Digital Gamification to Enhance Vaccine Knowledge and Uptake: Scoping Review.
Vaccine hesitancy is a growing threat to population health, and effective interventions are needed to reduce its frequency. Digital gamification is a promising new approach to tackle this public health issue. The purpose of this scoping review was to assess the amount and quality of outcomes in studies evaluating gamified digital tools created to increase vaccine knowledge and uptake. We searched for peer-reviewed articles published between July 2009 and August 2019 in PubMed, Google Scholar, Journal of Medical Internet Research, PsycINFO, PsycARTICLES, Psychology and Behavioral Sciences Collection, and SocINDEX. Studies were coded by author, year of publication, country, journal, research design, sample size and characteristics, type of vaccine, theory used, game content, game modality, gamification element(s), data analysis, type of outcomes, and mean quality score. Outcomes were synthesized through the textual narrative synthesis method. A total of 7 articles met the inclusion criteria and were critically reviewed. Game modalities and gamification elements were diverse, but role play and a reward system were present in all studies. These articles included a mixture of randomized controlled trials, quasi-experimental studies, and studies comprising quantitative and qualitative measures. The majority of the studies were theory-driven. All the identified gamified digital tools were highly appreciated for their usability and were effective in increasing awareness of vaccine benefits and motivation for vaccine uptake. Despite the relative paucity of studies on this topic, this scoping review suggests that digital gamification has strong potential for increasing vaccination knowledge and, eventually, vaccination coverage.


Follow up: palmitic acid ester of tetrahydrocannabinol (THC) and palmitic acid diester of 11-hydroxy-THC - unsuccessful search for additional THC metabolites.
In a previous investigation we searched for the occurrence of palmitic acid ester compounds of delta9-tetrahydrocannabinol (THC) and its primary metabolite 11-hydroxy-delta9-THC (11-OH-THC) in human body fluids and tissues (THC palmitic acid monoester [THC-Pal] and 11-OH-THC palmitic acid diester [11-OH-THC-DiPal]). As those esters could not be detected in various human body fluids (e.g. blood) or tissues (e.g. adipose tissue) we extended the investigation analyzing adipose tissue samples of mice previously given synthetic THC or a cannabis extract. In total, 48 adipose tissue samples previously tested positive for THC by means of a liquid chromatographic triple quadrupole mass spectrometric (LC-QQQ-MS) method were analyzed for the presence of THC-Pal and 11-OH-THC-DiPal by means of LC-QQQ-MS. THC-Pal and 11-OH-THC-DiPal were not detected among the adipose tissue samples analyzed despite the presence of high THC concentrations within the adipose tissue. THC concentrations in adipose tissue were in a range of approximately 7-2,595 ng/g (median: 468 ng/g, average: 704 ng/g). A (site-specific) synthesis of 11-OH-THC palmitic acid monoesters (11-hydroxy-delta9-THC-1-palmitate and 11-palmitoyloxy-delta9-THC) still remains to be done. After synthesis of these monoesters, their presence in the body fluids and tissues after THC administration should be investigated.


p-Channel oxide thin film transistors using solution-processed copper oxide.
Cu2O thin films were synthesized on Si (100) substrate with thermally grown 200-nm SiO2 by sol-gel spin coating method and postannealing under different oxygen partial pressure (0.04, 0.2, and 0.9 Torr). The morphology of Cu2O thin films was improved through N2 postannealing before O2 annealing. Under relatively high oxygen partial pressure of 0.9 Torr, the roughness of synthesized films was increased with the formation of CuO phase. Bottom-gated copper oxide (CuxO) thin film transistors (TFTs) were fabricated via conventional photolithography, and the electrical properties of the fabricated TFTs were measured. The resulting Cu2O TFTs exhibited p-channel operation, and field effect mobility of 0.16 cm2/(V s) and on-to-off drain current ratio of ∼1×10(2) were observed in the TFT device annealed at PO2 of 0.04 Torr. This study presented the potential of the solution-based process of the Cu2O TFT with p-channel characteristics for the first time.


Generating mouse models for studying the function and fate of intrinsic cardiac adrenergic cells.
Embryos lacking the ability to synthesize epinephrine and norepinephrine die (probably due to cardiac failure) without exogenous supplementation while mutant neonates can grow into fertile adults without supplementation. These experiments define a critical period during embryogenesis, when norepinephrine and/or epinephrine are essential for mouse development. The critical period is prior to sympathetic innervation of the heart and prior to synthesis of catecholamines by the adrenal medullae. Recent work indicates that the developing heart is likely to be a major source of catecholamines in the developing mammalian embryo. The spatial pattern of biosynthetic enzymes suggests an association of the intrinsic cardiac adrenergic cells with the developing pacemaker and cardiac conduction cells. To address the functional characteristics and the fate of these cardiac adrenergic cells, we have developed two mouse models that allow us to identify and to characterize the adrenergic cells and their descendants.


Coupled reverse transcription-polymerase chain reaction (RT-PCR) as a sensitive and rapid method for isozyme genotyping.
We have developed a highly sensitive and rapid coupled reverse transcription-polymerase chain reaction (RT-PCR) technique for detection of alpha-amylase-encoding gene transcripts and for distinguishing between the human salivary (AMY1) and pancreatic (AMY2) gene transcripts. The two genes are 93-94% homologous. However, the AMY1 gene has an additional exon known as exon S, and an extra 32 bp in exon 1. Genotyping of the different AMYs by RT-PCR was based on this unique feature of the AMY1 mRNA sequence. Detection of AMY gene (AMY1 and AMY2) transcripts in cellular RNA was achieved with a set of primers common to both human AMY1 and AMY2 genes and derived from the exon 3-4 regions. In contrast, AMY1 gene transcripts were distinguished from the pancreatic AMY2 gene transcripts by use of primers specific to the exon S-1 regions of the AMY1 gene. To distinguish AMY1 transcripts from a mixture of AMY1 and AMY2, use was made of the differences in the ethidium bromide-stained agarose gel patterns obtained after digestion of the amplified exon 3-4 fragments with TaqI. AMY gene transcripts were detectable by autoradiography in RT-PCR amplified DNA obtained from as little as 5 pg of human pancreatic or parotid total RNA. A comparison of sensitivity of Northern blotting vs. RT-PCR suggested that the RT-PCR method is about 3-6 x 10(3)-fold more sensitive than Northern blotting in detecting AMY gene transcripts in human pancreatic total RNA.


Extended pathology reporting of resection specimens of colorectal liver metastases: the significance of a tumour pseudocapsule.
The aim of this study was to analyse the influence of factors reported in the minimum histopathology dataset for colorectal liver metastases (CRLM) and other pre-operative factors compared with additional data relating to the presence of tumour pseudocapsules and necrosis on recurrence 1 year after a resection. For a period of 14 months, extended histological reporting of CRLM specimens was performed, including the presence of pseudocapsules and necrosis in each tumour. The details of recurrence were obtained from surveillance imaging. In 66 patients there were 27 recurrences within 1 year. The rates were lower for patients with tumour pseudocapsules (8/27) than for patients without (19/36) (P = 0.030). Pseudocapsules were associated with a younger age (P = 0.005), nodal stage of the primary colorectal tumour (P = 0.025) and metachronous tumours (P = 0.004). In patients with synchronous disease and pseudocapsules, the recurrence rate was 2/12 compared with 13/23 patients without pseudocapsules (P = 0.026). These findings demonstrate that histological examination of resection specimens can provide significant additional prognostic information for patients after resection of CRLM, compared with clinical and radiological data. The present finding that the absence of a pseudocapsule in patients with synchronous CRLM is associated with a dramatically worse outcome may help direct patient-specific adjuvant treatment and care.


[Ectopic thyroid tissue: an unusual differential diagnosis of space-occupying mediastinal lesions].
The differential diagnosis of soft tissue masses of the anterior mediastinum includes cervical goiter extending into the mediastinum, germ-cell tumors, masses originating from the thymus, lymphoma and sternal tumors. A rare cause is ectopic mediastinal goiter without a link to the cervical thyroid. We report the case of a 36-year-old female patient with accidental chest X-ray finding of a large mass ([symbol: see text] 7 cm) in the anterior mediastinum. CT showed a hypodense mass with homogeneous enhancement and calcifications. There was no evidence of invasion in other organs. CT-guided biopsy revealed thyroid tissue. The cervical thyroid was normal in CT, ultrasound and 123I-scintigraphy; no link to the mediastinal goiter was detectable. Radionuclide uptake in the latter was homogeneous. Since malignancy could not be ruled out definitively, the mass was removed by thoracotomy and a vascular pedicle originating from the mediastinum was found. Pathologic evaluation confirmed the preoperative diagnosis of ectopic mediastinal goiter.


Observation of Topological p-Orbital Disclination States in Non-Euclidean Acoustic Metamaterials.
Disclinations-topological defects ubiquitously existing in various materials-can reveal the intrinsic band topology of the hosting material through the bulk-disclination correspondence. In low-dimensional materials and nanostructure such as graphene and fullerenes, disclinations yield curved surfaces and emergent non-Euclidean geometries that are crucial in understanding the properties of these materials. However, the bulk-disclination correspondence has never been studied in non-Euclidean geometry, nor in systems with p-orbital physics. Here, by creating p-orbital topological acoustic metamaterials with disclination-induced conic and hyperbolic surfaces, we demonstrate the rich emergent bound states arising from the interplay among the real-space geometry, the bulk band topology, and the p-orbital physics. This phenomenon is confirmed by clear experimental evidence that is consistent with theory and simulations. Our experiment paves the way toward topological phenomena in non-Euclidean geometries and will stimulate interesting research on, e.g., topological phenomena for electrons in nanomaterials with curved surfaces.


TETRASPANIN 8-1 from Phaseolus vulgaris plays a key role during mutualistic interactions.
Arbuscular mycorrhizal (AM) fungi and rhizobia form two of the most important plant-microbe associations for the assimilation of phosphorus (P) and nitrogen (N). Symbiont-derived signals are able to coordinate the infection process by triggering multiple responses in the plant root, such as calcium influxes and oscillations, increased reactive oxygen species (ROS), cytoskeletal rearrangements and altered gene expression. An examination was made of the role of tetraspanins, which are transmembrane proteins that self-organize into tetraspanin web regions, where they recruit specific proteins into platforms required for signal transduction, membrane fusion, cell trafficking, and ROS generation. In plant cells, tetraspanins are scaffolding proteins associated with root radial patterning, biotic and abiotic stress responses, cell fate determination, plasmodesmata and hormonal regulation. Some plant tetraspanins, such as Arabidopsis thaliana TETRASPANIN 8 and TETRASPANIN 9 (AtTET8 and AtTET9) are associated with exosomes during inter-kingdom communication. In this study, a homolog of AtTET8, PvTET8-1, in common bean (Phaseolus vulgaris L. var. Negro Jamapa) was examined in roots during interactions with Rhizobium tropici and Rhizophagus irregularis. The promoter of PvTET8-1 contained several cis-acting regulatory DNA elements potentially related to mutualistic interactions, and PvTET8-1 was transcriptionally activated during AM fungal and rhizobial associations. Silencing it decreased the size and number of nodules, nitrogen fixation, and mycorrhizal arbuscule formation, whereas overexpressing it increased the size and number of nodules, and mycorrhizal arbuscule formation but decreased nitrogen fixation. PvTET8-1 appears to be an important element in both of these mutualistic interactions, perhaps through its interaction with NADPH oxidase and the generation of ROS during the infection processes.


The fast-folding HP35 double mutant has a substantially reduced primary folding free energy barrier.
The LYS24/29NLE double mutant of villin headpiece subdomain (HP35) is the fastest folding protein known so far with a folding time constant of 0.6 micros. In this work, the folding mechanism of the mutant has been investigated by both conventional and replica exchange molecular dynamics (CMD and REMD) simulations with AMBER FF03 force field and a generalized-Born solvation model. Direct comparison to the ab initio folding of the wild type HP35 enabled a close examination on the mutational effect on the folding process. The mutant folded to the native state, as demonstrated by the 0.50 A C(alpha)-root mean square deviation (RMSD) sampled in both CMD and REMD simulations and the high population of the folded conformation compared with the denatured conformations. Consistent with experiments, the significantly reduced primary folding free energy barrier makes the mutant closer to a downhill folder than the wild type HP35 that directly leads to the faster transition and higher melting temperature. However, unlike the proposed downhill folding which envisages a smooth shift between unfolded and folded states without transition barrier, we observed a well-defined folding transition that was consistent with experiments. Further examination of the secondary structures revealed that the two mutated residues have higher intrinsic helical preference that facilitated the formation of both helix III and the intermediate state which contains the folded segment helix II/III. Other factors contributing to the faster folding include the more favorable electrostatic interactions in the transition state with the removal of the charged NH(3)(+) groups from LYS. In addition, both transition state ensemble and denatured state ensemble are shifted in the mutant.


Multiple steps in carcinogenesis involving alterations of multiple tumor suppressor genes.
Recent advances in molecular genetics have made it possible to understand the molecular mechanisms of human cancer progression. The results indicate that clinically evident tumor cells already carry multiple genetic alterations and further accumulation of genetic alteration occurs during tumor progression. It is widely accepted that tumor suppressor genes play a central role in the genesis and progression of human cancers, as frequent alterations of tumor suppressor genes have been found in a variety of human cancers. Molecular analyses of various stages of human cancers, from precancerous lesions to advanced or metastatic tumors, indicate that sequential accumulation of genetic alterations correlates with more malignant phenotypes of tumor cells. Furthermore, biological studies of tumor suppressor genes have revealed that a single gene defect is not sufficient for the cells to gain growth advantage and start clonal expansion in vivo. These results are consistent with the concept of human multistage carcinogenesis, indicated by experimental animal models and epidemiological studies. Although it is supposed that there are more than 20 tumor suppressor genes in the human genome, only a few tumor suppressor genes have been identified to date. Thus, further studies should focus on the identification and characterization of novel tumor suppressor genes, and molecular analysis of those genes in human cancer would be of great help in clarifying the multiple steps in the process of human carcinogenesis.


Board leadership development: the key to effective nursing leadership in the 21st century.
This article discusses the need for board leadership development of nurses. The authors provide an overview of the Sigma Theta Tau International Board Leadership Development program based on the experiences of nine Fellows who completed the program. Elements necessary for a self-developed board leadership development program are presented. Rationale is discussed as to why the Sigma Theta Tau Board Leadership Development program and future similar programs need to include the critical success factors in the development of nurses as board members. The authors discuss the variety of professional and personal benefits of a program of this importance.


Role of GALNT14 in lung metastasis of breast cancer.
Aberrant expression of the polypeptide N-acetyl-galactosaminyltransferase (GALNTs) has been associated with cancer, but their function(s) in metastasis remains elusive. We have recently identified GALNT14, one of the O-GalNAc glycosylationinitiating enzymes, as a prognostic marker for pulmonary relapse in breast cancer patients. Furthermore, we showed that GALNT14 promotes lung metastasis by the following novel mechanisms: 1) enhancing metastasis initiation by inhibiting the anti-metastatic effect of BMP produced from the lung stroma, 2) exploiting growth signals (e.g. FGF) supplied by macrophages, for their growth into macrometastases in the lung environment. These multi-faceted roles of GALNT14 in lung metastasis are achieved by GALNT14-mediated inhibition and activation of the BMP and FGF signaling pathways, respectively. The link among GALNT14, its downstream pathways and lung metastasis, provides us with an opportunity to develop effective therapeutic intervention for breast cancer. [BMB Reports 2017; 50(5): 233-234].


A Chlamydomonas homologue of the putative murine t complex distorter Tctex-2 is an outer arm dynein light chain.
Molecular analysis of a 19,000-Mr protein from the Chlamydomonas flagellum reveals that it is homologous to the t complex-encoded protein Tctex-2, which is a candidate for one of the distorter products that cause the extreme transmission ratio distortion (meiotic drive) of the murine t complex. The 19,000-Mr protein is extracted from the axoneme with 0.6 M NaCl and comigrates with the outer dynein arm in sucrose density gradients. This protein also is specifically missing in axonemes prepared from a mutant that does not assemble the outer arm. These data raise the possibility that Tctex-2 is a sperm flagellar dynein component. Combined with the recent identification of Tctex-1 (another distorter candidate) as a light chain of cytoplasmic dynein, these results lead to a biochemical model for how differential defects in spermiogenesis that result in the phenomenon of meiotic drive might be generated in wild-type vs t-bearing sperm.


Diabetes in the COVID-19 pandemic era.
To analyze the association between patients with diabetes mellitus and the increased severity and its complications that arise with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is a complementary review of literature in which 14 articles published in 2020 were selected. These reviewed articles were written in both Portuguese and English available in the SciELO and PubMed databases. This review also involved searching on websites of international and national organizations in order to gather information published by these bodies about diabetic population and coronavirus disease (COVID-19)-infected individuals. The presence of comorbidities in SARS-CoV-2-infected individuals causes an increase in the expression level of angiotensin-converting enzyme 2, facilitating the entry of the virus into the cell. Diabetes causes metabolic and vascular changes, thus weakening the immune system through the inhibition of the innate immune system and the secretion of various inflammatory cytokines. This hyperinflammation can lead to multiple organ failure. The interaction between this comorbidity and COVID-19 can worsen pre-existing diabetes or predispose the onset of diabetes in non-diabetic individuals. Diabetes mellitus is related to the increased severity and complications of COVID-19. The association between diabetes and COVID-19 creates a devastating double pandemic, as it worsens the prognosis of COVID-19.


Structure and dynamics of the CrIII ion in aqueous solution: Ab initio QM/MM molecular dynamics simulation.
Structural and dynamical properties of the Cr(III) ion in aqueous solution have been investigated using a combined ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulation. The hydration structure of Cr(III) was determined in terms of radial distribution functions, coordination numbers, and angular distributions. The QM/MM simulation gives coordination numbers of 6 and 15.4 for the first and second hydration shell, respectively. The first hydration shell is kinetically very inert but by no means rigid and variations of the first hydration shell geometry lead to distinct splitting in the vibrational spectra of Cr(H(2)O)(6) (3+). A mean residence time of 22 ps was obtained for water ligands residing in the second hydration shell, which is remarkably shorter than the experimentally estimated value. The hydration energy of -1108 +/- 7 kcal/mol, obtained from the QM/MM simulation, corresponds well to the experimental hydration enthalpy value.


Effect of customized healing abutments on the peri-implant linear and volumetric tissue changes at maxillary immediate implant sites: A 1-year prospective randomized clinical trial.
Immediate implant placement (IIP) associated with the use of bone substitutes and collagen matrices (CM) seems to reduce the amount of resorption at peri-implant areas. Recently, customized healing abutments (CA) appeared as another solution in order to seal the socket and preserve the original soft tissue contour. To evaluate peri-implant tissues dimensional changes after using customized healing abutments compared with the use of xenogeneic collagen matrices as socket sealing options in flapless maxillary immediate implant placement. The present study was designed as a prospective, randomized, controlled clinical trial. Patients were allocated into two groups depending on the socket sealing option: in the CM group a collagen matrix was used and in the CA group a customized abutment. Digital impressions were taken prior to extraction, 1, 4, and 12 months after implant insertion and the digital files allowed to evaluate linear buccal changes (MBC) and the buccal volumetric variation (BVv) between the different time points at peri-implant tissue areas. Additionally, mucosa variation was computed assessing the papilla presence and the midfacial mucosa height. Statistical significance was set at 0.05. Twenty-eight patients were observed during a 12-month period. Significant differences between mean values of BVv at the first month were observed at the CM and CA group (-9.75 ± 6.65% and -4.76 ± 5.29%, respectively) (p = 0.043). At the 1-year follow-up, no significant differences were found in terms of BVv between the two groups, although the thin bone phenotype (≤1 mm) significantly influenced the volumetric variations that occurred in each group. No significant differences were noticed in midfacial mucosa and papillae alteration between groups, after 1 year of treatment. Both treatment options are predictable solutions for socket sealing in IIP, although a higher volumetric variation can be expected in the presence of thin bone phenotypes.


Multi-Electron Oxidation of Anthracene Derivatives by Nonheme Manganese(IV)-Oxo Complexes.
Six-electron oxidation of anthracene to anthraquinone by a nonheme MnIV -oxo complex, [(Bn-TPEN)MnIV (O)]2+ , proceeds through a rate-determining electron transfer from anthracene to [(Bn-TPEN)MnIV (O)]2+ , followed by subsequent fast oxidation reactions to give anthraquinone. The reduced MnII complex ([(Bn-TPEN)MnII ]2+ ) is oxidized by [(Bn-TPEN)MnIV (O)]2+ rapidly to produce the μ-oxo dimer ([(Bn-TPEN)MnIII -O-MnIII (Bn-TPEN)]4+ ). The oxygen atoms of the anthraquinone product were found to derive from the manganese-oxo species by the 18 O-labelling experiments. In the presence of Sc3+ ion, formation of an anthracene radical cation was directly detected in the electron transfer from anthracene to a Sc3+ ion-bound MnIV (O) complex, [(Bn-TPEN)MnIV (O)-(Sc(OTf)3 )2 ]2+ , followed by subsequent further oxidation to yield anthraquinone. When anthracene was replaced by 9,10-dimethylanthracene, electron transfer from 9,10-dimethylanthracene to [(Bn-TPEN)MnIV (O)-(Sc(OTf)3 )2 ]2+ occurred rapidly to produce stable 9,10-dimethylanthracene radical cation. The driving force dependence of the rate constants of electron transfer from the anthracene derivatives to [(Bn-TPEN)MnIV (O)]2+ and [(Bn-TPEN)MnIV (O)-(Sc(OTf)3 )2 ]2+ was well-evaluated in light of the Marcus theory of electron transfer.


Efficacy of low-dose interferon with antiretroviral therapy in Kaposi's sarcoma: a randomized phase II AIDS clinical trials group study.
We wished to evaluate the efficacy and safety of a low and an intermediate daily dose of interferon-alpha2b (IFN-alpha2b) with didanosine in patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). HIV-seropositive subjects with biopsy-confirmed cutaneous KS were randomized to receive either a low (1 million IU) or an intermediate (10 million IU) dose of IFN-alpha2b once daily with twice daily doses of didanosine. Treatment assignment was stratified by CD4 count. Response, toxicity, changes in CD4 counts, and survival were evaluated. Sixty-eight eligible subjects were accrued, 35 to low-dose and 33 to intermediate-dose IFN-alpha2b. The response rate was 40% in the low-dose group (95% CI, 24-58) and 55% in the intermediate-dose group (95% CI, 36-72) (p = 0.338). The median response duration was approximately 110 weeks in both groups. Intermediate-dose IFN induced grade 3/4 neutropenia more often (21% vs. 3%, p = 0.048) and grade 3/4 toxicity faster (p = 0.0231) and necessitated treatment discontinuation earlier for drug-related toxicities (p = 0.0416) than low-dose IFN. There were no significant differences in survival between the treatment groups. Baseline CD4 count was the only significant factor predicting response. Once-daily low-dose and intermediate-dose IFN-alpha2b induced similar response rates, which were achieved without optimal antiretroviral therapy. The slightly higher response rate in the intermediate-dose group was offset by its significantly poorer tolerance. These findings justify the use of lower, well-tolerated IFN doses for treatment of KS with currently used antiretroviral regimens.


In vitro effects of beta-lactams combined with beta-lactamase inhibitors against methicillin-resistant Staphylococcus aureus.
The effects of combinations of beta-lactams with two beta-lactamase inhibitors, sulbactam and clavulanic acid, were determined in vitro against 22 clinical isolates of methicillin-resistant Staphylococcus aureus. Combinations of cefpirome, cefotaxime, and cefazolin with sulbactam (10 micrograms/ml) showed synergistic effects against more than 70% of the strains. Combinations of methicillin and penicillin G with sulbactam also showed synergistic effects against 50 and 68% of the strains, respectively, while cefotiam, moxalactam, flomoxef, and cefmetazole in combination with sulbactam showed such effects against only 40% or fewer. Clavulanic acid was synergistic only when combined with penicillin G, the effect probably being due to the beta-lactamase inhibition by the inhibitor. Sulbactam did not improve the antimicrobial activities of the beta-lactams against methicillin-susceptible S. aureus strains. At 42 degrees C the MICs of cefotaxime, methicillin, and flomoxef alone were markedly decreased from the values at 35 degrees C, and no synergy between these beta-lactams and sulbactam appeared. The resistance to penicillin G was not inhibited by incubation at 42 degrees C, and combinations of penicillin G with sulbactam and clavulanic acid showed synergy. The amounts of beta-lactamase produced were not related to the decreases in the MICs of the beta-lactams, except for penicillin G combined with sulbactam. Clavulanic acid showed slightly stronger beta-lactamase-inhibiting activity than sulbactam did. These results suggest that the synergy between sulbactam and the beta-lactams, except for penicillin G, may not be due to beta-lactamase inhibition but to suppression of the methicillin-resistant S. aureus-specific resistance based on other factors.


New family of biosensors for monitoring BTX in aquatic and edaphic environments.
Benzene, toluene, ethylbenzene and xylenes (BTEX) contamination is a serious threat to public health and the environment, and therefore, there is an urgent need to detect its presence in nature. The use of whole-cell reporters is an efficient, easy-to-use and low-cost approach to detect and follow contaminants outside specialized laboratories; this is especially important in oil spills that are frequent in marine environments. The aim of this study is the construction of a bioreporter system and its comparison and validation for the specific detection of monocyclic aromatic hydrocarbons in different host bacteria and environmental samples. Our bioreporter system is based on the two component regulatory system TodS-TodT of P. putida DOT-T1E, and the PtodX promoter fused to the GFP protein as the reporter protein. For the construction of different biosensors, this bioreporter was transferred into three different bacterial strains isolated from three different environments, and their performance was measured. Validation of the biosensors on water samples spiked with petrol, diesel and crude oil on contaminated waters from oil spills and on contaminated soils demonstrated that they can be used in mapping and monitoring some BTEX compounds (specifically benzene, toluene and two xylene isomers). Validation of biosensors is an important issue for the integration of these devices into pollution-control programmes.


Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients.
To investigate the relationship of circulating matrix Gla protein (MGP) species with incident cardiovascular disease (CVD) or coronary heart disease (CHD) in type 2 diabetic patients. EPIC-NL is a prospective cohort study among 40,011 Dutch men and women. At baseline (1993-1997), 518 participants were known to have type 2 diabetes. MGP levels were measured by ELISA techniques in baseline plasma samples. The incidence of fatal and nonfatal CVD and CVD subtypes-CHD, peripheral arterial disease (PAD), heart failure, and stroke-were obtained by linkage to national registers. Cox proportional hazard models were used to calculate hazard ratios (HRs), adjusted for sex, waist-to-hip ratio, physical activity, and history of CVD. During a median 11.2 years of follow-up, 160 cases of CVD were documented. Higher circulating desphospho-uncarboxylated MGP (dp-ucMGP) levels were significantly associated with higher risk of CVD, with an HR per SD (HRSD) of 1.21 (95% CI 1.06-1.38), PAD (HRSD 1.32 [95% CI 1.07-1.65]), and heart failure (HRSD 1.75 [95% CI 1.42-2.17]) after adjustment. Higher circulating dp-ucMGP levels were not related to risk of CHD (HRSD 1.12 [95% CI 0.94-1.34]) or stroke (HRSD 1.05 [95% CI 0.73-1.49]). Circulating desphospho-carboxylated MGP and circulating total-uncarboxylated MGP levels were not associated with CVD or CVD subtypes. High dp-ucMGP levels were associated with increased CVD risk among type 2 diabetic patients, especially with the subtypes PAD and heart failure, while other MGP species were not related to CVD risk. These results suggest that a poor vitamin K status is associated with increased CVD risk.


Crystallographic snapshots of ternary complexes of thermophilic secondary alcohol dehydrogenase from Thermoanaerobacter pseudoethanolicus reveal the dynamics of ligand exchange and the proton relay network.
Three-dimensional structures of I86A and C295A mutant secondary alcohol dehydrogenase (SADH) from Thermoanaerobacter pseudoethanolicus were determined by x-ray crystallography. The tetrameric structure of C295A-SADH soaked with NADP+ and dimethyl sulfoxide (DMSO) was determined to 1.85 Å with an Rfree of 0.225. DMSO is bound to the tetrahedral zinc in each subunit, with ligands from SG of Cys-37, NE2 of His-59, and OD2 of Asp-150. The nicotinamide ring of NADP is hydrogen-bonded to the N of Ala-295 and the O of Val-265 and Gly-293. The O of DMSO is connected to a network of hydrogen bonds with OG of Ser-39, the 3'-OH of NADP, and ND1 of His-42. The structure of I86A-SADH soaked with 2-pentanol and NADP+ contains (R)-2-pentanol bound in each subunit, ligated to the tetrahedral zinc, and connected to the proton relay network. The structure of I86A-SADH soaked with 3-methylcyclohexanol and NADP+ has alcohol bound in three subunits. Two of the sites have the alcohol ligated to the zinc in an axial position, with OE2 of Glu-60 in the other axial position of a trigonal bipyramidal complex. One site has 3-methylcyclohexanol bound noncovalently, with the zinc in an inverted tetrahedral geometry with Glu-60. The fourth site also has the zinc in a trigonal bipyramidal complex with axial Glu-60 and water ligands. These structures demonstrate that ligand exchange of SADH involves pentacoordinate and inverted zinc complexes with Glu-60. Furthermore, we see a network of hydrogen bonds connecting the substrate oxygen to the external solvent that is likely to play a role in the mechanism of SADH.


von Willebrand factor independently predicts long-term survival in patients with pulmonary arterial hypertension.
We hypothesized that higher plasma levels of von Willebrand factor (vWF) and reduced ristocetin cofactor activity (RCA)/vWF ratios at baseline and follow-up would be associated with an increased risk of death in patients with pulmonary arterial hypertension (PAH). Endothelial injury and dysfunction cause increased vWF levels in patients with cardiovascular disease. Increased vWF is associated with a higher risk of death in patients with coronary artery disease, congestive heart failure, and ARDS. In PAH, vWF is elevated and functions abnormally, resulting in reduced platelet binding. The ability of vWF to bind platelets is reflected by RCA. We performed a retrospective cohort study of 66 PAH patients who underwent initial evaluation at our center from January 1994 to June 2002. The primary outcome was death or lung transplantation. vWF level was directly associated with Factor VIII activity, RCA, fibrinogen, and prothrombin time (p < or = 0.01). vWF levels at baseline and follow-up were associated with the risk of death (hazard ratio [HR] per 50% increase, 1.4; 95% confidence interval [CI], 1.1 to 1.8 [p = 0.02]; and HR per 50% increase, 1.5; 95% CI, 1.1 to 2.0 [p = 0.011]; n = 48, respectively). RCA/vWF ratios were not associated with outcome. These results were unaffected by adjustment for demographics, baseline hemodynamics, laboratory results, or PAH therapy in multivariate analyses. Increased vWF levels at baseline and follow-up are associated with worse survival in patients with PAH; however, RCA/vWF ratios are not. The hemostatic effects of vWF do not account for these findings. This suggests that endothelial injury and dysfunction may persist despite treatment and may impact on disease course. Therapies that target endothelial injury may therefore improve outcomes for patients with PAH.


Quantitative label-free optical technique to analyze the ultrastructure changes and spatiotemporal relationship of enamel induced by Msx2 deletion.
New advances in the molecular mechanism of enamel mineralization reveal the practical significance of regenerative medicine in clinical transformation. Muscle segment homeobox 2 (MSX2), a transcription factor, is recently reported to be closely associated with the amelogenesis imperfecta (AI). To elucidate the biomineralization framework of AI enamel, herein, Msx2 gene mutant mice are investigated by dual-mode noninvasive spectroscopic analytical techniques for the first time. Optical coherence tomography (OCT) records the depth-resolved structural information of mice teeth, where a dramatic decrease in enamel thickness and quality occurred in Msx2 deficient (Msx2-/- ) enamel. And it has the advantages of fast, noninvasive and low cost. Raman spectroscopy, a powerful molecular fingerprint tool, further witnesses an imbalance of inorganic and organic contents in Msx2-/- enamel. In addition, abnormal expression of MSX2 also influences the spatial distribution of phosphate in enamel according to the Raman spectral imaging. Therefore, OCT integrated with Raman spectroscopy provides the quantitative label-free optical parameters of both the physical structure and chemical component in mice enamel, which strengthens the understanding of the biomineralization process underlying the Msx2-related amelogenesis imperfect.


Flawed mothering or infant signaling? The effects of deficient acoustic cues on ovine maternal response.
The neonate distress cry, which displays a similar acoustic structure across a range of mammalian species, is highly effective in attracting, even compelling, parental care. However, if this cry is defective, as found in human and rodent neonates with poor neurobehavioral function, is the signal less enticing? Using playback recordings of a ewe's own co-twins as stimuli in a two choice test, we compared the preference of each sheep dam for acoustic features of lamb distress calls to assess the impact of signal quality on maternal response. The results of this study indicate that lamb vocalizations with acoustic parameters reflecting poor vocal fold engagement and arousal were less likely to be preferred by their dam. Additionally, these calls were associated with delayed vocal initiation and poor infant survival behavior suggestive of subtle cognitive deficit; and support the possibility that, as in deer and rodents, ovine vocalizations within a specific fundamental frequency range may well be a trigger for optimal maternal behavior. This research has important implications for understanding failed maternal-young interactions in ungulate and other species, and for verifying standardization of infant stimuli used in maternal behavior studies.


Internal Disequilibria and Phenotypic Diversification during Replication of Hepatitis C Virus in a Noncoevolving Cellular Environment.
Viral quasispecies evolution upon long-term virus replication in a noncoevolving cellular environment raises relevant general issues, such as the attainment of population equilibrium, compliance with the molecular-clock hypothesis, or stability of the phenotypic profile. Here, we evaluate the adaptation, mutant spectrum dynamics, and phenotypic diversification of hepatitis C virus (HCV) in the course of 200 passages in human hepatoma cells in an experimental design that precluded coevolution of the cells with the virus. Adaptation to the cells was evidenced by increase in progeny production. The rate of accumulation of mutations in the genomic consensus sequence deviated slightly from linearity, and mutant spectrum analyses revealed a complex dynamic of mutational waves, which was sustained beyond passage 100. The virus underwent several phenotypic changes, some of which impacted the virus-host relationship, such as enhanced cell killing, a shift toward higher virion density, and increased shutoff of host cell protein synthesis. Fluctuations in progeny production and failure to reach population equilibrium at the genomic level suggest internal instabilities that anticipate an unpredictable HCV evolution in the complex liver environment.IMPORTANCE Long-term virus evolution in an unperturbed cellular environment can reveal features of virus evolution that cannot be explained by comparing natural viral isolates. In the present study, we investigate genetic and phenotypic changes that occur upon prolonged passage of hepatitis C virus (HCV) in human hepatoma cells in an experimental design in which host cell evolutionary change is prevented. Despite replication in a noncoevolving cellular environment, the virus exhibited internal population disequilibria that did not decline with increased adaptation to the host cells. The diversification of phenotypic traits suggests that disequilibria inherent to viral populations may provide a selective advantage to viruses that can be fully exploited in changing environments.


Interlinked DNA nano-circles for measuring topoisomerase II activity at the level of single decatenation events.
DNA nano-structures present appealing new means for monitoring different molecules. Here, we demonstrate the assembly and utilization of a surface-attached double-stranded DNA catenane composed of two intact interlinked DNA nano-circles for specific and sensitive measurements of the life essential topoisomerase II (Topo II) enzyme activity. Topo II activity was detected via the numeric release of DNA nano-circles, which were visualized at the single-molecule level in a fluorescence microscope upon isothermal amplification and fluorescence labeling. The transition of each enzymatic reaction to a micrometer sized labeled product enabled quantitative detection of Topo II activity at the single decatenation event level rendering activity measurements in extracts from as few as five cells possible. Topo II activity is a suggested predictive marker in cancer therapy and, consequently, the described highly sensitive monitoring of Topo II activity may add considerably to the toolbox of individualized medicine where decisions are based on very sparse samples.


Mastitis of dairy small ruminants.
Staphylococci are the main aetiological agents of small ruminants intramammary infections (IMI), the more frequent isolates being S. aureus in clinical cases and coagulase negative species in subclinical IMI. The clinical IMI, whose annual incidence is usually lower than 5%, mainly occur at the beginning of machine milking and during the first third of lactation. These features constitute small ruminant peculiarities compared to dairy cattle. Small ruminant mastitis is generally a chronic and contagious infection: the primary sources are mammary and cutaneous carriages, and spreading mainly occurs during milking. Somatic cell counts (SCC) represent a valuable tool for prevalence assessment and screening, but predictive values are better in ewes than in goats. Prevention is most often based on milking machine management, sanitation and annual control, and milking technique optimisation. Elimination mainly relies on culling animals exhibiting clinical, chronic and recurrent IMI, and on drying-off intramammary antibiotherapy; this treatment allows a good efficacy and may be used selectively by targeting infected udders only. Heritability values for lactation mean SCC scores are between 0.11 and 0.15. Effective inclusion of ewe's mastitis resistance in the breeding goal has recently been implemented in France following experimental and large scale estimations of genetic parameters for SCC scores.


Percutaneous Renal Ablation.
Incidental small renal cell cancers are increasingly being diagnosed on cross-sectional imaging. This review article describes the indications for percutaneous ablation of small renal cell cancers, choice of ablation technologies and imaging follow-up.


Enterobacter asburiae and Aeromonas hydrophila: soft tissue infection requiring debridement.
Enterobacter asburiae and Aeromonas hydrophila are gram-negative bacilli that have been isolated in soil and water. Enterobacter asburiae can cause an array of diseases, and exposure to A hydrophila can cause soft tissue infections, including necrotizing faciitis.A healthy-appearing 22-year-old man presented with an innocuous soft tissue injury to his leg due to an all-terrain vehicle crash. He received intravenous antibiotics and was discharged with prophylactic oral antibiotics. After the rapid onset of high fevers (102°F-103°F) <24 hours postinjury, he returned to the emergency department. Emergent surgical debridement was performed, and broad-spectrum intravenous antibiotics were started. Fevers persisted, and the patient underwent repeat extensive surgical debridement and antibiotic bead placement <30 hours after the initial surgical debridement and broad-spectrum antibiotics. Intraoperative cultures found E asburiae and A hydrophila in the wound. Following a long course of antibiotics and a skin graft, he fully recovered and had no functional deficits 1 year postoperatively.Extensive research revealed that these organisms are rare in soft tissue infections. E asburiae is opportunistic but has not been reported as a primary wound organism, and A hydrophila infections have been reported following motor vehicle crashes involving wound contamination. At presentation, it is challenging to determine rare organisms in a timely fashion; however, emergent extensive surgical intervention of an accelerated aberrant disease process should be considered to avoid catastrophic outcomes.


TESTING MODELS OF MIGRATION AND ISOLATION AMONG POPULATIONS OF CHINOOK SALMON (ONCORHYNCHUS TSCHAWYTSCHA).
The chinook salmon (Oncorhynchus tschawytscha) is a behaviorally, morphologically, and ecologically variable species distributed over a large geographic range. Although previous genetic surveys have revealed considerable genetic differences among populations with different life history types and from different major river drainages, it is not clear to what degree these genetically distinct populations are connected by low levels of gene flow. The work described in this paper addresses this question by surveying DNA restriction site variation at six nuclear genes from nine populations encompassing most of the species's North American range, and then attempting to fit the patterns of variation observed at these genes to five different evolutionary models using computer simulations of the coalescent process. Two commonly used constant population size models, one hypothesizing no migration among populations and one hypothesizing equal rates of migration among populations, were found to be statistically inconsistent with the observed patterns of variation. The other three models, which involved either recent divergence among populations coupled with large changes in populations size, unequal migration rates among populations, or selection, were all found to be consistent with the observed patterns of variation. Assuming selective neutrality, these results suggest that either the populations have all descended from a common ancestral population within the last ~50,000 years and have all suffered large declines in effective population size since that time, or that they have a more ancient divergence time but are connected by low levels of gene flow. These conclusions rest on the assumption of selective neutrality. With the methods employed, it was not possible to simultaneously test hypotheses of both selective neutrality and population structure.


One psychoanalysis or many?
This paper describes the historic development of psychoanalysis, the singular product of the genius of one man, Sigmund Freud, and which he made such strenuous efforts through his lifetime to maintain as a unified enterprise, defining out dissidents (like Adler, Jung, etc.), into what has become in the almost half-century since his death a science and a discipline characterized by an increasing diversity or pluralism, of theoretical perspectives, of linguistic and thought conventions, and of distinctive regional, cultural, and language emphases. I discuss both the understanding of this theoretical diversity and what, in the face of it, holds us together as common adherents of a shared psychoanalytic science and profession. My thesis is that what unites us is our shared focus on the clinical interactions in our consulting rooms, the phenomena encompassed by the 'present unconscious' (the Sandlers) or the 'clinical theory' (George Klein). When we look beyond that to an explanatory structure within which to conceptualize the genetic-developmental process, normal and abnormal mental functioning, psychopathology and its reversal (cure) i.e. the realm of the 'past unconscious' or the 'general theory', we posit our various theoretical, linguistic or thought perspectives, i.e.--at this stage of our historical development--our metaphors or our various explanatory symbolisms. Some implications of this viewing of our various theoretical perspectives in psychoanalysis (ego psychological, object-relational, self-psychological, Kleinian, Bionian, Lacanian, etc.) as but metaphoric expressions, are reviewed.


Differences in clinical importance of Bcl-2 in breast cancer according to hormone receptors status or adjuvant endocrine therapy.
Bcl-2 plays an anti-apoptotic role, resulting in poor clinical outcome or resistance to therapy in most tumor types expressing Bcl-2. In breast cancer, however, Bcl-2 expression has been reported to be a favorable prognostic factor. The positive correlation of Bcl-2 with estrogen receptor (ER)/progesterone receptor (PR) status, and endocrine therapy frequently given for hormone receptor-positive tumors, may obscure the independent pathobiological role of Bcl-2. We constructed a large systematic study to determine whether Bcl-2 has an independent role in breast cancer. Bcl-2 expression was immunohistochemically evaluated and compared with other clinicopathological factors, including clinical outcome, in 1081 breast cancer cases with long follow-up, separately analyzing 634 cases without any adjuvant therapy and 447 cases with tamoxifen monotherapy. The χ (2)-test for independence using a contingency table, the Kaplan-Meier method with the log-rank test, and a Cox proportional hazards model were used for the comparison of clinicopathological factors, assessment of clinical outcome, and multivariate analyses, respectively. In both patient groups, Bcl-2 expression strongly correlated with positive ER/PR status, low grade, negative human epidermal growth factor receptor 2 (HER2) status, and small tumor size, as previously reported. Bcl-2 expression did not independently predict clinical outcome in patients with ER-positive and/or PR-positive tumors or in those who received tamoxifen treatment; however, it was an independent unfavorable prognostic factor in patients with ER-negative/PR-negative or triple-negative (ER-negative/PR-negative/HER2-negative) tumors who received no adjuvant therapy. The latter was even more evident in postmenopausal women: those with hormone receptor-negative or triple-negative tumors lacking Bcl-2 expression showed a favorable outcome. Bcl-2 expression is an independent poor prognostic factor in patients with hormone receptor-negative or triple-negative breast cancers, especially in the absence of adjuvant therapy, suggesting that the anti-apoptotic effect of Bcl-2 is clearly exhibited under such conditions. The prognostic value of Bcl-2 was more evident in postmenopausal women. The present findings also highlight Bcl-2 as a potential therapeutic target in breast cancers lacking conventional therapeutic targets such as triple-negative tumors. The favorable prognosis previously associated with Bcl-2-positive breast cancer probably reflects the indirect effect of frequently coexpressed hormone receptors and adjuvant endocrine therapy.


Topical anesthesia and topical toxicity of bupivacaine combined with hydroxypolyethoxydodecane.
The biological effects of adding hydroxypolyethoxydodecane (HPED) to N-butylpipecolic acid 2,6-xyiidide (bupivacaine) has been studied in animals and in man. The topical toxicity of bupivacaine was somewhat aggravated by HPED 0.25-1.0%, and the topical anesthetic effect was strongly potentiated both in animals and in man. It was concluded that HPED increased the absorption of bupivacaine after topical application. It was also found that D(+)-bupivacaine was more potent as a topical anesthetic than L(-)-bupivacaine.


Chronic Subdural Hematoma Associated with Spontaneous Intracranial Hypotension: Therapeutic Strategies and Outcomes of 55 Cases.
Spontaneous intracranial hypotension (SIH) has increasingly been recognized, and it is well known that SIH is sometimes complicated by chronic subdural hematoma (SDH). In this study, 55 cases of SIH with SDH were retrospectively analyzed, focusing on therapeutic strategies and outcomes. Of 169 SIH cases (75 males, 84 females), 55 (36 males, 19 females) were complicated by SDH. SIH was diagnosed based on clinical symptoms, neuroimaging, and/or low cerebrospinal fluid pressure. Presence of orthostatic headache and diffuse meningeal enhancement on magnetic resonance imaging were regarded as the most important criteria. Among 55 SIH with SDH cases, 13 improved with conservative treatment, 25 initially received an epidural blood patch (EBP), and 17 initially underwent irrigation of the hematomas. Of the 25 initially treated with EBP, 7 (28.0%) needed SDH surgery and 18 (72.0%) recovered fully without surgery. Of 17 SDH cases initially treated with surgery, 6 (35.7%) required no EBP therapy and the other 11 (64.3%) needed EBP and/or additional SDH operations. In the latter group, 2 cases had transient severe complications during and after the procedures. One of these 2 cases developed a hoarse voice complication. Despite this single, non-severe complication, all enrolled in this study achieved good outcomes. The present study suggests that patients initially receiving SDH surgery may need additional treatments and may occasionally have complications. If conservative treatment is insufficient, EBP should be performed prior to hematoma irrigation.


[The expression of connective tissue growth factor in renal cortex of 5/6 nephrectomized rats and its modulation by fluvastatin].
To investigate the connective tissue growth factor (CTGF) mRNA expression in the renal cortex of 5/6 nephrectomized rats and its modulation by fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Twenty-four rats underwent operation 2 times: during the first operation 2/3 of the left kidney was resected, and the right kidney was resected completely one week after. The 24 5/6 nephrectomized rats were randomly divided into 2 groups: untreated 5/6 nephrectomized group (model group, n=12) and fluvastatin-treated 5/6 nephrectomized group (treatment group, fluvastatin was orally administered 7 mg.kg(-1).d(-1) for 13 weeks, n=12), and 6 sham-operated rats served as control (sham operation group). In the weeks 2, 4, 8, and 13 after the second operation metabolic cage was used to collect the 24-hour urine 2 times. Urine protein was examined by biuret reaction so as to calculate urinary protein excretion. By the end of experiment blood was collected to examine the serum cholesterol, triglyceride, urea nitrogen, and creatinine contents. The rats were killed and their kidneys taken out. The CTGF mRNA expression in the renal cortex was detected by RT-PCR. Immunohistochemistry was used to examine the expression of transforming growth factor-beta1 (TGF-beta1), type IV collagen and fibronectin in the glomeruli. Renal pathological changes and glomerular sclerosis index (GSI) were evaluated as well. At the end of the experiment, the mean urinary protein excretion in the model group was 305.4 mg/24 h, significantly higher than that in the treatment group (230.9 mg/24 h, P<0.01) and the sham operation group (5.6 mg/24 h, P<0.01) The serum urea nitrogen of the model group was (24.5 +/- 4.9) mmol/L, significantly higher than that of the treatment group [(15.8 +/- 3.9) mmol/L, P<0.05] and that of the sham-operated group (7.4 +/- 0.3 mmol/L, P<0.01). The serum creatinine (P<0.05) of the model group was 88 micromol/L +/- 14 micromol/L, significantly higher than that of the treatment group [(58 +/- 5) micromol/L, P<0.05)] and that of the sham-operated group [(54 +/- 5) micromol/L, P<0.05]. The creatinine clearance rate of the model group was (1.7 +/- 0.7) ml.min(-1).kg(-1), significantly lower than that of the treated group [(3.2 +/- 1.1) ml.min(-1).kg(-1), P<0.05] and that of the sham-operated group [(3.9 +/- 1.5) ml.min(-1).kg(-1), P<0.05]. The glomerular sclerosis index (GSI) in the model group was 41.8 +/- 11.5, significantly higher than that in the sham operation group (2.2 +/- 1.3, P<0.01) and the treatment group (23.4 +/- 6.1, P<0.05). The mean optical density of CTGF mRNA expression in the renal cortex of the model group was a 3 times that of the sham operation group, and the mean optical density of CTGF mRNA expression in the renal cortex of the treatment group was lower by 55.4% compared with that of the model group (P<0.01). The glomerular expressions of TGF-beta1, type IV collagen and fibronectin were significantly up-regulated in the model group in comparison with those in the sham operation group (all P<0.01). The glomerular protein expressions of TGF-beta1, type IV collagen and fibronectin were significantly weaker in the fluvastatin treatment group as compared with the model group (all P<0.01). CTGF mRNA expression is markedly upregulated in the renal cortex of 5/6 nephrectomized rats. Fluvastatin suppresses the increased CTGF mRNA expression in renal cortex and ameliorates the glomerular extracellular matrix accumulation.


Performance Fatigability and Neuromuscular Responses Are Not Joint Angle Specific Following a Sustained Isometric Forearm Flexion Task Anchored to a High Perceptual Intensity in Women.
To examine the effects of joint angle (JA) on maximal voluntary isometric contractions (MVIC) and neuromuscular responses following a sustained, isometric forearm flexion task anchored to a rating of perceived exertion (RPE) of 8 (RPE=8). Nine women (age: 20.7±2.9 yrs; height: 168.8±7.2 cm; body mass: 66.3±6.8 kg) performed 2,3s forearm flexion MVICs at JAs of 75°, 100°, and 125° prior to and following a sustained, isometric forearm flexion task anchored to RPE=8 to task failure (torque reduced to zero) at JA100. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from the biceps brachii. The MVIC at JA100 (collapsed across Time) was significantly greater (p<0.05) than JA75 and JA125. The pre-test MVIC was significantly greater (p<0.001) than the post-test. For EMG amplitude (AMP) and EMG mean power frequency (MPF), pre-test values were significantly greater (p<0.05) than the post-test values, with no differences between JAs. For MMG AMP and MMG MPF, there were no significant (p>0.05) differences between Time or JAs. Pre-test neuromuscular efficiency (normalized MVIC/normalized EMG AMP) was significantly greater (p=0.005) than post-test. Following a sustained, isometric forearm flexion task anchored to RPE=8 at JA100, the fatigue-induced MVIC and neuromuscular responses were not affected by JA.


Dietary tryptophan reverses alcohol-induced impairment of facial recognition but not verbal recall.
The present study demonstrates that alcohol-induced memory impairment can be attenuated by pretreatment with an oral tryptophan supplementation. These results provide support for the role of a brain serotonin deficit in this impairment and highlight the impact a dietary manipulation can have on a complex behavioral process.


Targeting Inflammatory-Mitochondrial Response in Major Depression: Current Evidence and Further Challenges.
The prevalence of psychiatric disorders has increased in recent years. Among existing mental disorders, major depressive disorder (MDD) has emerged as one of the leading causes of disability worldwide, affecting individuals throughout their lives. Currently, MDD affects 15% of adults in the Americas. Over the past 50 years, pharmacotherapy, psychotherapy, and brain stimulation have been used to treat MDD. The most common approach is still pharmacotherapy; however, studies show that about 40% of patients are refractory to existing treatments. Although the monoamine hypothesis has been widely accepted as a molecular mechanism to explain the etiology of depression, its relationship with other biochemical phenomena remains only partially understood. This is the case of the link between MDD and inflammation, mitochondrial dysfunction, and oxidative stress. Studies have found that depressive patients usually exhibit altered inflammatory markers, mitochondrial membrane depolarization, oxidized mitochondrial DNA, and thus high levels of both central and peripheral reactive oxygen species (ROS). The effect of antidepressants on these events remains unclear. Nevertheless, the effects of ROS on the brain are well known, including lipid peroxidation of neuronal membranes, accumulation of peroxidation products in neurons, protein and DNA damage, reduced antioxidant defenses, apoptosis induction, and neuroinflammation. Antioxidants such as ascorbic acid, tocopherols, and coenzyme Q have shown promise in some depressive patients, but without consensus on their efficacy. Hence, this paper provides a review of MDD and its association with inflammation, mitochondrial dysfunction, and oxidative stress and is aimed at thoroughly discussing the putative links between these events, which may contribute to the design and development of new therapeutic approaches for patients.


Serum potassium, calcium and magnesium in patients receiving ESHAP chemotherapy for relapsed lymphomas.
Etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) is one of the mostly widely used chemotherapy regimens for patients with relapsed lymphomas. Cisplatin administration is commonly associated with electrolyte imbalance. Careful monitoring of renal function and serum electrolytes is therefore essential in this setting. To review the practice of electrolyte monitoring - potassium (K), calcium (Ca) and magnesium (Mg) - in patients receiving ESHAP and the frequency and severity of abnormalities and their management. Twenty-one consecutive patients received ESHAP. The medical records of 16 patients were retrievable and reviewed retrospectively. Results of serum K, Ca and Mg were collected prior to and after cycles 1, 2 and 3 of ESHAP, if measured. Serum K levels prior to every cycle did not show any noticeable change. The means were 4.42, 4.34 and 4.43 mmol/l before cycles 1, 2 and 3, respectively. In one patient hypokalaemia was severe, refractory and symptomatic when preceded by hypomagnesaemia. Serum-adjusted calcium levels showed only minimal reduction. The means were 2.46, 2.40 and 2.38 mmol/l before cycles 1, 2 and 3 respectively. Mean serum Mg levels prior to every cycle showed progressive reduction; 0.84, 0.75 and 0.67 mmol/l before cycles 1, 2 and 3, respectively. This was associated with a progressive increase in the amount of required Mg supplementation. Serum K, Ca and Mg was measured prior to 100%, 67% and 35% of administered cycles, respectively. In patients receiving ESHAP, hypokalaemia can occasionally be seen, especially if preceded by hypomagnesaemia. Mild cumulative hypocalcaemia is recognised. Hypomagnesaemia is a progressive complication and physicians need be aware of its importance. alcaemia is recognised. Hypomagnesaemia is a progressive complication and physicians need be aware of its importance.


Granulomatous, hepatolithiasis and hepatomegaly caused by Capillaria hepatica infection: first case report of Thailand.
This is the first case report in Thailand of a Capillaria hepatica infection causing a granulomatous hepatic lesion, bile duct dilatation, hepatolithiasis and hepatomegaly. The patient's chief complaint was abdominal pain with fever and chills. Imaging of the liver revealed a 3-cm mass in the postero-inferior sub-segment of the right lobe of the liver with bile duct dilatation. Right hepatectomy and cholecystectomy were performed. Gross pathology of the right hepatectomy revealed focal intrahepatic duct dilatation with prominent periductal fibrosis. The histopathological section revealed chronic inflammation and some granuloma formation surrounding the bile ducts, generalized portal infiltration, prominence of eosinophils and hepatolithiasis. Histopathotogical section revealed oblique sections of C. hepatica egg (size 35.4+/-6.38 microm in width) and brown amorphous pigment.


Surface tension of liquid ternary Fe-Cu-Mo alloys measured by electromagnetic levitation oscillating drop method.
For the liquid Fe-Cu-Mo ternary system, the surface tensions of three selected alloys, i.e., three typical monotectic alloys, were measured by the electromagnetic levitation oscillating drop method over a broad temperature range, including both superheated and undercooled states. The maximum undercooling attained is up to 173 K. The experimental results show a good linear correlation between the surface tension and the temperature. By applying on the Butler equation, the surface tensions were also calculated and they are in good agreement with the measured ones, except that in the undercooled state, the calculated value is slightly larger than the measured results. Interestingly, both the measured and calculated results indicate that the enriched element on the droplet surface is much more conspicuous than other elements in influencing the surface tension. Besides, the viscosity and the density of the liquid Fe-Cu-Mo ternary alloys are also derived on the grounds of the experimentally measured surface tensions.


Sr3CrN3: A New Electride with a Partially Filled d-Shell Transition Metal.
Electrides are ionic crystals in which the electrons prefer to occupy free space, serving as anions. Because the electrons prefer to be in the pockets, channels, or layers to the atomic orbitals around the nuclei, it has been challenging to find electrides with partially filled d-shell transition metals, since an unoccupied d-shell provides an energetically favorable location for the electrons to occupy. We recently predicted the existence of electrides with partially filled d-shells using high-throughput computational screening. Here, we provide experimental support using X-ray absorption spectroscopy and X-ray and neutron diffraction to show that Sr3CrN3 is indeed an electride despite its partial d-shell configuration. Our findings indicate that Sr3CrN3 is the first known electride with a partially filled d-shell transition metal, in agreement with theory, which significantly broadens the criteria for the search for new electride materials.


Disk-generation/ring-collection scanning electrochemical microscopy: theory and application.
The potential of ring-disk ultramicroelectrodes (RD UMEs) as probes for scanning electrochemical microscopy (SECM) was investigated both theoretically and experimentally. In particular, the disk-generation/ring-collection (DG/RC) mode of operation was considered. In this case, the interaction of two species with the substrate under investigation can be followed simultaneously from single tip current-distance measurement (approach curve) to the substrate. Theoretical approach curves for DG/RC were calculated by numerical methods. Such approach curves to both insulating and conducting substrates indicate a strong tip response dependence on the ring radius while the response was relatively insensitive to ring thickness and overall tip radius. The RD tip was characterized by fitting experimental approach curves recorded at insulating and conducting substrates to simulated curves for a given tip geometry. DG/RC SECM was then applied to investigate the partitioning of iodine across a liquid-liquid interface.


[The relationship between adolescent body size and health promoting behavior and biochemical indicator factors].
Tainan City has the third highest prevalence of junior high school student obesity of all administrative districts in Taiwan. School nurses play an important role in promoting student health. Understanding the factors that significantly impact student weight is critical to designing effective student health promotion programs. This study explored the relationships between health promotion behavior and serum biomarker variables and body size. Researchers used a cross-sectional descriptive study design and stratified cluster random sampling. Subjects were 7th graders who received an in-school health checkup with blood test at 41 public junior high schools in Tainan City between July 2010 and May 2011. Research instruments included the adolescent health promotion (AHP) scale, serum biochemical profile and BMI (body mass index). Obtained data were analyzed using descriptive and inferential statistics. Of the 726 students who participated in this study, 22.2% were underweight and 23.8% were overweight or obese. Higher AHP scores correlated with better biomarkers and body size. Multivariate analysis found factors that increased the risk of being overweight included: being male, having a father with a relatively low level of education, playing video games frequently, and doing little or no exercise (odds ratio = 1.93, 1.75, 1.07, 1.04, respectively). Participants with relatively healthy behaviors had better biomarkers and a lower risk of being overweight. Findings can support the development of evidence-based school programs to promote student health.


Water movement in tendon in response to a repeated static tensile load using one-dimensional magnetic resonance imaging.
Rabbit Achilles tendons (N = 8) were subjected to tensile loading while internal water movements were followed using NMR. The distribution of the internal water in tendons was measured using a one-dimensional proton-density map that was collected along a radial line oriented transverse to the tendon's long axis. The proton density map was created from fits to T2 relaxation data. The experimental design included two cycles of loading (7.5 N tensile load) and relaxation. The first load application was for 42.67 min: unloaded for 21.33 min, reloaded for 21.33 min, and then unloaded for 21.33 min. Water was redistributed in a time-dependent fashion upon loading: proton density decreased in the core region and increased in the rim region. In addition there was evidence that tensile loading caused water to become NMR visible. In separate, parallel experiments, we studied the mechanical behavior of tendons using identical conditions of uniaxial loading (N = 7). The time constants of water movements were very different from the time constants of mechanical relaxation, indicating that water redistribution is not the sole determining factor of mechanical behavior.


Dynamical changes of hemoglobin and its surrounding water during thermal denaturation as studied by quasielastic neutron scattering and temperature modulated differential scanning calorimetry.
We have investigated the dynamical behavior of both the protein hemoglobin and its surrounding water during the denaturation process using modulated temperature differential scanning calorimetry, quasielastic neutron scattering, and frequency dependent conductivity measurements. To distinguish between the scattering from the protein and its surrounding water, neutron scattering measurements were performed on both a fully hydrogenated sample as well as a sample where the water and the exchangeable hydrogen atoms on the protein surface were deuterated. The experimental data show that the unfolding and aggregation processes are substantially overlapping in temperature. The unfolding process occurs in the approximate temperature range of 315-345 K, whereas the aggregation process starts around 330-335 K and is completed at 360 K. Furthermore, the results suggest that the secondary structure of the protein unfolds at about 325 K, and that this leads to an increased number of water molecule hydrogen bonded to the protein. Thus, the unfolding of the secondary structure reduces the number of mobile (on the experimental time scale of about 50-100 ps) water molecules. In contrast, the aggregation of protein molecules seems to have a minor effect on the dynamics of its surrounding water. In the case of the protein dynamics there are competing effects from unfolding and aggregation. The unfolding process increases the flexibility of the protein, whereas the initial aggregation reduces its dynamics. The conductivity seems to be negatively affected by both reduced water mobility and an aggregation of protein molecules.


Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes.
Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin‑methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633‑MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid‑sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36‑fold uptake in receptor‑specific cellular delivery in the FcRn‑expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co‑localization further confirmed that uptake of the nanoconjugates involved receptor‑mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633‑MP ameliorated puromycin aminonucleoside‑induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome.


Thermal Plasma Synthesis of Crystalline Gallium Nitride Nanopowder from Gallium Nitrate Hydrate and Melamine.
Gallium nitride (GaN) nanopowder used as a blue fluorescent material was synthesized by using a direct current (DC) non-transferred arc plasma. Gallium nitrate hydrate (Ga(NO₃)₃∙xH₂O) was used as a raw material and NH₃ gas was used as a nitridation source. Additionally, melamine (C₃H₆N₆) powder was injected into the plasma flame to prevent the oxidation of gallium to gallium oxide (Ga₂O₃). Argon thermal plasma was applied to synthesize GaN nanopowder. The synthesized GaN nanopowder by thermal plasma has low crystallinity and purity. It was improved to relatively high crystallinity and purity by annealing. The crystallinity is enhanced by the thermal treatment and the purity was increased by the elimination of residual C₃H₆N₆. The combined process of thermal plasma and annealing was appropriate for synthesizing crystalline GaN nanopowder. The annealing process after the plasma synthesis of GaN nanopowder eliminated residual contamination and enhanced the crystallinity of GaN nanopowder. As a result, crystalline GaN nanopowder which has an average particle size of 30 nm was synthesized by the combination of thermal plasma treatment and annealing.


Are some gestalt principles deployed more readily than others during early development? The case of lightness versus form similarity.
Four experiments investigated how readily infants achieve perceptual organization by lightness and form similarity. Infants were (a) familiarized with elements that could be organized into rows or columns on the basis of lightness or form similarity and tested with vertical versus horizontal bars depicting the familiar versus novel organization or (b) familiarized with bars and tested with elements. For lightness similarity, generalization occurred in both tasks; however, for form similarity, generalization occurred only in the elements --> bars task. The findings indicate that lightness similarity is more readily deployed than form similarity and are discussed in the context of (a) whether the difference reflects speed of application or experience-based learning, (b) evidence from visual agnosic patients and the time course of application of the principles in healthy adults, and (c) development of dorsal and ventral visual processing streams.


Enantioselective [2+2] annulation of simple aldehydes with isatin-derived ketimines via oxidative N-heterocyclic carbene catalysis.
An asymmetric [2+2] annulation reaction through direct α-carbon functionalization of simple aldehydes via oxidative N-heterocyclic carbene catalysis is disclosed. These in situ generated triazolium enolate intermediates undergo a highly stereoselective Mannich reaction with isatin-derived ketimines followed by intramolecular lactamization to afford enantioenriched spirooxindole β-lactams bearing two vicinal stereogenic centers.


An unusual presentation of Kartagener's syndrome.
Kartagener's syndrome is a rare disorder which is seen in nearly half of the cases of primary ciliary dyskinesia. We report an unusual case of Kartagener's syndrome where the patient had associated ventricular septal defect, pectus excavatum and was fertile.


Parents' views on childhood obesity: qualitative analysis of discussion board postings.
Childhood obesity is an increasing concern for parents and health professionals alike. Parents' perception of obesity as a current health issue for their children is important for the everyday parenting and health choices parents make. As parents are frequently going online to seek and exchange information about parenting and child health, asynchronous online discussion forums provide an opportunity to investigate their perceptions and concerns. Understanding parents' perceptions, beliefs and attitudes is important in any childhood obesity prevention and intervention. To explore parents' perceptions, perspectives and concerns regarding childhood obesity expressed on asynchronous online discussion forums. A qualitative descriptive approach using template analysis to analyse a novel data collection strategy of 34 purposefully sampled threads from two Australian-based asynchronous online discussion forums. Parents on the discussion forum displayed an understanding of childhood obesity as a public health concern, the discussion incorporated issues such as providing a healthy diet and lifestyle for children. Parents shared their own opinions and experiences that challenged or conceded to the status quo of the discussion. Parents discussed the role of health professionals in obesity prevention. There were varied opinions on the relevance of health professionals, particularly nurses, monitoring of growth and risk of obesity. This exploratory study highlights that parents perceive childhood obesity as an important public health concern, and that they understand the key public health messages of prevention and intervention. Yet, for many it is difficult to successfully implement these messages into their everyday lives. Health professionals need to play a key role in providing non-judgemental, innovative support and advice to parents to successfully implement prevention and intervention strategies.


Differential expression of connective tissue growth factor in inflammatory bowel disease.
Inflammatory bowel disease consists of Crohn's disease (CD) and ulcerative colitis (UC). A major clinical problem in some patients is to differentiate clearly between these entities, which is important when planning appropriate medical and surgical treatment. Connective tissue growth factor (CTGF), a novel peptide involved in fibrotic disorders, was analyzed in the present study in CD and UC patients to evaluate its possible role in these two disorders. Twenty-five normal human intestinal tissue samples were obtained through an organ donor program. CD tissues were obtained from 28 individuals undergoing partial intestinal resection (17 small bowel; 11 large bowel) due to complications of the disease. UC tissue samples were obtained from 16 patients undergoing colectomy due to complications of the disease. Expression of CTGF was studied by Northern blot analysis. In situ hybridization was used to localize mRNA moieties in the tissue samples. Northern blot analysis revealed an average 5-fold increase in CTGF mRNA expression in 89% (25/28) of CD tissue samples by comparison with normal controls (p < 0.0001). In contrast, in UC samples CTGF mRNA levels were comparable to those of normal controls. However, UC tissue samples exhibited enhanced TGF-beta1 mRNA levels (4-fold; p < 0.05). In situ hybridization in CD samples showed CTGF mRNA localized especially in fibroblasts within the submucosal layer, around lymph follicles and in some areas of intense damage in the proximity of the luminal surface, whereas inflammatory cells were devoid of any CTGF mRNA signal. The present data indicate that CTGF plays a different role in IBD and might be useful, especially in those cases with unusual disease presentation, to better differentiate UC and CD. In addition, our data indicate a crucial role for CTGF in CD, where fibrosis and stenosis are frequent complications that require surgery.


Transgenic over-expression of plasminogen activator inhibitor-1 results in age-dependent and gender-specific increases in bone strength and mineralization.
The plasminogen activation system (PAS) and its principal inhibitor, plasminogen activator inhibitor-1 (PAI-1), are recognized modulators of matrix. In addition, the PAS has previously been implicated in the regulation of bone homeostasis. Our objective was to study the influence of active PAI-1 on geometric, biomechanical, and mineral characteristics of bone using transgenic mice that over-express a variant of human PAI-1 that exhibits enhanced functional stability. Femora were isolated from male and female, wildtype (WT) and transgenic (PAI-1.stab) mice at 16 and 32 weeks of age (n=10). Femora were imaged via DEXA for BMD and muCT for cortical mid-slice geometry. Torsional testing was employed for biomechanical properties. Mineral composition was analyzed via instrumental neutron activation analysis. Female femora were further analyzed for trabecular bone histomorphometry (n=11). Whole animal DEXA scans were performed on PAI-1.stab females and additional transgenic lines in which the functional domains of the PAI-1 protein were specifically disrupted. Thirty-two week female PAI-1.stab femora exhibited decreased mid-slice diameters and reduced polar moment of area compared to WT, while maintaining similar cortical bone width. Greater biomechanical strength and stiffness were demonstrated by 32 week PAI-1.stab female femora in addition to a 52% increase in BMD. PAI-1.stab trabecular bone architecture was comparable to WT. Osteoid area was decreased in PAI-1.stab mice while mineral apposition rate increased by 78% over WT. Transgenic mice expressing a reactive-site mutant form of PAI-1 showed an increase in BMD similar to PAI-1.stab, whereas transgenic mice expressing a PAI-1 with reduced affinity for vitronectin were comparable to WT. Over-expression of PAI-1 resulted in increased mineralization and biomechanical properties of mouse femora in an age-dependent and gender-specific manner. Changes in mineral preceded increases in strength/stiffness and deterred normal cross-sectional expansion of cortical bone in females. Trabecular bone was not altered in PAI-1.stab mice whereas MAR increased significantly, further supporting mineral changes as the underlying factor in strength differences. The primary influence of PAI-1 occurred during a period of basal bone remodeling, attributing a role for this system in remodeling as opposed to development. Comparison of transgenic lines indicates that PAI-1's influence on bone is dependent on its ability to bind vitronectin, and not on its proteolytic activity. The impact of PAI-1 on mouse femora supports a regulatory role of the plasminogen activation system in bone homeostasis, potentially elucidating novel targets for the treatment of bone disease.


Cloning and expression of a codon-optimized gene encoding the influenza A virus nucleocapsid protein in Lactobacillus casei.
Lactic acid bacteria (LAB) species are envisioned as promising vehicles for the mucosal delivery of therapeutic and prophylactic molecules, including the development of oral vaccines. In this study, we report on the expression of a synthetic nucleocapsid (NP) gene of influenza A virus in Lactobacillus casei. The NP gene was re-designed based on the tRNA pool and the codon usage preference of L. casei BL23. The codon-optimized NP gene was then cloned and expressed in L. casei RCEID02 under the control of a constitutive promoter, that of the lactate dehydrogenase (ldh) gene. The synthetic NP gene was further expressed in L. casei EM116 under the control of an inducible promoter, that of the structural gene of nisin (nisA) from Lactococcus lactis. Based on Western blot analysis, the specific protein band of NP, with a molecular mass of 56.0 kDa, was clearly detected in both expression systems. Thus, our study demonstrates the success of expressing a codon-optimized influenza A viral gene in L. casei. The suitability of the recombinant LAB strains for immunization purposes is currently under evaluation.


Assessing the effect of interspecies oocyte nucleolar material dosage on embryonic development.
Sequence differences are considered to be the basic cause of developmental failure in interspecies embryos when more distant species are combined. However, other phenomena, such as insufficient or excessive quantity of specific cellular factors, might also influence the outcome. These effects are usually not considered. One of the organelles shown to contain different amount of proteins is the oocyte nucleolus-like body. Here we show that upon interspecies transfer, a single porcine nucleolus-like body is unable to support the development of a mouse parthenogenetic embryo derived from an enucleolated oocyte. However, when the amount of the porcine nucleolar material is increased to equalize the amount of mouse nucleolar material by transferring two nucleolus-like bodies, mouse embryos are able to pass the developmental block elicited by enucleolation. These embryos progress to the blastocyst stage at rates comparable to controls. Thus, using the model of an interspecies nucleolus-like body transplantation between mouse and pig oocytes, we show that an inadequate amount of nucleolar factors, rather than the species origin, affects the development. In a wider context of interspecies nuclear transfer schemes, the observed incompatibility between more distant species might not stem simply from sequence differences but also from improper dosage of key cellular factors.


Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9).
Hypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidation, with borneol as the initial raw material, using the strategy of combinatorial molecular chemistry. The structure of the compound was confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry, with a purity of more than 99.5%. The compound 221s (2,9) can significantly reduce the systolic and diastolic blood pressure of SHR rats by about 50 mmHg and 35 mmHg after 4 weeks of administration. The antihypertensive effect of 221s (2,9) is equivalent to that of captopril. The use of 221s (2,9) can reduce the content of Ren, Ang II and ACE in the serum of SHR rats, inhibit the RAAS and enhance the vascular endothelial function by upregulating the level of NO. Pathological studies in this area have shown that high dosage of 221s (2,9) can notably protect myocardial fibrosis in rats and reduce the degeneration and necrosis of myocardial fibers, inflammatory cell infiltration, and proliferation of fibrous tissue in the heart of rat. Therefore, the existing work provided a foundation for preclinical research and follow-up clinical research of 221s (2,9) as a new drug.


Work engagement: a practical measure for workplace health promotion?
The objectives of this study were to investigate whether psychological job demands, personal control and social support affect the negative health measure of depression differently than the positive measure of work engagement and to investigate whether work engagement mediates the effects of job demands and resources on the level of depression. We discuss the implications of using engagement as an outcome measure in workplace health promotion. We performed a cross-sectional questionnaire study among a general working population in Norway (n = 605). In the multivariate analysis, high psychological job demands as well as high control and social support correlated significantly with high work engagement. High demands as well as low control and social support correlated significantly with high levels of depression. When we included engagement as an independent variable together with demands, control and social support in the multivariate analysis, the positive correlation between demands and depression remained as well as the significant correlations between the level of depression and control and social support became non-significant. This indicates that engagement mediates the effects of control and social support on the level of depression. Encouraging enterprises to improve engagement in addition to focusing on preventing diseases may be worthwhile in workplace health promotion. Promoting engagement may have more positive organizational effects than a more traditional disease prevention focus, because engagement is contagious and closely related to good work performance and motivation.


Availability, Use, and Barriers to Cardiac Rehabilitation in LMIC.
Cardiac rehabilitation (CR) is a cornerstone of secondary prevention of ischemic heart disease. It is critically important in low- and middle-income countries (LMIC), where the burden of ischemic heart disease is substantial and growing. However, the availability and utilization of CR in LMIC is not systematically known. This study sought to characterize the availability, use, and barriers to the use of CR. Electronic databases (Cochrane Library, EMBASE, PubMed, Web of Science) were searched from January 1, 1980 to May 31, 2013 for articles on CR in LMIC. Citations on availability, use, and/or barriers to CR were screened for inclusion by title, abstract, and full text. Data were summarized by region or country to determine the characteristics of CR in LMIC and gaps in the peer-reviewed biomedical publications. Our search yielded a total of 5,805 citations, of which 34 satisfied full inclusion and exclusion criteria. The total number of CR programs available ranged from 1 in Algeria and Paraguay to 51 in Serbia. Referral rates for CR ranged from 5.0% in Mexico to 90.3% in Lithuania. Attendance rates ranged from 31.7% in Bulgaria to 95.6% in Lithuania, and CR attendance was correlated with higher educational background. The most commonly cited barrier to CR in LMIC was lack of physician referral. Our results illustrate that the published reports reflects heterogeneity of CR availability and use in LMIC. Overall, CR is insufficiently available and underutilized. Further characterization of CR in LMIC, especially in Asia and Africa, is necessary to develop targeted strategies to improve availability and utilization. Patient, physician, and systems factors must be addressed to overcome barriers to participation in CR in LMIC.


Outbreak of COVID-19 infection in children: fear and serenity.
The recent outbreak of SARS-CoV-2 greatly involves the resources of the global healthcare system, as it affects newborns, adults, and elders. This infection runs in three major stages: a mild cold-like illness, a moderate respiratory syndrome and a severe acute interstitial pneumonia. SARS-CoV-2 infection seems to have a more benign evolution in children. As a matter of fact, low susceptibility and minor aggressivity have been highlighted in most cases. There are currently no effective antiviral drugs treatment for the affected children. No sufficient results have been reached by the use of interferon (IFN), lopinavir/ritonavir, orbidol, and oseltamivir in the treatment of the coronaviruses infection. The aim of this short review is to highlight the differences existing between COVID-19 cases in adults and children.


[A case of spinal cord infarction caused by cervical disc herniation].
A 40-year-old previously healthy female was diagnosed with acute progressive paraparesis. Neurological examination revealed bilateral four-limb weakness predominant in the distal part of the upper limbs and superficial sensory impairment below the cervical region. T2-weighted image on MRI showed an area of hyperintensity in the gray matter of the cervical cord with disc herniation at the C4/C5 vertebral level. Laboratory investigation showed no evidence of infections, autoimmune, inflammatory, or neoplastic causes. A follow-up MRI study 3 days after admission showed that the region of hyperintensity was had enlarged without contrast enhancement. Spinal angiography was performed 21 days after admission and demonstrated that the anterior spinal artery originated from the fourth segment of the left vertebral artery and occluded at the level of C4/C5, which coincided with the location of disc herniation. We hypothesized that she developed anterior spinal artery syndrome which caused disc herniation. Although we frequently encountered disc herniation, there are few cases developed spinal cord infarction. We discuss the etiology and pathogenetic relation between disc herniation and spinal cord infarction.


[Combined vaccination of birds with inactivated and live vaccines].
Studies were carried out on the immune response of birds-parental forms of broilers--in the combined use of an inactivated vaccine Dessau and a live avirulent vaccine La Sota. The dynamics was followed up till the age of 58 weeks of the changes taking place at an antidody level, and the resistance of the birds after challenging with a virulent virus. After the first immunization with a killed vaccine there was an average geometric titer of 78.65, and the resistance of the birds was low. The revaccination with an inactivated vaccine caused an increase in the amount of antibodies and a rise in the level of resistance. In the immunization with a live La Sota vaccine there was an abrupt rise of the immune titer--214.31 (in the twenty-eighth week), and 207.60 (in the thirty-eighth week). During the following periods there was a gradual drop of the antibody level, however, this was accompanied by a comparatively high resistance of the birds at challenge. The results obtained are in relation to some immunogenic properties of the experimental vaccine Dessau the use of which develops an immunogenic background at which, with a two-fold reimmunization applying a live vaccine La Sota the immunogenesis process is strongly enhanced.


Nonperturbative quasilinear approach to the shear dynamo problem.
We study large-scale dynamo action due to turbulence in the presence of a linear shear flow. Our treatment is quasilinear and equivalent to the standard "first-order smoothing approximation." However it is non perturbative in the shear strength. We first derive an integrodifferential equation for the evolution of the mean magnetic field, by systematic use of the shearing coordinate transformation and the Galilean invariance of the linear shear flow. We show that, for nonhelical turbulence, the time evolution of the cross-shear components of the mean field do not depend on any other components excepting themselves; this is valid for any Galilean-invariant velocity field, independent of its dynamics. Hence, to all orders in the shear parameter, there is no shear-current-type effect for non helical turbulence in a linear shear flow in quasilinear theory in the limit of zero resistivity. We then develop a systematic approximation of the integro-differential equation for the case when the mean magnetic field varies slowly compared to the turbulence correlation time. For nonhelical turbulence, the resulting partial differential equations can again be solved by making a shearing coordinate transformation in Fourier space. The resulting solutions are in the form of shearing waves, labeled by the wave number in the sheared coordinates. These shearing waves can grow at early and intermediate times but are expected to decay in the long time limit.


Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics.
Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic D-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.