[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[Study of incubation period of infection with 2019-nCoV Omicron variant BA.5.1.3].

Objective: To study the incubation period of the infection with 2019-nCoV Omicron variant BA.5.1.3. Methods: Based on the epidemiological survey data of 315 COVID-19 cases and the characteristics of interval censored data structure, log-normal distribution and Gamma distribution were used to estimate the incubation. Bayes estimation was performed for the parameters of each distribution function using discrete time Markov chain Monte Carlo algorithm. Results: The mean age of the 315 COVID-19 cases was (42.01±16.54) years, and men accounted for 30.16%. A total of 156 cases with mean age of (41.65±16.32) years reported the times when symptoms occurred. The log-normal distribution and Gamma distribution indicated that the M (Q1, Q3) of the incubation period from exposure to symptom onset was 2.53 (1.86, 3.44) days and 2.64 (1.91, 3.52) days, respectively, and the M (Q1, Q3) of the incubation period from exposure to the first positive nucleic acid detection was 2.45 (1.76, 3.40) days and 2.57 (1.81, 3.52) days, respectively. Conclusions: The incubation period by Bayes estimation based on log-normal distribution and Gamma distribution, respectively, was similar to each other, and the best distribution of incubation period was Gamma distribution, the difference between the incubation period from exposure to the first positive nucleic acid detection and the incubation period from exposure to symptom onset was small. The median of incubation period of infection caused by Omicron variant BA.5.1.3 was shorter than those of previous Omicron variants.

[Preliminary application of real-time fluorescence recombinase polymerase amplification in Candida albicans].

Objective: To explore the preliminary application effect of real-time fluorescence recombinase polymerase amplification (RPA) in the detection of Candida albicans. Methods: (1) Candida albicans standard strain and negative control bacteria of Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Escherichia coli, Candida glabrata standard strains of respectively 1 mL were collected and their DNA were extracted by yeast/bacterial genomic kit. The specificity of polymerase chain reaction (PCR), real-time fluorescent quantitative PCR, and real-time fluorescence RPA in detecting Candida albicans were analyzed. (2) One Candida albicans standard strain and one negative control bacteria of Candida glabrata standard strain were collected, resuscitated, and counted. Candida albicans was diluted 10 times to 1×10(7) to 1×10(1) colony-forming unit (CFU)/mL. The DNA of the two bacteria were extracted as experiment (1). The sensitivity of PCR, real-time fluorescent quantitative PCR, and real-time fluorescence RPA in detecting Candida albicans were analyzed. The number of cycles for amplification curve to reach the threshold in real-time fluorescent quantitative PCR, and time of appearance of specific amplification curve in real-time fluorescence RPA were recorded and compared with the results in PCR. The detection limit and rate of the above-mentioned 3 methods in detecting Candida albicans were analyzed, and the correlation between concentration of Candida albicans in real-time fluorescence RPA and detection time was analyzed. (3) One standard strain of Candida albicans was collected, and the DNA was extracted as experiment (1) and detected by PCR, real-time fluorescent quantitative PCR, and real-time fluorescence RPA. The total detection time of the above-mentioned 3 methods was recorded, respectively. (4) The DNA of 31 clinical samples of suspected Candida albicans infection and 1 clinical sample of Candida albicans collected from cotton swab were extracted, PCR and real-time fluorescence RPA were carried out, and the positive detection rates of the above-mentioned methods were calculated. The DNA of the clinical samples with positive results in both PCR and real-time fluorescence RPA were extracted by yeast/bacterial genomic kit, chelex-100 boiling method, and repeatedly freeze-thawing with liquid nitrogen method, and real-time fluorescence RPA and PCR were carried out. The negative control bacteria was Candida glabrata in real-time fluorescence RPA, while negative control bacteria in PCR were the same as experiment (1). The positive results in PCR and real-time fluorescence RPA were observed and time for amplification curve to reach the fluorescence threshold in real-time fluorescence RPA was recorded, respectively. Data were processed with linear correlation analysis and t test. Results: (1) Three methods showed positive results in detecting standard strain of Candida albicans, and none of the 5 negative control bacteria showed positive results. (2) As the concentration of bacterial solution of Candida albicans decreased, the number of cycles for the amplification curve to reach the threshold increased in real-time fluorescent quantitative PCR, the time for appearance of specific amplification curve prolonged in real-time fluorescence RPA, and brightness of the gel strip weakened in PCR. None of the negative control bacteria in the above-mentioned 3 detection methods showed corresponding positive results. The detection limit of Candida albicans in real-time fluorescence RPA, PCR, and real-time fluorescent quantitative PCR was 1×10(1) CFU/mL. There was a significant negative correlation between the concentration of Candida albicans and the detection time in real-time fluorescence RPA (r=-0.95, P<0.01). The positive detection rates of PCR and real-time fluorescent quantitative PCR for Candida albicans of 1×10(1) to 1×10(7) CFU/mL were 100%. The positive detection rate of real-time fluorescence RPA for Candida albicans of 1×10(1) CFU/mL was 78%, and the positive detection rate of real-time fluorescence RPA for Candida albicans of 1×10(2) to 1×10(7) CFU/mL was 100%. (3) The total time of PCR, real-time fluorescent quantitative PCR, and real-time fluorescence RPA detection for Candida albicans was 133, 93, and 35 min, respectively. (4) The positive detection rate of real-time fluorescence RPA for 31 clinical samples of suspected Candida albicans infection was 32.26% (10/31), which was slightly lower than 35.48% (11/31) of PCR. Eleven clinical samples showed positive results both in real-time fluorescence RPA and PCR detection. No positive result was observed in the negative control bacteria detected both by real-time fluorescence RPA and PCR. The DNA was extracted by yeast/bacterial genomic extraction kit and chelex-100 boiling method for real-time fluorescence RPA detection. The time for the amplification curve to reach the threshold was (438±13) and (462±12) s, respectively, which was close (t=1.32, P>0.05). The DNA was extracted by repeatedly freeze-thawing with liquid nitrogen method for real-time fluorescence RPA, and the time for the amplification curve to reach the threshold in real-time fluorescence RPA was (584±15) s, which was significantly longer than that in the other 2 methods (t=7.55, 6.39, P<0.01). Conclusions: Real-time fluorescence RPA has advantages of rapid detection, simple operation, high sensitivity, and good specificity in detecting Candida albicans, which is worthy of clinical application.

Behavioural responses of piglets to different types of music.

Music or other background sounds are often played in barns as environmental enrichment for animals on farms or to mask sudden disruptive noises. Previous studies looking at the effects of this practice on non-human animal well-being and productivity have found contradictory results. However, there is still a lack of discussion on whether piglets have the ability to distinguish different types of music. In this study, we exposed piglets to different music conditions to investigate whether the piglets preferred certain music types, in which case those types would have the potential to be used as environmental enrichment. In total, 30 piglets were tested for music type preference to determine whether growing pigs respond differently to different types of music. We used music from two families of instruments (S: string, W: wind) and with two tempos (S: slow, 65 beats/min (bpm); F: fast, 200 bpm), providing four music-type combinations (SS: string-slow; SF: string-fast; WS: wind-slow; WF: wind-fast). The piglets were given a choice between two chambers, one with no music and the other with one of the four types of music, and their behaviour was observed. The results showed that SS and WF music significantly increased residence time (P<0.01) compared with the other music conditions. Compared with the control group (with no music), the different music conditions led to different behavioural responses, where SS music significantly increased lying (P<0.01) and exploration behaviour (P<0.01); SF music significantly increased tail-wagging behaviour (P<0.01); WS music significantly increased exploration (P<0.01); and WF music significantly increased walking, lying, standing and exploration (all P<0.01). The results also showed that musical instruments and tempo had little effect on most of the behaviours. Fast-tempo music significantly increased walking (P=0.02), standing (P<0.01) and tail wagging (P=0.04) compared with slow-tempo music. In conclusion, the results of this experiment show that piglets are more sensitive to tempo than to musical instruments in their response to musical stimulation and seem to prefer SS and WF music to the other two types. The results also suggest a need for further research on the effect of music types on animals.

[Application of recombinase polymerase amplification in the detection of Pseudomonas aeruginosa].

Objective: To establish an optimized method of recombinase polymerase amplification (RPA) to rapidly detect Pseudomonas aeruginosa in clinic. Methods: (1) The DNA templates of one standard Pseudomonas aeruginosa strain was extracted and detected by polymerase chain reaction (PCR), real-time fluorescence quantitative PCR and RPA. Time of sample loading, time of amplification, and time of detection of the three methods were recorded. (2) One standard Pseudomonas aeruginosa strain was diluted in 7 concentrations of 1×10(7,) 1×10(6,) 1×10(5,) 1×10(4,) 1×10(3,) 1×10(2,) and 1×10(1) colony forming unit (CFU)/mL after recovery and cultivation. The DNA templates of Pseudomonas aeruginosa and negative control strain Pseudomonas putida were extracted and detected by PCR, real-time fluorescence quantitative PCR, and RPA separately. The sensitivity of the three methods in detecting Pseudomonas aeruginosa was analyzed. (3) The DNA templates of one standard Pseudomonas aeruginosa strain and four negative control strains (Staphylococcus aureus, Acinetobacter baumanii, Candida albicans, and Pseudomonas putida) were extracted separately, and then they were detected by PCR, real-time fluorescence quantitative PCR, and RPA. The specificity of the three methods in detecting Pseudomonas aeruginosa was analyzed. (4) The DNA templates of 28 clinical strains of Pseudomonas aeruginosa preserved in glycerin, 1 clinical strain of which was taken by cotton swab, and negative control strain Pseudomonas putida were extracted separately, and then they were detected by RPA. Positive amplification signals of the clinical strains were observed, and the detection rate was calculated. All experiments were repeated for 3 times. Sensitivity results were analyzed by GraphPad Prism 5.01 statistical software. Results: (1) The loading time of RPA, PCR, and real-time fluorescence quantitative PCR for detecting Pseudomonas aeruginosa were all 20 minutes. In PCR, time of amplification was 98 minutes, time of gel detection was 20 minutes, and the total time was 138 minutes. In real-time fluorescence quantitative PCR, amplification and detection could be completed simultaneously, which took 90 minutes, and the total time was 110 minutes. In RPA, amplification and detection could also be completed simultaneously, which took 15 minutes, and the total time was 35 minutes. (2) Pseudomonas putida did not show positive amplification signals or gel positive results in any of the three detection methods. The detection limit of Pseudomonas aeruginosa in real-time fluorescence quantitative PCR and PCR was 1×10(1) CFU/mL, and that of Pseudomonas aeruginosa in RPA was 1×10(2) CFU/mL. In RPA and real-time fluorescence quantitative PCR, the higher the concentration of Pseudomonas aeruginosa, the shorter threshold time and smaller the number of cycles, namely shorter time for detecting the positive amplified signal. In real-time fluorescence quantitative PCR, all positive amplification signal could be detected when the concentration of Pseudomonas aeruginosa was 1×10(1)-1×10(7) CFU/mL. In RPA, the detection rate of positive amplification signal was 0 when the concentration of Pseudomonas aeruginosa was 1×10(1) CFU/mL, while the detection rate of positive amplification signal was 67% when the concentration of Pseudomonas aeruginosa was 1×10(2) CFU/mL, and the detection rate of positive amplification signal was 100% when the concentration of Pseudomonas aeruginosa was 1×10(3)-1×10(7) CFU/mL. (3) In RPA, PCR, and real-time fluorescence quantitative PCR, Pseudomonas aeruginosa showed positive amplification signals and gel positive results, but there were no positive amplification signals or gel positive results in four negative control strains of Acinetobacter baumannii, Staphylococcus aureus, Candida albicans, and Pseudomonas putida. (4) In RPA, 28 clinical strains of Pseudomonas aeruginosa preserved in glycerin and 1 clinical strain of Pseudomonas aeruginosa taken by cotton swab showed positive amplification signals, while Pseudomonas putida did not show positive amplification signal. The detection rate of positive amplification signal of 29 clinical strains of Pseudomonas aeruginosa in RPA was 100%. Conclusions: The established optimized RPA technology for fast detection of Pseudomonas aeruginosa requires shorter time, with high sensitivity and specificity. It was of great value in fast detection of Pseudomonas aeruginosa infection in clinic.

microRNA-21 mediates the TGF-ß1-induced migration of keratinocytes via targeting PTEN.

OBJECTIVE: The aim of this study was to investigate the molecular mechanism into the keratinocyte migration, which is promoted by Transforming growth factor-ß1 (TGF-ß1) during wound healing. MATERIALS AND METHODS: In the present study, we investigated the regulation by TGF-ß1 on phosphatase and tensin homolog (PTEN) expression, and microRNA-21 (miR-21) level with real-time quantitative PCR or/and Western blotting, and then examined the regulatory role of miR-21 on the PTEN expression and the mesenchymal transition, with real-time quantitative PCR, western blotting and luciferase reporter assay, and the migration of keratinocytic HaCaT cells with scratch assay. RESULTS: It was demonstrated that miR-21 was upregulated by TGF-ß1 treatment in HaCaT cells; and the upregulated miR-21 targeted the 3' UTR of PTEN gene and downregulated the PTEN expression, along with the Smad3/4 upregulation. Moreover, the miR-21 manipulation with miR-21 mimics or miR-21 inhibitor not only upregulated or downregulated the miR-21 level, but also associated with the mesenchymal transition and the migration of HaCaT cells via promoting or downregulating the FSP1 and Collagen I and the E-cadherin, and via upregulating or downregulating the migration of HaCaT cells. CONCLUSIONS: Our results demonstrate that miR-21 mediates the TGF-ß1-promoted mesenchymal transition and migration of keratinocytes during skin wound healing via targeting PTEN. This study implies that miR-21 might be an important target to promote the skin wound healing.

Celecoxib inhibits cell growth and modulates the expression of matrix metalloproteinases in human osteosarcoma MG-63 cell line.

OBJECTIVE: The goal of this study was to determine the effect of celecoxib, a selective COX-2 inhibitor, on the growth inhibition of osteosarcoma and its potential anticancer mechanisms. MATERIALS AND METHODS: Human osteosarcoma cell line MG-63 was used as a model. The inhibitory effect of celecoxib on cell proliferation was assessed by MTT assay. Flow cytometric analysis was used to detect the effects of celecoxib on cell cycle and apoptosis. Western blot analysis was used to detect the protein expression of RECK, matrix metalloproteinase (MMP)-2 and MMP-9 in celecoxib-treated MG-63 cells. RESULTS: MTT assays showed that at a range of concentrations (0-80 µg/ml), celecoxib significantly inhibited the MG-63 cell proliferation in a time- and concentration-dependent manner. The half maximal inhibitory concentration (IC50) of celecoxib was 47.5 µg/ml for 24 h-treatment and 19.2 µg/ml for 48 h-treatment. Flow cytometric analysis demonstrated that treatment with 20 µg/ml celecoxib led to a significant cell cycle arrest at S-phase and an enhancement of apoptosis induction in MG-63 cells at 24 or 48h. Moreover, compared with 24 h-treatment, 48 h-treatment induced more S-phase arrest and apoptosis in MG-63 cells. Western blot analyses revealed that the expression of MMP-2 and MMP-9 was markedly down-regulated but RECK, an inhibitor of MMPs, was markedly up-regulated in MG-63 cells exposed to 20 µg/ml celecoxib for 24 or 48h. Furthermore, the effects of celecoxib on the expression of these molecules were more evident with the increase of treatment time. CONCLUSIONS: Celecoxib inhibits the MG-63 cells proliferation through S-phase arrest and apoptosis induction. Celecoxib-induced down-regulation of MMP-2 and MMP-9 and up-regulation of RECK may contribute to the apoptosis induction and an alteration in local tumor microenvironment. These findings suggest that celecoxib may exert at least in part of its anticancer effects via up-regulation of RECK to inhibit the expression of MMP-2 and MMP-9.

Effect of intravesical botulinum neurotoxin-A injection on detrusor hyperreflexia in spinal cord injured patients.

PURPOSE: To evaluate the effects of Botulinum Toxin A injection into the detrusor muscle on various voiding parameters in spinal cord injured patients with neurogenic detrusor hyperreflexia Materials and methods: 24 patients with spinal cord injuries who had detrusor overactivity and urinary incontinence and were refractory to oral medications, were injected 300 IU of BTX-A into the detrusor muscle. The pre-and post-treatment evaluations included determination of bladder urinary continence status, frequency/volume chart of CIC, Incontinence Quality of Life questionnaire (I-QOL) and patient satisfaction. The urodynamic parameters measured included maximum cystometric capacity (MCC), reflex detrusor volume (RDV) and maximum detrusor pressure during bladder contraction (MDP) were analyzed at the outset and during the follow-up (2, 6, and 24 weeks) examinations. RESULTS: The evaluation of urodynamic parameters during follow-up examinations (2, 6 and 24 weeks) revealed significant increase in mean reflex volume (p<0.05) and cystometric capacity (p<0.05), on the other detrusor pressure decreased significantly (p<0.05). In majority of patients there was considerable reduction in incontinence episodes and no complications or side effects were reported. Most of the patents were satisfied with the treatment. CONCLUSION: The use of Botulinum toxin type A for treatment of neurogenic detrusor overactivity in spinal cord injured patients is safe and efficacious. In our 24-week study period, there was significant improvement in most urodynamic parameters with consistence and subjective satisfaction indicated by the treated patients.

Reduction of galectin-3 expression reduces pituitary tumor cell progression.

We investigated the role of galectin 3 in the development and progression of pituitary tumors. We used RNA interference to depress Gal-3 gene expression; MTT and flow cytometry were applied to detect changes in cell proliferation and apoptosis levels in pituitary tumor cells. Expression of apoptosis-associated genes, Bcl-2 and Baxk was analyzed by Western blot. Inhibition of Gal-3 gene expression by RNA interference decreased GH3 cell proliferation and increased cell apoptosis; the expression levels of Gal-3 protein significantly decreased, along with those of Bcl-2, although Bax levels did not change. We conclude that Gal-3 has an important role in pituitary tumor cell proliferation and progression; and it may be useful as a target for the treatment of aggressive pituitary tumors.

A randomized trial to compare pain control using oral analgesia with epidural analgesia after cesarean section following combined spinal-epidural anesthesia.

This study aimed to evaluate whether combined oral oxycodone hydrochloride-controlled release tablets plus paracetamol and tramadol hydrochloride tablets are more effective than epidural analgesia for postoperative pain control and side effects after cesarean section. We randomly enrolled 60 patients scheduled for cesarean section into either: patient-controlled epidural analgesia with 0.1% ropivacaine+0.1 µg/mL sufentanil (for postoperative 48 h)+injected pethidine on demand (E group); or controlled-release oxycodone (2x15 mg for the first postoperative 24 h; 2x10 mg for the second postoperative 24 h)+paracetamol and tramadol hydrochloride tablets (8x1 tablet for the postoperative 48 h) orally+injected pethidine on demand (O group). The E group experienced more evoked pain and uterine cramping pain at all times postoperatively. The patients who received oral analgesia had less resting pain at 6, 12, 24, and 36 h after surgery. Two patients in the E group injected pethidine (150 mg total) during the oxytocin infusion, whereas none of the O group patients injected pethidine. Pruritus was more common in the E group (P<0.05). Maternal satisfaction with the analgesia regimen was lower in the E group (P<0.01). The median duration of hospital stay was about 5 days for both groups. Postoperative pain control after cesarean section with oral oxycodone hydrochloride-controlled release tablets plus paracetamol and tramadol hydrochloride tablets is preferable to epidural analgesia, even when side effects and maternal satisfaction are taken into account.

Significant pathways detection in osteoporosis based on the bibliometric network.

BACKGROUND: Osteoporosis is a significant public health issue worldwide. The underlying mechanism of osteoporosis is an imbalance between bone resorption and bone formation. However, the exact pathology is still unclear, and more related genes are on demand. AIM: Here, we aim to identify the differentially expressed genes in osteoporosis patients and control. MATERIALS AND METHODS: Biblio-MetReS, a tool to reconstruct gene and protein networks from automated literature analysis, was used for identifying potential interactions among target genes. Relevant signaling pathways were also identified through pathway enrichment analysis. RESULTS: Our results showed that 56 differentially expressed genes were identified. Of them, STAT1, CXCL10, SOCS3, ADM, THBS1, SOD2, and ERG2 have been demonstrated involving in osteoporosis. Further, a bibliometric network was constructed between DEGs and other genes through the Biblio-MetReS. CONCLUSIONS: The results showed that STAT1 could interact with CXCL10 through Toll-like receptor signaling pathway and Chemokine signaling pathway. STAT1 interacted with SOCS3 through JAK/STAT pathway.

The effects of metabotropic glutamate receptor 7 allosteric agonist N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride on developmental sevoflurane neurotoxicity: role of extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase signaling pathway.

The present study was designed to evaluate the possible neuroprotective effects of metabotropic glutamate receptor (mGluR7) allosteric agonist N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082) on developmental sevoflurane neurotoxicity. To achieve the objective, hippocampal cultures (7 DIV, 7 day in vitro) were treated with different doses of L-(+)-2-amino-4-phosphonobutyric acid (L-AP4, an agonist of group III mGluRs), (RS)-α-Methylserine-O-phosphate (MSOP, an antagonist of group III mGluRs), AMN082 or cis-2-[[(3,5-dichlorophenyl)amino]carbonyl]cyclohexanecarboxylic acid (VU0155041, an agonist of mGluR4) before exposed to sevoflurane. Cell apoptosis were determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)-staining. For in vivo study, rat pups (7 PND, 7 postnatal day) were injected with AMN082, L-AP4 or saline before sevoflurane exposure. Extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, caspase-3, Bcl-2, and Bax were detected by Western blot. The locomotor activity and cognitive functions were evaluated by open-field test and Morris water maze (MWM), respectively. We found that L-AP4 prevented sevoflurane-induced cell apoptosis, but MSOP promoted. Specially, application of AMN082 contributed to the relief of sevoflurane-induced apoptosis in vitro, whereas VU0155041 did not. In addition, sevoflurane treatment led to a decrease of Bcl-2 and an increase of caspase-3 and Bax, which were mitigated by AMNO82 in vivo. Moreover, we showed that sevoflurane treatment resulted in a remarkable suppression of phospho-ERK1/2, which was restored by AMN082. Application of U0126 (an inhibitor of MEK) abolished the neuroprotective effects of AMN082 on sevoflurane neurotoxicity both in vitro and in vivo. In addition, sevoflurane exposure also led to an increase of phospho-JNK, but SP600125 (an inhibitor of JNK) did not attenuate sevoflurane-induced apoptosis. The total and phosphorylated p38 remained unchanged in sevoflurane-treated rat pups. Finally, AMN082 improved the learning and memory defects caused by postnatal sevoflurane exposure without alternations in emotion or locomotor activity. These preliminary data indicate that AMN082 may protect immature brain against sevoflurane neurotoxicity, and the ERK1/2 MAP kinase signaling is likely to be involved. Further studies are needed to fully assess the neuroprotective role of mGluR7 agonist AMN082 in developmental anesthetic neurotoxicity.

Changes of axial and radial diffusivities in cerebral white matter led by normal aging.

PURPOSE: Purpose of the study is to reveal the changes of directional diffusion in cerebral white matter (WM) by normal aging. MATERIALS AND METHODS: Thirty-nine volunteers were recruited to examine the changes in the directional diffusion of cerebral white matter (WM) due to normal aging. RESULTS: No significant difference between the older and younger group (P>.05) was detected in the axial diffusivity (λ(ll)) of any of the regions of interest (ROI), while radial diffusivity (λ(perpendicular)) was significantly higher in the older group (P<.05) except for occipital lobe WM. CONCLUSION: λ(ll) and λ(perpendicular) may be used as in vivo markers that differentially and specifically reflect the WM changes of normal aging.

Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding.

The tumor suppressor activity of the BRCA1 gene product is due, in part, to functional interactions with other tumor suppressors, including p53 and the retinoblastoma (RB) protein. RB binding sites on BRCA1 were identified in the C-terminal BRCT domain (Yarden and Brody, 1999) and in the N-terminus (aa 304-394) (Aprelikova et al., 1999). The N-terminal site contains a consensus RB binding motif, LXCXE (aa 358-362), but the role of this motif in RB binding and BRCA1 functional activity is unclear. In both in vitro and in vivo assays, we found that the BRCA1:RB interaction does not require the BRCA1 LXCXE motif, nor does it require an intact A/B binding pocket of RB. In addition, nuclear co-localization of the endogenous BRCA1 and RB proteins was observed. Over-expression of wild-type BRCA1 (wtBRCA1) did not cause cell cycle arrest but did cause down-regulation of expression of RB, p107, p130, and other proteins (e.g., p300), associated with increased sensitivity to DNA-damaging agents. In contrast, expression of a full-length BRCA1 with an LXCXE inactivating mutation (LXCXE-->RXRXH) failed to down-regulate RB, blocked the down-regulation of RB by wtBRCA1, induced chemoresistance, and abrogated the ability of BRCA1 to mediate tumor growth suppression of DU-145 prostate cancer cells. wtBRCA1-induced chemosensitivity was partially reversed by expression of either Rb or p300 and fully reversed by co-expression of Rb plus p300. Our findings suggest that: (1) disruption of the LXCXE motif within the N-terminal RB binding region alters the biologic function of BRCA1; and (2) over-expression of BRCA1 inhibits the expression of RB and RB family (p107 and p130) proteins.

Etiologic studies of epidemic hemorrhagic fever (hemorrhagic fever with renal syndrome).

Two strains of epidemic hemorrhagic fever (EHF) virus were isolated from the lung tissues of Apodemus agrarius mice that were captured in an area where EHF is endemic. The strains were isolated by passages in A. agrarius mice from a nonendemic area. Identification of the isolates by usual procedures was confirmed by repeated blind tests with coded sera. Contamination with certain known viruses such as reovirus, adenovirus (types 3 and 7), and other pathogens, such as murine typhus rickettsiae and Leptospira, which may be naturally present in wild rodents, appeared to have been ruled out. The antigen slides made from these isolates are in use in the specific diagnosis and seroepidemiologic studies of EHF. The first successful application is the serodiagnosis of a mild type of hemorrhagic fever that occurs with characteristic epidemiologic features in certain provinces of China.