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BACKGROUND: Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear. METHODS: One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed. RESULTS: Cognitive impairment (global cognition, verbal memory, language, visual-spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS. CONCLUSIONS: Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.
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BACKGROUND: Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. METHODS: Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software. RESULTS: Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001). CONCLUSION: Our data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor.
Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Humans , Depressive Disorder, Major/genetics , Bipolar Disorder/genetics , Cytochrome P-450 CYP2C19/genetics , Protective Factors , East Asian People , Genotype , Polymorphism, Single Nucleotide , ATP Binding Cassette Transporter, Subfamily B/geneticsABSTRACT
Quantitative assessment of spatial relations between tumor and tumor-infiltrating lymphocytes (TIL) is increasingly important in both basic science and clinical aspects of breast cancer research. We have developed and evaluated convolutional neural network analysis pipelines to generate combined maps of cancer regions and TILs in routine diagnostic breast cancer whole slide tissue images. The combined maps provide insight about the structural patterns and spatial distribution of lymphocytic infiltrates and facilitate improved quantification of TILs. Both tumor and TIL analyses were evaluated by using three convolutional neural network networks (34-layer ResNet, 16-layer VGG, and Inception v4); the results compared favorably with those obtained by using the best published methods. We have produced open-source tools and a public data set consisting of tumor/TIL maps for 1090 invasive breast cancer images from The Cancer Genome Atlas. The maps can be downloaded for further downstream analyses.
Subject(s)
Breast Neoplasms/pathology , Deep Learning , Lymphocytes, Tumor-Infiltrating/pathology , Breast Neoplasms/immunology , Female , Humans , Lymphocytes, Tumor-Infiltrating/immunology , SEER ProgramABSTRACT
Charge-transfer (CT) complexes, formed by noncovalent bonding between electron-rich (donor, D) and electron-deficient (acceptor, A) molecules (or moieties) have attracted considerable attention due to their fascinating structures and potential applications. Herein, we demonstrate that anion coordination is a promising strategy to promote CT complex formation between anion-binding, electron-rich tris(urea) donor ligands (D) and electron-deficient viologen cation acceptors (A), which form co-crystals featuring infinite â â â DADAâ â â or discrete (circular DADA or three-decker DAD) π-stacking interactions. These CT complexes were studied by X-ray diffraction, UV/Vis spectroscopy, electric conductivity measurements, charge displacement curve (CDC) calculations, and DFT computations.
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Coal mining has environmental impacts on surrounding areas, including heavy metal contamination of soil. This study explores the feasibility of using hyperspectral remote sensing to determine the heavy metal (Cr, Ni, Cu, Zn, Cd, Pb) content of soils in a coal-mining area in the city of Zoucheng, Shandong Province, China. We used a plasma mass spectrometer to measure the heavy metal contents of soils and an ASD Field Spec4 spectrometer to measure soil hyperspectral data. Savitzky-Golay (SG) convolution smoothing and multiplicative scatter correction (MSC) were applied to the data, along with multiple mathematical transformations. Finally, a regression model for estimating heavy metal content of soils was developed using partial least squares regression (PLSR) analysis. Results show that the average heavy metal content of study soils was lower than the national standard value of soil environmental quality. The model's predictive accuracy is extremely high for Ni ( = 0.923 and RMSE = 0.831 by modeling; = 0.879 and RMSE = 1.292 by testing); ideal for Cr, Cu, Zn, and Pb; and insufficient for Cd. Preprocessing the reflectance spectra with SG convolution smoothing in combination with MSC and reciprocal logarithm transformation yields the highest model accuracy. Hyperspectral PLSR modeling can effectively predict heavy metal content of soils in coal-mining areas, and preprocessing spectral data is crucial for achieving high prediction accuracy.
Subject(s)
Coal Mining , Metals, Heavy , Soil Pollutants , China , Cities , Environmental Monitoring , Mining , SoilABSTRACT
We propose a sparse Convolutional Autoencoder (CAE) for simultaneous nucleus detection and feature extraction in histopathology tissue images. Our CAE detects and encodes nuclei in image patches in tissue images into sparse feature maps that encode both the location and appearance of nuclei. A primary contribution of our work is the development of an unsupervised detection network by using the characteristics of histopathology image patches. The pretrained nucleus detection and feature extraction modules in our CAE can be fine-tuned for supervised learning in an end-to-end fashion. We evaluate our method on four datasets and achieve state-of-the-art results. In addition, we are able to achieve comparable performance with only 5% of the fully- supervised annotation cost.
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BACKGROUND: Retinoic acid (RA), an active metabolite of vitamin A, possesses enormous protective effects on vascular systems. It may also be positively related to good functional outcome after ischemic stroke. However, whether circulating RA concentration is associated with poststroke cognitive impairment (PSCI) remains unclear. This study aimed to detect the association between RA level and PSCI among patients with first-ever acute ischemic stroke. METHODS: Two hundred and 61 consecutive patients were prospectively recruited during March 2018 and March 2019. Serum RA concentration was measured at admission for all patients. We also performed cognitive function examination using the Montreal Cognitive Assessment (MoCA) at admission and at every follow-up visit. Patients with MoCA score less than 26 were identified as developing PSCI. RESULTS: The median serum RA level was 2.0 ng/mL (interquartile range, 1.1-3.2 ng/mL) after admission. Patients diagnosed as PSCI at admission, 1-month and 3-month were 53 (20.3%), 91 (34.6%), and 141 (54.0%), respectively. Univariate analysis showed that reduced RA level was correlated with PSCI at 3-month (Pâ¯=â¯.003), but not at admission (Pâ¯=â¯.416) and 1-month poststroke (P = .117). After adjusting for all potential confounders, the odds ratio for the lowest tertile of RA, compared with the highest tertile, was 1.97 (95% confidence interval, 1.01-3.83, Pâ¯=â¯.046) for PSCI at 3 months. Furthermore, multiple-adjusted spline regression model further confirmed the dose-response relationships between RA level and 3-month PSCI (P < .001). CONCLUSIONS: Decreasing serum RA level might be associated with 3-month PSCI in ischemic stroke patients.
Subject(s)
Brain Ischemia/blood , Cognition , Cognitive Dysfunction/etiology , Stroke/blood , Tretinoin/blood , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Brain Ischemia/complications , Brain Ischemia/diagnosis , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Stroke/complications , Stroke/diagnosis , Time FactorsABSTRACT
BACKGROUND: The pattern of neuropsychiatric features of patients with neurosyphilis and the impact of the severity of cognitive impairment on neuropsychiatric syndromes are unknown. OBJECTIVE: We aim to assess the neuropsychiatric features of patients with neurosyphilis, and compare the impact of the severity of cognitive impairment on the neuropsychiatric syndromes between neurosyphilis and Alzheimer disease (AD). METHODS: Neuropsychiatric symptoms and the degree of cognitive impairment were assessed in a case-control study of 91 neurosyphilis, 162 AD, 157 mild cognitive impairment, and 139 normal controls by the Neuropsychiatric Inventory (NPI) scale and Clinical Dementia Rating scale, respectively. Factor analysis was performed on the 12 NPI items. RESULTS: Factor analysis showed that patients with neurosyphilis showed more severe neuropsychiatric syndromes at the dementia stage than those neurosyphilis patients at the mild cognitive impairment stage, while neuropsychiatric manifestations were equally common among the different stages of dementia (all p < 0.05). Frontal lobe syndrome was more severe in patients with neurosyphilis than in patients with AD from the early mild cognitive impairment stage to the moderate dementia stage (all p < 0.01). CONCLUSIONS: Patients with neurosyphilis show different patterns of neuropsychiatric syndromes at the mild cognitive impairment and dementia stages, and differ from patients with AD.
Subject(s)
Cognitive Dysfunction , Dementia , Aged , Aged, 80 and over , Alzheimer Disease/complications , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Case-Control Studies , China/epidemiology , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Dementia/complications , Dementia/diagnosis , Dementia/psychology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Neurosyphilis/complications , Neurosyphilis/diagnosis , Neurosyphilis/epidemiology , Neurosyphilis/psychology , Severity of Illness IndexABSTRACT
BACKGROUND: Previous studies have shown cognitive impairment in patients with spinocerebellar ataxia type 3 (SCA3). However, there is a lack of data on Chinese patients with SCA3. METHOD: We investigated 22 native Chinese with SCA3 and 18 controls matched for age, education as well as mental status. Cognitive assessments were carefully carried out to measure verbal fluency, memory, attention, executive function, visuospatial and visuoconstructive functions. RESULTS: The most common impairments of cognition in native Chinese with SCA3 were disruption of phonemic verbal fluency and frontal executive dysfunction. Deficits in semantic fluency were detected in about 31.8% patients. Impaired visuospatial function and verbal memory were also found in native Chinese with SCA3. The degree of ataxia, CAG repeat length and education were found to correlate with cognitive performance. Multivariate binary logistic regression suggested that an oculomotor disorder and depression are predictors of cognitive impairment. CONCLUSION: Native Chinese with SCA3 had cognitive impairment of frontal executive function, temporal and parietal functions. An oculomotor disorder might be an index of cognitive dysfunction.
Subject(s)
Cognition Disorders/complications , Spinocerebellar Ataxias/complications , Adult , China , Cognition Disorders/genetics , Depression/complications , Depression/genetics , Educational Status , Executive Function , Female , Humans , Logistic Models , Male , Memory , Multivariate Analysis , Neuropsychological Tests , Oculomotor Nerve Diseases/complications , Oculomotor Nerve Diseases/genetics , Oculomotor Nerve Diseases/psychology , Semantics , Severity of Illness Index , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/psychology , Trinucleotide RepeatsABSTRACT
Partial denitrification (PD) is an alternative to providing NO2- for the anaerobic ammonium oxidation (anammox) process. In this study, three upflow anaerobic sludge blankets (UASB) were used to investigate the effect of an external electric field on PD performance. The results indicated that the maximum nitrite transformation ratio (NTR) reached 76.3 %, with an average NTR of 54.1 %, in the presence of external electric field, whereas the average NTR of the control was only 49.8 %. The fitted maximum specific nitrate reduction rates of PD1, PD2, and PD3 were 83.7, 90.5, and 92.3 mg N g-1VSS h-1, respectively, according to the Haldane model analysis. Microbial community analysis demonstrated that the abundance of Thauera, Comamonas, and Accumulibacter increased with electric assistance. In summary, UASB reactor with electrodes set in the upper region was most feasible for the stable PD process, providing an alternative for developing a coupled PD-anammox process.
Subject(s)
Denitrification , Sewage , Anaerobiosis , Nitrogen/analysis , Bioreactors , Oxidation-Reduction , NitritesABSTRACT
BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model. METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks. RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aß40, Aß42, IL-1ß, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet. CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.
Subject(s)
Alzheimer Disease , Amyloid beta-Protein Precursor , Caloric Restriction , Gastrointestinal Microbiome , Mice, Transgenic , Animals , Gastrointestinal Microbiome/physiology , Caloric Restriction/methods , Alzheimer Disease/microbiology , Alzheimer Disease/diet therapy , Alzheimer Disease/prevention & control , Male , Mice , Amyloid beta-Protein Precursor/genetics , Presenilin-1/genetics , Amyloid beta-Peptides/metabolism , Disease Models, Animal , Maze Learning/physiology , Brain/metabolism , Mice, Inbred C57BLABSTRACT
BACKGROUND: Helicobacter pylori (H. pylori) infection can cause extensive apoptosis of gastric epithelial cells, serving as a critical catalyst in the progression from chronic gastritis, gastrointestinal metaplasia, and atypical gastric hyperplasia to gastric carcinoma. Prompt eradication of H. pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer. Acacetin, which has multifaceted pharmacological activities such as anti-cancer, anti-inflammatory, and antioxidative properties, has been extensively investigated across various domains. Nevertheless, the impact and underlying mechanisms of action of acacetin on H. pylori-infected gastric mucosal epithelial cells remain unclear. AIM: To explore the defensive effects of acacetin on apoptosis in H. pylori-infected GES-1 cells and to investigate the underlying mechanisms. METHODS: GES-1 cells were treated with H. pylori and acacetin in vitro. Cell viability was assessed using the CCK-8 assay, cell mortality rate via lactate dehydrogenase assay, alterations in cell migration and healing capacities through the wound healing assay, rates of apoptosis via flow cytometry and TUNEL staining, and expression levels of apoptosis-associated proteins through western blot analysis. RESULTS: H. pylori infection led to decreased GES-1 cell viability, increased cell mortality, suppressed cell migration, increased rate of apoptosis, increased expressions of Bax and cle-caspase3, and decreased Bcl-2 expression. Conversely, acacetin treatment enhanced cell viability, mitigated apoptosis induced by H. pylori infection, and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3. CONCLUSION: Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H. pylori-infected GES-1 cells, thereby exerting a protective effect on gastric mucosal epithelial cells.
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The overlapping clinical features of Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB) make differentiation difficult in the clinical environment. Evaluating the CSF levels of biomarkers in AD and DLB patients could facilitate clinical diagnosis. CSF Visinin-like protein-1 (VILIP-1), a calcium-mediated neuronal injury biomarker, has been described as a novel biomarker for AD. The aim of this study was to investigate the diagnostic utility of CSF VILIP-1 and VILIP-1/Aß1-42 ratio to distinguish AD from DLB. Levels of CSF VILIP-1, t-tau, p-tau181P , Aß1-42 , and α-synuclein were measured in 61 AD patients, 32 DLB patients, and 40 normal controls using commercial ELISA kits. The results showed that the CSF VILIP-1 level had significantly increased in AD patients compared with both normal controls and DLB patients. The CSF VILIP-1 and VILIP-1/Aß1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. Additionally, CSF VILIP-1 levels were positively correlated with t-tau and p-tau181P within each group and with α-synuclein in the AD and control groups. We conclude that CSF VILIP-1 could be a diagnostic marker for AD, differentiating it from DLB. The analysis of biomarkers, representing different neuropathologies, is an important approach reflecting the heterogeneous features of AD and DLB. Neuronal Ca(2+) -sensor protein VILIP-1 has been implicated in the calcium-mediated neuronal injury and pathological change of AD. The CSF VILIP-1 and VILIP-1/Aß1-42 levels had enough diagnostic accuracy to allow the detection and differential diagnosis of AD. CSF VILIP-1 is a useful biomarker for AD. Evaluating the CSF levels of VILIP-1 in AD and DLB patients could facilitate clinical diagnosis.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Alzheimer Disease/diagnosis , Cerebrospinal Fluid/metabolism , Lewy Body Disease/cerebrospinal fluid , Lewy Body Disease/diagnosis , Neurocalcin/cerebrospinal fluid , Adult , Aged , Aged, 80 and over , Amyloid beta-Peptides/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Peptide Fragments/cerebrospinal fluid , Plaque, Amyloid/cerebrospinal fluid , Plaque, Amyloid/diagnosis , ROC Curve , Sensitivity and Specificity , alpha-Synuclein/cerebrospinal fluid , tau Proteins/cerebrospinal fluidABSTRACT
In recent years, high entropy alloy (HEA) matrix composites have undergone rapid development. In this work, the effects of different WC contents (10 wt.%, 20 wt.%, and 30 wt.%) on the microstructure, mechanical properties, and wear resistance of FeCoCrNi HEA matrix composites prepared by spark plasma sintering (SPS) were studied. The results show that the WC-HEA composites are mainly composed of an FCC matrix phase (Ni, Fe) and carbide phases (Cr7C3, Co3W3C, WC, etc.). The hardness of the 30 WC-HEA composites was the highest at 459.2 HV, which is 71.2% higher than the 268.3 HV of the pure matrix material. Similarly, the compressive yield strength of the 30 WC-HEA composite was the largest, reaching 1315.1 MPa, which is 112.1% higher than that of the pure matrix material. However, the compression deformation rate of the 30 WC-HEA composite significantly decreased to 16.6%. Under the same dry friction conditions, the addition of an appropriate amount of WC particles can reduce the friction coefficient of the HEA matrix. The wear volume of the composites decreased rapidly with the increase of WC content. The wear volume of 30 WC-HEA was the lowest, only 3.17% of that of the pure matrix material.
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Background: Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear. Objective: The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function. Methods: One hundred and five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Participants underwent clinical assessment, olfactory testing, cognitive assessments, and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC. Results: Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex, and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI. Conclusion: Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.
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RATIONALE: Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, inner ear malformations, goiter, and abnormal organification of iodide. It is caused by mutations in SLC26A4 gene, which encodes pendrin (a transporter of chloride, bicarbonate, and iodide). Pendred syndrome is a common cause of syndromic deafness, but the metabolic abnormalities it causes are often overlooked. Here, we report the case of a patient diagnosed with Pendred syndrome with hypokalemia. PATIENT CONCERNS: A 53-year-old deaf-mute woman was hospitalized due to severe limb asthenia. The emergency examination showed that her blood potassium level was 1.8 mmol/L. DIAGNOSES: Through the genetic test, we found a mutation of SLC26A4 gene in NM_000441: c.2027T>A, p.L676Q, as well as the SLC26A4 exon 5-6 deletion. These genetic variations pointed to Pendred syndrome (an autosomal recessive disorder that mainly affects the inner ear, thyroid, and kidney) which is a common cause of syndromic deafness. INTERVENTIONS: The patient was treated with potassium supplements and screened for the cause of hypokalemia. OUTCOMES: The patient was discharged after her potassium levels rose to the normal range. LESSONS: Patients with Pendred syndrome may also have certain metabolic abnormalities; thus, more attention should be paid to them during clinical diagnosis.
Subject(s)
Deafness , Goiter, Nodular , Hearing Loss, Sensorineural , Hypokalemia , Bicarbonates , Chlorides , Female , Goiter, Nodular/complications , Goiter, Nodular/diagnosis , Goiter, Nodular/genetics , Hearing Loss, Sensorineural/diagnosis , Hearing Loss, Sensorineural/genetics , Humans , Hypokalemia/genetics , Iodides/metabolism , Middle Aged , Mutation , Potassium , Sulfate Transporters/geneticsABSTRACT
This study examined the structural brain differences across individuals of different BD stages and the risks of developing bipolar disorder (BD) associated with these brain differences. A total of 221 participants who were recruited from the Guangzhou Brain Hospital and the community were categorized into four groups: NC (healthy control) (N = 77), high risk (HR) (N = 42), ultra-high risk (UHR) (N = 38), and bipolar disorder (BD) (N = 64) based on a list of criteria. Their demographics, clinical characteristics, and diffusion magnetic resonance imaging (dMRI) data were collected. ANCOVA results showed that the HR group had significantly reduced mean diffusivity (MD) (p = 0.043) and radial diffusivity (RD) (p = 0.039) of the left portico-ponto-cerebellar tracts when compared with the BD group. Moreover, logistic regression results showed that the specific diffusivity measures of cerebellar tracts (e.g., cortico-ponto-cerebellar tract), particularly the RD and MD revealed differences between groups at different BD stages after controlling for the covariates. The findings suggested that specific diffusivity (RD and MD) of cerebellar tracts (e.g., cortico-ponto-cerebellar tract) revealed differences between groups at different BD stages which is helpful in detecting the trajectory changes in BD syndromes in the early stages of BD, particularly when the BD syndromes start from HR stage.
Subject(s)
Bipolar Disorder , Cerebellum , Bipolar Disorder/epidemiology , Bipolar Disorder/pathology , Cerebellum/diagnostic imaging , Diffusion Tensor Imaging , HumansABSTRACT
OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1â¶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-ß-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION: PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.
Subject(s)
Pneumonia, Pneumocystis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Caspofungin/therapeutic use , Child , Child, Preschool , Dyspnea , Female , Humans , Male , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Respiratory Sounds , Retrospective StudiesABSTRACT
(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.
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AIMS: The present study aimed to compare temporal variability in the spontaneous fluctuations of activity and connectivity between amnestic MCI (aMCI) and nonamnestic MCI (naMCI), which enhances the understanding of their different pathophysiologies and provides targets for individualized intervention. METHODS: Sixty-five naMCI and 48 aMCI subjects and 75 healthy controls were recruited. A sliding window analysis was used to evaluate the dynamic amplitude of low-frequency fluctuations (dALFF), dynamic regional homogeneity (dReHo), and dynamic functional connectivity (dFC). The caudal/rostral hippocampus was selected as the seeds for calculating dFC. RESULTS: Both aMCI and naMCI exhibited abnormal dALFF, dReHo, and hippocampal dFC compared with healthy controls. Compared with individuals with naMCI, those with aMCI exhibited (1) higher dALFF variability in the right putamen, left Rolandic operculum, and right middle cingulum, (2) lower dReHo variability in the right superior parietal lobule, and (3) lower dFC variability between the hippocampus and other regions (left superior occipital gyrus, middle frontal gyrus, inferior cerebellum, precuneus, and right superior frontal gyrus). Additionally, variability in dALFF, dReHo, and hippocampal dFC exhibited different associations with cognitive scores in aMCI and naMCI patients, respectively. Finally, dReHo variability in the right superior parietal lobule and dFC variability between the right caudal hippocampus and left inferior cerebellum exhibited partially mediated effects on the different memory scores between people with aMCI and naMCI. CONCLUSION: The aMCI and naMCI patients exhibited shared and specific patterns of dynamic brain activity and connectivity. The dReHo of the superior parietal lobule and dFC of the hippocampus-cerebellum contributed to the memory heterogeneity of MCI subtypes. Analyzing the temporal variability in the spontaneous fluctuations of brain activity and connectivity provided a new perspective for exploring the different pathophysiological mechanisms in MCI subtypes.