A modified lung ultrasound score to evaluate short-term clinical outcomes of bronchopulmonary dysplasia.

BACKGROUND: Lung ultrasound (LUS) is a useful tool for assessing the severity of lung disease, without radiation exposure. However, there is little data on the practicality of LUS in assessing the severity of bronchopulmonary dysplasia (BPD) and evaluating short-term clinical outcomes. We adapted a LUS score to evaluate BPD severity and assess the reliability of mLUS score correlated with short-term clinical outcomes. METHODS: Prospective diagnostic accuracy study was designed to enroll preterm infants with gestational age < 34 weeks. Lung ultrasonography was performed at 36 weeks postmenstrual age. The diagnostic and predictive values of new modified lung ultrasound (mLUS) scores based on eight standard sections were compared with classic lung ultrasound (cLUS) scores. RESULTS: A total of 128 infants were enrolled in this cohort, including 30 without BPD; 31 with mild BPD; 23 with moderate BPD and 44 with severe BPD. The mLUS score was significantly correlated with the short-term clinical outcomes, superior to cLUS score. The mLUS score well correlated with moderate and severe BPD (AUC = 0.813, 95% CI 0.739-0.888) and severe BPD (AUC = 0.801, 95% CI 0.728-0.875), which were superior to cLUS score. The ROC analysis of mLUS score to evaluate the other short-term outcomes also showed significant superiority to cLUS score. The optimal cutoff points for mLUS score were 14 for moderate and severe BPD and 16 for severe BPD. CONCLUSIONS: The mLUS score correlates significantly with short-term clinical outcomes and well evaluates these outcomes in preterm infants.

Characterization of lung ultrasound imaging in preterm infants with bronchopulmonary dysplasia.

BACKGROUND: Lung ultrasound (LUS) is a bedside technique that can be used on diagnosis and follow-up of neonatal respiratory diseases. However, there are rare reports on the ultrasound features of bronchopulmonary dysplasia (BPD) which is one of the most common chronic lung diseases in preterm infants. OBJECTIVE: To describe the ultrasound features of different BPD levels, and to investigate the value of ultrasound in evaluating moderate-to-severe BPD. METHODS: In this prospective cohort study, newborns of less than 37 weeks' gestational age in neonatal intensive care unit (NICU) were included. The LUS characteristics including pleural line, alveolar-interstitial syndrome (AIS), retrodiaphragmatic hyperechogenicity and diaphragmatic morphology were observed and recorded. The reliability of LUS in evaluating moderate and severe BPD were compared and calculated. RESULTS: A total of 108 infants were enrolled in our study: 39, 24, 29, 16 infants had non, mild, moderate and severe BPD. The median(IQR) pleura thickness in the moderate-to-severe BPD group was 1.7(1.6-1.85) mm, which was thicker than that in the none-to-mild BPD infants (P < 0.001), meanwhile the proportions of rough pleural lines, diffuse AIS, retrodiaphragmatic hyperechogenicity, small cysts above the diaphragm and rough diaphragm in the moderate-to-severe BPD group were also higher than those in none-to-mild BPD group (86.7% vs 36.5, 57.8% vs 7.9%, 37.8% vs 0, 33.3% vs 0, P < 0.001). In evaluating moderate-to-severe BPD, rough pleura had 91.1% (95% confidence interval [CI]: 0.793-0.965) in sensitivity, 91.3% (95% CI: 0.797-0.966) in negative predictive value (NPV), and 66.7% (95% CI: 0.544-0.771) in specificity. Small cysts had 100% (95% CI: 0.941-1) in specificity, 100% (95% CI: 0.816-1) in positive predictive value (PPV), and 37.8% in sensitivity (95% CI: 0.251-0.524). Rough diaphragm had 100% (95% CI: 0.943-1) in sensitivity, 100% (95% CI: 0.796-1) in PPV and 33.3% (95% CI: 0.211-0.478) in specificity. CONCLUSIONS: Depending on its unique advantages such as convenient, no radiation and repeatable, LUS is a valuable imaging method in assessing the severity of BPD, especially in moderate and severe BPD.

Early reoccurrence of traumatic posterior atlantoaxial dislocation without fracture: A case report.

BACKGROUND: In general, atlantoaxial dislocation is rare due to the stability of the C1-C2 complex. Traumatic atlantoaxial dislocations are usually anterior and accompanied by odontoid fractures. Posterior atlantoaxial dislocations are rare, and complete posterior dislocation without associated fracture is even more rare. A case of early recurrence of posterior atlantoaxial dislocation without fracture being in therapy of first closed reduction and then open reduction has not been previously reported. CASE SUMMARY: A 45-year-old female presented with traumatic posterior atlantoaxial dislocation (TPAD) of C1-C2 without associated fractures, and Frankel Grade B spinal cord function. She was successfully managed by immediate closed reduction under skull traction. Unexpectedly, 17 d later, re-dislocation was discovered. On day 28, closed reduction was performed as before but failed. Then, open reduction and posterior internal fixation with autologous iliac bone grafts was performed. By 6 mo after surgery, atlantoaxial joint fusion was achieved, and neurological function had recovered to Frankel Grade E. At 12 mo follow-up, she had lost only 15° of cervical rotation, and atlantoaxial complex instability in joint flexing and extending were no longer observed under fluoroscopy. CONCLUSION: Early assessment of transverse ligament is critical for TPAD without fracture avoiding re-dislocation after closed reduction.

Age-related Changes of Posterior Tibial Slope and Its Roles in Anterior Cruciate Ligament Injury.

Nearly all previous studies in posterior tibial slope (PTS) and anterior cruciate ligament (ACL) injuries ignored age-related changes, and the published data are inconsistent. The objective of this study was to reveal age-related changes of PTS and its roles in ACL injury. Data for 2618 lower limbs were included initially based on the availability of lateral radiographs and a suitable femoro-tibial angle. The final 1431 subjects were analyzed according to age, gender, side, and injury status. Student's t-tests, one-way analysis of variance, and curve fitting were used to analyze data. The PTS in males was greater than that in females in the 0-9 and 30-39-year-old groups, but this pattern reversed in the 40-49, 60-69, 70-79, and 80-89-year-old groups. The PTS was greater on the left side than on the right side in the 0-9, 10-19, 50-59, 60-69, and 80-89-year-old groups. The curve fitting for PTS demonstrated a trend of first decreasing and then increasing with aging. The PTS values differed significantly between knees with an ACL injury and those without in the 20-29, 30-39, and 40-49-year-old groups but not in the 50-59-year-old group. The PTS follows a trend of first decreasing and then increasing, and its role in ACL injury changes with advancing age. The higher PTS is only unrelated to the risk of ACL injury in age groups with a lower mean PTS value.

Exploratory analysis of the relationship between home health agency engagement in a national campaign and reduction in acute care hospitalization in US home care patients.

RATIONALE, AIMS AND OBJECTIVES: To determine whether US home health agencies that intensively engaged with the 2010 Home Health Quality Improvement National Campaign were more likely to reduce acute care hospitalization (ACH) rates than less engaged agencies. METHOD: We included all Medicare-certified agencies that accessed Campaign resources in the first month of the Campaign and also responded to an online survey of resource utilization at month two. We used the survey data and item response theory to estimate a latent construct we called engagement with the campaign. ACH rates were calculated from the Centers for Medicare & Medicaid Services Outcome and Assessment Information Set for pre- and post-intervention periods (March-November 2009 and 2010, respectively). RESULTS: Staff from 1077 agencies accessed resources in the first month of the Campaign. Of these, 382 provided information about resource use and had 10 or more monthly discharges throughout the measurement periods. Dividing these agencies into quartiles based on engagement score, we found an association between engagement and reduction in ACH rates, P=0.049 (χ(2) for trend). Exploratory path analysis revealed the effect of engagement score on reduction in ACH rate to be partially mediated through reduction in average length of service rates. CONCLUSION: We found evidence that early intensity of engagement with the Campaign, as measured through use of activities and resources, was positively associated with improvement. To continue the investigation of this relationship, future work in this and other campaigns should focus on further development of engagement measures.

Supramolecular micellar nanoaggregates based on a novel chitosan/vitamin E succinate copolymer for paclitaxel selective delivery.

BACKGROUND: Nowadays, many cytotoxic anticancer drugs exhibit low solubility and poor tumor selectivity, which means that the drug formulation is very important. For example, in the case of paclitaxel (PTX), Cremophor EL(®) (BASF, Ludwigshafen, Germany) needs to be used as a solubilizer in its clinical formulation (Taxol(®), Bristol-Myers Squibb, New York, NY), although it can cause serious side effects. Nanomicellar systems are promising carriers to resolve the above problems, and the polymer chosen is the key element. METHODS: In this study, a novel amphiphilic chitosan/vitamin E succinate (CS-VES) copolymer was successfully synthesized for self-assembling polymeric micelles. Proton nuclear magnetic resonance spectroscopy and infrared were used to characterize the molecular structure of the copolymer. The PTX-loaded CS-VES polymeric micelles (PTX-micelles) were characterized by dynamic light scattering, transmission electron microscopy, X-ray diffraction, and differential scanning calorimetry. RESULTS: The critical micelle concentration of CS-VES was about 12.6 µg/mL, with the degree of amino group substitution being 20.4%. PTX-micelles were prepared by a nanoprecipitation/dispersion technique without any surfactant being involved. PTX-micelles exhibited a drug loading as high as 21.37% and an encapsulation efficiency of 81.12%, with a particle size ranging from 326.3 to 380.8 nm and a zeta potential of +20 mV. In vitro release study showed a near zero-order sustained release, with 51.06%, 50.88%, and 44.35% of the PTX in the micelles being released up to 168 hours at three drug loadings of 7.52%, 14.09%, and 21.37%, respectively. The cellular uptake experiments, conducted by confocal laser scanning microscopy, showed an enhanced cellular uptake efficiency of the CS-VES micelles in MCF-7 cells compared with Taxol. The PTX-micelles exhibited a comparable but delayed cytotoxic effect compared with Taxol against MCF-7 cells, due to the sustained-release characteristics of the nanomicelles. More interestingly, blank nanomicelles based on CS-VES copolymer demonstrated significant cytotoxicity against MCF-7 cells. CONCLUSION: The supramolecular micellar aggregates based on CS-VES copolymer is a promising nanocarrier and efficacy enhancer when used as an anticancer drug-delivery system.

Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys.

The worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development. Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity. Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1.

First examples of extended structures based on {PMo(12)Sb(2)O(40)} polyoxoanions.

Three novel heteropolyanions [PMo(12)Sb(2)O(40)][Cu(enMe)(2)].4H(2)O (), [PMo(12)Sb(2)O(40)][Ni(enMe)(2)].4H(2)O (2) and [PMo(12)Sb(2)O(40)][Cu(en)(2)].H(3)O.H(2)O (3) (enMe = 1,2-diaminopropane, en = ethylene diamine) have been synthesized and characterized by IR spectroscopy, X-ray photoelectron spectroscopy (XPS), thermogravimetric analyses and elemental analyses. Single-crystal X-ray diffraction analyses reveal that these three compounds represent the first examples of compounds based on the novel polyoxoanion {PMo(12)Sb(2)O(40)} and different transition metal coordination complexes. 1 and 2 are isostructural and both exhibit novel 1-D structures. In contrast to 1 and 2, 3 exhibits a substantially distinct novel 1-D structure. In addition, 3 is the first example of an extended structure constructed from polyoxoanions and Cu(+) transition metal coordination complexes.

Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans.

The immunologic basis for the potential enhanced HIV-1 acquisition in adenovirus serotype 5 (Ad5)-seropositive individuals who received the Merck recombinant Ad5 HIV-1 vaccine in the STEP study remains unclear. Here we show that baseline Ad5-specific neutralizing antibodies are not correlated with Ad5-specific T lymphocyte responses and that Ad5-seropositive subjects do not develop higher vector-specific cellular immune responses as compared with Ad5-seronegative subjects after vaccination. These findings challenge the hypothesis that activated Ad5-specific T lymphocytes were the cause of the potential enhanced HIV-1 susceptibility in the STEP study.

Nuclear import of influenza A viral ribonucleoprotein complexes is mediated by two nuclear localization sequences on viral nucleoprotein.

BACKGROUND: The influenza A virus replicates in the nucleus of its host cell. Thus, entry of the influenza genome into the cell nucleus is necessary for establishing infection. The genome of the influenza A virus consists of eight single-stranded, negative-sense RNA molecules, individually packed with several copies of the viral nucleoprotein (NP) into ribonucleoprotein particles (vRNPs). These vRNPs are large, rod-shaped complexes containing a core of NP, around which the RNA is helically wrapped. The vRNPs are the entities that enter the nucleus, and their nuclear import must be mediated by nuclear localization sequences (NLSs) exposed on the vRNPs. NP contains at least two putative NLSs, one at the N-terminus (NLS1) and one in the middle (NLS2) of the protein. These NP NLSs have been shown to mediate the nuclear import of recombinant NP molecules. However, it remains to be determined which NLS mediates the nuclear import of influenza vRNP complexes. RESULTS: To directly track the nuclear import of the influenza A genome, we developed an experimental assay based on digitonin-permeabilized cells and fluorescently-labeled vRNPs isolated from the influenza A virus. We used this assay to determine the contribution of the two proposed NLSs on NP to the nuclear import of influenza vRNP complexes. Peptides that mimic each of the two NLSs on NP were used to compete with vRNPs for their nuclear import receptors. In addition, antibodies against the two NP NLSs were used to block the NLSs on the vRNP complexes, and thereby inhibit vRNP nuclear import. Both peptide competition and antibody inhibition of either sequence resulted in decreased nuclear accumulation of vRNPs. The two sequences act independently of each other, as inhibition of only one of the two NLSs still resulted in significant, though diminished, nuclear import of vRNPs. Furthermore, when both sequences were blocked, vRNP nuclear import was almost completely inhibited. Antibody inhibition studies further showed that NLS1 on NP is the main contributor to the nuclear import of vRNPs. CONCLUSION: Our results demonstrate that both NLS1 and NLS2 on NP can mediate the nuclear uptake of influenza A vRNPs.

Impact of release characteristics of sinomenine hydrochloride dosage forms on its pharmacokinetics in beagle dogs.

AIM: To investigate the effect of release behavior of sustained-release dosage forms of sinomenine hydrochloride (SM.HCl) on its pharmacokinetics in beagle dogs. METHODS: The in vitro release behavior of two SM.HCl dosage forms, including commercial 12-h sustained-release tablets and 24-h sustained-release pellets prepared in our laboratory, was examined. The two dosage forms were orally administrated to beagle dogs, and then the in vivo SM.HCl pharmacokinetics was investigated and compared. RESULTS: The optimal SM.HCl sustained-release formulation was achieved by mixing slow- and rapid-release pellets (9:1, w/w). The SM.HCl release profiles of the sustained-release pellets were scarcely influenced by the pH of the dissolution medium. Release from the 12-h sustained-release tablets was markedly quicker than that from the 24-h sustained-release pellets, the cumulative release up to 12-h was 99.9% vs 68.7%. From a pharmacokinetic standpoint, the 24-h SM.HCl sustained-release pellets had longer tmax and lower Cmax compared to the 12-h sustained-release tablets, the tmax being 2.67+/-0.52 h vs 9.83+/-0.98 h and the Cmax being 1 334.45+/-368.76 ng/mL vs 893.12+/-292.55 ng/mL, respectively. However, the AUC(0-tn) of two SM.HCl dosage forms was comparable and both preparations were statistically bioequivalent. Furthermore, the two preparations had good correlations between SM.HCl percentage absorption in vivo and the cumulative percentage release in vitro. CONCLUSION: The in vitro release properties of the dosage forms strongly affect their pharmacokinetic behavior in vivo. Therefore, managing the in vitro release behavior of dosage forms is a promising strategy for obtaining the optimal in vivo pharmacokinetic characteristics and safe therapeutic drug concentration-time curves.