A shift from open to endovascular repair in the treatment of ruptured middle cerebral artery aneurysms: a single institution experience.

PURPOSE: Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion. We compare clinical outcomes of patients presenting with acute subarachnoid hemorrhage from ruptured middle cerebral artery aneurysms undergoing either open or endovascular repair. METHODS: We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from January 2008 to March 2019 to compare endovascular and open surgical outcomes. RESULTS: Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period, there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p = .002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0-2) compared to those undergoing open surgery. Long-term follow-up data (endovascular 54.9 ± 37.9 months vs clipping 18.6 ± 13.4 months) showed no difference in rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p = 0.691) in both groups. CONCLUSION: Our series suggests equipoise in the treatment of ruptured middle cerebral artery aneurysms and demonstrates endovascular repair as a potentially feasible treatment strategy. Future randomized trials could clarify the roles of these treatment modalities.

Disparities in who is asked about their perinatal mental health: an analysis of cross-sectional data from consecutive national maternity surveys.

BACKGROUND: The perinatal period is a vulnerable time, with one in five women experiencing mental health problems. Antenatal and postnatal appointments are key contact points for identifying women in need of support. Since 2014, the UK National Institute for Health and Care Excellence (NICE) has recommended that all women be asked about their mental health at their antenatal booking appointment and early in the postnatal period. The aim of this study was to assess the proportions of women who reported being asked about their mental health during the perinatal period across consecutive national maternity surveys (NMS) in England and to evaluate sociodemographic disparities in who was asked. METHODS: Secondary analysis was performed on cross-sectional data from the NMS in 2014-2020. In each survey, women reported whether they had been asked about their mental health antenatally (during their booking appointment) and postnatally (up to six months after giving birth). The proportions of women in each survey who reported being asked about their mental health were calculated and compared according to key sociodemographic characteristics and across survey years. Logistic regression was conducted to identify disparities in who was asked. RESULTS: The proportion of women who reported being asked about their mental health antenatally increased from 80.3% (95%CI:79.0-81.5) in 2014 to 83.4% (95%CI:82.1-84.7) in 2020, yet the proportion of women who reported being asked postnatally fell from 88.2% (95%CI:87.1-89.3) in 2014 to 73.7% (95%CI:72.2-75.2) in 2020. Ethnic minority women (aOR range:0.20 ~ 0.67) were less likely to report being asked about their mental health antenatally and postnatally across all surveys compared to White women. Women living in less socioeconomically advantaged areas (aOR range:0.65 ~ 0.75) and women living without or separately from a partner (aOR range:0.61 ~ 0.73) were also less likely to report being asked about their mental health, although there was less consistency in these disparities across the antenatal and postnatal periods and across surveys. CONCLUSIONS: Despite NICE recommendations, many women are still not asked about their mental health during the perinatal period, particularly after giving birth. Women from ethnic minority backgrounds are less likely to be asked and these disparities have persisted over time.

Identification and Pharmacological Characterization of a Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) for at least 3 h. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and produced dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and with significantly reduced signs of naloxone-precipitated withdrawal, which suggested reduced physical dependence compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

Filamentous prophage capsid proteins contribute to superinfection exclusion and phage defence in Pseudomonas aeruginosa.

Filamentous prophages in Pseudomonas aeruginosa PAO1 are converted to superinfective phage virions during biofilm development. Superinfection exclusion is necessary for the development of resistance against superinfective phage virions in host cells. However, the molecular mechanisms underlying the exclusion of superinfective Pf phages are unknown. In this study, we found that filamentous prophage-encoded structural proteins allow exclusion of superinfective Pf phages by interfering with type IV pilus (T4P) function. Specifically, the phage minor capsid protein pVII inhibits Pf phage adsorption by interacting with PilC and PilJ of T4P, and overproduction of pVII completely abrogates twitching motility. The minor capsid protein pIII provides partial superinfection exclusion and interacts with the PilJ and TolR/TolA proteins. Furthermore, pVII provides full host protection against infection by pilus-dependent lytic phages, and pIII provides partial protection against infection by pilus-independent lytic phages. Considering that filamentous prophages are common in clinical Pseudomonas isolates and their induction is often activated during biofilm formation, this study suggests the need to rethink the strategy of using lytic phages to treat P. aeruginosa biofilm-related infections.

Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy.

BACKGROUND: Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. METHODS: We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. RESULTS: Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). CONCLUSION: Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.

One-Pot High-throughput Synthesis of N3-Substituted 5-Arylidene-2-Thiohydantoin Amides and Acids.

A one-pot high-throughput solid-phase method for the synthesis of N3-substituted 5-arylidene-2-thiohydantoin amide and acid has been developed. A tandem ring-closure and ring-open pathway is proposed as the mechanism of forming the two products.

Terahertz Wave Enhances Permeability of the Voltage-Gated Calcium Channel.

A deficiency of Ca2+ fluxes arising from dysfunctional voltage-gated calcium channels has been associated with a list of calcium channelopathies such as epilepsy, hypokalemic periodic paralysis, episodic ataxia, etc. Apart from analyzing the pathogenic channel mutations, understanding how the channel regulates the ion conduction would be instructive to the treatment as well. In the present work, in relating the free energetics of Ca2+ transport to the calcium channel, we demonstrate the importance of bridging Ca2+ hydration waters, which form hydrogen bonds with channel -COO- and -C═O groups and enable a long-distance effect on the Ca2+ permeation. By firing a terahertz wave which resonates with the stretching mode of either the -COO- or the -C═O group, we obtain significantly enhanced selectivity and conductance of Ca2+. The Ca2+ free energy negatively grows nearly 5-fold. The direct evidence is the reinforced hydrogen bonds. In addition, thanks to forced vibrations, -COO- contributes to raised permeation as well even under a field in resonance with -C═O, and vice versa. Since the resonant terahertz field could manipulate the conduction of calcium channels, it has potential applications in therapeutic intervention such as rectifying a Ca2+ deficiency in degraded calcium channels, inducing apoptosis of tumor cells with overloaded calcium etc.

Mercapto-functionalized polyhedral oligomeric silsesquioxane as a soluble support for the synthesis of peptide thioesters.

The revival of peptide-based drugs has led to the increasing demand for the development of large-scale synthesis of these complex molecules. To meet this demand, the use of mercapto-functionalized polyhedral oligomeric silsesquioxane (POSS-SH) as a soluble support for the synthesis of a model pentapeptide POSS-thioester is reported. The synthetic process provided a total yield of 62% for the pentapeptide POSS-thioester and the 1H NMR spectra validated the high purity of the products. The successful synthesis of the pentapeptide POSS-thioester with high yield and purity provides a promising way to the scale-up chemical synthesis of peptide thioesters, peptides, peptide amides, cyclic peptides, and even proteins.

Excisionase in Pf filamentous prophage controls lysis-lysogeny decision-making in Pseudomonas aeruginosa.

Pf filamentous prophages are prevalent among clinical and environmental Pseudomonas aeruginosa isolates. Pf4 and Pf5 prophages are integrated into the host genomes of PAO1 and PA14, respectively, and play an important role in biofilm development. However, the genetic factors that directly control the lysis-lysogeny switch in Pf prophages remain unclear. Here, we identified and characterized the excisionase genes in Pf4 and Pf5 (named xisF4 and xisF5, respectively). XisF4 and XisF5 represent two major subfamilies of functional excisionases and are commonly found in Pf prophages. While both of them can significantly promote prophage excision, only XisF5 is essential for Pf5 excision. XisF4 activates Pf4 phage replication by upregulating the phage initiator gene (PA0727). In addition, xisF4 and the neighboring phage repressor c gene pf4r are transcribed divergently and their 5'-untranslated regions overlap. XisF4 and Pf4r not only auto-activate their own expression but also repress each other. Furthermore, two H-NS family proteins, MvaT and MvaU, coordinately repress Pf4 production by directly repressing xisF4. Collectively, we reveal that Pf prophage excisionases cooperate in controlling lysogeny and phage production.

Antitoxin HigA inhibits virulence gene mvfR expression in Pseudomonas aeruginosa.

Toxin/antitoxin (TA) systems are ubiquitous in bacteria and archaea and participate in biofilm formation and stress responses. The higBA locus of the opportunistic pathogen Pseudomonas aeruginosa encodes a type II TA system. Previous work found that the higBA operon is cotranscribed and that HigB toxin regulates biofilm formation and virulence expression. In this study, we demonstrate that HigA antitoxin is produced at a higher level than HigB and that higA mRNA is expressed separately from a promoter inside higB during the late stationary phase. Critically, HigA represses the expression of mvfR, which is an important virulence-related regulator, by binding to a conserved HigA palindrome (5'-TTAAC GTTAA-3') in the mvfR promoter, and the binding of HigB to HigA derepresses this process. During the late stationary phase, excess HigA represses the expression of mvfR and higBA. However, in the presence of aminoglycoside antibiotics where Lon protease is activated, the degradation of HigA by Lon increases P. aeruginosa virulence by simultaneously derepressing mvfR and higB transcription. Therefore, this study reveals that the antitoxin of the P. aeruginosa TA system is integrated into the key virulence regulatory network of the host and functions as a transcriptional repressor to control the production of virulence factors.

Symbiosis of a P2-family phage and deep-sea Shewanella putrefaciens.

Almost all bacterial genomes harbour prophages, yet it remains unknown why prophages integrate into tRNA-related genes. Approximately 1/3 of Shewanella isolates harbour a prophage at the tmRNA (ssrA) gene. Here, we discovered a P2-family prophage integrated at the 3'-end of ssrA in the deep-sea bacterium S. putrefaciens. We found that ~0.1% of host cells are lysed to release P2 constitutively during host growth. P2 phage production is induced by a prophage-encoded Rep protein and its excision is induced by the Cox protein. We also found that P2 genome excision leads to the disruption of wobble base pairing of SsrA due to site-specific recombination, thus disrupting the trans-translation function of SsrA. We further demonstrated that P2 excision greatly hinders growth in seawater medium and inhibits biofilm formation. Complementation with a functional SsrA in the P2-excised strain completely restores the growth defects in seawater medium and partially restores biofilm formation. Additionally, we found that products of the P2 genes also increase biofilm formation. Taken together, this study illustrates a symbiotic relationship between P2 and its marine host, thus providing multiple benefits for both sides when a phage is integrated but suffers from reduced fitness when the prophage is excised.

Ethnic differences in singleton preterm birth in England and Wales, 2006-12: Analysis of national routinely collected data.

BACKGROUND: Data recorded at birth and death registration in England and Wales have been routinely linked with data recorded at birth notification since 2006. These provide scope for detailed analyses on ethnic differences in preterm birth (PTB). OBJECTIVES: We aimed to investigate ethnic differences in PTB and degree of prematurity in England and Wales, taking into account maternal sociodemographic characteristics and to further explore the contribution of mother's country of birth to these ethnic differences in PTB. METHODS: We analysed PTB and degree of prematurity by ethnic group, using routinely collected and linked data for all singleton live births in England and Wales, 2006-2012. Logistic regression was used to adjust for mother's age, marital status/registration type, area deprivation and mother's country of birth. RESULTS: In the 4 634 932 births analysed, all minority ethnic groups except 'Other White' had significantly higher odds of PTB compared with White British babies (ORs between 1.04-1.25); highest odds were in Black Caribbean, Indian, Bangladeshi and Pakistani groups. Ethnic differences in PTB tended to be greater at earlier gestational ages. In all ethnic groups, odds of PTB were lower for babies whose mothers were born outside the UK. CONCLUSIONS: In England and Wales, Black Caribbean, Indian, Bangladeshi, Pakistani and Black African babies all have significantly increased odds of being born preterm compared with White British babies. Bangladeshis apart, these groups are particularly at risk of extremely PTB. In all ethnic groups, the odds of PTB are lower for babies whose mothers were born outside the UK. These ethnic differences do not appear to be wholly explained by area deprivation or other sociodemographic characteristics.

Characterization of Two Toxin-Antitoxin Systems in Deep-Sea Streptomyces sp. SCSIO 02999.

Toxin-antitoxin (TA) systems are ubiquitous and abundant genetic elements in bacteria and archaea. Most previous TA studies have focused on commensal and pathogenic bacteria, but have rarely focused on marine bacteria, especially those isolated from the deep sea. Here, we identified and characterized three putative TA pairs in the deep-sea-derived Streptomyces sp. strain SCSIO 02999. Our results showed that Orf5461/Orf5462 and Orf2769/Orf2770 are bona fide TA pairs. We provide several lines of evidence to demonstrate that Orf5461 and Orf5462 constitute a type-II TA pair that are homologous to the YoeB/YefM TA pair from Escherichia coli. Although YoeB from SCSIO 02999 was toxic to an E. coli host, the homologous YefM antitoxin from SCSIO 02999 did not neutralize the toxic effect of YoeB from E. coli. For the Orf2769/Orf2770 TA pair, Orf2769 overexpression caused significant cell elongation and could lead to cell death in E. coli, and the neighboring Orf2770 could neutralize the toxic effect of Orf2769. However, no homologous toxin or antitoxin was found for this pair, and no direct interaction was found between Orf2769 and Orf2770. These results suggest that Orf2769 and Orf2770 may constitute a novel TA pair. Thus, deep-sea bacteria harbor typical and novel TA pairs. The biochemical and physiological functions of different TAs in deep-sea bacteria warrant further investigation.

A comparison of intrapartum interventions and adverse outcomes by parity in planned freestanding midwifery unit and alongside midwifery unit births: secondary analysis of 'low risk' births in the birthplace in England cohort.

BACKGROUND: For low risk women, there is good evidence that planned birth in a midwifery unit is associated with a reduced risk of maternal interventions compared with planned birth in an obstetric unit. Findings from the Birthplace cohort study have been interpreted by some as suggesting a reduced risk of interventions in planned births in freestanding midwifery units (FMUs) compared with planned births in alongside midwifery units (AMUs). However, possible differences have not been robustly investigated using individual-level Birthplace data. METHODS: This was a secondary analysis of data on 'low risk' women with singleton, term, 'booked' pregnancies collected in the Birthplace national prospective cohort study. We used logistic regression to compare interventions and outcomes by parity in 11,265 planned FMU births and 16,673 planned AMU births, adjusted for potential confounders, using planned AMU birth as the reference group. Outcomes considered included adverse perinatal outcomes (Birthplace primary outcome measure), instrumental delivery, intrapartum caesarean section, 'straightforward vaginal birth', third or fourth degree perineal trauma, blood transfusion and maternal admission for higher-level care. We used a significance level of 1% for all secondary outcomes. RESULTS: There was no significant difference in adverse perinatal outcomes between planned AMU and FMU births. The odds of instrumental delivery were reduced in planned FMU births (nulliparous: aOR 0.63, 99% CI 0.46-0.86; multiparous: aOR 0.41, 99% CI 0.25-0.68) and the odds of having a 'straightforward vaginal birth' were increased in planned FMU births compared with planned AMU births (nulliparous: aOR 1.47, 99% CI 1.17-1.85; multiparous: 1.86, 99% CI 1.35-2.57). The odds of intrapartum caesarean section did not differ significantly between the two settings (nulliparous: p = 0.147; multiparous: p = 0.224). The overall pattern of findings suggested a trend towards lower intervention rates and fewer adverse maternal outcomes in planned FMU births compared with planned AMU births. CONCLUSIONS: The findings support the recommendation that 'low risk' women can be informed that planned birth in an FMU is associated with a lower rate of instrumental delivery and a higher rate of 'straightforward vaginal birth' compared with planned birth in an AMU; and that outcomes for babies do not appear to differ between FMUs and AMUs.

Endotoxemia Following Multiple Trauma: Risk Factors and Prognostic Implications.

OBJECTIVE: To evaluate the prevalence and time course of systemic endotoxemia following severe multiple trauma, to define its risk factors, and to explore the correlation between post-trauma endotoxemia and organ dysfunction. DESIGN: Prospective single-center cohort study. SETTING: Emergency department and ICU of adult tertiary care level I trauma center. PATIENTS: Forty-eight severely injured (Injury Severity Score ≥ 16) patients, admitted to ICU within 24 hours of injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Endotoxemia was not evident on initial presentation, but developed subsequently in 75% of patients, even in the absence of Gram-negative infection. Nonsurviving patients had higher endotoxin levels than survivors on day 1 (endotoxemia, 0.48 vs 0.28; p = 0.048). Shock at admission, or surgery within the first 48 hours after trauma, was associated with higher endotoxin levels and predicted subsequent maximal endotoxemia, after adjusting for other significant covariates. Maximal endotoxemia levels were higher in patients who developed organ dysfunction, reflected in a cumulative Multiple Organ Dysfunction Score greater than 25, and patients with an intermediate endotoxemia level (≥ 0.4) had more cardiovascular dysfunction. CONCLUSIONS: It is the first study to detect increasing levels of endotoxemia following multiple trauma. Shock and early surgery predict the development of endotoxemia; endotoxemia is particularly associated with cardiovascular dysfunction. However, Gram-negative infections are uncommon in these patients, suggesting that the gastrointestinal tract is the dominant reservoir of endotoxin. Endotoxin may be an appropriate therapeutic target in patients who have sustained severe multiple trauma.

Identification of 5,6-dihydroimidazo[2,1-b]thiazoles as a new class of antimicrobial agents.

In an effort to develop novel antimicrobial agents against drug-resistant bacterial infections, 5,6-dihydroimidazo[2,1-b]thiazole compounds were synthesized and tested for their antimicrobial activity. Eight compounds comprised by two sub-scaffolds were identified as hits against methicillin-resistant Staphylococcus aureus (MRSA). These hits were modified at 6-position by replacing (S)-6 to (R)-6 configuration and the (R)-isomers increased their antimicrobial activities by two-fold. The most active compound showed a MIC90 value of 3.7µg/mL against MRSA in a standard microdilution bacterial growth inhibitory assay. This compound protected wax moth worms against MRSA at a dose of 5× MIC using a worm infectious model. This compound also exhibited inhibition of DNA gyrase activity in a DNA gyrase supercoil assay, suggesting the 5,6-dihydroimidazo[2,1-b]thiazoles may target DNA gyrase for the antimicrobial action.

Women's birth place preferences in the United Kingdom: a systematic review and narrative synthesis of the quantitative literature.

BACKGROUND: Current clinical guidelines and national policy in England support offering 'low risk' women a choice of birth setting, but despite an increase in provison of midwifery units in England the vast majority of women still give birth in obstetric units and there is uncertainty around how best to configure services. There is therefore a need to better understand women's birth place preferences. The aim of this review was to summarise the recent quantitative evidence on UK women's birth place preferences with a focus on identifying the service attributes that 'low risk' women prefer and on identifying which attributes women prioritise when choosing their intended maternity unit or birth setting. METHODS: We searched Medline, Embase, PsycINFO, Science Citation Index, Social Science Index, CINAHL and ASSIA to identify quantitative studies published in scientific journals since 1992 and designed to describe and explore women's preferences in relation to place of birth. We included experimental stated preference studies, surveys and mixed-methods studies containing relevant quantitative data, where participants were 'low risk' or 'unselected' groups of women with experience of UK maternity services. RESULTS: We included five experimental stated preference studies and four observational surveys, including a total of 4201 respondents. Most studies were old with only three conducted since 2000. Methodological quality was generally poor. The attributes and preferences most commonly explored related to pain relief, continuity of midwife, involvement/availability of medical staff, 'homely' environment/atmosphere, decision-making style, distance/travel time and need for transfer. Service attributes that were almost universally valued by women included local services, being attended by a known midwife and a preference for a degree of control and involvement in decision-making. A substantial proportion of women had a strong preference for care in a hospital setting where medical staff are not necessarily involved in their care, but are readily available. CONCLUSIONS: The majority of women appear to value some service attributes while preferences differ for others. Policy makers, commissioners and service providers might usefully consider how to extend the availability of services that most women value while offering a choice of options that enable women to access services that best fit their needs and preferences.

Application and Evaluation of Knowledge Retention Related to Advanced Trauma Care for Nurses (ATCN) Course Content: A Preliminary Study.

The Advanced Trauma Care for Nurses (ATCN) course was designed to help nurses increase their knowledge in management of the multiple trauma patient. To determine whether the trauma-related knowledge of ATCN course takers differed from nontakers, assess the factors associated with ATCN content knowledge among course takers, and explore the extent to which the ATCN content was used by course takers in their clinical practice. A cross-sectional online survey of 78 ATCN takers (nurses who had successfully completed the ATCN course within the previous 3 years) and 58 ATCN nontakers (a control group of nurses who had not taken the course but who worked in comparable clinical settings) was conducted. The survey consisted of demographic questions and a 15-item knowledge test spanning the ATCN course content. ATCN takers were also asked about the frequency with which a specific ATCN content had been used in their practice since taking the course. ATCN takers had a significantly higher (mean ± SD = 10.6 ± 2.2) total score on the study test than the ATCN nontakers (mean ± SD = 6.4 ± 2.6); t(134) = -10.0, p < .001. A shorter time since course completion was associated with higher knowledge scores. ATCN takers rated the clinical relevance and applicability of the course content as high. The findings suggest that completing the ATCN course increases knowledge levels of trauma patient management and that the ATCN course content is clinically relevant to the nurses. However, higher knowledge scores were observed for the most recent study participants, suggesting that booster sessions for ATCN course participants may be warranted.

[Prevention and treatment mechanism of qingxia therapy (based on yinchenhao decoction and dachengqi decoction) on hepatocyte apoptosis in rats with acute hepatic injury induced by lipopolysaccharide/D-galactosamine].

OBJECTIVE: To study the prevention and treatment mechanism of Qingxia therapy (based on Yinchenhao Decoction and Dachengqi Decoction) on hepatocyte apoptosis in rats with acute hepatic injury induced by lipopolysaccharide plus D-galactosamine (LPS/D-GalN). METHODS: The acute hepatic injury model was established by LPS/D-GalN and then intervened with Qingxia therapy. Serum liver function, PT and liver tissue pathology were observed, hepatocyte apoptosis index was detected by Tunel, protein expressions of BCL-2, BAX and Caspase-3 were detected by Western blotting. RESULTS: Qingxia therapy could significantly decrease serum ALT, AST and TBIL levels (P < 0.01 or 0.05), reduce hepatocyte necrosis and inflammatory cell infiltration. There were more apoptotic cells in model group, which had significant differences compared with Qingxia group and control group. Protein expressions of BAX and Caspase-3 in model group were significantly higher than those in control group and Qingxia group (P < 0.05), but BCL-2 protein expression in model group was lower (P < 0.05). CONCLUSION: Qingxia therapy can ameliorate the liver function and hepatic tissue pathology of rats with hepatic injury induced by LPS/D-GalN, alleviate hepatocyte apoptosis in rats, prevent and treat hepatocyte apoptosis by down-regulating the protein expressions of Caspase-3 and BAX, up-regulating the protein expression of BCL-2, and adjusting the balance of BCL-2/BAX.

Synthesis and Identification of Heterobivalent Anticancer Compounds Containing Urea and 5-Arylidene-2-Thiohydantoin Motifs.

Urea and thiohydantoin are among the important privileged structures for drug discovery. We have developed a synthetic approach to the high-throughput synthesis of the heterobivalent compounds containing both urea and 5-arylidene-2-thiohydantoin functional groups. This synthetic methodology was applied to the synthesis of a mixture-based library containing a total of 5280 compounds in a positional scanning format. The library was screened for its antiproliferative activity against cancer cells using a tetrazolium dye (MTT) based assay. Deconvolution of the library identified six hit compounds exhibiting moderate inhibitory potency against cancer cell proliferation.