A Multimodal Neural Activity Readout Integrated Circuit for Recording Fluorescence and Electrical Signals

Monitoring the electrical neural signals is an important method for understanding the neuronal mechanism. In particular, in order to perform a cell-type-specific study, it is necessary to observe the concentration of calcium ions using fluorescent indicators in addition to measuring the electrical neural signal. This paper presents a multimodal multichannel neural activity readout integrated circuit that can perform not only electrical neural recording but also fluorescence recording of neural activity for the cell-type-specific study of heterogeneous neuronal cell populations. For monitoring the calcium ions, the photodiode generates the current according to the fluorescence expressed by the reaction between the genetically encoded calcium indicators and calcium ions. The time-based fluorescence recording circuit then records the photodiode current. The electrical neural signal captured by the microelectrode is recorded through the low-noise amplifier, variable gain amplifier, and analog-to-digital converter. The proposed integrated circuit is fabricated in a 1-poly 6-metal (1P6M) 0.18- ??m CMOS process. The fluorescence recording circuit achieves a recording range of 81 dB (75 pA to 860 nA) and consumes a power of 724 nW/channel. The electrical recording circuit achieves an input-referred noise of 2.7 ??Vrms over the bandwidth of 10 kHz, while consuming the power of 4.9 ??W /channel. The functionality of the proposed circuits is verified through the in vivo and in vitro experiments. Compared to the conventional neuroscience tools, which consist of bulky off-chip components, this neural interface is implemented in a compact size to perform multimodal neural recording while consuming low power

Manual Acupuncture at PC6 Ameliorates Acute Restraint Stress-Induced Anxiety in Rats by Normalizing Amygdaloid Noradrenergic Response

Acupuncture improves ethanol withdrawal-induced anxiety in rats in an acupoint-dependent manner. Thus, the present study investigated the effects of acupuncture on acute restraint stress- (ARS-) induced anxiety. Male rats were exposed to ARS for 3 h followed by acupuncture at either PC6 (Neiguan), HT7 (Shenmen), or a nonacupoint (tail) once a day for three consecutive days. Five minutes after the third acupuncture treatment, anxiety-like behavior was evaluated in an elevated plus maze (EPM). Additionally, plasma corticosterone (CORT) levels were measured by radioimmunoassay and the concentrations of norepinephrine (NE) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the central nucleus of the amygdala (CeA) were determined using high-performance liquid chromatography. Acupuncture at PC6, but not HT7 or a nonacupoint, attenuated anxiety-like behavior, but this attenuation was abolished by a postacupunctural intra-CeA infusion of NE. Acupuncture at PC6 also reduced the oversecretion of plasma CORT and inhibited increases in amygdaloid NE and MHPG induced by ARS. Further, Western blot analyses and real-time polymerase chain reaction assays revealed that acupuncture at PC6 prevented ARS-induced enhancements in the protein and mRNA expressions of tyrosine hydroxylase in the CeA. These results suggest that acupuncture performed specifically at acupoint PC6 reduces ARS-induced anxiety-like behavior by dampening amygdaloid noradrenergic responses

Helicobacter pylori infection combined with DENA revealed altered expression of p53 and 14-3-3 isoforms in Gulo−/− mice

AbstractUnlike most other mammals, human bodies do not have the ability to synthesize vitamin C inside of their own bodies. Therefore, humans must obtain vitamin C through daily diet. Gulo−/− mice strain is known with deficiency, in which vitamin C intake can be controlled by diet like human, and would be valuable for investigating the molecular mechanism of various diseases. In the present study, we established Gulo−/− mice model and investigated the differentially expressed proteins in stomach tissue of Gulo−/− mice after Helicobacter pylori-infected, and followed by DENA, using immunohistochemistry and proteomic approach. The results of immunohistochemistry analysis of stomach tissue showed that the tumor suppressor, p53 protein, expression was significantly decreased (p<0.05) but not messenger RNA (mRNA) transcriptional level, and 14-3-3ε, 14-3-3δ, Ki-67 and cleaved caspase 3 expressions were significantly increased (p<0.05) by H. Pylori infection, and followed by DENA treatment in Gulo−/− mice. Moreover, knockdown of 14-3-3 isoforms (14-3-3ε, 14-3-3σ, 14-3-3ζ and 14-3-3η) were significantly increased sub-G1 phase (characteristics of apoptosis) in AGS cells and, phenotypic changes like cell shrinkage, density and cleaved nuclei were also observed. Proteome analyses showed that 14-3-3σ, 14-3-3η, and tropomyosin alpha-1 chain were down-regulated, and Hspd1 protein and HSC70 were up-regulated after H. Pylori-infection, and followed by DENA. The combined results of immunohistochemistry and proteomic analysis suggest that H. pylori altered the p53 and 14-3-3 isoforms expression and DENA further enhanced the H. pylori effect, which might be involved in carcinogenesis and metastasis of gastric cancer on Gulo−/− mice

Role of age and sex in determining antibiotic resistance in febrile urinary tract infections

SummaryObjectivesTo identify the age- and sex-specific antimicrobial susceptibility patterns of Gram-negative bacteria (GNB) in outpatient febrile urinary tract infections (UTIs) in Korea.MethodsA total 2262 consecutive samples collected from patients aged 1–101 years with febrile UTIs, during the period January 2012 to December 2014, were analyzed in this multicentre, retrospective cohort study.ResultsThe sensitivities to cefotaxime and cefoxitin were over 85% for females but under 75% for males. Sex played an important role in the susceptibility of GNB to cefotaxime (p<0.001) and cefoxitin (p<0.001). The sensitivity to ciprofloxacin (age >20 years) was under 75% in both sexes, and was not influenced by sex (p=0.204). Age distributions of the incidences of resistance to cefotaxime, cefoxitin, and ciprofloxacin (age >20 years) were similar to the age distribution of the incidence of GNB, which indicates that the resistance patterns to these drugs were not affected by age (Kolmogorov–Smirnov test, female/male: p=0.927/p=0.509, p=0.193/p=0.911, and p=0.077/p=0.999, respectively).ConclusionsAge is not a considerable factor in determining the antibiotic resistance in febrile UTIs. Ciprofloxacin should be withheld from both sexes until culture results indicate its use. Second- or third-generation cephalosporins such as cefoxitin and cefotaxime can be used empirically only in females

Elevated red cell distribution width is associated with advanced fibrosis in NAFLD

Background/AimsThe red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores.MethodsThis study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively.ResultsAfter adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61±0.41% (mean±SD), 12.70±0.70%, 12.77±0.62%, 12.87±0.82%, and 13.25±0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71±0.72%, 12.79±0.66%, and 13.23±1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and ≥2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of ≥1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score.ConclusionsElevated RDW is independently associated with advanced fibrosis in NAFLD

Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head

<p>Abstract</p> <p>Background</p> <p>The pathogenesis of osteonecrosis of the femoral head (ONFH) has been implicated in hypofibrinolysis and blood supply interruption. Previous studies have demonstrated that decreased fibrinolytic activity due to elevated plasminogen activator inhibitor-1 (PAI-1) levels correlates with ONFH pathogenesis. The -675 4G/5G single nucleotide polymorphism (SNP rs1799889) in the PAI-1 gene promoter is associated with PAI-1 plasma level. We investigated whether rs1799889 and two other SNPs of the PAI-1 gene (rs2227631, -844 G/A in the promoter; rs11178, +10700 C/T in the 3'UTR) are associated with increased ONFH risk.</p> <p>Methods</p> <p>Three SNPs in PAI-1 were genotyped in 206 ONFH patients and 251 control subjects, using direct sequencing and a TaqMan^®5' allelic discrimination assay. We performed association analysis for genotyped SNPs and haplotypes with ONFH.</p> <p>Results</p> <p>The 4G allele of rs1799889, A allele of rs2227631, and C allele of rs11178 were significantly associated with increased ONFH risk (p = 0.03, p = 0.003, and p = 0.002, respectively). When we divided the population according to gender, an association between the three SNPs and increased risk of ONFH was found only in men. In another subgroup analysis based on the etiology of ONFH, rs2227631 (A allele) and rs11178 (C allele) in the idiopathic subgroup (p = 0.007 and p = 0.021) and rs1799889 (4G allele) and rs11178 (C allele) in the alcohol-induced subgroup (p = 0.042 and p = 0.015) were associated with increased risk of ONFH. In addition, a certain haplotype (A-4G-C) of PAI-1 was also significantly associated with ONFH (p < 0.001).</p> <p>Conclusion</p> <p>Our findings demonstrated that three SNPs (rs1799889, rs2227631, and rs11178) of the PAI-1 gene were associated with ONFH risk. This study also suggests that PAI-1 SNPs may play an important role in ONFH.</p

Effects of dietary Na+ deprivation on epithelial Na+ channel (ENaC), BDNF, and TrkB mRNA expression in the rat tongue

<p>Abstract</p> <p>Background</p> <p>In rodents, dietary Na⁺deprivation reduces gustatory responses of primary taste fibers and central taste neurons to lingual Na⁺stimulation. However, in the rat taste bud cells Na⁺deprivation increases the number of amiloride sensitive epithelial Na⁺channels (ENaC), which are considered as the "receptor" of the Na⁺component of salt taste. To explore the mechanisms, the expression of the three ENaC subunits (α, β and γ) in taste buds were observed from rats fed with diets containing either 0.03% (Na⁺deprivation) or 1% (control) NaCl for 15 days, by using <it>in situ </it>hybridization and real-time quantitative RT-PCR (qRT-PCR). Since BDNF/TrkB signaling is involved in the neural innervation of taste buds, the effects of Na⁺deprivation on BDNF and its receptor TrkB expression in the rat taste buds were also examined.</p> <p>Results</p> <p><it>In situ </it>hybridization analysis showed that all three ENaC subunit mRNAs were found in the rat fungiform taste buds and lingual epithelia, but in the vallate and foliate taste buds, only α ENaC mRNA was easily detected, while β and γ ENaC mRNAs were much less than those in the fungiform taste buds. Between control and low Na⁺fed animals, the numbers of taste bud cells expressing α, β and γ ENaC subunits were not significantly different in the fungiform, vallate and foliate taste buds, respectively. Similarly, qRT-PCR also indicated that Na⁺deprivation had no effect on any ENaC subunit expression in the three types of taste buds. However, Na⁺deprivation reduced BDNF mRNA expression by 50% in the fungiform taste buds, but not in the vallate and foliate taste buds. The expression of TrkB was not different between control and Na⁺deprived rats, irrespective of the taste papillae type.</p> <p>Conclusion</p> <p>The findings demonstrate that dietary Na⁺deprivation does not change ENaC mRNA expression in rat taste buds, but reduces BDNF mRNA expression in the fungiform taste buds. Given the roles of BDNF in survival of cells and target innervation, our results suggest that dietary Na⁺deprivation might lead to a loss of gustatory innervation in the mouse fungiform taste buds.</p

Newly formed cystic lesions for the development of pneumomediastinum in Pneumocystis jirovecii pneumonia

<p>Abstract</p> <p>Background</p> <p><it>Pneumocystis jirovecii</it>, formerly named <it>Pneumocystis carinii</it>, is one of the most common opportunistic infections in human immunodeficiency virus (HIV)-infected patients.</p> <p>Case presentations</p> <p>We encountered two cases of spontaneous pneumomediastinum with subcutaneous emphysema in HIV-infected patients being treated for <it>Pneumocystis jirovecii </it>pneumonia with trimethoprim/sulfamethoxazole.</p> <p>Conclusion</p> <p>Clinicians should be aware that cystic lesions and bronchiectasis can develop in spite of trimethoprim/sulfamethoxazole treatment for <it>P. jirovecii </it>pneumonia. The newly formed bronchiectasis and cyst formation that were noted in follow up high resolution computed tomography (HRCT) but were not visible on HRCT at admission could be risk factors for the development of pneumothorax or pneumomediastinum with subcutaneous emphysema in HIV-patients.</p