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Although individuals with Asperger syndrome (AS) are often described to be semantic-pragmatic disordered, it is still unclear to what extent their semantic comprehension is impaired. The primary goal of this study is to understand the sentence comprehension of adults with AS by investigating their reading processes of sentences involving the conjunctive entailment of disjunction. More specifically, their on-line processes of reading globally ambiguous sentences containing huo 'or' in Mandarin Chinese, which can be understood as either a conjunction or a disjunction in simple negative statements, were recorded. The results indicated that both AS and typically developing groups tended to interpret the ambiguous huo as a conjunction. Additionally, both groups consistently spent significantly more time judging the appropriateness of disjunction-biased sentences. It is argued that, for adults with AS, at least some aspects of semantic knowledge are intact. Future studies are suggested to focus on different sentence types to further explore to what extent that semantics is impaired among individuals with AS.

Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is E-resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17β-estradiol and the synthetic estrogen E-diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. However, the therapeutic application of resveratrol is limited due to its low bioavailability. To improve its bioavailability and pharmacological activity, some resveratrol derivatives have been designed and synthesized by substitutions of methoxy, hydroxyl, and other functional groups or heterocyclic esterification either on the "A" or "B" ring, and double bonds were replaced by imine bonds and isometric heterocycles such as naphthyl and imidazole, or synthetic resveratrol oligomers. The structures, synthetic routes, and evaluation of the biological activities of these compounds are discussed. These are aimed at providing some references for the study of resveratrol derivatives in anti-breast cancer treatment.

This study examines the nature of stop accuracy and substitute patterns of word-initial Japanese and Mandarin stops produced by Mandarin-Japanese bilingual children. The purpose of the study is to understand phonological development in bilinguals. The sample consists of 36 bilingual children between the ages of three and six, who simultaneously acquired Japanese and Mandarin from birth. The results were as follows: (1) most of the bilingual children were able to produce Mandarin and Japanese stops by the age of three and the accuracy of the target stops were found to develop with age; (2) the age of developing the target consonants is slightly different in the two languages; (3) substitution patterns observed in each language reveals a mixture of child-specific patterns, language specific systems and language influence as well as individual differences. These findings indicate that Mandarin-Japanese bilingual children possess a unique phonological development system, which is a monolinguallike pattern with cross-linguistic interaction. These results constitute a new body of descriptive reference materials documenting the phonological development of bilingual children for speech therapists or pathologists.

Purpose This study explored the speech characteristics of Mandarin-speaking children with cerebral palsy (CP) and typically developing (TD) children to determine (a) how children in the 2 groups may differ in their speech patterns and (b) the variables correlated with speech intelligibility for words and sentences. Method Data from 6 children with CP and a clinical diagnosis of moderate dysarthria were compared with data from 9 TD children using a multiple speech subsystems approach. Acoustic and perceptual variables reflecting 3 speech subsystems (articulatory-phonetic, phonatory, and prosodic), and speech intelligibility, were measured based on speech samples obtained from the Test of Children's Speech Intelligibility in Mandarin (developed in the lab for the purpose of this research). Results The CP and TD children differed in several aspects of speech subsystem function. Speech intelligibility scores in children with CP were influenced by all 3 speech subsystems, but articulatory-phonetic variables had the highest correlation with word intelligibility. All 3 subsystems influenced sentence intelligibility. Conclusion Children with CP demonstrated deficits in speech intelligibility and articulation compared with TD children. Better speech sound articulation influenced higher word intelligibility, but did not benefit sentence intelligibility.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

Canonical babbling (CB) is critical in forming foundations for speech. Research has shown that the emergence of CB precedes first words, predicts language outcomes, and is delayed in infants with several communicative disorders. We seek a naturalistic portrayal of CB development, using all-day home recordings to evaluate the influences of age, language, and social circumstances on infant CB production. Thus we address the nature of very early language foundations and how they can be modulated. This is the first study to evaluate possible interactions of language and social circumstance in the development of babbling. We examined the effects of age (6 and 11 months), language/culture (English and Chinese), and social circumstances (during infant-directed speech [IDS], during infant overhearing of adult-directed speech [ADS], or when infants were alone) on canonical babbling ratios (CBR = canonical syllables/total syllables). The results showed a three-way interaction of infant age by infant language/culture by social circumstance. The complexity of the results forces us to recognize that a variety of factors can interact in the development of foundations for language, and that both the infant vocal response to the language/culture environment and the language/culture environment of the infant may change across age.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

This study sought to improve an existing live attenuated influenza vaccine (LAIV) by including nucleoprotein (NP) from wild-type virus rather than master donor virus (MDV). H7N9 LAIV reassortants with 6:2 (NP from MDV) and 5:3 (NP from wild-type virus) genome compositions were compared with regard to their growth characteristics, induction of humoral and cellular immune responses in mice, and ability to protect mice against homologous and heterologous challenge viruses. Although, in general, the 6:2 reassortant induced greater cell-mediated immunity in C57BL6 mice than the 5:3 vaccine, mice immunized with the 5:3 LAIV were better protected against heterologous challenge. The 5:3 LAIV-induced CTLs also had better in vivo killing activity against target cells loaded with the NP366 epitope of recent influenza viruses. Modification of the genome of reassortant vaccine viruses by incorporating the NP gene from wild-type viruses represents a simple strategy to improve the immunogenicity and cross-protection of influenza vaccines.

To explore the correlation between blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) signal and neurotransmitter γ-aminobutyric acid (GABA) concentration in the prefrontal cortex area after acupuncture or Von Frey filament stimulation (epidermal stimulation) at the right Hegu (LI4).A total of 76 healthy volunteers (23 men and 53 women, 24.5±1.4 years in age) were recruited in the pre-sent study. Each volunteer received two sessions of fMRI magnetic resonance scanning (MRS) examinations, with an interval of one week between two sessions. The MRI scan sequences included pre-task MRS, resting state BOLD and task MRS, BOLD. A region of Interest (ROI) of 35 mmExtensive deactivations were induced by both stimulations, mainly involving the midline regions as the medial prefrontal lobe, and limbic lobe. The deactivation effect of manual acupuncture stimulation was more extensive and intensive than that of Von Frey filament stimulation, especially in the medial prefrontal lobe. Data from 66 volunteers (after exclusion of 10 participants due to bigger standard deviation of GABA/Glx) showed no marked correlation between the GABA concentration and BOLD activation in the anterior cingulate cortex area in both groups(manual acupuncture stimulation group:Acupuncture of LI4 elicits a stronger and broader negative activation effect in the limbic-paralimbic-neocortical network including the medial prefrontal cortex in comparison with Von Frey filament stimulation, but no apparent correlation was found between the GABA concentration and BOLD activation in the anterior cingulate cortex after manual acupuncture and Von Frey stimulation.

This study aimed at improving the understanding of speech characteristics of fricatives produced by five-year-old Mandarin-acquiring children with cerebral palsy (CP). Productions from nine CP children and nine gender-and-age-matched typically developing (TD) children were collected and analyzed. Results from transcription indicated that the CP group had lower production accuracy rates for all the five fricatives in Mandarin Chinese. Additionally, when the CP children failed to articulate the target fricative segments, they tended to delete them or convert them into non-continuant segments. Results from acoustic analyses indicated that the M2 values of the labiodental [f] and the M1 and M2 values of the alveolar [s] were higher among the CP children. The experimental results revealed that: (1) Observable differences were available once the age of the groups was properly controlled and acoustical measurements were adopted; (2) the lack of finer-grained speech motor control abilities among CP children were reflected in the M1 and M2 values; (3) for segments at the anterior places, the clinical group failed to extend the articulatory gestures to the desirable positions. It is suggested that future studies focusing on different age groups and children with different native languages would help to approach the nature of articulatory barriers among individuals with CP.

Aim This study explored the influences of transformational leadership on nurse innovation behaviour and the mediating role of organisational climate. Background Recently, global nursing experts have been aggressively encouraging nurses to pursue innovation in nursing in order to improve nursing outcomes. Nursing innovation, in turn, is affected by nursing leadership. Method We employed a questionnaire survey to collect data, and selected a sample of nurses from hospitals in Taiwan. A total of 439 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. Result The mean values of agreement of nurse innovation behaviour and transformational leadership were 3.40 and 3.78, respectively. Patient safety climate and innovation climate were found to have full mediating effects on the relationship between transformational leadership and innovation behaviour. Conclusion Organisational climate has a significant impact on innovation behaviour. Transformational leadership has indirect effects on innovation behaviour via the mediation of patient safety climate and innovation climate. Implications for nursing management Hospitals should enhance transformational leadership by designing leadership training programmes and establishing transformational culture. In addition, nursing managers should foster nursing innovation through improvements in organisational climate.

H7 subtype influenza viruses have demonstrated an ocular tropism in humans, causing conjunctivitis and not respiratory symptoms in many infected individuals. However, the molecular determinants which confer ocular tropism are still poorly understood. Here, we used a murine model of ocular inoculation to demonstrate that H7 influenza viruses are more likely to cause infection following ocular exposure than are non-H7 subtype viruses. We included investigation regarding the potential role of several properties of influenza viruses with murine infectivity following ocular inoculation, including virus lineage, pathogenicity, and HA cleavage site composition. Furthermore, we examined the potential contribution of internal proteins to murine ocular infectivity. These studies establish a link between H7 subtype viruses and the risk of heightened infectivity in a mammalian species following ocular exposure, and support the development of non-traditional inoculation methods and models to best understand the human risk posed by influenza viruses of all subtypes.

Two different training strategies to improve turning performance in individuals with Parkinson’s disease (PD) were designed and investigated in this study. Subjects were randomly assigned to a specific exercise group, turning-based training group, or control group to receive training that emphasized balance and strengthening, turning-based treadmill training, and general exercise training, respectively. A total of 12 30-min training sessions followed by 10 min of turning training on a level surface were administered over 4 to 6 weeks. The results (n = 12 for each group) showed that both the specific exercise and turning-based training group experienced improved turning performance, the primary outcome, compared with the control group (specific exercise, 33% change, p = 0.016; turning-based training, 35% change, p = 0.021). For the secondary outcomes, the specific exercise group performed better than the control group on the Tinetti balance scale, limit of stability test and lower extremity extensor and abductor strength. The turning-based training groups performed better than the control group in sensory organization and ankle plantar flexor strength. In summary, specific exercise training and turning-based treadmill training were both effective in improving turning performance in participants with PD. However, the improvements in turning performance of these two groups resulted from improving different aspects of impairment in individuals with PD.

The objective of this case study is to present our experience of a surgical approach for vaginal agenesis using an acellular porcine small intestinal submucosa (SIS) graft. The present report involved 2 patients diagnosed as having vaginal agenesis due to Meyer-von-Rokitansky-Küster-Hauser syndrome. The operation procedure involved the creation of a neovaginal tunnel and then a mold wrapped with the SIS graft was placed in the neovagina. The duration of surgery was less than 45 min with minimal blood loss and no operative and postoperative complications. Epithelialization of the neovagina was achieved within 2 months after surgery. The neovagina created with this procedure was the same as that of a normal adult vagina histologically and physiologically. In conclusion, the creation of a neovagina using a SIS graft resulted in a favorable outcome and this approach may be a potential alternative to the management of vaginal agenesis.

There is little information available related to the reproductive health of people with intellectual disability (ID). The aims of the present study are to describe caregiver attitudes and to examine determinants of gynaecological health for women with ID.We recruited 1152 caregivers (response rate=71.87%) and analysed their responses to a mailed-out, self-administered, structured questionnaire. We divided attitudinal perceptions of reproductive health into 4 domains: menstruation, menopause, sex education, and preventive healthcare. Each domain in turn had 5 issues (questions), with scores of 1 to 4 given according to the level of agreement with each issue (low to high score: strongly disagree, disagree, agree, and strongly agree). The total sum score for each domain was 5-20 (total score range: 20-80).The respondents' attitudinal mean score was 57.78±4.64 (range: 48-75). The multiple logistic regression model revealed that the factors of "workplace training in reproductive health" (OR=1.793, 95% CI=1.31-2.46), "felt satisfied with public reproductive health services for the client" (OR=0.694, 95% CI=0.53-0.92), and "scores of reproductive health knowledge" (OR=1.735, 95% CI=1.29-2.34) were significantly correlated with attitudinal score level toward gynaecological health for women with ID.The study highlights that service authorities should address health policy initiatives to continue providing workplace training in reproductive health, public reproductive health services. There is also a need for caregivers to increase their knowledge of reproductive health.

We generated influenza virus-like particles (VLPs) containing the wild type (WT) H5 hemagglutinin (HA) from A/Viet Nam/1203/04 virus or a mutant H5 HA with a deletion of the multibasic cleavage motif. VLPs containing mutant H5 HA were found to be as immunogenic as VLPs containing WT HA. A single intramuscular vaccination with either type of H5 VLPs provided complete protection against lethal challenge. In contrast, the recombinant H5 HA vaccine was less immunogenic and vaccination even with a 5 fold higher dose did not induce protective immunity. VLP vaccines were superior to the recombinant HA in inducing T helper type 1 immune responses, hemagglutination inhibition titers, and antibody secreting cells, which significantly contribute to inducing protective immunity after a single dose vaccination. This study provides insights into the potential mechanisms of improved immunogenicity by H5 VLP vaccines as an approach to improve the protective efficacy against potential pandemic viruses.

This article investigates general physician service use by a national sample of non-Hispanic white and Hispanic Medicare beneficiaries age 65 and older. Using the health behavior model as the conceptual framework, Oaxaca decomposition multivariate analyses were conducted to examine predictors for contact with a physician and the number of physician's office visits. Racial and ethnic differences were found in the predictor variables of initial contact with the physician and volume of physician service use. Besides needs factors, poverty level and having Medicaid were also significant predictors. Oaxaca decomposition analysis indicated that Hispanic beneficiaries' being less likely to make the initial physician contact could not be explained only by racial and ethnic differences. Although findings point to the equitable and nondiscriminatory treatment of Hispanic beneficiaries already using physician services, there is variance in the entry point of contact with a general physician for this minority group. Implications for social work are discussed.

This study aims to establish evidence-based data to explore the perceptions and experience of primary care physicians in the Pap smear screening provision for women with intellectual disabilities (ID), and to analyze the associated factors in the delivery of screening services to women with ID in Taiwan. Data obtained by a cross-sectional survey by a structured, self-administered questionnaire (12 perceptional issues), and were posted to all primary care settings (N = 168) which provided Pap smear tests for women with ID in Taichung and I-Lan counties in Taiwan, Republic of China during the period of 2009. The vital primary care physician of each healthcare setting was the main respondent of the questionnaire. Finally, there were 69 valid questionnaires returned, giving a response rate of 41.7%. The main findings showed that 72.5% medical care settings provide Pap smear services and 51.5% have practical experience on conducting the tests for women with ID. Among the respondents, nearly 90% primary care physicians expressed that women with ID need Pap smear test regularly. With regard to the associated factors in the delivery of Pap smear screening services to women with ID. The study found that experienced healthcare settings in Pap smear tests for women with ID were more likely to be in public healthcare settings, felt confident in providing screening tests, having a rapid screening program and having a reminding follow-up system. Those respondents felt necessity in Pap smear test for women with ID were more likely to express it is needed to set up a special screening clinic for this group of women. The present study suggests that women with ID need thoughtful, well-coordinated care from primary care physicians, to increase access to health care providers may be helpful in improving Pap screening tests for this population.

Although little is known about the incidence of cervical cancer in women with intellectual disabilities (ID), Pap smear screening is an effective public health program to prevent cervical cancer to this group of people. The purposes of this study were to identify and evaluate the factors regarding the utilization of the Pap smears in women with ID seen in the preventive health screening program. We employed a cross-sectional survey "2009 National Survey on Preventive Health Use and Determinants among People with Disabilities", with the study sample 508 women with ID (agedor =15 years) participated in the research in Taiwan. Results showed that there were 22.1% women with ID had ever used Pap smear screening previously and mean age of the first screening was nearly 40 years old. Comparing to the general population in Taiwan, the ID women at age group35 years was less likely to use screening and the age groupor =35 years was more likely to use Pap smears than did the general women. Finally, a logistic regression analysis showed that marital status and had experience of accepted tubal ligation surgery were two factors which predicted Pap smear test use in the study. Those women with ID who had marital status were 8.99 times (95% CI=1.65-49.15) more likely than those had not marital status to use Pap smear test. Women with ID had experience on tubal ligation surgery were 10.48 times (95% CI=1.40-78.26) more likely to use Pap smear test than their counterparts. This study highlights that to acknowledge the rights of women with ID to access Pap smear screening service, health professionals will need to become more flexible and competent in the service that they provide.

BACKGROUND: Prostasin is a glycosylphosphatidylinositol-anchored extracellular serine protease with a role in epidermal growth factor receptor (EGFR) signal modulation. EGFR signaling has been shown to be important for regulating cytotrophoblast (CT) cell proliferation in human placenta. We investigated the impact of prostasin expression regulation on this cellular function as well as the molecular mechanisms involved in human cytotrophoblastic cells. METHODS: An immortalized normal human CT cell line (B6Tert-1) was used as an in vitro cell model. Prostasin expression in B6Tert- 1 cells was knocked down by transfection of a short interfering RNA. Lentivirus-mediated expression of recombinant human prostasin under tetracycline regulation was performed to obtain stable B6Tert-1 cell sublines that over-expressed prostasin. Changes in cell proliferation and EGFR signaling were evaluated by immunocytochemistry for Ki67 and western blot analysis, respectively, in B6Tert-1 cells with knocked-down or increased prostasin expression. RESULTS: Prostasin knock-down in B6Tert-1 cells resulted in inhibition of cell proliferation, in association with down-regulated EGFR protein expression (both P < 0.05 versus control) as well as reduced phosphorylation of c-raf, mitogen-activated protein kinase (MAPK) kinases (MEK1/2) and extracellular signal-regulated kinases (Erk1/2) (all P < 0.05 versus control). Over-expression of prostasin led to up-regulation of the EGFR protein, but had no effect on cell proliferation or phosphorylation of MAPK signaling molecules in the B6Tert-I cells. CONCLUSIONS: Prostasin may regulate trophoblast cell proliferation via modulating the EGFR-MAPK signaling pathway.

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

A recombinant live attenuated influenza virus DeltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the DeltaH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the DeltaH5N1 vaccine in mice.

Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines., Monoclonal antibodies with broadly neutralizing activity are being developed as potential treatment of influenza infections. Here, the authors describe a broadly neutralizing antibody with an unusual mode of binding to viral haemagglutinin, which has been isolated from patients convalescent from pandemic H1N1 influenza infection.

Type III protein secretion systems, which are organelles with the capacity to deliver bacterial proteins into host cells, have been adapted to deliver heterologous antigens for vaccine development. A limitation of these antigen delivery systems is that some proteins are not amenable to secretion through this pathway. We show here that proteins from the simian and human immunodeficiency viruses that are not permissive for secretion through aSalmonella entericaserovar Typhimurium type III secretion system can be modified to travel this secretion pathway by introduction of discrete mutations. Proteins optimized for secretion were presented more efficiently via the major histocompatibility complex class I pathway and were able to induce a better immune response.

Bacterial vectors may offer many advantages over other antigen delivery systems for cancer vaccines. We engineered a Salmonella typhimurium vaccine strain to deliver the NY-ESO-1 tumor antigen (S. typhimurium-NY-ESO-1) through a type III protein secretion system. The S. typhimurium-NY-ESO-1 construct elicited NY-ESO-1-specific CD8+ and CD4+ T cells from peripheral blood lymphocytes of cancer patients in vitro. Oral administration of S. typhimurium-NY-ESO-1 to mice resulted in the regression of established NY-ESO-1-expressing tumors. Intratu-moral inoculation of S. typhimurium-NY-ESO-1 to NY-ESO-1-negative tumors resulted in delivery of antigen in vivo and led to tumor regression in the presence of preexisting NY-ESO-1-spedific CD8+ T cells. Specific T cell responses against at least 2 unrelated tumor antigens not contained in the vaccine were observed, demonstrating epitope spreading. We propose that antigen delivery through the S. typhimurium type III secretion system is a promising novel strategy for cancer vaccine development.

Serine proteases have been documented to play key roles in uterine matrix turnover and trophoblastic invasion during implantation. Roles of prostasin serine protease in these processes, however, are currently unclear. The present study was first conducted to investigate the colocalization of prostasin and its cognate serpin, protease nexin-1 (PN-1), in rhesus monkey endometrium and placenta on days 12, 18, and 26 of pregnancy by using in situ hybridization (ISH) and immunohistochemistry. With ISH, expression of prostasin mRNA was intensely localized in the glandular epithelium on days 12 and 18 and in the placental villi, trophoblastic column, trophoblastic shell, and fetal-maternal border on days 18 and 26. With the progress of pregnancy, expression level in the glandular epithelium was significantly decreased, and the accumulation in the placental compartments was further increased. In addition, the stroma and arterioles exhibited modest levels of prostasin signals. However, expression level of PN-1 in these compartments on adjacent sections in the three stages of early pregnancy was weak or below the level of detection. Prostasin protein expression in the endometrium was found to be consistent with the distribution patterns revealed in the ISH experiments. It may be suggested from these results that prostasin is involved in endometrial epithelial morphology establishment, tissue remodeling, and trophoblastic invasion during early pregnancy. The cognate serpin PN-1 was not coordinately expressed along with prostasin, creating a tissue environment favorable for proteolytic activities of prostasin during early pregnancy events.

The spread of highly pathogenic avian influenza H5N1 viruses across Asia in 2003 and 2004 devastated domestic poultry populations and resulted in the largest and most lethal H5N1 virus outbreak in humans to date. To better understand the potential of H5N1 viruses isolated during this epizootic event to cause disease in mammals, we used the mouse and ferret models to evaluate the relative virulence of selected 2003 and 2004 H5N1 viruses representing multiple genetic and geographical groups and compared them to earlier H5N1 strains isolated from humans. Four of five human isolates tested were highly lethal for both mice and ferrets and exhibited a substantially greater level of virulence in ferrets than other H5N1 viruses isolated from humans since 1997. One human isolate and all four avian isolates tested were found to be of low virulence in either animal. The highly virulent viruses replicated to high titers in the mouse and ferret respiratory tracts and spread to multiple organs, including the brain. Rapid disease progression and high lethality rates in ferrets distinguished the highly virulent 2004 H5N1 viruses from the 1997 H5N1 viruses. A pair of viruses isolated from the same patient differed by eight amino acids, including a Lys/Glu disparity at 627 of PB2, previously identified as an H5N1 virulence factor in mice. The virus possessing Glu at 627 of PB2 exhibited only a modest decrease in virulence in mice and was highly virulent in ferrets, indicating that for this virus pair, the K627E PB2 difference did not have a prevailing effect on virulence in mice or ferrets. Our results demonstrate the general equivalence of mouse and ferret models for assessment of the virulence of 2003 and 2004 H5N1 viruses. However, the apparent enhancement of virulence of these viruses in humans in 2004 was better reflected in the ferret.

Most studies on CV co-occurrence patterns in early phonetic development have been based on Indo-European languages. Data from infants learning Mandarin, which has a substantially different phonological system from Indo-European languages, can confirm or refute the findings of previous studies, thus shedding further light on the theoretical bases of CV association. Spontaneous vocalizations were recorded in 45-minute sessions for each of 24 Mandarin-learning infants aged 0;7 to 1;6. In addition, the speech production of 24 caregivers was audio-recorded during their natural daily interactions with the infants at home. Both infants' vocalizations and adults' speech were transcribed and analysed for consonant–vowel co-occurrence patterns. These patterns were similar to those in other language groups, but language-specific patterns were evident by 1;0. Combinations of alveolars+front vowels and velars+back vowels confirm Davis & MacNeilage's (1990, 1995) frame-then-content theory and Clements's (1991) model of unified features for consonants and vowels. However, our finding of a language-specific pattern (labials+back vowels) suggests the need to reexamine the ‘pure frame’ of Davis & MacNeilage and Clements's grouping of labials and rounded vowels.

This case–control study with a Fujian population investigated whether self-reported occupational and recreational physical activity may be associated with lung cancer. The population comprised 1622 patients with newly diagnosed primary lung cancer and 1622 age- and gender-matched healthy controls. High-intensity occupational physical activity was associated with significantly higher risk of lung cancer (OR = 1.354, 95% CI: 1.068–1.717), especially nonsmall cell lung carcinoma (OR = 1.384, 95% CI: 1.087–1.762). Moderate or low intensity recreational physical activity was associated with reduced risk of lung cancer. The protective effect of recreational physical activity was observed in current or former smokers, but not never-smokers, and in subjects with normal or high BMI, but not low BMI, as well as people without a history of chronic lung disease. The frequency of recreational physical activity was associated with a linear reduction in the risk of lung cancer (P

Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

Improving market orientation and patient safety have become the key concerns of nursing management. For nurses, establishing a patient safety climate is the key to enhancing nursing quality. This study explores how market orientation affects the climate of patient safety among hospital nurses. We proposed adopting a cross-sectional research design and using questionnaires to collect responses from nurses working in two Taiwanese hospitals. Three-hundred and forty-three valid samples were obtained. Multiple regression and path analyses were conducted to test the study. Market orientation was defined as the combination of customer orientation, competitor orientation, and interfunctional coordination. Customer orientation directly affects the climate of patient safety. Although the findings only supported Hypothesis 1, competitor orientation and interfunctional coordination positively affected the patient safety climate through the mediating effects of hospital support for staff. Health care managers could encourage nurses to adopt customer-oriented perspectives to enhance their nursing care. In addition, to enhance competitor orientation, interfunctional coordination, and the patient safety climate, hospital managers could strengthen their support for staff members.

STUDY OBJECTIVE: The accuracy of the official statistic on infant deaths in Taiwan has been questioned. This study aimed to survey infant deaths nationwide, to measure associated vital statistics, and compare them with the official statistics to assess accuracy. DESIGN AND PARTICIPANTS: A nationwide survey of all gestational outcomes occurring at > or = 20 weeks' gestation over a three day study period (15-17 May 1989) was conducted to collect data from 23 counties and cities nationwide using a two stage data collection procedure. MAIN RESULTS: The survey derived infant death rate was 9.72 per 1000 live births, which was higher than the reported official statistic of 5.71 per 1000 live births. A more detailed examination of data on infant deaths showed that the estimated neonatal death rate of 6.68 per 1000 live births (95% confidence intervals: 3.33, 11.96 per 1000 live births) was significantly higher than the published official statistic of 1.94 per 1000 live births, while the postneonatal mortality of 3.04 per 1000 live births was comparable to the reported statistic of 3.37 per 1000 live births. CONCLUSIONS: This study empirically documented the underregistration of infant deaths in Taiwan, particularly those occurring during the first 27 days of life.

Underreporting and misclassification of maternal deaths are universal. The purposes of this study were to quantify the level of underestimation of maternal mortality and to analyze possible factors that contribute to underreporting and misclassification of maternal mortality.An interview census of all registered deaths that occurred during 1984-1988 in women of reproductive age was undertaken in Taiwan. Pregnancy-related deaths were screened from all collected questionnaires and death certificates by the researchers. The screened pregnancy-related deaths were then reviewed and evaluated by obstetrician-gynecologists; a cause of each death was assigned.For the five years, on average, the rate of underreporting of maternal mortality is 58.38% and the correct/confirmed rate of classification is 53.28%. Underreported and misclassified maternal deaths are more likely for women aged 20-24, with stillbirth and fetal death, care sought for non-obstetric reasons, care received in private hospitals and clinics, occurrence in the home, certification by non-obstetrician-gynecologists and court doctors, and death from non-obstetric causes.This study shows the limitations of official vital registration and concludes that dependence on death certificates alone to identify maternal deaths is incomplete and incorrect.This study determines the reliability of death certificate information on maternal mortality in Taiwan. A file was constructed of death certificates of all females 10-49 years old who died during 1984-88 in Taiwan. Trained public health nurses and midwives interviewed family members of deceased persons. Cause of death was taken from the death certificate. Obstetricians-gynecologists determined whether a pregnancy-related death was due to obstetric or unrelated causes, according to the International Classification of Disease-9, Clinical Modification codes. Based on the physicians reviews, 520 women died during pregnancy or within 42 days postpartum, of which 246 were nonmaternal deaths. 173 of the 274 deaths were previously determined by the routine procedure of death certificate reporting to be maternal deaths. Obstetrician-gynecologists identified 101 deaths as maternal deaths. 146 of the 173 certificate maternal deaths were verified as maternal deaths. 27 deaths were minor misclassifications. The adjusted proportion of maternal deaths was 54.8% rather than 34.6%. The greatest rate of underreporting was 86.59% in 1988. The smallest rate of underreporting was 39.29% in 1987. The official death certificate maternal group had a significantly higher percentage of women 30-34 years old. The underreported group had a significantly higher percentage of women 20-24 years old. The underreported group had a higher proportion of stillbirths and fetal deaths among mothers who died. The reported group had higher proportions of deaths from hypertension, embolism, hemorrhage, and more mothers who sought care at clinics and hospitals. The misclassified group had more information provided by physicians and family. Underreporting is attributed to confusing coding criteria, neglect of physicians, incomplete information, specific indicators, and avoidance of blame.

This study was aimed to investigate the relation of reinfused hematopoietic stem cell volume and recipient's leukocyte count at reinfusion with prognosis of disease in allo-hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 37 patients received allo-HSCT in our hospital were analyzed retrospectively. The 37 patients were divided into agranulocytosis and non-agranulocytosis groups according to the recipient's leukocyte count at reinfusion, and were divided into the high dose and low dose groups according to the median number of reinfused mononuclear cells (MNC) and CD34(+) cells. Then, hematopoietic reconstructions,GVHD, relapse and death rates of patients were compared. The results showed that the hematopoietic reconstruction of patients in non-agranulocytosis group and high dose MNC group were earlier than that in agranulocytosis group and low dose MNC group. There was no significant difference of hematopoietic reconstruction between the groups of high dose CD34(+) cells and low dose CD34(+) cells. The GVHD incidence was higher in high dose MNC group and non-agranulocytosis group than that in low dose MNC group and agranulocytosis group (P0.05). There were no statistical differences of relapsed and death rates between different reinfused number of HSC and recipient's leukocyte count at reinfusion.It is concluded that the infused MNC number and the recipient's leukocyte count at reinfusion in allo-HSCT correlated with hematopoietic reconstruction, the GVHD incidence is high in high dose MNC and non-agranulocytosis groups, the reinfused HSC volume and the recipient's leukocyte count at reinfusion not significantly relate with relapse and death rates.

This study was aimed to investigate the effects of different mobilization methods on mobilization and collection of peripheral blood stem cells in healthy donors and the adverse effect of collection, as well as hematopoietic construction in recipients. A total of 43 donors between January 2008 and May 2013 were divided into the simple mobilization group and the combined mobilization group. The simple group was subcutaneously injected with 5.0-10.0 µg/(kg·d) recombinant human granulocyte colony-stimulating factor (rhG-CSF), and the combined mobilization group was treated with rhG-CSF and intravenously dripped with 10 mg dexamethasone for 2-4 hours before collection. The acquisition and count of MNC and CD34(+) cells in different groups, the relationship between the stem cells and MNC count in blood before collection, and the adverse reactions were analyzed; the hematopoietic reconstruction of recipients was investigated. The results showed that the hematopoietic stem cell number of the two groups meet the demands. The count of MNC and CD34(+) cells in the simple mobilization group was more than that in the combined mobilization group. The MNC count in two groups positively correlated with peripheral blood MNC count before collection. The decline of hemoglobin and platelet levels was more obvious in the simple mobilization group than that in combined mobilization group. The adverse reactions of collection in the simple mobilization group could be well tolerated and reversed. There was no adverse reaction in the combined mobilization group. The differences of conditioning regimens between two groups were not statistically significant and the hematopoietic reconstruction time of combined group was shorter than that in the simple mobilization group.It is concluded that the adverse reactions in process of collection can be reduced, and enough hematopoietic stem cells can be collected by G-CSF plus dexamethasone in mobilization of peripheral blood stem cells. The count of MNC in peripheral blood before collection can be still used as a reference index to evaluate the acquisition of MNC. Especially the combination with dexamethasone for stem cell mobilization can promote the hematopoietic reconstruction of the recipients.

The kallikrein-kinin system participates in blood pressure regulation. One of the kallikrein-kinin system components, kallikrein-binding protein, binds to tissue kallikrein and inhibits its activity in vitro. To investigate potential roles of rat kallikrein-binding protein (RKBP) in vivo, we have developed transgenic mice that express an RKBP gene under the control of the mouse metallothionein metal-responsive promoter. Expression of the transgene, RKBP, was detected in the liver, kidney, lung, heart, pancreas, salivary glands, spleen, brain, testis, and adrenal gland at the mRNA and protein levels. Systolic blood pressures of homozygous transgenic mice were 88.5 +/- 0.8 mm Hg (mean +/- S.E., n = 19, P < 0.001) for one line and 88.8 +/- 1.6 mm Hg (mean +/- S.E., n = 19, P < 0.001) for another, as compared with 100.5 +/- 0.8 mm Hg (mean +/- S.E., n = 18) for control mice. Direct blood pressure measurements of these transgenic mice through an arterial cannula showed similar reductions of blood pressure. Intravenous injection of purified RKBP into mice via a catheter produced a dose-dependent reduction of the mean arterial blood pressure. Our findings suggest that RKBP may function as a vasodilator in vivo, independent of regulating the activity of tissue kallikrein.

Kallistatin, a human serine proteinase inhibitor, is a newly identified tissue kallikrein inhibitor. It binds strongly to tissue kallikrein but weakly to other serine proteinases such as chymotrypsin and elastase. The tissue distribution and changes in kallistatin levels in human diseases were characterized by using specific monoclonal and polyclonal antibodies against kallistatin. Kallistatin antigen levels in blood cells, fluids, and tissues measured with a specific enzyme-linked immunosorbent assay showed displacement curves that were parallel with those in purified kallistatin, indicating their immunologic identity. Expression of kallistatin mRNA in platelets, neutrophils, lymphocytes, monocytes, endothelial cells, hepatocytes, and colon and prostate carcinoma cells was identified by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Plasma kallistatin concentration was 22.1 +/- 3.5 micrograms/ml in 30 normal subjects and 21.1 +/- 3.8 micrograms/ml in 5 patients with C1 inhibitor deficiency. A significantly reduced kallistatin level (7.2 +/- 2.5 micrograms/ml, p0.001) was seen in plasma samples from 9 patients with liver disease and 10 patients with sepsis (7.7 +/- 3.5 micrograms/ml, p0 .001). Further, kallistatin levels in 10 women taking oral contraceptives (19.8 +/- 3.8 micrograms/ml) and 21 pregnant women (14.9 +/- 3.3 microg/ml) were significantly lower than those seen in healthy individuals. These data suggest that kallistatin is found in plasma, is produced mostly in the liver, and can be consumed during sepsis. Its consumption in sepsis may indicate a protective role to prevent blood pressure lowering.

Maternal cigarette smoking has adverse effects on pregnancy outcomes. The granulocyte-macrophage colony-stimulating factor (GM-CSF) is an essential cytokine for a normal pregnancy. We investigated the impact of cigarette smoke extract (CSE) on GM-CSF expression in human cytotrophoblast cells and suggested a cellular mechanism underlying the CSE-induced GM-CSF expression. An immortalized normal human trophoblast cell line (B6Tert-1) was treated with CSE. The viability and proliferation of the CSE-treated B6Tert-1 cells were evaluated, and the expression of GM-CSF in these cells was quantified at the mRNA and the protein levels by means of reverse-transcription and quantitative polymerase chain reaction (RT-qPCR); and enzyme-linked immunosorbent assay (ELISA), respectively. Human trophoblast cells treated with CSE had an increased expression of GM-CSF at both the mRNA and the protein levels. The CSE-induced GM-CSF expression was synergistically enhanced by the addition of the proteasome inhibitor MG-132, but inhibited by AG-1478, an inhibitor of the epidermal growth factor receptor (EGFR) kinase. Furthermore, CSE treatment increased the phosphorylation of the extracellular-signal regulated kinases (ERK1/2) in the trophoblast cells. The expression of other growth factors such as heparin-binding epidermal growth factor-like growth factor (HB-EGF) and vascular endothelial growth factor (VEGF) was also evaluated. Our data suggested that cigarette smoking and proteasome inhibition synergistically up-regulate GM-CSF cytokine expression by activating the EGFR signaling pathway.

The bradykinln B2 receptor (BDKRB2) has high affinity for the intact kinins, which mediate a wide spectrum of biological effects, including pain, inflammation, vasodilation, and smooth mnscle contraction and relaxation. In the present study, we have cloned and sequenced the gene encoding human bradyklnin B2 receptor from a human genomic library. The B2 receptor gene contains three exons separated by two introns. The first and second exons are noncoding, while the third exon contains the full-length coding region, which encodes a protein of 364 amino acids forming 7 transmembrane domains. The human B2 gene shares high sequence identity with rat and mouse B2 receptor genes and significant similarity with the gene encoding the angiotensin 11 type I receptor in the nucleotide sequence and exon-intron arrangement. In the 5′ flanking region, a consensus TATA box and several putative transcription factor-binding sites have been identified. Genomic Southern blot analysis showed that the B2 receptor is encoded by a single-copy gene that was localized to chromosome 14q32 by in situ hybridization. In a Southern blot analysis following reverse transcription and polymerase chain reaction, the human B2 receptor was found to be expressed in most human tissues.

Glucose intolerance and cardiovascular risk factors were assessed among 215 subjects aged 27-86 years in Ho-long, Taiwan. An oral glucose tolerance test (OGTT) was normal in 107 subjects, impaired in 41 subjects, and abnormal in 67 subjects (as noninsulin dependent diabetes mellitus, NIDDM). Body fatness, blood pressure, carbohydrate and lipid metabolic factors were examined. One-way ANCOVA was used to compare age- and/or BMI-adjusted differences among these groups. Male subjects with NIDDM and impaired glucose tolerance (IGT) had higher systolic (SBP) and diastolic (DBP) blood pressures, plasma insulin (fasting and 1-hour after OGTT), serum triglycerides (TG), heavier body weight, and larger BMI than normal. IGT subjects were also found to have higher TG, insulin (2-hour) and larger insulin area under curve (IAUC) after OGTT than NIDDM. In females, subjects with NIDDM had higher TG, insulin (fasting and 1-hour after OGTT), and larger IAUC than normal. Moreover, female IGT subjects were also found to have significantly higher SBP, DBP, insulin (1-and 2-hour after OGTT), and larger IAUC than both normal and NIDDM subjects. These results suggest that adverse cardiovascular risk factors are present not only in NIDDM subjects, but also in IGT subjects.

To observe the influences upon the degree of diaphragmatic excursion during deep cervical plexus block at the third cervical vertebra (C3) and compare the safety and anesthetic effect of modified cervical plexus block by ultrasonic guidance and blocking of cervical plexus at one point.Part I: 30 patients of ASA (American society of anesthesiologists) I-II scheduled for thyroid surgery were selected for bilateral cervical plexus block at C3 and bilateral skin nerve branches via ultrasonic guidance. Diaphragmatic excursion was recorded. Part II: 80 patients of ASAI-II scheduled for thyroid surgery were randomly divided into 2 groups: experimental group (Group U) and control group (Group C). In Group U, modified cervical plexus block was used to fix both sides of C3 and skin nerve branches. The anesthetic mixture with 2% lidocaine and 0.75% ropivacaine was injected. And anesthetic effects and complications were detected. In control group, traditional one-point method for blocking cervical plexus was employed.High-frequency Doppler sonography could clearly visualize important neck structures and precisely guide the injection of mixture to the transverse process of C3. Diaphragmatic excursion decreased significantly at 15 and 30 min post-blocking (P0.05). And no paralysis of diaphragmatic muscle occurred. Hoverer 3 cases had partial diaphragmatic paralysis. Both blood pressure and heart rate increased significantly post-blocking in both groups (P0.05 or 0.01). In comparison with Group C, the range of blood pressure was notably lower at 10 and 20 min in Group U. And heart rate was notably lower at 5, 10, 20 and 30 min (P0.05 or 0.01). Furthermore the onset time of skin nerve branches was significantly shorter in Group U (P0.01). And the anesthetic effect score was better than that in Group C (P0.01). The incidence of complications, such as hoarseness, was significantly lower in Group U (12 cases in Group C but none in Group U, P0.01) and Horner's syndrome (2 cases in Group C). The number of cases requiring hypotensor and heart rate control drug was significantly smaller in Group U than that in Group C (P0.01).The improving effect of ultrasound-guided cervical plexus block upon the degree of diaphragmatic movement is within the compensatory range of body. In comparison with the traditional one-point blocking of cervical plexus, the modified cervical plexus block with ultrasonic guidance offers better anesthetic effects, fewer complications and convenient anesthetic localization. Thus it may be clinically applicable.

The NS1 protein of human influenza A viruses binds the 30-kDa subunit of the cleavage and polyadenylation specificity factor (CPSF30), a protein required for 3′ end processing of cellular pre-mRNAs, thereby inhibiting production of beta interferon (IFN-β) mRNA. The NS1 proteins of pathogenic 1997 H5N1 viruses contain the CPSF30-binding site but lack the consensus amino acids at positions 103 and 106, F and M, respectively, that are required for the stabilization of CPSF30 binding, resulting in nonoptimal CPSF30 binding in infected cells. Here we have demonstrated that strengthening CPSF30 binding, by changing positions 103 and 106 in the 1997 H5N1 NS1 protein to the consensus amino acids, results in a remarkable 300-fold increase in the lethality of the virus in mice. Unexpectedly, this increase in virulence is not associated with increased lung pathology but rather is characterized by faster systemic spread of the virus, particularly to the brain, where increased replication and severe pathology occur. This increased spread is associated with increased cytokine and chemokine levels in extrapulmonary tissues. We conclude that strengthening CPSF30 binding by the NS1 protein of 1997 H5N1 viruses enhances virulence in mice by increasing the systemic spread of the virus from the lungs, particularly to the brain.

we Clone the ZNF185 gene and detect the position of ZNF185 in the mouse testis.extracted from mouse testis RNA, by RT-PCR, and then the obtained fragment was cloned and identified; extracted from mouse liver, testis and ovary proteins were Western blot analysis; preparation of frozen sections of mouse testes, immunofluorescence techniques analysis.(1) ZNF185 gene cloning was correct. (2) Western blot showed that the most abundant in the testes ZNF185. (3) Immunofluorescence showed, ZNF185 located in Leydig cells and sperm, Leydig cells in the weak, and in round spermatids and mature sperm were highly expressed.the gene cloning of ZNF185 was successful and initially proved the position of ZNF185 in the mouse testis.

A simple method suitable for self-administration of vaccine would improve mass immunization, particularly during a pandemic outbreak. Influenza virus-like particles (VLPs) have been suggested as promising vaccine candidates against potentially pandemic influenza viruses, as they confer long-lasting immunity but are not infectious. We investigated the immunogenicity and protective efficacy of influenza H5 VLPs containing the hemagglutinin (HA) of A/Vietnam/1203/04 (H5N1) virus delivered into the skin of mice using metal microneedle patches and also studied the response of Langerhans cells in a human skin model. Prime-boost microneedle vaccinations with H5 VLPs elicited higher levels of virus-specific IgG1 and IgG2a antibodies, virus-specific antibody-secreting cells, and cytokine-producing cells up to 8 months after vaccination compared to the same antigen delivered intramuscularly. Both prime-boost microneedle and intramuscular vaccinations with H5 VLPs induced similar hemagglutination inhibition titers and conferred 100% protection against lethal challenge with the wild-type A/Vietnam/1203/04 virus 16 weeks after vaccination. Microneedle delivery of influenza VLPs to viable human skin using microneedles induced the movement of CD207+Langerhans cells toward the basement membrane. Microneedle vaccination in the skin with H5 VLPs represents a promising approach for a self-administered vaccine against viruses with pandemic potential.

To evaluate the effect of use of deltopectoral flaps with delayed expansion in repairing large scar on face.Thirteen patients with large scars on face received above-mentioned surgery. The cutaneous branches of thoracoacromial artery and transverse cervical artery of patients were divided when the expander was implanted. As a result, the blood supply of expanded deltopectoral flaps principally depended on the second and third intercostal branches of internal thoracic artery, and a delaying effect was achieved. The distribution of vascular net in the flap and the state of blood supply of the flap were observed to evaluate the effect of delaying.The vascular net of expanded flap increased and thickened. No blood supply disorder occurred at the distal end of the transferred flap. Patients were followed up for 4 to 18 months. The outline of the burn side of face was in accord with the opposite side, which was not fat and clumsy. The complexion of the flap was similar to that of normal skin of the face, and the flap was soft in texture.The application of delaying can better ensure the blood supply of transferred deltopectoral flap. The result of applying delayed expansion of deltopectoral flaps in repairing large scars on face was good.

Background: The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel mechanisms of action are needed to combat novel and resistant influenza strains. DAS181 (Fludase)™) is a sialidase fusion protein in early clinical development with in vitro and in vivo preclinical activity against a variety of seasonal influenza strains and highly pathogenic avian influenza strains (A/H5N1). Here, we use in vitro, ex vivo, and in vivo models to evaluate the activity of DAS181 against several pandemic influenza A(H1N1) viruses. Methods and Findings: The activity of DAS181 against several pandemic influenza A(H1N1) virus isolates was examined in MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181 efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains. DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181 antiviral activity against pandemic influenza A(H1N1) strains was comparable to that observed against seasonal influenza virus including the H274Y oseltamivir-resistant influenza virus. Conclusions: The sialidase fusion protein DAS181 exhibits potent inhibitory activity against pandemic influenza A(H1N1) viruses. As inhibition was also observed with oseltamivir-resistant IFV (H274Y), DAS181 may be active against the antigenically novel pandemic influenza A(H1N1) virus should it acquire the H274Y mutation. Based on these and previous results demonstrating DAS181 broad-spectrum anti-IFV activity, DAS181 represents a potential therapeutic agent for prevention and treatment of infections by both emerging and seasonal strains of IFV., published_or_final_version

Controlled invasion of the uterine wall by the trophoblast cells is pivotal for the successful pregnancy, and various kinds of protease are involved in this process. Serine protease prostasin has been shown to participate in the proteolytic activation of epithelial sodium channel as well as cleavage of epidermal growth factor receptor extracellular domain in human epithelial cells. Its physiological significance in human placentation has been suggested but not validated. In the present study, we found that prostasin was expressed at a relatively high level in human placenta trophoblasts in early pregnant weeks. In the in vitro cultured human choriocarcinomal JEG-3 cells, treatment with functional antibody against prostasin led to promotion in cell invasion capability, as well as increase in the production of MMP-2, MMP-26, TIMP-1, and TIMP-4. Our data indicated that this serine protease may function as an invasion suppressor in human trophoblast, participating in the invasion-restrictive regulation of trophoblasts to avoid their over-penetration into the uterine wall.

The early development of vocalic and consonantal production in Mandarin-learning infants was studied at the transition from babbling to producing first words. Spontaneous vocalizations were recorded for 24 infants grouped by age: G1 (0 ; 7 to 1 ; 0) and G2 (1 ; 1 to 1 ; 6). Additionally, the infant-directed speech of 24 caregivers was recorded during natural infant–adult interactions to infer language-specific effects. Data were phonetically transcribed according to broad categories of vowels and consonants. Vocalic development, in comparison with reports for children of other linguistic environments, exhibited two universal patterns: the prominence of [ɛ] and [ə], and the predominance of low and mid vowels over high vowels. Language-specific patterns were also found, e.g. the early appearance and acquisition of low vowels [ɑ]. Vowel production was similar in G1 and G2, and a continuum of developmental changes brought infants' vocalization closer to the adult model. Consonantal development showed two universal patterns: labials and alveolars occurred more frequently than velars; and nasals developed earlier than fricatives, affricates and liquids. We also found two language-specific patterns: alveolars were more prominent than labials and affricates developed early. Universal and language-specific characteristics in G1 continued to be prominent in G2. These data indicate that infants are sensitive to the ambient language at an early age, and this sensitivity influences the nature of their vocalizations.

Background: Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic. Methodology/Principal Findings: Influenza virus-like particles (VLPs) produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1) hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro. Conclusions/Significance: These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.

To compare the anesthesia efficacy, hemodynamics, recovery of passage of gas by anus and bladder function in elderly patients with operation of intertrochanteric femoral fracture with epidural or lumbar plexus block.Sixty patients with intertrochanteric femoral fracture, aged 65-97, were randomly divided into 3 equal groups: lumbar plexus group (Group A, undergoing posterior lumbar plexus block) and epidural group (Group B, undergoing epidural block at L(1-2) interspace). The block onset time, anesthesia efficacy, transfusion amount during operation, blood pressure and heart rate change 1 h after anesthesia, and recovery after anesthesia were observed.The block onset time on femoral nerve, lateral cutaneous nerve of thigh, obturator nerve, and saphenous nerve of Group A were (2.7 +/- 2.0) min, (3.1 +/- 3.4) min, (3.5 +/- 3.3) min, and (3.7 +/- 3.1) min respectively, all significantly shorter than those of Group B [(13.5 +/- 2.1) min, (13.5 +/- 2.1) min, (13.5 +/- 2.1) min, and (13.5 +/- 2.1) min respectively, all P0.01]. The duration of postoperative analgesia of Group A was (420 +/- 152) min, significantly longer than that of Group B [(204 +/- 44) min, P0.05]. There were no significant differences in the change of blood pressure and heart rate between these 2 groups. The blood pressure decreased significantly 10 - 60 min after anesthesia in Group B, and remained stable in Group A. The transfusion amount of Group A was (773 +/- 353) ml, significantly fewer than that in Group B [(1483 +/- 444) ml, P0.01]. Passage of gas by anus started (1.1 +/- 0.6) h after operation in Group A, a time significantly shorter than that in Group B (5.9 +/- 1.2) h, P0.01). Urinary retention was seen in 8 patients of Group B, however, no patient in Group A showed incidence of urinary retention (P0.01). Forty-eight patients, 20 in Group A and 28 in Group B got excellent anesthesia effect, and 12 of them, 10 in Group A and 2 in Group B, got relatively good anesthesia (P0.05).Both lumbar plexus block and epidural block provide satisfactory anesthetic efficacy for operation of intertrochanteric femoral fracture in elderly patients. Epidural block provide better efficacy, and lumbar plexus block shows faster recovery of digestive system and urinary system after operation.