[Characteristics and recovery of hearing loss in 573 patients with bacterial meningitis].

Objective: To analyze the characteristics and prognosis of hearing loss in children with bacterial meningitis. Methods: This was a single-center retrospective cohort study. Patients diagnosed with bacterial meningitis who were hospitalized in Beijing Children's Hospital between 2010 and 2016 and older than 28 days and younger than 18 years at symptom onset were included in this study (n=573). All clinical information including hearing assessment results during hospitalization were reviewed. All patients with hearing loss were followed up to repeat their hearing test and assess their hearing condition with parents' evaluation of aural and (or) oral performance of children (PEACH). Patients were grouped according to their hearing assessment results, and Logistic regression analysis was used to analyze the risk factors for hearing loss in patients with bacterial meningitis. Results: Five hundred and seventy-three patients were enrolled in this study, including 347 males and 226 females. The onset age ranged from 29 days to 15.8 years. Two hundred and forty-six patients had identified causative pathogens, among whom 92 cases (37.4%) were pneumococcal meningitis cases. Hearing loss was found in 160 cases (27.9%) during hospitalization, involving 240 ears. Permanent hearing loss was found in 20 cases (16.9%), involving 32 ears. In the patients with permanent hearing loss, 87.5% (28/32) of ears were identified as severe or profound hearing loss during hospitalization. Logistic regression analysis showed that dystonia, the protein concentration level in cerebrospinal fluid>1 g/L, glucose concentration level lower than 1 mmol/L and subdural effusion were independent risk factors for hearing loss (OR=2.426 (1.450-4.059), 1.865 (1.186-2.932), 1.544 (1.002-2.381) and 1.904 (1.291-2.809)). Conclusions: Hearing loss is a common sequela of bacterial meningitis in children. Most patients have transient hearing loss, but patients with severe or profound hearing impairment have a higher risk of developing permanent hearing loss.

Roles of peripheral B1 cells in the individualized treatment of adult idiopathic thrombocytopenic purpura.

We aimed to explore the changes of peripheral B1 cells before and after treatment of adult idiopathic thrombocytopenic purpura (ITP) and to investigate the association of these changes with the disease condition and prognosis. Ninety-seven ITP patients were divided into the effective or ineffective groups, based on their response to hormone therapy. Forty healthy volunteers were enrolled into the control group (HC). The percentages of CD19+ cells, B1 cells, and platelet-associated immunoglobulin (PAIg) in peripheral blood from healthy volunteers and ITP patients before and after treatment were evaluated, and blood platelet (PLT) counts were determined. The percentages of CD19+ cells [(21 ± 10.0) vs (11.2 ± 7.1)%], B1 cells [(8.85 ± 5.23) vs (2.2 ± 1.3)%], and PAIg [(28 ± 19) vs (11.7 ± 8)%] in whole blood from ITP patients before treatment were significantly higher than those in whole blood from healthy controls (P < 0.05). Before treatment, the percentage of B1 cells and PAIg in ITP patients was negatively correlated with the PLT level (r = -0.89, P < 0.05 and r = -0.814, P < 0.05, respectively). Further, the B1 cell percentage was positively associated with the PAIg percentage in ITP patients before treatment. In the effective group, the B1 cell percentage was reduced sharply at 1 month after treatment [(2.45 ± 1.75) vs (8.74 ± 5.04)%, P < 0.05)], so as at 3 and 6 months. However, in the ineffective group, there was no difference in the B1 cell percentage before and after treatment [(7.9 ± 5.6) vs (8.76 ± 5.26)%]. This obvious association of changes in peripheral B1 cells with disease condition and prognosis in ITP patients may be of certain clinical significance for guiding the individualized treatment of ITP.

Long-term inhibition of Rho-kinase restores the LTP impaired in chronic forebrain ischemia rats by regulating GABAA and GABAB receptors.

We previously demonstrated that inactivation of Rho-kinase by hydroxyfasudil could impact N-methyl-d-aspartate (NMDA) excitatory interneurons in the hippocampus and attenuate the spatial learning and memory dysfunction of rats caused by chronic forebrain hypoperfusion ischemia. Complementary interactions between the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter GABA form the molecular basis of synaptic plasticity and cognitive performance. However, whether the GABAergic inhibitory interneurons are involved in the mechanisms underlying these processes remains unclear. Here, we further examined the role of GABAergic interneurons in the neuroprotective effect of the Rho-kinase inhibitor. Chronic forebrain ischemia was induced in Wistar rats by bilateral common carotid artery occlusion (BCAO). The general synaptic transmission and long-term potentiation (LTP) of hippocampal CA3 neurons were evaluated at 30 days after sham surgery or BCAO. Real-time PCR and Western blot analyses were conducted to determine the effect of the Rho-kinase inhibitor hydroxyfasudil on GABAergic inhibitory interneuron expression and function after ischemia. Hydroxyfasudil showed no significant effect on general synaptic transmission, but it could abolish the inhibition of LTP induced by chronic forebrain ischemia. Moreover, the mRNA and protein levels of GABAA and GABAB in three brain regions after ischemia were markedly decreased, and hydroxyfasudil could up-regulate all mRNA and protein expression levels in these areas except for GABAA mRNA in the cerebral cortex and striatum. Using phosphorylation antibodies against specific sites on the GABAA and GABAB receptors, we further demonstrated that hydroxyfasudil could inhibit GABAergic interneuron phosphorylation triggered by the theta burst stimulation. In summary, our results indicated that the inactivation of Rho-kinase could enhance GABAA and GABAB expressions by different mechanisms to guarantee the induction of hippocampal LTP, and it could decrease the phosphorylation level of GABAergic inhibitory interneurons to promote the LTP induction rate and magnitude, hence improving the cognitive deficit suffered after chronic forebrain ischemia.

ZNT7 and Zn2+ are present in different cell populations in the mouse testis.

The aim of the present study was to investigate the relation of the spatial distribution between ZNT7 and chelatable zinc ions in the mouse testis. Immunohistochemical results demonstrated a wide distribution of ZNT7 in both seminiferous tubules and interstitial tissues of the testis. The spermatocytes and spermatids in the seminiferous tubules showed strong ZNT7 immunoreactivity whereas zinc autometallographic (AMG) staining was absent. Spermatozoa showed a high level of free zinc, but were void of ZNT7 immunoreactivity. No ZNT7 immunoreactivity and AMG grains were found in spermatogonia. Both ZNT7 and chelatable zinc were detected in Sertoli and Leydig cells. Furthermore, double immunofluorescence study demonstrated that the ZNT7 staining overlapped with that of TGN38 (a trans-Golgi marker), suggesting that ZNT7 was localized in the Golgi apparatus in the ZNT7-positive cells. In conclusion, ZNT7 and chelatable zinc were distributed in different cell populations except for Sertoli and Leydig cells in the mouse testis. ZNT7 may be involved in zinc transportation into the Golgi apparatus for protein packaging in the mouse testis.

The impact of components of fine particulate matter on cardiovascular mortality in susceptible subpopulations.

BACKGROUND: Several studies have demonstrated associations between daily mortality and ambient particulate matter less than 2.5 microns in diameter (fine particles or PM2.5). Few, however, have examined the relative toxicities of PM2.5 constituents, including elemental carbon and organic carbon (EC and OC, respectively), nitrates and transition metals. There is also little information about whether associations between PM2.5 constituents and mortality are modified by socioeconomic and demographic factors. AIM: To examine associations of daily cardiovascular mortality with PM2.5 and its constituents after stratification by gender, race/ethnicity and education, using data from six California counties during 2000 to 2003. METHODS: The association of daily counts of cardiovascular mortality with PM2.5 components was analysed using time-series regression analyses. Poisson models with natural splines were used to control for time-varying covariates such as season and weather. Separate models were run after stratification by gender, race/ethnicity (White, Hispanic, Black) and education (high school graduation or not). Models were run for each county and results were combined using random effects meta-analysis. RESULTS: Daily counts of cardiovascular mortality were associated with PM2.5 and several of its species including EC, OC, nitrates, sulphates, potassium, copper and iron. For many of these species, there were significantly higher effect estimates among those with lower educational attainment and Hispanic individuals. For example, while essentially no association was observed for individuals who graduated from high school, an interquartile change in several of the components of PM2.5 was associated with a 3-5% increase in daily mortality among non-high school graduates. CONCLUSION: There is evidence that several PM2.5 constituents may represent important contributors to cardiovascular mortality. Many of these constituents are generated by motor vehicles, especially those with diesel engines, and by residential wood combustion. In addition, factors associated with low educational attainment may increase susceptibility to PM2.5 and its components.

Biobleach boosting effect of recombinant xylanase B from the hyperthermophilic Thermotoga maritima on wheat straw pulp.

The recombinant xylanase B (XynB) of Thermotoga maritima MSB8 was found to be highly specific towards xylans and exhibit very low activity towards carboxymethylcellulose in previous study. XynB was thermostable at neutral to alkaline pH region at 90 degrees C and retained more than 90% activity after 1 h over the pH range of pH 6.1 to 11.1. The suitability of XynB for use in the biobleaching of wheat straw pulp was investigated. Pretreatment of the pulp with XynB resulted in a substantial improvement in the bleachability of wheat straw pulp. When XynB at 10 U g(-1) was used to treat wheat straw pulp, it reduced pulp kappa number by 1.1 point, enhanced pulp brightness by 5.5% (% ISO) and improved other pulp properties, such as tensile index and breaking length. Biobleaching of wheat straw pulp with XynB saved active chlorine up to 34.5% while still maintaining the brightness at the control level. Besides, pretreatment of pulp with XynB was also effective at an alkaline pH as high as pH 10.1. This is the first report on the potential application of XynB from T. maritima MSB8 in the pulp and paper sector.

Characterization of a cellulase-free, neutral xylanase from Thermomyces lanuginosus CBS 288.54 and its biobleaching effect on wheat straw pulp.

A xylanase purified from the thermophilic fungus Thermomyces lanuginosus CBS 288.54 was characterized and its potential application in wheat straw pulp biobleaching was evaluated. Xylanase was purified 33.6-fold to homogeneity with a recovery yield of 21.5%. It appeared as a single protein band on SDS-PAGE gel with a molecular mass of approx. 26.2 kDa. The purified xylanase had a neutral optimum pH ranging from pH 7.0 to pH 7.5, and it was also stable over pH 6.5-10.0. The optimal temperature of the xylanase was 70-75 degrees C and it was stable up to 65 degrees C. The purified xylanase was found to be not glycosylated. The xylanase was highly specific towards xylan, but did not exhibit other enzyme activity. Apparent Km values of the xylanase for birchwood, beechwood, soluble oat-spelt and insoluble oat-spelt xylans were 4.0, 4.7, 2.0 and 23.4 mg ml-1, respectively. The potential application of the xylanase was further evaluated in biobleaching of wheat straw pulp. The brightness of bleached pulps from the xylanase pretreated wheat straw pulp was 1.8-7.79% ISO higher than that of the control, and showed slightly lower tensile index and breaking length than the control. Although chlorine consumption was reduced by 28.3% during bleaching, the xylanase pretreated pulp (15 U g-1 pulp) still maintained its brightness at the control level. Besides, pretreatment of pulp with the xylanase was also effective at an alkaline pH as high as pH 10.0.

A preliminary study of chromium distribution in chromium-rich brewer's yeast cell by NAA.

The purpose of this study was to assess the chromium (Cr) distribution in chromium-rich brewer's yeast cell. The chromium concentrations in the cell wall and protoplast fractions of the chromium-rich yeast were determined by neutron activation analysis (NAA). Moreover, the combined state of chromium and amino acid content in the Cr-rich brewer's yeasts was analyzed and measured. The experimental results indicate that the introduction of water-soluble chromium(III) salt as a component of the culture medium for yeasts results in a substantial amount of chromium absorbed through the cell wall by the yeast, among which 80.9% are accumulated in the protoplast. It implies that, under optimal conditions, yeasts are capable of accumulating large amounts of chromium and incorporating chromium into organic compounds.

The mechanism of orotidine 5'-monophosphate decarboxylase: catalysis by destabilization of the substrate.

The mechanism of orotidine 5'-monophosphate decarboxylase (OMP decarboxylase, ODCase) was studied using the decarboxylation of orotic acid analogues as a model system. The rate of decarboxylation of 1,3-dimethylorotic acid and its analogues as well as the stability of their corresponding carbanion intermediates was determined. The results have shown that the stability of the carbanion intermediate is not a critical factor in the rate of decarboxylation. On the other hand, the reaction rate is largely dependent on the equilibrium constant for the formation of a zwitterion. Based on these results, we have proposed a new mechanism in which ODCase catalyzes the decarboxylation of OMP by binding the substrate in a zwitterionic form and providing a destabilizing environment for the carboxylate group of OMP.

DNA structures generated during recombination initiated by mismatch repair of UV-irradiated nonreplicating phage DNA in Escherichia coli: requirements for helicase, exonucleases, and RecF and RecBCD functions.

During infection of homoimmune Escherichia coli lysogens ("repressed infections"), undamaged nonreplicating lambda phage DNA circles undergo very little recombination. Prior UV irradiation of phages dramatically elevates recombinant frequencies, even in bacteria deficient in UvrABC-mediated excision repair. We previously reported that 80-90% of this UvrABC-independent recombination required MutHLS function and unmethylated d(GATC) sites, two hallmarks of methyl-directed mismatch repair. We now find that deficiencies in other mismatch-repair activities--UvrD helicase, exonuclease I, exonuclease VII, RecJ exonuclease--drastically reduce recombination. These effects of exonuclease deficiencies on recombination are greater than previously observed effects on mispair-provoked excision in vitro. This suggests that the exonucleases also play other roles in generation and processing of recombinagenic DNA structures. Even though dsDNA breaks are thought to be highly recombinagenic, 60% of intracellular UV-irradiated phage DNA extracted from bacteria in which recombination is low--UvrD-, ExoI-, ExoVII-, or Rec(J-)--displays (near-)blunt-ended dsDNA ends (RecBCD-sensitive when deproteinized). In contrast, only bacteria showing high recombination (Mut+ UvrD+ Exo+) generate single-stranded regions in nonreplicating UV-irradiated DNA. Both recF and recB recC mutations strikingly reduce recombination (almost as much as a recF recB recC triple mutation), suggesting critical requirements for both RecF and RecBCD activity. The mismatch repair system may thus process UV-irradiated DNA so as to initiate more than one recombination pathway.

Reactions of proton-bound dimers.

Thermal reactions of proton-bound dimers, (CH3CN)2H (+), (CH3OCH3)2H (+), and (CH3COCH3)2H(+), were studied using a selected ion flow tube. Reactions observed include association, switching, and proton transfer. The association channel was observed only for base molecules that had hydrogen bonding protons such as NH3, CH3NH2, (CH3)2NH, and CH3OH. An association-insertion mechaniSoc was proposed in which the central proton of the symmetrically bound dimers is replaced by a protonated base, for example, NH 4 (+) . These reactions are relatively slow, which demonstrates a central barrier along the potential energy surface. Ether-containing dimers do not demonstrate this insertion reaction, except for diethers, for example, CH3OCH2CH2OCH3, which can form stable bicyclic structures. Dimers such as (HCOOH)2H(+), which possess hydrogen bonding protons in the periphery, undergo switching reactions with ammonia and no insertion.

Recombinagenic processing of UV-light photoproducts in nonreplicating phage DNA by the Escherichia coli methyl-directed mismatch repair system.

Nonreplicating lambda phage DNA in homoimmune Escherichia coli lysogens provides a useful model system for study of processes that activate DNA for homologous recombination. We measured recombination by extracting phage DNA from infected cells, using it to transfect recA recipient cells, and scoring the frequency of recombinant infective centers. With unirradiated phage, recombinant frequencies were less than 0.1%. However, recombination could be increased over 300-fold by prior UV irradiation of the phages. The dependence of recombination on UvrA function varied greatly with UV dose. With phage irradiated to 20 J/m2, recombinant frequencies in repressed infections of uvr+ bacteria were one-fifth those in uvrA infections; with phages irradiated to 100 J/m2, frequencies in uvr+ infections were thirty times higher than in uvrA infections. Most UV-stimulated recombination in uvrA infections appeared to depend on the bacterial methyl-directed mismatch-repair system: frequencies were depressed 5-20-fold in uvrA bacteria also lacking MutH, MutL or MutS functions, and recombinant frequencies decreased with increasing GATC-adenine methylation of phage stocks. The biological activity of nonreplicating UV-irradiated phage DNA declined with time after infection of uvrA cells; this decline was photoproduct-dependent, more marked for undermethylated than overmethylated phage DNA, and depended on host MutHLS functions. In uvr+ bacteria, where the UvrABC system provided an alternative, apparently less efficient, route to recombinagenic DNA, UV-stimulated recombinant frequencies were about twice as high in mutH or mutLS as in mut+ cells, in agreement with hyper-rec mut effects previously described by others.