Mutualistic growth of the sulfate-reducer Desulfovibrio vulgaris Hildenborough with different carbohydrates.
Desulfovibrio vulgaris Hildenborough genome presents a phosphotransferase system putatively involved in the transport of carbohydrates. However, utilization of sugars by this sulfate-reducing bacterium has never been reported. Herein, we have observed proliferation of D. vulgaris Hildenborough with some carbohydrates, in mutualism with Stenotrophomonas maltophilia, a non-fermentative, gram-negative gammaproteobacterium, or Microbacterium, a gram-positive actinobacterium. These results suggest the importance of feedback interactions between different heterotrophic bacterial species including the alternative for D. vulgaris of exploiting additional organic resources and novel habitats. Thus, D. vulgaris strongly participates in the mineralization of carbohydrates both in complex natural and artificial systems.


A comparative study between the PAM and the laser interferometer in cataracts.
We conducted a prospective study on 35 consecutive eyes undergoing cataract extraction to compare the Guyton-Minkowski Potential Acuity Meter (PAM) and the Laser Interferometer (LI) in determining potential visual acuity. The eyes were divided into: group A, which had good visualization of optic disc details, and group B, whose media allowed only disc outline or less to be seen. We found that in group A eyes, both instruments were reliable (with accuracies of 94% for the PAM and 88% for the LI). However, in group B eyes (advanced cataracts), both instruments were unreliable (accuracies of 33% for the PAM and 53% for the LI). Interestingly, in a subgroup of high myopes (axial length greater than 29 mm) with moderate cataracts and poor visual acuties, both instruments were very reliable and helpful in determining how much of the vision loss was due to the cataracts. We therefore strongly recommend potential acuity testing in high myopes with moderate cataracts and poor visual acuity.


Intrauterine cardiothoracic surgery: the fetal lamb model.
We have developed fetal lamb models of congenital cardiothoracic lesions that have been allowed to progress through birth for physiological study. Simulated lesions, simulated repairs, actual lesions, and actual repairs have been performed in this model. Sixty-two fetal lambs comprised the study group, including 48 in which models were created and 14 controls. Models included pulmonary stenosis, aortic stenosis, and diaphragmatic hernia. Gestational age ranged from 90 to 120 days (0.6 of normal gestation). In each pregnant ewe, laparotomy and hysterotomy were performed under general anesthesia, with care taken to avoid placental vessels. The foreleg was exposed, the appropriate anterior chest wall was isolated, and a thoracotomy was done. Thoracic or cardiac procedures then were performed under controlled transplacental anesthesia and perfusion. Following completion of the procedure, the fetal thoracotomy was closed, sterile antibiotic solution was placed in the amniotic sac, and the hysterotomy and laparotomy were closed. Subsequently the fetus either was allowed to progress to birth and infant study or underwent subsequent intrauterine repair and then was allowed to progress to birth and neonatal study. This fetal lamb model provides reproducible anatomical and pathophysiological lesions to facilitate the development of techniques for repair of such lesions in early infancy. Further, it offers the potential for developing methods of intrauterine cardiothoracic surgical repair.


Products of activated lymphocytes stimulate Schwann cell mitosis in vitro.
Culture of Schwann cells and endoneurial fibroblasts from newborn rat sciatic nerves in the presence of supernatants obtained from concanavalin A (Con-A)-stimulated rat mononuclear cells resulted in proliferation of both cell types. Con-A did not induce Schwann cell or fibroblast proliferation. Supernatant from a Gibbon T-cell lymphoma and chromatographically purified rat interleukin-2 (IL-2) induced fibroblast but not Schwann cell proliferation, and cloned human IL-2 did not induce proliferation of either cell type. Proliferation of Schwann cells and endoneurial fibroblasts induced by activated mononuclear inflammatory cells may be important in inflammatory demyelinative neuropathies.


Early diagnosis of pancreatobiliary duct malignancies by brush cytology and biopsy.
Two hundred and five preoperative intraductal samplings (brushing and biopsy) were evaluated from 113 patients with biliary or Wirsung duct strictures. One hundred and three strictures could be specified by histology of the operative specimens, autopsy, or by the patients' clinical course. Preoperative diagnostic efficacy depended on the tumor location (it was the best for ampullary and para-papillary tumors), but the average quantitative indices for sensitivity, absolute sensitivity, specificity, positive and negative predictive values, diagnostic accuracy of cytology were 53%, 20%, 100%, 100%, 25%, 59%, respectively. The same values for biopsy were 43%, 34%, 100%, 100%, 36% and 56%. These figures improved after simultaneous cytology and biopsy. Close cooperation with the endoscopist was necessary in cases of negative, inconclusive and dysplastic (27%) samples. Repetition of sampling improved the results by 8%. Among the 26 preoperative false negative cases, sampling-, technical- and interpretative errors occurred in 84%, 4% and 12%, respectively. Revision of samples revealed 4 malignant cases among the false negative cytologic brushings. Reclassification of specimens considering the latest criteria - primary and secondary malignant features, pancreatic intraepithelial neoplasia (PanINs), etc. - resulted in improvement of the diagnostic efficiency.


Obstructive Sleep Apnoea: Children are not little Adults.
During a child's development, several important developmental physiological sleep processes occur, and, occasionally, pathological disorders occur, which results in differences between obstructive sleep apnoea (OSA) in adults and children. There are major differences in sleep and respiratory physiology as well as OSA symptoms and treatment options between children and adults. Many practitioners do not realize these differences, which results in delays in the diagnosis and treatment of OSA in children. The treatment options for OSA in children are markedly different compared with adults, effective in most children. The use of positive airway pressure (PAP) therapy delivered through continuous or bi-level positive airway pressure modes is successful in children and even in infants; however, there are several challenges facing parents and practitioners to achieve good compliance. The early recognition and treatment of paediatric OSA are essential to prevent deleterious consequences. This article discusses the major differences between paediatric and adult OSA and demonstrates why children are not little adults.


[Use of ultrasound for evaluating structural changes of the renal parenchyma in chronic primary glomerulopathies].
Ultrasound was used to measure echogenesis, renal cortex thickness and kidney length in 59 patients with various types of the primary glomerulonephritis. The obtained results have shown that the measured parameters correlated with the progress in renal failure. An increase in the intensity of echo from the cortex, thinning of the renal cortex, and the decrease in renal length are typical signs of the advancement of renal failure. As renal function deteriorates in the consequence of destruction of its parenchyma, ultrasound examination might be an illustration of the pathological changes in the kidney. Considering the fact that ultrasound is perfectly safe, it may be used in monitoring of the disease progress and the results of treatment.


Seasonal shift from C3 photosynthesis to Crassulacean Acid Metabolism in Mesembryanthemum crystallinum growing in its natural environment.
Changes in δ13C value, diurnal malate content, water content and Na+, K+ and Cl- content of the annual Mesembryanthemum crystallinum (Aizoaceae) were followed in a natural population on a coastal cliff at the Mediterranean Sea shore close to Caesarea (Israel). Plants germinated in the middle of the rainy season in December 1976/January 1977. Diurnal malate fluctuations in the leaves were not detected until the end of March. Later on, at the start of the dry season, pronounced diurnal changes in malate developed. This was correlated with a progressive change in δ 13C value from about -26‰ to about -16‰ which is consistent with a change from normal C3 photosynthetic CO2 fixation to a predominantly nocturnal CO2 assimilation pattern involving Crassulacean Acid Metabolism.


Targeting poly(ADP-ribosyl)ation: a promising approach in cancer therapy.
Recent progress in the field of DNA repair has demonstrated that transient inhibition of DNA damage detection or repair using potent poly(ADP-ribose) polymerase (PARP) inhibitors could improve the efficacy of cancer treatments. Although more study is needed, recent publications lead to optimism that the inhibition of poly(ADP-ribose) synthesis could selectively kill cancer cells when used to treat tumours with defective BRCA proteins. These reports and others shed some light on the DNA damage signalling and repair processes involving PARPs. However, a better understanding of the molecular mechanisms regulated by poly(ADP-ribose) metabolism will be essential before optimism can be replaced by clinical realization.


Extramural extension as indicator for postoperative adjuvant chemotherapy in Stage IIA (pT3N0) colon cancer.
The usefulness of adjuvant chemotherapy (CMT) in patients with Stage IIA colon cancer remains unclear. The present study aimed to investigate extramural extension as an indicator for adjuvant CMT. Data were reviewed from 202 consecutive patients with Stage IIA colon cancer that underwent curative surgery between 1995 and 2007. The distance of the extramural extension (DEE) was measured histologically. The optimal prognostic cut-off point of the DEE for oncologic outcomes was statistically determined. The eligible surviving patients had been followed for a median period of 75 months (range: 2-210 months). Patients were subdivided into two groups according to the optimal cut-off point; DEE ≤5 mm (pT3a) and DEE >5 mm (pT3b). The pT3b was the most powerful independent risk factor for postoperative recurrence (P = 0.0324, HR: 3.04, 95% CI: 1.098-8.408), and was significantly correlated with distant metastasis (P = 0.0161 HR: 5.19, 95% CI: 1.765-15.239). The recurrence-free and cancer-specific 5-year survival rates in patients with pT3b were significantly lower than in patients with pT3a (81.5% vs. 95.4%, P = 0.0003 and 85.9% vs. 97.4%, P = 0.0007, respectively). pT3b could be an important risk factor for distant metastasis in Stage IIA colon cancer. Postoperative adjuvant CMT may be indicated for patients with pT3b.


Syntheses of two enantiomeric pairs of myo-inositol(1,2,4,5,6) and -(1,2,3,4,5) pentakisphosphate.
Two enantiomeric pairs of myo-inositol(1,2,4,5,6)P5 and -(1,2,3,4,5)P5 have efficiently been synthesized by means of the lipase catalyzed acetylation of 1,2:5,6-di-O-isopropylidene-myo-inositol and the benzoyl migration procedure.


Ratiometric fluorometric and visual determination of cyanide based on the use of carbon dots and gold nanoclusters.
An optical method is described for the ratiometric fluorometric determination of cyanide ions. It is based on the use of a mixture of aqueous solutions of blue-emitting carbon dots (CDs) and red-emitting gold nanoclusters (AuNCs). The presence of cyanide reduces the red fluorescence of the AuNCs through the formation of a stable complex [Au(CN)2-]. The blue emission of the CDs, in contrast, stays constant. Hence, the color of fluorescence changes from red to purple to blue. The ratio of the fluorescence intensities located at 612 and 438 nm varies over a wide range, with 2 linear responses ranges (from 8 nM to 12.5 μM, and from 12.5 to 75 μM). The method was applied to the determination and visual discrimination of cyanide in food and drink samples. Graphical abstract A ratiometric method for determination of cyanide detection is described that is based on mixing carbon dots (CDs) and gold nanoclusters (AuCNs). The presence of cyanide reduces the red fluorescence of the AuNCs through the formation of a stable complex Au(CN)2-. The blue emission of the CDs, in contrast, stays constant. The fluorescence intensity ratios show linear response to cyanide with a concomitant red-purple-blue fluorescence color change.


Dicentric Robertsonian translocation in man. 17 cases studied by R,C, and N banding.
The authors studied 17 cases of Robertsonian translocation. In all cases but one C banding showed that a dicentric translocation was involved. Silver staining demonstrated the presence of an NOR between the two centromeres in only one case.


Different types of opioid receptors involved in the suppression of LH secretion in lactating sheep.
To learn the involvement of endogenous opioid peptides (EOP) in the regulation of reproductive activity in ruminants, the effects of different opioid antagonists on luteinizing hormone (LH) secretion were determined in sheep during the early stage of lactation. The opioid receptor antagonists: naloxone (all types of receptors, n=5), naloxonazine (μ receptor, n=5), GNTI- (κ receptor, n=5), naltrindole (δ receptor, n=5) or the vehicle (control, n=5) were infused intracerebroventricularly in a series of five 30-min infusions (60μg/60μl) at 30-min intervals. The period of the experiment included the non-suckling (10:00-12.30) and suckling (12.30-15.00) periods. Blood samples were collected from 10.00 to 15.00 at 10-min intervals, and plasma LH concentration was assayed by the radioimmunoassay method. The obtained results showed that blocking of the EOP action within the central nervous system in lactating sheep caused a significant (p<0.001) increase in LH concentration in all treated groups, in comparison to the control. In the naloxone-treated group, a significant (p<0.05) increase in LH secretion also occurred during suckling. The amplitude of LH pulses increased significantly in the naloxonazine- (p<0.01) and naltrindole- (p<0.05) treated ewes compared to the control; there were no significant differences in the frequency of LH pulses among the groups. In conclusion, our study indicates that EOP play a crucial role in the mechanism inhibiting GnRH/LH axis activity in lactating sheep and that the ligands for μ opioid receptor may have the highest inhibitory effect.


The Missouri Cardiovascular Health Plan: a focus on prevention.
The authors describe a framework for planning, implementing, and evaluating cardiovascular health programs in Missouri. Populations targeted for intervention are identified, and the role of the physician in supporting community-based cardiovascular health promotion is explored.


Do subjective memory complaints predict senile Alzheimer dementia?
Many elderly complain about their memory and undergo dementia screening by the Mini-Mental State Examination (MMSE). While objective memory impairment always precedes Alzheimer dementia (AD) it is unclear whether subjective memory complaints are predicting AD. We tried to answer this question in a prospective cohort study. The 75-years old non-demented inhabitants of Vienna-Transdanube were investigated for conversion to AD after 30 months. The predictive value of subjective memory complaints was analysed in two groups: subjects with high MMSE-score (28-30) and subjects with low MMSE-score (23-27). Only in subjects with high MMSE univariate analyses showed an association between subjective memory complaints and incident AD. In both groups the verbal memory test was the main predictor of AD in multivariate analyses. We suggest to perform memory testing in subjects complaining about memory irrespective of their performance in a screening procedure like the MMSE.


In vitro effects of acridine intercalation on RNA polymerase interactions with supercoiled DNA.
In vitro transcription of supercoiled DNA by purified E. coli RNA polymerase was inhibited by Acridine Orange in a bimodal manner while N-10 benzyl substituted Acridine Orange is about one-third as inhibitory and effects monophasic inhibition. The inhibition correlates with the supercoil unwinding abilities of these two intercalators with Acridine Orange unwinding supercoiled DNA at 1/3 the concentration required for the substituted acridine orange. Direct visualization of DNA-RNA polymerase complex on agarose gels showed that these intercalators directly interfere with this association and the more effective the drug is in unwinding DNA supercoils the more effective it is in interfering with the DNA-enzyme complex. In addition, specific intercalators differentially affect the stability of DNA-RNA polymerase-RNA ternary complexes.


Role for estradiol in female-typical brain and behavioral sexual differentiation.
The importance of estrogens in controlling brain and behavioral sexual differentiation in female rodents is an unresolved issue in the field of behavioral neuroendocrinology. Whereas, the current dogma states that the female brain develops independently of estradiol, many studies have hinted at possible roles of estrogen in female sexual differentiation. Accordingly, it has been proposed that alpha-fetoprotein, a fetal plasma protein that binds estrogens with high affinity, has more than a neuroprotective role and specifically delivers estrogens to target brain cells to ensure female differentiation. Here, we review new results obtained in aromatase and alpha-fetoprotein knockout mice showing that estrogens can have both feminizing and defeminizing effects on the developing neural mechanisms that control sexual behavior. We propose that the defeminizing action of estradiol normally occurs prenatally in males and is avoided in fetal females because of the protective actions of alpha-fetoprotein, whereas the feminizing action of estradiol normally occurs postnatally in genetic females.


Trends in state/territorial obesity prevalence by race/ethnicity among U.S. low-income, preschool-aged children.
Understanding state/territorial trends in obesity by race/ethnicity helps focus resources on populations at risk. This study aimed to examine trends in obesity prevalence among low-income, preschool-aged children from 2008 through 2011 in U.S. states and territories by race/ethnicity. We used measured weight and height records of 11.1 million children aged 2-4 years who participated in federally funded health and nutrition programmes in 40 states, the District of Columbia and two U.S. territories. We used logistic regression to examine obesity prevalence trends, controlling for age and sex. From 2008 through 2011, the aggregated obesity prevalence declined among all racial/ethnic groups (decreased by 0.4-0.9%) except American Indians/Alaska Natives (AI/ANs); the largest decrease was among Asians/Pacific Islanders (A/PIs). Declines were significant among non-Hispanic whites in 14 states, non-Hispanic blacks in seven states/territories, Hispanics in 13 states, A/PIs in five states and AI/ANs in one state. Increases were significant among non-Hispanic whites in four states, non-Hispanic blacks in three states, Hispanics in two states and A/PIs in one state. The majority of the states/territories had no change in obesity prevalence. Our findings indicate slight reductions in obesity prevalence and variations in obesity trends, but disparities exist for some states and racial/ethnic groups.


Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study.
Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~115nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense.


Multi-chamber apparatus for preparative isoelectric focusing.
A multi-chamber apparatus for preparative isoelectric focusing is described. The apparatus is constructed of 32 separation chambers and 2 electrode chambers, all separated by uncharged porous membranes. The total volume of the 32 separation chambers is 660 mL. A cooling system and a stirring system are built in. Human serum proteins were separated by isoelectric focusing in a natural pH gradient. The fractionation was monitored by fused rocket immunoelectrophoresis. The number of proteins in each fraction was monitored by crossed immunoelectrophoresis. The apparent pI values of IgG, transferrin and alpha-1-antitrypsin are as found in the literature. Orosomucoid (alpha-1-acid glycoprotein) (pI = 1.8) is concentrated at the acid end of the pH gradient.


Abnormal Oculomotor Functions in Amyotrophic Lateral Sclerosis.
Although traditionally regarded as spared, a range of oculomotor dysfunction has been recognized in amyotrophic lateral sclerosis (ALS) patients. ALS is nowadays considered as a neurodegenerative disorder of a third compartment comprising widespread areas of extra-motor brain including cerebellum. Our objective was to perform an observational study to examine for ocular motor dysfunction in patients with ALS and for any differences between bulbar-onset and spinal-onset patients. Thirty two ALS patients (bulbar onset: 10, spinal onset: 22) underwent the standardized systemic evaluations using video-oculography. Oculomotor dysfunctions such as square wave jerks, saccadic dysmetria, abnormal cogwheeling smooth pursuits and head shaking and positional nystagmus of central origin have been observed in the ALS patients at a relatively early stage. Abnormal smooth pursuits and saccadic dysmetria were increased in the bulbar-onset compared to the spinal-onset (p<0.05). These oculomotor abnormalities may be a marker of neuro-degeneration beyond motor neurons in ALS, especially in bulbar-onset disease. Future longitudinal studies of eye movement abnormalities have provided insights into the distribution and nature of the disease process.


Longitudinal associations between the neighborhood social, natural, and built environment and mental health: A systematic review with meta-analyses.
This review aimed to assess the longitudinal associations between neighborhood social, natural, and built environments, and multiple mental health outcomes (i.e., depression, anxiety, common mental disorder, and pooled mental disorders). Of 6,785 records retrieved, 30 studies fulfilled the inclusion criteria. Meta-analytical results primarily obtained from developed country studies showed that composite neighborhood socioeconomic status was negatively associated with depression (p = 0.007) and pooled mental disorders (p = 0.002), while neighborhood urbanicity was positively associated with depression (p = 0.012) and pooled mental disorders (p = 0.005). Future longitudinal studies with similar designs and standardized exposure assessments are warranted.


Localization of the oncogene c-erbA2 to human chromosome 3.
The human c-erbA1 gene has been previously mapped to chromosome 17. We have now mapped c-erbA2 to the short arm of chromosome 3, using a human genomic probe in Southern analysis of DNA from a panel of human/mouse somatic cell hybrids. In situ hybridization using the same probe on metaphase chromosomes has enabled fine chromosome mapping of c-erbA2 to the chromosome region 3p21-pter.


Thermal stress responses of Sodalis glossinidius, an indigenous bacterial symbiont of hematophagous tsetse flies.
Tsetse flies (Diptera: Glossinidae) house a taxonomically diverse microbiota that includes environmentally acquired bacteria, maternally transmitted symbiotic bacteria, and pathogenic African trypanosomes. Sodalis glossinidius, which is a facultative symbiont that resides intra and extracellularly within multiple tsetse tissues, has been implicated as a mediator of trypanosome infection establishment in the fly's gut. Tsetse's gut-associated population of Sodalis are subjected to marked temperature fluctuations each time their ectothermic fly host imbibes vertebrate blood. The molecular mechanisms that Sodalis employs to deal with this heat stress are unknown. In this study, we examined the thermal tolerance and heat shock response of Sodalis. When grown on BHI agar plates, the bacterium exhibited the most prolific growth at 25oC, and did not grow at temperatures above 30oC. Growth on BHI agar plates at 31°C was dependent on either the addition of blood to the agar or reduction in oxygen levels. Sodalis was viable in liquid cultures for 24 hours at 30oC, but began to die upon further exposure. The rate of death increased with increased temperature. Similarly, Sodalis was able to survive for 48 hours within tsetse flies housed at 30oC, while a higher temperature (37oC) was lethal. Sodalis' genome contains homologues of the heat shock chaperone protein-encoding genes dnaK, dnaJ, and grpE, and their expression was up-regulated in thermally stressed Sodalis, both in vitro and in vivo within tsetse fly midguts. Arrested growth of E. coli dnaK, dnaJ, or grpE mutants under thermal stress was reversed when the cells were transformed with a low copy plasmid that encoded the Sodalis homologues of these genes. The information contained in this study provides insight into how arthropod vector enteric commensals, many of which mediate their host's ability to transmit pathogens, mitigate heat shock associated with the ingestion of a blood meal.


Co-delivery of a CD4 T cell helper epitope via covalent liposome attachment with a surface-arrayed B cell target antigen fosters higher affinity antibody responses.
Liposomal vaccines incorporating adjuvant and CD4 T cell helper peptides enhance antibody responses against weakly immunogenic B cell epitopes such as found in the membrane proximal external region (MPER) of the HIV-1 gp41 subunit. While the inclusion of exogenous helper peptides in vaccine formulations facilitates stronger and more durable antibody responses, the helper peptide incorporation strategy per se may influence the overall magnitude and quality of B cell target antigen immunogenicity. Both variability in individual peptide encapsulation as well as the potential for liposome surface-associated helper peptides to misdirect the humoral response are potential parameters impacting outcome. In this study, we used MPER/liposome vaccines as a model system to examine how the mode of the potent LACK T helper peptide formulation modulates antibody responses against the MPER antigen. We directly compared liposome surface-arrayed palmitoyl LACK (pLACK) versus soluble LACK (sLACK) encapsulated in the liposomes and free in solution. Independent of LACK formulation methods, dendritic cell activation and LACK presentation were equivalent in vivo. The frequency of MPER-specific GC B cells promoted by sLACK was higher than that stimulated by pLACK formulation, a finding associated with a significantly greater frequency of LACK-specific GC B cells induced by pLACK. While there were no significant differences in the quantity of MPER-specific serological responses, the MPER-specific antibody titer trended higher with sLACK formulated vaccines at the lower dose of LACK. However, pLACK generated relatively greater MPER-specific antibody affinities than those induced by sLACK-formulated vaccines. Overall, the results suggest that liposomal surface-associated LACK enhances immunogenicity of LACK through better engagement of LACK-specific B cells. Of note, this is not detrimental to the induction of MPER-specific immune responses; rather, the elicitation of higher affinity anti-MPER antibodies benefits from augmented help delivered via covalent linkage of the pLACK CD4 T cell epitope in conjunction with MPER/liposome presentation.


Change and improvement 50 years in the making: a scoping review of the use of soft systems methodology in healthcare.
Improving the quality of healthcare has proven to be a challenging task despite longstanding efforts. Approaches to improvements that consider the strong influence of local context as well as stakeholders' differing views on the situation are warranted. Soft systems methodology (SSM) includes contextual and multi-perspectival features. However, the way SSM has been applied and the outcomes of using SSM to stimulate productive change in healthcare have not been sufficiently investigated. This scoping review aimed to examine and map the use and outcomes of SSM in healthcare settings. The review was based on Arksey and O'Malley's framework. We searched six academic databases to January 2019 for peer-reviewed journal articles in English. We also reviewed reference lists of included citations. Articles were included if they were empirical studies focused on the application of SSM in a healthcare setting. Two reviewers conducted the abstract review and one reviewer conducted the full-text review and extracted data on study characteristics, ways of applying SSM and the outcomes of SSM initiatives. Study quality was assessed using Hawker's Quality Assessment Tool. A total of 49 studies were included in the final review. SSM had been used in a range of healthcare settings and for a variety of problem situations. The results revealed an inconsistent use of SSM including departing from Checkland's original vision, applying different tools and involving stakeholders idiosyncratically. The quality of included studies varied and reporting of how SSM had been applied was sometimes inadequate. SSM had most often been used to understand a problem situation and to suggest potential improvements to the situation but to a lesser extent to implement and evaluate these improvements. SSM is flexible and applicable to a range of problem situations in healthcare settings. However, better reporting of how SSM has been applied as well as evaluation of different types of outcomes, including implementation and intervention outcomes, is needed in order to appreciate more fully the utility and contribution of SSM in healthcare.


Development and validation of a clinical radiomics nomogram to predict secondary loss of response to infliximab in Crohn's disease patients.
Infliximab (IFX) is the first-line treatment for Crohn's disease (CD). However, the secondary loss of response (LOR) is common in IFX therapy. Therefore, non-invasive assessment of LOR in CD patients is the goal pursued by clinicians. A multicenter study involving 181 CD patients was conducted, with patients being split into a training cohort (n = 102), testing cohort (n = 45), and validation cohort (n = 34). The study evaluated various clinical factors to establish a clinical model, and a radiomics signature was constructed based on reproducible features from computed tomography enterography (CTE). Logistic regression modeling was used to create models based on the radiomics signature and significant clinical factors, with the receiver operating characteristic curve (ROC) used to compare their performance. The study found that 64 of the 181 CD patients included experienced secondary LOR. The radiomics signature performed well in predicting secondary LOR, showing good discrimination in the training cohort (AUC [area under the curve], 0.947; 95% confidence interval [CI], 0.910-0.976), the testing cohort (AUC, 0.860; 95% CI, 0.768-0.941), and the validation cohort (AUC, 0.921; 95% CI: 0.831-1.000). Decision curve analysis (DCA) demonstrated the clinical value of the radiomics nomogram. The CTE-based radiomics model showed good performance in predicting secondary LOR in CD patients. The nomogram can help clinicians choose alternative biologics early for CD patients.


A new plasmid-based microRNA inhibitor system that inhibits microRNA families in transgenic mice and cells: a potential new therapeutic reagent.
Current tools for the inhibition of microRNA (miR) function are limited to modified antisense oligonucleotides, sponges and decoy RNA molecules and none have been used to understand miR function during development. CRISPR/Cas-mediated deletion of miR sequences within the genome requires multiple chromosomal deletions to remove all functional miR family members because of duplications. Here, we report a novel plasmid-based miR inhibitor system (PMIS) that expresses a new RNA molecule, which inhibits miR family members in cells and mice. The PMIS engineered RNA optimal secondary structure, flanking sequences and specific antisense miR oligonucleotide sequence bind the miR in a stable complex to inhibit miR activity. In cells, one PMIS can effectively inhibit miR family members that share the same seed sequence. The PMIS shows no off-target effects or toxicity and is highly specific for miRs sharing identical seed sequences. Transgenic mice expressing both PMIS-miR-17-18 and PMIS-miR-19-92 show similar phenotypes of miR-17-92-knockout mice. Interestingly, mice only expressing PMIS-miR-17-18 have developmental defects distinct from mice only expressing PMIS-miR-19-92 demonstrating usefulness of the PMIS system to dissect different functions of miRs within clusters. Different PMIS miR inhibitors can be linked together to knock down multiple miRs expressed from different chromosomes. Inhibition of the miR-17-92, miR-106a-363 and miR-106b-25 clusters reveals new mechanisms and developmental defects for these miRs. We report a new tool to dissect the role of miRs in development without genome editing, inhibit miR function in cells and as a potential new therapeutic reagent.


Mathematical modelling for health systems research: a systematic review of system dynamics and agent-based models.
Mathematical modelling has been a vital research tool for exploring complex systems, most recently to aid understanding of health system functioning and optimisation. System dynamics models (SDM) and agent-based models (ABM) are two popular complementary methods, used to simulate macro- and micro-level health system behaviour. This systematic review aims to collate, compare and summarise the application of both methods in this field and to identify common healthcare settings and problems that have been modelled using SDM and ABM. We searched MEDLINE, EMBASE, Cochrane Library, MathSciNet, ACM Digital Library, HMIC, Econlit and Global Health databases to identify literature for this review. We described papers meeting the inclusion criteria using descriptive statistics and narrative synthesis, and made comparisons between the identified SDM and ABM literature. We identified 28 papers using SDM methods and 11 papers using ABM methods, one of which used hybrid SDM-ABM to simulate health system behaviour. The majority of SDM, ABM and hybrid modelling papers simulated health systems based in high income countries. Emergency and acute care, and elderly care and long-term care services were the most frequently simulated health system settings, modelling the impact of health policies and interventions such as those targeting stretched and under resourced healthcare services, patient length of stay in healthcare facilities and undesirable patient outcomes. Future work should now turn to modelling health systems in low- and middle-income countries to aid our understanding of health system functioning in these settings and allow stakeholders and researchers to assess the impact of policies or interventions before implementation. Hybrid modelling of health systems is still relatively novel but with increasing software developments and a growing demand to account for both complex system feedback and heterogeneous behaviour exhibited by those who access or deliver healthcare, we expect a boost in their use to model health systems.


Regional differences in diagnosing asthma and other allergic diseases in Estonian schoolchildren.
The aim of this study was to estimate the prevalence of asthma and other allergic diseases among Estonian schoolchildren of the cities lacking special (pediatric allergological) health care. The study, carried out through 1 March to 8 May, 2003, enrolled 5th- to 12th-grade schoolchildren of 4 schools in different regions of Estonia. A three-step protocol was followed: screening questionnaire, examination by a pulmonary resident, and consultation by a pediatric allergologist. Of the 3132 questionnaires distributed, 1561 (49%) were returned. A total of 828 schoolchildren answered positively to any of the questions about possible allergic disease. After examination by the pulmonary resident, 255 schoolchildren (15.7%) were referred to an allergologist for final diagnosis. Asthma was diagnosed in 4.8%, allergic rhinoconjunctivitis in 4.9%, and atopic eczema in 8.3% of schoolchildren. Asthma, allergic rhinoconjunctivitis, and urticaria occurred more frequently in Narva as compared with Võru. The 12-month prevalence of asthma among Estonian schoolchildren was 4.8%, and the prevalence of allergic diseases varied from region to region. Less than half (40%) of all asthma cases identified during the study were newly diagnosed, and this clearly indicates that there is a considerable underdiagnosis of the disease among schoolchildren living outside of the centers in Estonia.


Increased incidence of germ cell testicular cancer in New Zealand Maoris.
A higher incidence of germ cell testicular cancer was found in Maoris (6.84/100,000) compared with non-Maoris (5.26/100,000) in New Zealand from 1975 to 1986, especially in the 15-49 year age group (Maoris 12.30/100,000, non-Maoris 9.47/100,000; P = 0.04). Previous studies have shown Whites to have the highest incidence of this malignancy. Possible reasons for this and some other epidemiological features are discussed.


Systematic review and meta-analysis of the complications of salvage total laryngectomy.
Management paradigms in laryngeal cancer have shifted to "organ preservation" chemoradiotherapy protocols. In the event of treatment failure, salvage total laryngectomy remains the only curative treatment option. However a comprehensive review of the complications of this procedure has not been reported. A systematic review of the literature was performed using keywords "salvage laryngectomy" to retrieve relevant publications between January 2000 and August 2015. Of the 407 articles retrieved from the literature search, 50 studies encompassing 3292 patients were included. Forty-nine studies reported pharyngocutaneous fistula which occurred in 859 patients (pooled incidence 28.9%; 95% confidence intervals 25.5-32.5%). Twenty-four studies reported complications in addition to PCF and these included wound complications (infection, dehiscence and necrosis), dysphagia, bleeding, and pharyngeal and stomal stenosis. Overall complication rate was 67.5%, Pharyngocutaneous fistula was the commonest complication with a pooled incidence of 28.9%.


Dihydropyridine receptor-ryanodine receptor interactions in skeletal muscle excitation-contraction coupling.
Much recent progress has been made in our understanding of the mechanism of sarcoplasmic reticulum Ca2+ release in skeletal muscle. Vertebrate skeletal muscle excitation-contraction (E-C) coupling is thought to occur by a "mechanical coupling" mechanism involving protein-protein interactions that lead to activation of the sarcoplasmic reticulum (SR) ryanodine receptor (RyR)/Ca2+ release channel by the voltage-sensing transverse (T-) tubule dihydropyridine receptor (DHPR)/Ca2+ channel. In a subsequent step, the released Ca2+ amplify SR Ca2+ release by activating release channels that are not linked to the DHPR. Experiments with mutant muscle cells have indicated that skeletal muscle specific DHPR and RyR isoforms are required for skeletal muscle E-C coupling. A direct functional and structural interaction between a DHPR-derived peptide and the RyR has been described. The interaction between the DHPR and RyR may be stabilized by other proteins such as triadin (a SR junctional protein) and modulated by phosphorylation of the DHPR.


The cellular mechanism of thalamic ponto-geniculo-occipital waves.
The cellular mechanisms underlying the genesis of thalamic ponto-geniculo-occipital waves were studied in reserpinized cats under urethane anaesthesia. Simultaneous field potential and intracellular recordings were performed in the lateral geniculate nucleus after acute lesions of retinal and visual cortical inputs. In most relay cells, reserpine-induced ponto-geniculo-occipital waves were associated with a transient depolarization that was often interrupted by a unitary inhibitory postsynaptic potential. The depolarization grew in size with membrane hyperpolarization and was accompanied by an increase in membrane conductance. The inhibitory postsynaptic potential is likely to have resulted from the activation of intrageniculate interneurons since perigeniculate cells were always inhibited during the occurrence of ponto-geniculo-occipital waves. Under reserpine, thalamic ponto-geniculo-occipital waves could also be triggered by peribrachial or auditory stimulation. These evoked ponto-geniculo-occipital waves were associated with intracellular events identical to those occurring spontaneously after reserpine administration. In addition, thalamic spindle oscillations were readily blocked by the occurrence of spontaneous or evoked ponto-geniculo-occipital waves. On the basis of the present results and those already published in the literature, the conclusion is reached that lateral geniculate ponto-geniculo-occipital waves result from a nicotinic activation of relay cells and from a parallel muscarinic inhibition of perigeniculate cells by peribrachial afferents. The functional significance of the ponto-geniculo-occipital activity is discussed on the basis of the antagonistic action of these signals on thalamic oscillations. It is proposed that these signals are the central correlates of orienting reactions elicited by sensory stimuli during waking (the so-called eye movement potentials) and by internally generated drives during paradoxical sleep.


Flow modelling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation.
The problem of donor scarcity has led to the recent development of tissue engineering technologies, which aim to create implantable tissue equivalents for clinical transplantation. These replacement tissues are being realised through the use of biodegradable polymer scaffolds; temporary/permanent substrates, which facilitate cell attachment, proliferation, retention and differentiated tissue function. To optimise gas transfer and nutrient delivery, as well as to mimic the fluid dynamic environment present within the body, a dynamic system might be chosen. Experiments have shown that dynamic systems enhance tissue growth, with the aid of scaffolds, as compared to static culture systems. Very often, tissue growth within scaffolds is only seen to occur at the periphery. The present study utilises the Computational Fluid Dynamics package FLUENT, to provide a better understanding of the flow phenomena in scaffolds, within our novel bioreactor system. The uni-axial and bi-axial rotational schemes are studied and compared, based on a vessel rotating speed of 35 rpm. The wall shear stresses within and without the constructs are also studied. Findings show that bi-axial rotation of the vessel results in manifold increases of fluid velocity within the constructs, relative to uni-axial rotation about the X- and Z-axes, respectively.


The Retrosigmoid Petrosal Fissure Transpeduncular Approach to Central Pontine Lesions.
The advent of improved surgical instruments and neuronavigation and descriptions of safe-entry zones have allowed neurosurgeons to resect brainstem lesions with an acceptable morbidity. The authors describe the technique of petrosal fissure dissection to the lateral transpeduncular safe-entry zone at the middle cerebellar peduncle (MCP) for resection of deep-seated central pontine pathologies. This approach allows the surgeon to obtain less cerebellar retraction and a more direct, more shallow, and shorter approach compared with the approach without opening this fissure. An illustrative case is used to highlight the technique of dissecting the petrosal fissure to obtain a direct surgical corridor to the MCP. Anatomic dissections are used to define better the relative relationships of this fissure to the MCP and adjacent structures. Dissection of the petrosal fissure provides a direct trajectory to the lateral transpeduncular entry zone at the MCP and can enhance exposure of this structure, while minimizing morbidity to the corticospinal tract and cerebellum during approaches to central pontine pathologies. For resection of lesions within the pons via the retrosigmoid craniotomy, dissection of the petrosal fissure allows for a more direct and shorter route to the central pontine and lateral pontine lesion compared with an approach without expansion of this potential space.


Endoscopic resection of benign tumors of the duodenal papilla without and with intraductal growth.
Endoscopic papillectomy of benign papillary tumor is still not widely practiced. Intraductal growth has been considered a contraindication for endoscopic therapy. This prospective study evaluates endoscopic papillectomy for treatment of benign papillary tumors without and with intraductal growth. Monofilament snare and monopolar electrocoagulation were used for papillectomy. A 7F stent was placed in the pancreatic duct. Patients with distal intraductal growth underwent sphincterotomy and endoscopic resection after exclusion of more proximal growth. Between February 1985 and April 2004, 106 patients (109 lesions), 68 women, 38 men, median age 68 years (range 29-88 years) were included. Median tumor size was 2 cm (range 0.5-6 cm) with one session (range 1-8) required for removal. Nine patients had invasive carcinoma (8%). Surgery for incomplete removal or recurrence was performed in 12% of 75 patients without and 37% of 31 patients with intraductal growth (p < 0.01), respectively. Fifteen patients had recurrence (15%); but, only 4 required surgery. Endoscopic resection was curative (median follow-up, 43 months) in 83% without and 46% with intraductal growth (p < 0.001). Endoscopic papillectomy is safe and effective, and may be feasible in cases of intraductal growth. Surveillance and, if required, re-treatment are mandatory because of the risk of recurrence.


Stereoselective Barbier-type allylation reaction of trifluoromethyl aldimines.
Trifluoromethyl aldimines could react, under Barbier conditions in the presence of activated zinc, in DMF at room temperature or in THF at reflux, with various allyl bromides to provide the corresponding homoallylamines. Secondary homoallyl trifluoromethylamines were stereoselectively obtained from the optically active aldimine 12 with an excellent diastereoisomeric excess (98%).


A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes.
Increased ribosomal DNA transcription has been proposed to limit muscle protein synthesis, making ribosome biogenesis central to skeletal muscle hypertrophy. We examined the relationship between ribosomal RNA (rRNA) production and IGF-1-mediated myotube hypertrophy in vitro Primary skeletal myotubes were treated with IGF-1 (50 ng/ml) with or without 0.5 µM CX-5461 (CX), an inhibitor of RNA polymerase I. Myotube diameter, total protein, and RNA and DNA levels were measured along with markers of RNA polymerase I regulatory factors and regulators of protein synthesis. CX treatment reduced 45S pre-rRNA expression (-64 ± 5% vs. IGF-1; P < 0.001) and total RNA content (-16 ± 2% vs. IGF-1; P < 0.001) in IGF-1-treated myotubes. IGF-1-mediated increases in myotube diameter (1.27 ± 0.09-fold, P < 0.05 vs. control) and total protein (+20 ± 2%; P < 0.001 vs. control) were not prevented by CX treatment. Suppression of rRNA synthesis during IGF-1 treatment did not prevent early increases in AKT (+203 ± 39% vs. CX; P < 0.001) and p70 S6K1 (269 ± 41% vs. CX; P < 0.001) phosphorylation. Despite robust inhibition of the dynamic ribosomal biogenesis response to IGF-1, myotube diameter and protein accretion were sustained. Thus, while ribosome biogenesis represents a potential site for the regulation of skeletal muscle protein synthesis and muscle mass, it does not appear to be a prerequisite for IGF-1-induced myotube hypertrophy in vitro.-Crossland, H., Timmons, J. A., Atherton, P. J. A dynamic ribosomal biogenesis response is not required for IGF-1-mediated hypertrophy of human primary myotubes.


Basal cell epithelioma in black patients.
The occurrence of cutaneous carcinoma in black patients is an unusual phenomenon, with basal cell carcinoma being particularly uncommon. We present five cases of basal cell epithelioma in black patients collected from the Texas Medical Center to graphically illustrate the varied and often atypical clinical presentations of such tumors. This report supports recent series of basal cell epithelioma in black patients derived from retrospective chart reviews.


Bone Marrow Aspirate Concentrate in Animal Long Bone Healing: An Analysis of Basic Science Evidence.
Long bone fractures that fail to heal or show a delay in healing can lead to increased morbidity. Bone marrow aspirate concentrate (BMAC) containing bone mesenchymal stem cells (BMSCs) has been suggested as an autologous biologic adjunct to aid long bone healing. The purpose of this study was to systematically review the basic science in vivo evidence for the use of BMAC with BMSCs in the treatment of segmental defects in animal long bones. The PubMed/MEDLINE and EMBASE databases were screened in July 14-25, 2014. The following search criteria were used: [("bmac" OR "bone marrow aspirate concentrate" OR "bmc" OR "bone marrow concentrate" OR "mesenchymal stem cells") AND ("bone" OR "osteogenesis" OR "fracture healing" OR "nonunion" OR "delayed union")]. Three authors extracted data and analyzed for trends. Quality of evidence score was given to each study. Results are presented as Hedge G standardized effect sizes with 95% confidence intervals. The search yielded 35 articles for inclusion. Of studies reporting statistics, 100% showed significant increase in bone formation in the BMAC group on radiograph. Ninety percent reported significant improvement in earlier bone healing on histologic/histomorphometric assessment. Eighty-one percent reported a significant increase in bone area on micro-computed tomography. Seventy-eight percent showed a higher torsional stiffness for the BMAC-treated defects. In the in vivo studies evaluated, BMAC confer beneficial effects on the healing of segmental defects in animal long bone models when compared with a control. Proof-of-concept has been established for BMAC in the treatment of animal segmental bone defects.


Assessing Resting Metabolic Rate in Overweight and Obese Adolescents With a Portable Indirect Calorimeter: A Pilot Study for Validation and Reliability.
Indirect calorimetry measured via the traditional indirect calorimeter is considered the "gold standard" for determining resting metabolic rate (RMR). Portable devices for assessing RMR are a less expensive option for measuring RMR in the clinical setting. This pilot study tested the reliability and validity of a portable device for measuring RMR, specifically in overweight and obese adolescents. Participants aged 17-19 years (n = 19) and ≥85th percentile on the Centers for Disease Control and Prevention body mass index growth curves for age and sex were recruited from a university campus. Participants completed testing on a traditional indirect calorimeter and a portable indirect calorimeter in a randomized order on 2 separate testing days. A paired samples t test comparing the means of the portable device and the traditional indirect calorimeter found no significant difference (P = .22). The test-retest intraclass correlation coefficient for assessing RMR was 0.91, indicating reliability of the portable indirect calorimeter. Compared with measured RMR, the Mifflin-St Jeor equation demonstrated 37% accuracy, and the Molnar equation demonstrated 57% accuracy. This pilot study found portable indirect calorimetry to be reliable and valid for assessing RMR in an overweight and obese adolescent population. In addition, this study indicates that portable indirect calorimetry may be an acceptable option for assessing RMR in this population compared with the traditional indirect calorimeter or predictive equations.


Single-cell RNA sequencing in dissecting microenvironment of age-related macular degeneration: Challenges and perspectives.
Age-related macular degeneration (AMD) is the leading cause of blindness in individuals over the age of 50 years, yet its etiology and pathogenesis largely remain uncovered. Single-cell RNA sequencing (scRNA-seq) technologies are recently developed and have a number of advantages over conventional bulk RNA sequencing techniques in uncovering the heterogeneity of complex microenvironments containing numerous cell types and cell communications during various biological processes. In this review, we summarize the latest discovered cellular components and regulatory mechanisms during AMD development revealed by scRNA-seq. In addition, we discuss the main challenges and future directions in exploring the pathophysiology of AMD equipped with single-cell technologies. Our review underscores the importance of multimodal single-cell platforms (such as single-cell spatiotemporal multi-omics and single-cell exosome omics) as new approaches for basic and clinical AMD research in identifying biomarker, characterizing cellular responses to drug treatment and environmental stimulation.


The effects of nutrition on plasma cholinesterase activity and cocaine toxicity in mice.
Low plasma cholinesterase activity is associated with severe cocaine toxicity in human subjects and animal experiments. Exogenously enhanced plasma cholinesterase activity is protective against cocaine toxicity in animals. Cocaine users tend to have lower plasma cholinesterase activity than controls. Yet, when cocaine users are allowed to use cocaine in controlled settings without dietary restriction, their plasma cholinesterase activity increases. This study evaluates the influence of diet on plasma cholinesterase activity and cocaine toxicity. Forty-five Swiss albino mice were maintained on a high (30%) protein diet for 3 weeks. They were then randomized into equal groups and given either the high protein diet, an isocaloric low protein diet, or a protein and calorie deficient diet which consisted of reduced intake of the high protein diet. Body weights and plasma cholinesterase activities were measured after a 21-day study period. All animals then received a fixed dose of intraperitoneal cocaine and were observed for seizures and death. Body weights and plasma cholinesterase activities of the high protein animals remained stable. Weights for the low protein and reduced intake animals fell by 5% and 15%, respectively (p < 0.05 for both vs baseline). Similarly, plasma cholinesterase activities for the low protein and reduced intake animals fell by 4% and 10%, respectively (p = 0.06 for low protein and < 0.05 for reduced intake vs baseline). Cocaine caused seizures in 67% of the high protein animals as compared to 93% and 100% of the low protein and reduced intake animals, respectively (p < 0.05 for high protein vs reduced intake). None of the high protein animals died as compared to 20% and 100% of the low protein and reduced intake animals, respectively (p < 0.05 for high protein vs reduced intake). Protein and calorie malnutrition is associated with a reduction in plasma cholinesterase activity and enhanced cocaine toxicity in mice. Further study is needed to determine if dietary factors are partially responsible for variations in plasma cholinesterase activity and cocaine susceptibility in humans.


Constructing built-in electric field via ruthenium/cerium dioxide Mott-Schottky heterojunction for highly efficient electrocatalytic hydrogen production.
Ensuring the consumption rate of noble metals while guaranteeing satisfactory hydrogen evolution reaction (HER) performance at different pH values is imperative to the development of Ru-based catalysts. Herein, we design a Mott-Schottky electrocatalyst (Ru/CeO2) with a built-in electric field (BEF) based on density functional theory (DFT). The Ru/CeO2 achieves the criterion current density of 10 mA cm-2 at overpotentials of 55 mV, 80 mV, and 120 mV in alkaline, acidic and neutral media, respectively. Both theoretical calculations and experimental analysis confirm that the improved HER activity in the Ru/CeO2 catalyst could be due to the successful construction of BEF at the interface between the prepared Ru clusters and CeO2. Under the action of BEF, the electron-deficient Ru atoms can optimize the adsorption energy of H* and H2O and thus promote HER kinetics. Furthermore, the Ru/CeO2 catalyst delivers a power density of approximately 94.5 mW cm-2 in alkaline-acidic Zn-H2O cell applications while maintaining good H2 production stability. In this work, we optimize the electrocatalytic performance of the Ru/CeO2 catalyst through examination of the interfacial BEF electrical charge, which combines hydrogen production with power generation and provides a promising method for sustainable energy conversion.


Scavenger and antioxidant properties of ten synthetic flavones.
To study the effect of the hydroxyl groups on biological activities of flavones, we synthesized 10 polyhydroxyflavones with varied substitution patterns. The abilities of the 10 compounds to act as radical scavengers were investigated using chemiluminescence in two biological models: the xanthine/xanthine oxidase system and the oxidative burst of rat alveolar macrophages. Stable radical formation was observed by electron spin resonance (ESR) spectroscopy. We found that the presence of the pyrogallol moiety in the B component of flavones gave rise to radical scavenger activity and that C-6 substituted hydroxyl group may also provide the basis for biological activity. Furthermore, compounds with a hydroxyl at C-7 position appeared to be xanthine oxidase inhibitors. One particular compound exhibited radical scavenger activity and xanthine oxidase inhibition. This type of compound should prove to be useful in the treatment of ischemia, for which both properties were required.


GABAA-receptor-mediated effects of progesterone, its ring-A-reduced metabolites and synthetic neuroactive steroids on neurogenic oedema in the rat meninges.
1. The effects of progesterone, its A-ring-reduced metabolites, allopregnanolone, tetrahydroxydeoxycorticosterone and the synthetic neuroactive steroid alphaxalone were evaluated in a rat model of plasma extravasation within the meninges following unilateral electrical stimulation (ES) of the trigeminal ganglion (0.6 mA, 5 ms, 5 min) or substance P administration (1 nmol kg-1, i.v.). 2. When administered 55 min prior to electrical stimulation, progesterone (> or = 500 micrograms, s.c.) dose-dependently decreased plasma extravasation within the meninges (ED50: 650 micrograms) but not within conjunctiva and tongue. Promegestone (R5020), a non-metabolized progesterone agonist (1000 micrograms, i.p.) was ineffective. The administration of progestrone (> or = 500 micrograms s.c.) 55 min prior to substance P partially suppressed plasma extravasation within the meninges (ED50: 550 micrograms). 3. The GABAA-antagonist, bicuculline (ED50: 8.2 micrograms kg-1, i.p.) but not the GABAB-antagonist, phaclofen (100 micrograms kg-1, i.p.) attenuated the effects of progesterone after electrical stimulation and substance P administration. 4. The metabolites of progesterone, allopregnanolone (3 alpha-hydroxy-5 alpha- pregnan-20-one (THP); ED50: 0.58 micrograms kg-1, i.p.), tetrahydroxydeoxycorticosterone (3 alpha,21- dihydroxy-5 alpha-pregnan-20-one (THDOC); ED50: 1.2 micrograms kg-1, i.p.) as well as the synthetic steroid alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11,20-dione; ED50: 1.8 micrograms kg-1, i.p.) suppressed plasma extravasation dose-dependently following ES, whereas the epimer of allopregnanolone, 3 beta-hydroxy-5 alpha-pregnan-20-one (100 micrograms kg-1, i.p.), did not. Extravasation caused by SP administration was partially suppressed by allopregnanolone (> or = 1 microgram kg-1, i.p.) (ED50: 2.1 micrograms kg-1). 5. The effect of progesterone (1000 micrograms, s.c.) and allopregnanolone (100 micrograms kg-1, i.p.) on neurogenic plasma extravasation was reversed by bicuculline (10 micrograms kg-1, i.p.) or by a congener, bicuculline-methiodide (10 micrograms kg-1, i.p.) which does not cross the blood brain barrier. 6. Progesterone (1000 micrograms, s.c.) had no effect on mean arterial blood pressure or heart rate when measured for 60 min after administration. 7. These results indicate that neurosteroid modulation of a GABAA-receptor located outside the blood brain barrier suppresses neurogenic and substance P-induced plasma extravasation within the meninges. The findings are consistent with previously reported data showing that valproic acid and muscimol inhibit meningeal oedema by bicuculline-sensitive mechanisms. Drugs which activate GABAA-receptors and its modulatory sites might be clinically effective in the treatment of migraine and cluster headache.


Application of aluminosilicate clay mineral-based composites in photocatalysis.
Aluminosilicate clay mineral (ACM) is a kind of typical raw materials that used widely in manufacturing industry owing to the abundant reserve and low-cost exploring. In past two decades, in-depth understanding on unique layered structure and abundant surface properties endows ACM in the emerging research and application fields. In field of solar-chemical energy conversion, ACM has been widely used to support various semiconductor photocatalysts, forming the composites and achieving efficient conversion of reactants under sunlight irradiation. To date, classic ACM such as kaolinite and montmorillonite, loaded with semiconductor photocatalysts has been widely applied in photocatalysis. This review summaries the recent works on ACM-based composites in photocatalysis. Focusing on the properties of surface and layered structure, we elucidate the different features in the composition with various functional photocatalysts on two typical kinds of ACM, i.e., type 1:1 and type 2:1. Not only large surface area and active surface hydroxyl group assist the substrate adsorption, but also the layered structure provides more space to enlarge the application of ACM-based photocatalysts. Besides, we overview the modifications on ACM from both external surface and the inter-layer space that make the formation of composites more efficiently and boost the photo-chemical process. This review could inspire more upcoming design and synthesis for ACM-based photocatalysts, leading this kind of economic and eco-friendly materials for more practical application in the future.


The Effect of Prone Positioning After Lung Transplantation.
Prone positioning has become a standard therapy in acute respiratory distress syndrome to improve oxygenation and decrease mortality. However, little is known about prone positioning in lung transplant recipients. This large, singe-center analysis investigated whether prone positioning improves gas exchange after lung transplantation. Clinical data of 583 patients were analyzed. Prone position was considered in case of impaired gas exchange Pao2/fraction of oxygen in inhaled air (<250), signs of edema after lung transplantation, and/or evidence of reperfusion injury. Patients with hemodynamic instability or active bleeding were not proned. Impact of prone positioning (n = 165) on gas exchange, early outcome and survival were determined and compared with patients in supine positioning (n = 418). Patients in prone position were younger, more likely to have interstitial lung disease, and had a higher lung allocation score. Patients were proned for a median of 19 hours (interquartile range,15-26) hours). They had significantly lower Pao2/fraction of oxygen in inhaled air (227 ± 96 vs 303 ± 127 mm Hg, P = .004), and lower lung compliance (24.8 ± 9.1 mL/mbar vs 29.8 ± 9.7 mL/mbar, P < .001) immediately after lung transplantation. Both values significantly improved after prone positioning for 24 hours (Pao2/fraction of oxygen ratio: 331 ± 91 mm Hg; lung compliance: 31.7 ± 20.2 mL/mbar). Survival at 90 days was similar between the 2 groups (93% vs 96%, P = .105). Prone positioning led to a significant improvement in lung compliance and oxygenation after lung transplantation. Prospective studies are needed to confirm the benefit of prone positioning in lung transplantation.


Risk of thyroid cancer after the Fukushima nuclear power plant accident.
The appropriateness of the initial response and countermeasures taken following the Fukushima nuclear power plant accident after the Great East Japan Earthquake on March 11, 2011 should be further examined. Implementation of a prospective epidemiological study on human health risks from low-dose radiation exposure and comprehensive health protection from radiation should be emphasized on a basis of the lessons learnt from the Chernobyl nuclear power plant accident. In contrast, the doses to a vast majority of the population in Fukushima were not high enough to expect to see any increase in incidence of cancer and health effects in the future, however, public concerns about the long-term health effects of radioactive environmental contamination have increased in Japan. Since May 2011, the Fukushima Prefecture started the Fukushima Health Management Survey Project with the purpose of long-term health care administration and early medical diagnosis/treatment for prefectural residents. In this report, risk and countermeasures of thyroid cancer occurrence after nuclear accidents, especially due to early exposure of radioactive iodine, will be focused upon to understand the current situation of risk of thyroid cancer in Fukushima, and the difficult challenges surrounding accurate estimations of low-dose and low-dose rate radiation exposures will be discussed.


Surface treatments for microfluidic biocompatibility.
Microfluidic systems allow small volumes of liquids to be manipulated, either by being passed through channels or moved around as liquid droplets. Such systems have been developed to separate, purify, analyze, and deliver molecules to reaction zones. Although volumes are small, reaction rates, catalysis, mixing, and heat transfer can be high, enabling the accurate sensing of tiny quantities of agents and the synthesis of novel products. The incorporation of multiple components, such as pumps, valves, mixers, and heaters, onto a single microfluidic platform has brought about the field of lab-on-a-chip devices or micro total analysis systems (μTAS). Although used in the research laboratory for numerous years, few of these devices have made it into the commercial market, due to their complexity of fabrication and limited choice of material. As the dimensions of these systems become smaller, interfacial interactions begin to dominate in terms of device performance. Appropriate selection of bulk materials, or the application of surface coatings, can allow control over surface properties, such as the adsorption of (bio)molecules. Here we review current microfluidic technology in terms of biocompatibility issues, examining the use of modification strategies to improve device longevity and performance.


Implementing the care programme for the last days of life in an acute geriatric hospital ward: a phase 2 mixed method study.
To improve the quality of end-of-life care in geriatric hospital wards we developed the Care Programme for the Last Days of Life. It consists of 1) the Care Guide for the Last Days of Life, 2) supportive documentation and 3) an implementation guide. The aim of this study is (1) to determine the feasibility of implementing the Care Programme for the Last Days of Life in the acute geriatric hospital setting and (2) to explore the health care professionals' perceptions of the effects of the Care Programme on end-of-life care. A phase 2 mixed methods study according with the MRC framework was performed in the acute geriatric ward of Ghent University Hospital between 1 April and 30 September 2013. During the implementation process a mixed methods approach was used including observation, interviews and the use of a quantitative process evaluation tool. This tool measured the success of implementation using several indicators, such as whether a steering group was formed, whether and how much of the health care staff was informed and trained and how many patients were cared for according to the Care Guide for the Last Days of Life. The process evaluation tool showed that implementing the Care Programme for the Last Days of Life in the geriatric ward was successful and thus feasible; a steering group was formed consisting of two facilitators, health care staff of the geriatric ward were trained in using the Care Guide for the Last Days of Life which was subsequently introduced onto the ward and approximately 57% of all dying patients were cared for according to the Care Guide for the Last Days of Life. With regard to health care professionals' perceptions, nurses and physicians experienced the Care Guide for the Last Days of Life as improving the overall documentation of care, improving communication among health care staff and between health care staff and patient/family and improving the quality of end-of-life care. Barriers to implementing the Care Programme for the Last Days of Life successfully are, among others, difficulties with the content of the documents used within the Care Programme for the Last Days of Life and the low participation rate of physicians in the training sessions and audits. Results of this mixed methods study suggest that implementing the Care Programme for the Last Days of Life is feasible and that it has favorable effects on end-of-life care as reported by health care professionals. Based on the identified barriers during the implementation process, we were able to make recommendations for future implementation and further refine the Care Programme for the Last Days of Life before implementing it in a phase 3 cluster randomized controlled trial for the evaluation of its effectiveness.


Electrostatic influence of active-site waters on the nucleophilic aromatic substitution catalyzed by 4-chlorobenzoyl-CoA dehalogenase.
The 4-chlorobenzoyl-CoA dehalogenase catalyzes the hydrolytic dechlorination of 4-chlorobenzoyl-CoA via a two-step mechanism, namely nucleophilic aromatic substitution and ester hydrolysis. The mutation of an active-site Histidine residue has been shown to reduce the catalytic activity in both the substitution and subsequent hydrolysis steps. In this communication, we report a quantum mechanical/molecular mechanical simulation of the potential of mean force for the substitution step, which confirms the increased barrier height in the H90Q mutant and provides evidence on the electrostatic influence of two active-site waters on the rate-limiting barrier.


Chemerin-9 Peptide Enhances Memory and Ameliorates Aβ1-42-Induced Object Memory Impairment in Mice.
Accumulating evidence suggests that the inhibition of neuroinflammation is a potential target for therapeutic or preventive strategies for Alzheimer's disease (AD). Chemerin has attracted particular attention for its role in the regulation of inflammation. In addition, amyloid β1-42 (Aβ1-42) can interact with chemokine-like receptor 1 (CMKLR1), the receptor for chemerin, and induce microglial chemotaxis. Meanwhile, CMKLR1 is expressed in the brain, and both chemerin and Aβ1-42 share the same receptor. Thus, we hypothesized that chemerin (C9), a chemerin-derived nonapeptide, may have the potential to ameliorate Aβ1-42 mediated AD disease progression. The results showed that an intracerebroventricular (i.c.v.) injection of C9 (8 µg/kg) facilitated memory formation and improved memory retention, as evidenced by the results of both the novel object recognition test (NOR) and object location recognition (OLR) tasks. These memory-enhancing effects of C9 were also observed after C9 (2 µg/kg) was infused into the hippocampus. Moreover, we found that treatment with C9 reversed the deficits in memory and learning ability induced by oligomeric Aβ1-42. Meanwhile, C9 also significantly inhibited Aβ1-42-induced increases in the levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the hippocampus. The same results were obtained for Western blotting and enzyme-linked immunosorbent assay (ELISA) experiments. Finally, we observed that C9 did not affect locomotor activity, suggesting that its improvement of memory is not a false positive induced by hypolocomotion. In conclusion, C9 may facilitate memory formation, prolong memory retention, and ameliorate Aβ1-42-induced memory impairment, suggesting that C9 may potentially represent a novel strategy for the treatment of AD.


Atonia after carbachol microinjections near the locus coeruleus in cats.
The effect of microinjections of carbachol into the dorsolateral pontine tegmentum on the behaviour of cats is investigated. Injections of small amounts (50 and 500ng) of carbachol into the pontine reticular formation induced muscular atonia in otherwise awake animals. The atonia is not due to cholinergic stimulation of the noradrenergic cells of the locus coeruleus or the dorsolateral pons, since the most effective sites were situated ventrally to the locus coeruleus and alpha- and beta-adrenergic blocking agents did not affect the antonia. The results are discussed in view of the postulated role of the locus coeruleus in paradoxical sleep.


Hypertrophic protein-losing gastropathy and vitiligo. Report of a second case.
A second patient with hypertrophic protein-losing gastropathy and extensive vitiligo was studied. Upper gastrointestinal radiographs and endoscopy revealed multiple polyps of the upper half of the stomach. The patient was achlorhydric to pentagastrin stimulation. Clearance of 51Cr-labeled protein by the gastrointestinal tract was about 15 times normal. A total gastrectomy was done for relief of persistent epigastric pain and correction of hypoproteinemia. Histologically the polyps consisted of hypertrophied mucosal glands with cystic dilatation deep to the glandular layer. The similarity of this patient to a patient previously seen at our hospital led us to report the possible association of hypertrophic protein-losing gastropathy with vitiligo.


Multiple squamous cells in thyroid fine needle aspiration: Friends or foes?
Abundant squamous cells are rarely encountered in thyroid FNA with only few case reports noted in the literature. Their presence and cytologic features may pose a diagnostic dilemma and challenges for proper classification and follow-up. We intend to gain more insight into the frequency of this finding and its clinical significance. Our electronic records were searched over 16 years to reveal 15 thyroid FNAs with abundant squamous cells. The available cytology and surgical resection slides were reviewed and radiologic records and clinical follow-up was documented. Only 15 out of 8811 thyroid FNAs from our department contained predominantly squamous cells (0.17%) of which two were interpreted as nondiagnostic, four as atypical, eight as benign, and one malignant. Surgical follow-up was available in eight cases only with benign lesions representing the majority of the cases (squamous metaplasia in Hashimoto thyroiditis, benign epidermoid/branchial cleft or thyroglossal duct cysts, and one case squamous cell carcinoma). The cases without surgical resection were stable on subsequent ultrasound studies. Thyroid aspirates with predominance of squamous cells cannot be classified in the current Bethesda categories. Even when interpreted as atypical or equivocal, the squamous cells present in our small case series were mostly benign. The only malignant case was easily identified cytologically because of its higher degree of differentiation. The most common pitfall for atypical squamous cells in these aspirates was squamous metaplasia in the setting of Hashimoto thyroiditis and degenerative changes. Diagn. Cytopathol. 2016;44:676-681. © 2016 Wiley Periodicals, Inc.


Specific detection of human coagulation factor IX in cynomolgus macaques.
After screening for species-specific antihuman factor (F)IX monoclonal antibodies, we found that antibody 3A6 did not bind to cynomolgus FIX. The 3A6 epitope was found to include Ala262 of human FIX. The 3A6 antibody was used as a catching antibody in an enzyme immunoassay (EIA) for specific detection of human FIX in cynomolgus macaque plasma. No significant increase of substrate hydrolysis was observed when EIA buffer containing cynomolgus macaque plasma was subjected to the 3A6-based EIA. Addition of up to 30% cynomolgus macaque plasma or canine plasma to the assay did not alter detection of human FIX. Three cynomolgus macaques were injected with human FIX (10 U kg-1; i.v.) and the circulating human FIX was quantified in the macaque plasma. The FIX level in the circulation increased to 470 +/- 37.6 ng mL-1 at 1 h after the injection and gradually decreased to 1.79 +/- 1.1 ng mL-1 by day 5, which is approximately 0.06% of the normal human plasma FIX concentration. These data suggest that the cynomolgus macaque can be used as a primate model for studying hemophilia B gene therapy by transduction of macaque organs with vectors to express human FIX in vivo and detection of human FIX using the 3A6 monoclonal antibody.


Net carbon flux from agricultural ecosystems: methodology for full carbon cycle analyses.
Agricultural ecosystems have the potential to sequester carbon in soils by altering agricultural management practices (i.e. tillage practice, cover crops, and crop rotation) and using agricultural inputs (i.e. fertilizers and irrigation) more efficiently. Changes in agricultural practices can also cause changes in CO2 emissions associated with these practices. In order to account for changes in net CO2 emissions, and thereby estimate the overall impact of carbon sequestration initiatives on the atmospheric CO2 pool, we use a methodology for full carbon cycle analysis of agricultural ecosystems. The analysis accounts for changes in carbon sequestration and emission rates with time, and results in values representing a change in net carbon flux. Comparison among values of net carbon flux for two or more systems, using the initial system as a baseline value, results in a value for relative net carbon flux. Some results from using the full carbon cycle methodology, along with US national average values for agricultural inputs, indicate that the net carbon flux averaged over all crops following conversion from conventional tillage to no-till is -189 kg C ha(-1) year(-1) (a negative value indicates net transfer of carbon from the atmosphere). The relative net carbon flux, using conventional tillage as the baseline, is -371 kg C ha(-1) year(-1), which represents the total atmospheric CO2 reduction caused by changing tillage practices. The methodology used here illustrates the importance of (1) delineating system boundaries, (2) including CO2 emissions associated with sequestration initiatives in the accounting process, and (3) comparing the new management practices associated with sequestration initiatives with the original management practices to obtain the true impact of sequestration projects on the atmospheric CO2 pool.


Asymmetric [N-I-N]+ halonium complexes.
The first asymmetric halogen-bonded iodonium complexes [I(py)(4-DMAP)]PF6 (2c) and [I(py)(4-Etpy)]PF6 (2e) were prepared via [N-Ag-N]+ → [N-I-N]+ cation exchange of their analogous 2-coordinate silver complexes. The complexes were characterised by 1H and 1H-15N HMBC NMR spectroscopy, and single crystal X-ray crystallography.


T cells with FC receptors in myeloma; suppression of growth and secretion of MOPC-315 by T alpha cells.
We have previously demonstrated that 1) BALB/c mice and patients with IgA myeloma developed a marked expansion of T cells with surface IgA-Fc receptors (T alpha cells), 2) the FcR alpha were induced by direct interaction of soluble myeloma IgA with T cells, and 3) the T alpha cells induced in IgA myeloma were Lyt-1-2+, IgA isotype-specific suppressor cells in normal immune responses. These findings established that the host with IgA myeloma responds to the large amounts of Ig produced by the tumor by activating an otherwise normal IgA isotype-specific suppressor circuit. In the present studies, we extend our previous observations and show that T alpha cells can suppress both the growth and secretion of MOPC-315 myeloma tumor cells. Thus, the isotype-specific immunoregulatory circuit activated in myeloma is capable of suppressing tumor cells as well as normal cells.


Compartmentation of protein folding in vivo: sequestration of non-native polypeptide by the chaperonin-GimC system.
The functional coupling of protein synthesis and chaperone-assisted folding in vivo has remained largely unexplored. Here we have analysed the chaperonin-dependent folding pathway of actin in yeast. Remarkably, overexpression of a heterologous chaperonin which traps non-native polypeptides does not interfere with protein folding in the cytosol, indicating a high-level organization of folding reactions. Newly synthesized actin avoids the chaperonin trap and is effectively channelled from the ribosome to the endogenous chaperonin TRiC. Efficient actin folding on TRiC is critically dependent on the hetero-oligomeric co-chaperone GimC. By interacting with folding intermediates and with TRiC, GimC accelerates actin folding at least 5-fold and prevents the premature release of non-native protein from TRiC. We propose that TRiC and GimC form an integrated 'folding compartment' which functions in cooperation with the translation machinery. This compartment sequesters newly synthesized actin and other aggregation-sensitive polypeptides from the crowded macromolecular environment of the cytosol, thereby allowing their efficient folding.


Structurally engineered colloidal quantum dot phosphor using TiO2 photonic crystal backbone.
Photonic crystal (PhC) phosphor, in which the phosphor material is periodically modulated for an enhancement in color-conversion efficiency via resonant absorption of excitation photons, is a paradigm-shifting structural phosphor platform. Two-dimensional (2D) square-lattice PhC phosphor is currently considered the most advanced platform because of not only its high efficiency, but also its immunity to excitation polarization. In the present study, two major modifications are made to further improve the performance of the 2D PhC phosphor: increasing the refractive index contrast and planarizing the surface. The index contrast is improved by replacing the PhC backbone material with TiO2 whereas the surface planarization is achieved by removing excessive colloidal quantum dots from the surface. In comparison with the reference phosphor, the upgraded PhC phosphor exhibits ~59 times enhanced absorption (in simulations) and ~7 times enhanced emission (in experiments), both of which are unprecedentedly high. Our results not only brighten the viability and applicability of the PhC phosphor but also spur the phosphor development through structural engineering of phosphor materials.


Risk factors for chronic thromboembolic pulmonary hypertension - Importance of thyroid disease and function.
Although a number of risk factors for chronic thromboembolic pulmonary hypertension (CTEPH) have been reported, the exact prevalence is controversial and varies between published cohorts. The aim of the present study was to investigate the prevalence of risk factors in operable CTEPH patients with special emphasis on thyroid disease and function. Overall, 228 CTEPH patients (47.7% female; median age 63 [IQR 52-72] years) scheduled for pulmonary endarterectomy between 01/2014 and 12/2015 were studied. Prevalence of risk factors was assessed, and patients were classified according to their thyroid function based on laboratory measurements. As many as 86.0% of patients reported a history of pulmonary embolism (PE; of those, 24.5% were diagnosed with "acute" PE less than six months before the diagnosis of CTEPH), 80.7% of patients had a blood group non-0 and 24.1% of patients had known thyroid disease (of those, 78.2% hypothyroidism). Laboratory measurements revealed thyroid dysfunction in 10.5% of patients (of those, 54.8% had no known thyroid disease). Patients with hypothyroid function had higher WHO functional classes, NT-proBNP levels and a lower cardiac index compared to patients with euthyroid function. The prevalence of a history of PE and blood group non-0 was higher than previously reported. However, a relevant proportion of patients might have suffered from pre-existing CTEPH rather than acute PE. Thyroid disease and dysfunction were frequent and hypothyroid function associated with more severe disease.


Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.
Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.


Studies with the Plasmodium falciparum hexokinase reveal that PfHT limits the rate of glucose entry into glycolysis.
To characterise plasmodial glycolysis, we generated two transgenic Plasmodium falciparum lines, one expressing P. falciparum hexokinase (PfHK) tagged with GFP (3D7-PfHK(GFP)) and another overexpressing native PfHK (3D7-PfHK(+)). Contrary to previous reports, we propose that PfHK is cytosolic. The glucose analogue, 2-deoxy-d-glucose (2-DG) was nearly 2-fold less toxic to 3D7-PfHK(+) compared with control parasites, supporting PfHK as a potential drug target. Although PfHK activity was higher in 3D7-PfHK(+), they accumulated phospho-[(14)C]2-DG at the same rate as control parasites. Transgenic parasites overexpressing the parasite's glucose transporter (PfHT) accumulated phospho-[(14)C]2-DG at a higher rate, consistent with glucose transport limiting glucose entry into glycolysis.


The effect of leukotrienes C4 and D4 on the microvasculature of guinea-pig skin.
The effects of chemically-synthesised leukotrienes C4 and D4 (5(S) hydroxy-6(R)-gamma-glutamylcysteinylglycinyl-7,9,11,14-eicosa-4 tetraenoic acid, LTC4; 5(S) hydroxy-6(R)-cysteinylglycinyl-7,9,11,14-eicosatetraenoic acid, LTD4 on the microvasculature have been measured in guinea-pig skin using [125I]-albumin accumulation to measure plasma exudation and 133Xe clearance to measure blood flow changes. As previously shown using biosynthetic material, LTD4 caused vasoconstriction resulting in reduced blood flow. Similarly, LTC4 was found to have vasoconstrictor activity but was more potent and had a steeper dose-response curve than LTD4. There was no evidence of conversion of exogenous arachidonic acid to vasoconstrictor activity in the skin in vivo (in the absence of another stimulus): intradermally injected arachidonic acid produced vasodilatation, but induced little change in blood flow in animals pretreated with indomethacin. The vasodilator effect of arachidonic acid is presumed to be due to conversion to either PGE2 or PGI2. These results suggest that cyclo-oxygenase is normally active in the skin, whilst lipoxygenase requires activation in some way. As reported in a previous study, LTD4 induced plasma exudation when injected into the skin, but pronounced responses could only be induced by LTD4 mixed with a vasodilator prostaglandin such as PGE2. In contrast, LTC4 induced no exudation when tested alone and little when PGE2 was added. However, evidence was obtained that LTC4 has some permeability-increasing activity which is masked by its potent vasoconstrictor activity.


Ultrasonographic approach to the neonatal foot: preliminary study.
We report our preliminary experience with use of ultrasound in clubfoot and describe our protocol and initial results in the use of this technique.


How Do Psychiatrists in Japan Choose Involuntary Admission, and What Do They Think of Supported Decision Making? A Thematic Analysis of Peer to Peer Interviews.
To include people with disabilities as equal citizens, CRPD (Convention on the Rights of Persons with Disabilities) promotes direct or supported decision-making by people with disabilities. However, involuntary psychiatry admission is considered in many countries to be necessary for people with psychosocial disabilities. To overcome the tension and implement CRPD, it is essential to understand the experiences and concerns of service users, family members, and medical professionals in each country. To understand the process and the factors that make psychiatrists decide involuntary psychiatric admission in Japan, and explore their attitudes toward direct or supported decision-making by people with psychosocial disabilities. Psychiatrists who had authorized involuntary admission and who were in charge of the service users were recruited at hospitals in Japan. The interviews were individual, peer to peer, and semi-structured. The interviews were audio-recorded, transcribed verbatim, and the analysis followed reflexive thematic analysis using NVIVO 12. Six psychiatrists (five designated psychiatrists and one psychiatric resident) participated in the study at two hospitals in urban Japan. The study found that the psychiatrists assessed symptoms, behaviors, and perceptions of the service users together with supports and wishes of their families. The psychiatrists decided on involuntary admission when they saw self-harm or violence, weak insights and judgment abilities, family's wishes, or when they wanted to avoid the service users leaving the hospital with incomplete treatment. The psychiatrists felt that the service users would not understand any explanations, which made their communications minimal. The psychiatrists thought it was hard to imagine a system other than the current involuntary admission mechanism. If it was to change, they felt the essential things were to avoid abuse, clarify who is responsible, make plans medically valid and feasible, and assess and plan through everyday life, not just in crisis. During a crisis, the psychiatrists were most careful about complying with the Mental Health Act and responded to the family's wish. The psychiatrists justified involuntary admission as they believed that people in a psychiatric crisis cannot decide or understand and need protection. Related protocols, laws, and expectations from family members shapes the values and practices of psychiatrists in Japan. The paper concludes with several recommendations to regard people with psychosocial disabilities as equal citizens, and promoting the aim of reducing or ending involuntary admission.


Stroke literacy in the population of the Eastern Province of Saudi Arabia; immediate steps are essential to bridge the gap.
Stroke is a medical emergency that demands early recognition for time sensitive acute management. Knowledge about stroke in public has not been found satisfactory in most of the studies worldwide. Studies describing the awareness of public about recognition of stroke and its treatment from Saudi Arabia (SA) are deficient. This study aimed to assess the knowledge of general population living in the Eastern Province of SA about stroke in relation to recognition of warning signs, risk factors and available acute treatment. A prospective, cross sectional study was conducted using a structured questionnaire distributed through an electronic web site over a period of six months. The data was analyzed with SPSS version 22.0. Among a total of 1,213 respondents, 62.4% were women. Three fourth identified the affected organ correctly. Psychological stress was the most commonly identified risk factor (73.5%) followed by hypertension (63.8%). More than half of the respondents (58.5%) were not aware of diabetes mellitus as a risk factor for stroke. Speech difficulty was the most commonly identified stroke warning sign (64.4%) followed by focal weakness (62.4%). More than half (59.9%) did not recognize facial asymmetry as stroke warning sign. Nearly three fourth of the participants were unaware of t-PA (73.7%) and nearest available health care center for acute stroke management (74.9%). Our survey found the stroke literacy in the population of the Eastern Province of SA as non- satisfactory and highlights the importance of taking immediate measure such as mass media campaign and hospital based activities to improve it.


Risk factors of brucellosis (re-)incidence in sheep and goat flocks in an endemic area of Portugal.
This study aimed to determinate the main risk factors of brucellosis recurrence or highest animal incidence in flocks, under pastoralism, in an endemic area of Northeast Portugal. An epidemiological survey was performed on 25 recurrent (n = 18) or highest seropositive (n = 7) sheep and mixed goat flocks and 19 historical (≥ 10 years) brucellosis-free flock, between 2014 and 2017, within the same epidemiological area presenting an average annual incidence around 6%. According to the multivariable logistic model (P < 0.001), the lack of neighboring brucellosis-free flocks (odds ratio OR = 7.79; CI % 1.49-65.06), the occurrence of more than 50% of lambing or kidding in common paths and pastures (OR = 24.17; CI % 3.0-606.54), and the animal replacement with Rev.1 non-vaccinated young animals (OR = 18.47; CI % 2.54-408.21) were the causes that influence the recurrence and highest animal incidence in flocks. In extensive production systems, the confinement of the peri-parturient and the small ruminant replacement with Rev.1 vaccinated young females seems to play a major role on brucellosis control and eradication.


An animal model to study the molecular basis of tardive dyskinesia.
Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects. This limitation presents a marked therapeutic challenge. The present method (21 days administration of haloperidol, 5 mg/kg, i.p.) has been established to gain deeper insight into the molecular etiology (inflammation and apoptosis) of haloperidol-induced cellular death. In the present model, besides the corresponding increase in the vacuous chewing movements (VCMs), enhanced oxidative stress, there was a significant increase in cellular markers of inflammation and apoptotic protein (caspase-3), leading to cellular death. We also suggest that this model will be effective in preclinical testing of new chemical entities for the treatment of haloperidol induced tardive dyskinesia and related symptoms.


Plastic material used to optimize radiotherapy of head and neck tumors and the mammary carcinoma.
In order to improve head and neck tumor therapy, face masks were developed. The physical and mechanical properties of 11 apparently suitable materials were tested using a phantom. According to our studies "HEXCELITE" (supplied by Medimex, Hamburg, F.R.G.) proved to be the best material. Plastic breast molds were made to optimize the dose distribution for radiation therapy with fast electrons of post-mastectomy breast tumors. Here too the mechanical and physical properties of nine different materials were tested. The most suitable of these proved to be the gel mat "PRIMAMED" (supplied by Schülke and Mayr, Norderstedt, F.R.G.). The two materials mentioned have been well tolerated by more than 200 patients.