural magnetic resonance imaging data were acquired from 100 first-episode drug-naïve adolescent MDD patients and 80 healthy controls (HCs). Whole-brain GM structural network was constructed for each subject, and a graph theory analysis was used to calculate the topological metrics of GM networks. Adolescent MDD patients showed significantly lower cluster coefficient and local efficiency compared to HCs. Compared to controls, adolescent MDD patients showed higher nodal centralities in the bilateral cuneus, left lingual gyrus, and right middle occipital gyrus and lower nodal centralities in the bilateral dorsolateral superior frontal gyrus, bilateral middle frontal gyrus, right anterior cingulate and paracingulate gyri, bilateral hippocampus, bilateral amygdala, bilateral caudate nucleus, and bilateral thalamus. Nodal centralities of the hippocampus were negatively associated with symptom severity and illness duration. Our findings suggest disrupted topological organization of GM structural networks in adolescent MDD patients. Impaired local segregation and abnormal nodal centralities in the prefrontal-subcortical-limbic areas and visual cortex regions may play important roles in the neurobiology of adolescent-onset MDD.
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Trastorno Depresivo Mayor , Humanos , Adolescente , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Corteza Cerebral/patología , Corteza Prefrontal/patología , Amígdala del Cerebelo , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
Gray matter (GM) abnormalities have been reported in both adults and children/adolescents with histories of childhood maltreatment (CM). A comparison of effects in youth and adulthood may be informative regarding life-span effects of CM. Voxel-wise meta-analyses of whole-brain voxel-based morphometry studies were conducted in all datasets and age-based subgroups respectively, followed by a quantitative comparison of the subgroups. Thirty VBM studies (31 datasets) were included. The pooled meta-analysis revealed increased GM in left supplementary motor area, and reduced GM in bilateral cingulate/paracingulate gyri, left occipital lobe, and right middle frontal gyrus in maltreated individuals compared to the controls. Maltreatment-exposed youth showed less GM in the cerebellum, and greater GM in bilateral middle cingulate/paracingulate gyri and bilateral visual cortex than maltreated adults. Opposite GM alterations in bilateral middle cingulate/paracingulate gyri were found in maltreatment-exposed adults (decreased) and children/adolescents (increased). Our findings demonstrate different patterns of GM changes in youth closer to maltreatment events than those seen later in life, suggesting detrimental effects of CM on the developmental trajectory of brain structure.
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OBJECTIVE: This study analyzed the characteristics and outcomes of veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to COVID-19 versus non-COVID causes at US academic centers. BACKGROUND DATA: V-V ECMO support has been utilized for COVID-19 patients with ARDS since the beginning of the pandemic. Mortality for ECMO in COVID-19 has been reported to be high but similar to reported mortality for ECMO support for non-COVID causes of respiratory failure. METHODS: Using ICD-10 codes, data of patients who underwent V-V ECMO for COVID-19 ARDS were compared with patients who underwent V-V ECMO for non-COVID causes between April 2020 and December 2022. The primary outcome was in-hospital mortality. Secondary outcome measures included length of stay and direct cost. Multivariate logistic regression modeling was performed to analyze differences in mortality between COVID and non-COVID groups, adjusting for other important risk factors (age, sex, and race/ethnicity). RESULTS: We identified and compared 6382 patients who underwent V-V ECMO for non-COVID causes to 6040 patients who underwent V-V ECMO for COVID-19. There was a significantly higher proportion of patients aged ≥ 65 years who underwent V-V ECMO in the non-COVID group compared with the COVID group (19.8% vs. 3.7%, respectively, P <0.001). Compared with patients who underwent V-V ECMO for non-COVID causes, patients who underwent V-V ECMO for COVID had increased in-hospital mortality (47.6% vs. 34.5%, P <0.001), length of stay (46.5±41.1 days vs. 40.6±46.1, P <0.001), and direct hospitalization cost ($207,022±$208,842 vs. $198,508±205,510, P =0.02). Compared with the non-COVID group, the adjusted odds ratio (OR) for in-hospital mortality in the COVID group was 2.03 (95% CI: 1.87-2.20, P <0.001). In-hospital mortality for V-V ECMO in COVID-19 improved during the study time period (50.3% in 2020, 48.6% in 2021, and 37.3% in 2022). However, there was a precipitous drop in the ECMO case volume for COVID starting in quarter 2 of 2022. CONCLUSIONS: In this nationwide analysis, COVID-19 patients with ARDS requiring V-V ECMO support had increased mortality compared with patients who underwent V-V ECMO for non-COVID etiologies.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/terapia , COVID-19/complicaciones , Resultado del Tratamiento , Hospitalización , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/terapia , Estudios RetrospectivosRESUMEN
INTRODUCTION: Previous studies have revealed abnormal resting-state brain activity in patients with end-stage renal disease (ESRD); however, the results are inconsistent. Thus, we conducted a coordinate-based meta-analysis of whole-brain resting-state functional neuroimaging studies in ESRD to identify the most consistent neural activity alterations in ESRD patients and explore their relation to serological indicators. METHODS: A comprehensive literature search strategy was applied to select pertinent studies up to December 2022 in PubMed, Web of Science, and Embase databases. Voxel-wise meta-analysis was conducted via the latest meta-analytic algorithm, seed-based d mapping with permutation of subject images software. Meta-regression analyses were also conducted to explore the potential effect of clinical variables on resting-state neural activity. RESULTS: Eleven studies comprising 304 patients with ESRD and 296 healthy controls (HCs) were included. Compared with HCs, ESRD patients showed decreased brain activity in the default mode network (DMN) regions, including the bilateral anterior cingulate cortex/medial prefrontal cortex, bilateral midcingulate cortex/posterior cingulate cortex, bilateral precuneus, and right angular gyrus. The neural activities in the bilateral midcingulate cortex, bilateral midcingulate cortex/posterior cingulate cortex, and right angular gyrus were significantly associated with serological indexes including hemoglobin, urea, and creatinine levels. CONCLUSION: The present study provides a quantitative overview of brain activity alterations in patients with ESRD, and the results confirm the essential role of the DMN in ESRD patients, which may be the potential neural basis of their cognitive deficits. Additionally, some serological indicators may be used as predictive markers for progressive impairment of brain function.