Neural Activity During Mental Rotation in Deaf Signers: The Influence of Long-Term Sign Language Experience.

OBJECTIVES: Mental rotation is the brain's visuospatial understanding of what objects are and where they belong. Previous research indicated that deaf signers showed behavioral enhancement for nonlinguistic visual tasks, including mental rotation. In this study, we investigated the neural difference of mental rotation processing between deaf signers and hearing nonsigners using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). DESIGN: The participants performed a block-designed experiment, consisting of alternating blocks of comparison and rotation periods, separated by a baseline or fixation period. Mental rotation tasks were performed using three-dimensional figures. fMRI images were acquired during the entire experiment, and the fMRI data were analyzed with Analysis of Functional NeuroImages. A factorial design analysis of variance was designed for fMRI analyses. The differences of activation were analyzed for the main effects of group and task, as well as for the interaction of group by task. RESULTS: The study showed differences in activated areas between deaf signers and hearing nonsigners on the mental rotation of three-dimensional figures. Subtracting activations of fixation from activations of rotation, both groups showed consistent activation in bilateral occipital lobe, bilateral parietal lobe, and bilateral posterior temporal lobe. There were different main effects of task (rotation versus comparison) with significant activation clusters in the bilateral precuneus, the right middle frontal gyrus, the bilateral medial frontal gyrus, the right interior frontal gyrus, the right superior frontal gyrus, the right anterior cingulate, and the bilateral posterior cingulate. There were significant interaction effects of group by task in the bilateral anterior cingulate, the right inferior frontal gyrus, the left superior frontal gyrus, the left posterior cingulate, the left middle temporal gyrus, and the right inferior parietal lobe. In simple effects of deaf and hearing groups with rotation minus comparison, deaf signers mainly showed activity in the right hemisphere, while hearing nonsigners showed bilateral activity. In the simple effects of rotation task, decreased activities were shown for deaf signers compared with hearing nonsigners throughout several regions, including the bilateral parahippocampal gyrus, the left posterior cingulate cortex, the right anterior cingulate cortex, and the right inferior parietal lobe. CONCLUSION: Decreased activations in several brain regions of deaf signers when compared to hearing nonsigners reflected increased neural efficiency and a precise functional circuitry, which was generated through long-term experience with sign language processing. In addition, we inferred tentatively that there may be a lateralization pattern to the right hemisphere for deaf signers when performing mental rotation tasks.

Spatial working memory impairment in primary onset middle-age type 2 diabetes mellitus: An ethology and BOLD-fMRI study.

PURPOSE: To explore mild cognitive dysfunction and/or spatial working memory impairment in patients with primary onset middle-age type 2 diabetes mellitus (T2DM] using ethology (behavior tests) and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). MATERIALS AND METHODS: Eighteen primary onset T2DM patients and 18 matched subjects with normal blood glucose levels were all tested using the Montreal cognitive assessment scale test, the Wechsler Memory Scale Chinese-revised test, and scanned using BOLD-fMRI (1.5T, EPI sequence) while performing the n-back task to find the activation intensity of some cognition-related areas. RESULTS: The ethology results showed that T2DM patients had a mild cognitive impairment and memory dysfunction (P < 0.05). The fMRI scan identified a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), bilateral parietal lobe (PA), and anterior cingulate cortex (ACC) / supplementary motor area (SMA) that was activated during the n-back task, with right hemisphere dominance. However, only the right PA and ACC/SMA showed a load effect via quantitative analysis in the T2DM group; the activation intensity of most working memory-related brain areas for the T2DM group were lower than for the control group under three memory loads. Furthermore, we found that the activation intensity of some cognition-related areas, including the right insular lobe, left caudate nucleus, and bilateral hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. CONCLUSION: Diabetes-related brain damage of primary onset middle-age T2DM patients with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial working memory and mild cognitive dysfunction.

Spatial working memory impairment in subclinical hypothyroidism: an FMRI study.

OBJECTIVE: Using a block-designed BOLD-fMRI to explore the neural basis of spatial working memory impairment in patients with subclinical hypothyroidism (SCH) performing an n-back task. METHODS: Sixteen patients with SCH before and after being treated with levothyroxine (LT4) for 6 months and 16 matched euthyroid subjects were scanned by fMRI under the n-back task. RESULTS: The fMRI scan found that a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), bilateral premotor area (PreMA), supplementary motor area/anterior cingulate cortex, bilateral parietal lobe (PA) and right caudate nucleus/thalamus was activated, with right hemisphere dominance. In euthyroid subjects, all these regions of interest (ROIs) showed load effect; however, only left DLPFC, left PA, bilateral PreMA and right caudate nucleus/thalamus showed the same effect in Pre-SCH patients. Furthermore, activation intensities of most ROIs (especially DLPFC and right PA) for Pre-SCH patients were lower than those in the euthyroid subjects (F <3.046, p > 0.062). Importantly, after a 6-month treatment with LT4, the load effect in SCH patients appeared the same as in the euthyroid subjects in all the ROIs (F >13.176, p < 0.0001). CONCLUSION: Our previous study shows that verbal working memory of SCH patients is impaired with abnormal activity in bilateral frontal areas. In this study, the results indicated that SCH patients may also have spatial working memory impairments, and the altered activities of right DLPFC and right posterior parietal lobe may be one of the underlying neural mechanisms. Most importantly, this study shows that LT4 replacement therapy can improve the memory impairment and reverse the altered neural activity network.

[Simultaneous determination of 43 antibacterials from nine categories in water using automatic sample loading-solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry].

Antibacterials represent a pharmaceutical class that is extensively used and consumed worldwide. The presence of a large number of antibacterial agents in water could result in antibiotic resistance. Thus, the development of a fast, accurate, and high-throughput method to analyze these emerging contaminants in water is necessary. Herein, a method was developed to achieve the simultaneous determination of 43 antibacterials from nine pharmaceutical categories (i.e., sulfonamides, quinolones, fluoroquinolones, tetracyclines, lincosamides, macrolides, nitroimidazoles, diterpenes, and dihydrofolate reductase inhibitors) in water using automatic sample loading-solid phase extraction (SPE)-ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Because the properties of these 43 antibacterials are quite different, the main objective of this work is to develop an extraction procedure that would enable the simultaneous analysis of a wide range of multiclass antibacterials. Given this context, the work presented in this paper optimized the SPE cartridge type, pH, and sample loading amount. Multiresidue extraction was performed as follows. The water samples were filtered through 0.45 µm filter membranes, added with Na2EDTA and NaH2PO4, and pH-adjusted to 2.34 using H3PO4. The solutions were then mixed with the internal standards. An automatic sample loading device fabricated by the authors was used for sample loading, and Oasis HLB cartridges were used for enrichment and purification. The optimized UPLC conditions were as follows: chromatographic column, Waters Acquity UPLC BEH C18 column (50 mm×2.1 mm, 1.7 µm); mobile phases, methanol-acetonitrile (2∶8, v/v) solution containing 0.1% formic acid and 0.1% formic acid aqueous solution; flow rate, 0.3 mL/min; injection volume, 10 µL. The compounds were step scanned using an electrospray ionization source in the positive and multiple-reaction monitoring (MRM) modes, and analyzed by internal and external standard methods. The results showed that the 43 compounds achieved high linearity in their respective linear ranges, with correlation coefficients (r2) greater than 0.996. The limits of detection (LODs) of the 43 antibacterial agents ranged from 0.004 ng/L to 1.000 ng/L, and their limits of quantification (LOQs) ranged from 0.012 ng/L to 3.000 ng/L. The average recoveries ranged from 53.7% to 130.4%, and the relative standard deviations (RSDs) were between 0.9% and 13.2%. The method was successfully applied to the determination of six tap water samples from different districts and six water samples obtained from the Jiangyin section of the Yangtze River and Xicheng Canal. No antibacterial compound was detected in any of the tap water samples, but a total of 20 antibacterial compounds were detected in the river and canal water samples. Among these compounds, sulfamethoxazole showed the highest mass concentrations, ranging from 8.92 to 11.03 ng/L. The types and contents of antibacterials detected in the Xicheng Canal were greater than those found in the Yangtze River, and two kinds of diterpenes, namely tiamulin and valnemulin, were found easily and commonly in water sample. The findings indicate that antibacterial agents are widespread in environmental waters. The developed method is accurate, sensitive, rapid, and suitable for the detection of the 43 antibacterial compounds in water samples.

[The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells].

OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP+ cells was tested by colony-forming units assays (CFU). The cytotoxic effect was further detected by transplant assays ex vivo. Telomerase activity assay, C-circle assay were used to measure the effects of compound on the length mechanism of telomere, RT-PCR was used to detected the changes of telomere. RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP+ cells significantly, slightly arrests the cell cycle at G0/G1 phase, and significantly inhibits colony formation and prolong the progression in MLL-AF9 leukemia mice model. The expression showed that the compound could slow the disease progression in MLL-AF9 leukemia mice significantly. Mechanistically, Nilo 22 could reduce the length of telomere by inhibiting telomerase activity and alternative lengthening of telomere (ALT). CONCLUSION: Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.

Spatial Working Memory Impairment in Patients with Non-neuropsychiatric Systemic Lupus Erythematosus: A Blood-oxygen-level Dependent Functional Magnetic Resonance Imaging Study.

OBJECTIVE: Using ethology and functional magnetic resonance imaging (fMRI) to explore mild cognitive dysfunction and spatial working memory (WM) impairment in patients with systemic lupus erythematosus (SLE) without overt neuropsychiatric symptoms (non-NPSLE) and to study whether any clinical biomarkers could serve as predictors of brain dysfunction in this disease. METHODS: Eighteen non-NPSLE patients and 18 matched subjects were all tested using the Montreal cognitive assessment scale test and scanned using blood-oxygen-level dependent fMRI while performing the n-back task to investigate the activation intensity of some cognition-related areas. RESULTS: Ethology results showed that non-NPSLE patients had mild cognitive dysfunction and memory dysfunction (p < 0.05). The fMRI scan confirmed a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), premotor area, parietal lobe, and supplementary motor area (SMA)/anterior cingulate cortex (ACC) that was activated during the n-back task, with right hemisphere dominance. However, only the right SMA/ACC showed a load effect in the non-NPSLE group; the activation intensity of most WM-related brain areas for the non-NPSLE group was lower than for the control group under 3 memory loads. Further, we found that the activation intensity of some cognition-related areas, including the bilateral caudate nucleus/insula and hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. An inverse correlation existed between individual activation intensity and disease duration. CONCLUSION: Non-NPSLE-related brain damage with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial WM and mild cognitive dysfunction. Patients with longer disease duration would be expected to exhibit increased central nervous system damage.

Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study.

The term "minimal hepatic encephalopathy" (MHE) refers to a population of individuals who have no recognizable clinical symptoms but perform abnormally on neuropsychological and neurophysiological tests. Research shows that MHE patients have impairments in cognition affecting their daily lives that should be treated. This study explored the neural basis of spatial working memory impairment in MHE patients using behavioral test and BOLD-fMRI. Twelve normal controls, twelve cirrhosis patients without MHE and twelve MHE patients took part. The memory quotient of the MHE group (Wechsler Memory Scale-Chinese revised: WMS-CR) was lower than the normal control group and the cirrhosis-without-MHE group, and primarily concerned short-term memory and transient memory. Performance accuracy was lower for the MHE group than the control group and the cirrhosis-without-MHE group, and mean reaction time was prolonged. The fMRI data highlighted a neural network consisting of: bilateral prefrontal cortex (PFC), bilateral premotor area (PreMA), supplementary motor area (SMA) and bilateral parietal areas (PA), which was activated in the n-back task. The load effect of BOLD-fMRI response appeared in all regions of interest (ROI) for the normal control group, but only appeared in PreMA and PA, and did not vary with n-back load in PFC or SMA for the MHE group. Activation intensities for all ROIs were higher for the normal control group than the MHE group, especially in 2-back load. In conclusion, these results demonstrate that MHE patients have debilitated spatial working memory, and that impairments of bilateral PFC, PMA, SMA, and PA commonly lead to spatial working memory dysfunction. Furthermore, PFC impairment may form the neural basis of spatial working memory impairment.

Functional magnetic resonance imaging of methamphetamine craving.

The study aimed to explore the abnormal activation of special brain areas associated with methamphetamine craving using functional magnetic resonance imaging (fMRI) and to reveal the neurobiological basis of addiction. Twenty-six methamphetamine addicts and 26 healthy subjects were scanned by brain fMRI while watching pictures of happy, sad, or methamphetamine to acquire resource data. SPM5 was used to analyze fMRI data to get related brain activation map, and it was found that methamphetamine addicts had high brain activation in cingulate and low activation in frontal lobe when watching methamphetamine-cue pictures. This study demonstrated that methamphetamine addicts had emotion-related brain activation abnormalities.

[Removal of trace nitrobenzene in water by VUV/TiO2/O3].

The removal of trace nitrobenzene in water by the ozone-enhanced VUV photocatalysis process (VUV/TiO2/O3) was investigated, in which low-pressure mercury lamp emitting 185 nm vacuum ultraviolet and titanium dioxide film coated on the titanium plate were used as light source and photocatalyst respectively. The results show that, VUV/TiO2/O3 is an effective method to remove trace nitrobenzene in water, and the pseudo-first-order rate constant of nitrobenzene in the VUV/TiO2/O3 process is 102.8% and 30.8% higher than that in the UV/TiO2/O3 and VUV/O3 respectively. And 50 microg/L nitrobenzene in deionized water is totally removed within 60 s by the VUV/TiO2/O3 process. Higher ozone dosage is beneficial to accelerate nitrobenzene degradation, and the apparent rate constant at ozone dosage of 1.52 mg/L is 134.4% higher than that without ozone addition. Though the rate constant is slightly decreased with increase of nitrobenzene concentration, 170 microg/L nitrobenzene is removed to below the detection limit within 2 min. Common species such bicarbonate and humic acid in water significantly inhibit the removal of nitrobenzene, and the apparent rate constant is reduced 82.9% and 71.6% respectively when 2 mmol/L bicarbonate and 3.2 mg/L humic acid are added into the water. The inverse of the apparent rate constant is linear with the bicarbonate concentration. Trace nitrobenzene in surface water containing bicarbonate and natural organic matter can be removed fast and effectively by the VUV/TiO2/O3 process, and 96% nitrobenzene with initial concentration of 90 microg/L is removed within 4 min and the UV absorbance at 254 nm is also reduced 80%.