Randomized controlled trial: parental compliance with instructions to remain silent in the dental operatory.
The purposes of this study were to: (1) determine compliance in requesting parents to remain silent (noncommunicative) when accompanying their child into the dental operatory for restorative care; and (2) determine if any difference in parental compliance existed when combined written and verbal instructions were given to a parent vs written instructions only. Thirty-nine parents of 4- to 9-year-olds presenting for restorative care met eligibility criteria for the study. Parents were randomly assigned to a written instructions-only group or a group that received combined written and verbal instructions. Thirty-two of 39 parents (82%) followed instructions to remain silent. There was no statistical difference in parental compliance to remain silent comparing written instructions (78%) to combined written and verbal instructions (86%). Parents may be expected to comply with instructions to remain silent in the operatory when given either written or combined written and verbal instructions.


Platination of a GG site on single-stranded and double-stranded forms of a 14-base oligonucleotide with diaqua cisplatin followed by NMR and HPLC -- influence of the platinum ligands and base sequence on 5'-G versus 3'-G platination selectivity.
Detailed studies of the kinetics of platination of the single-stranded 14-base DNA oligonucleotide d(ATACATGGTACATA) and the corresponding duplex by cis-[Pt(NH3)2(H2O)2]2+ show that HPLC and NMR are complementary methods which provide similar results. The 5'-G and 3'-G monofunctional intermediates were trapped, separated and characterized by NMR (via 15NH3 labeling) and enzymatic digestion followed by mass spectrometry. The kinetic data are compared with those for the corresponding reactions of cis-[PtCl2(NH3)2] (cisplatin) and its monohydrolysed analogue. For both single and double strands of the oligonucleotide, the aqua complex shows little selectivity for the 5'-G or the 3'-G in the initial platination step, whereas the chloro-complex preferentially platinates the 3'-G. The base on the 3' side of the GG sequence appears to play an important role in controlling this selectivity; replacement of T by C increases the selectivity of duplex platination by the diaqua complex by a factor of about 6, and the selectivity of chelation of the 3'-G monofunctional adduct by a factor of about 3. In general the reactivity of the 5'-G in a GG sequence appears to be enhanced in a duplex compared with a single-strand. For both the aqua-monoadduct and chloro-monoadduct, cis-[Pt(NH3)2(N7G)(H2O or Cl)], the 5'-G monoadduct is much longer lived (t1/2 approximately 4 h at 288 K for aqua, 80 h at 298 K for chloro) than the 3'-G monoadduct (t1/2 < or = 45 min at 288 K for aqua, 6 h at 298 K for chloro). Inspection of molecular mechanics models of the end states of various monofunctional adducts provided insight into H-bonding and destacking interactions in these adducts and the sequence selectivity observed in their formation. Such adducts may play an important role in the mechanism of action of platinum anticancer drugs.


Protein regions important for plasminogen activation and inactivation of alpha2-antiplasmin in the surface protease Pla of Yersinia pestis.
The plasminogen activator, surface protease Pla, of the plague bacterium Yersinia pestis is an important virulence factor that enables the spread of Y. pestis from subcutaneous sites into circulation. Pla-expressing Y. pestis and recombinant Escherichia coli formed active plasmin in the presence of the major human plasmin inhibitor, alpha2-antiplasmin, and the bacteria were found to inactivate alpha2-antiplasmin. In contrast, only poor plasminogen activation and no cleavage of alpha2-antiplasmin was observed with recombinant bacteria expressing the homologous gene ompT from E. coli. A beta-barrel topology model for Pla and OmpT predicted 10 transmembrane beta-strands and five surface-exposed loops L1-L5. Hybrid Pla-OmpT proteins were created by substituting each of the loops between Pla and OmpT. Analysis of the hybrid molecules suggested a critical role of L3 and L4 in the substrate specificity of Pla towards plasminogen and alpha2-antiplasmin. Substitution analysis at 25 surface-located residues showed the importance of the conserved residues H101, H208, D84, D86, D206 and S99 for the proteolytic activity of Pla-expressing recombinant E. coli. The mature alpha-Pla of 292 amino acids was processed into beta-Pla by an autoprocessing cleavage at residue K262, and residues important for the self-recognition of Pla were identified. Prevention of autoprocessing of Pla, however, had no detectable effect on plasminogen activation or cleavage of alpha2-antiplasmin. Cleavage of alpha2-antiplasmin and plasminogen activation were influenced by residue R211 in L4 as well as by unidentified residues in L3. OmpT, which is not associated with invasive bacterial disease, was converted into a Pla-like protease by deleting residues D214 and P215, by substituting residue K217 for R217 in L4 of OmpT and also by substituting the entire L3 with that from Pla. This simple modification of the surface loops and the substrate specificity of OmpT exemplifies the evolution of a housekeeping protein into a virulence factor by subtle mutations at critical protein regions. We propose that inactivation of alpha2-antiplasmin by Pla of Y. pestis promotes uncontrolled proteolysis and contributes to the invasive character of plague.


Crouching tiger, hidden trouble: urban sources of Aedes albopictus (Diptera: Culicidae) refractory to source-reduction.
Our ultimate objective is to design cost-effective control strategies for Aedes albopictus, the Asian tiger mosquito, an important urban nuisance and disease vector that expanded worldwide during the last 40 years. We conducted mosquito larval surveys from May through October 2009 in the City of Trenton, New Jersey, USA, while performing intensive monthly source-reduction campaigns that involved removing, emptying, or treating all accessible containers with larvicides and pupicides. We examined patterns of occurrence of Ae. albopictus and Culex pipiens, another urban mosquito, among different container types by comparing observed and expected number of positive containers of each type. Expected use was based on the relative frequency of each container type in the environment. Aedes albopictus larvae and pupae were found significantly more often than expected in medium volumes of water in buckets and plant saucers but were rarely collected in small volumes of water found in trash items such as discarded cups and cans. They were also absent from large volumes of water such as in abandoned swimming pools and catch basins, although we consistently collected Cx. pipiens from those habitats. The frequency of Ae. albopictus in tires indicated rapid and extensive use of these ubiquitous urban containers. Standard larval-based indices did not correlate with adult catches in BG-Sentinel traps, but when based only on Ae. albopictus key containers (buckets, plant saucers, equipment with pockets of water, and tires) they did. Although we found that only 1.2% of the 20,039 water-holding containers examined contained immature Ae. albopictus (5.3% if only key containers were counted), adult populations were still above nuisance action thresholds six times during the 2009 mosquito season. We conclude that in urban New Jersey, effective source reduction for Ae. albopictus control will require scrupulous and repeated cleaning or treatment of everyday use containers and extensive homeowner collaboration.


Evolving the language-ready brain and the social mechanisms that support language.
We first review the mirror-system hypothesis on the evolution of the language-ready brain, stressing the important role of imitation and protosign in providing the scaffolding for protospeech. We then assess the role of social interaction and non-specific knowledge of language in the emergence of new sign languages in deaf communities (focusing on Nicaraguan Sign Language). (1) Readers will understand the difference between mirror systems in humans and monkeys, and see how the evolution of imitation and protosign required the biological evolution of mirror systems with linkages to diverse regions beyond the mirror system. (2) Readers will see how social structure complements brain mechanisms in yielding language through cultural evolution supported by having language-ready brains, rather than through possession of an innate Universal Grammar. (3) Readers will understand that ontogeny does not recapitulate phylogeny, but will appreciate what mechanisms currently operative in modern children acquiring language may also have served early humans during the cumulative invention of the idea of language.


Aggregation characteristics of ovalbumin in beta-sheet conformation determined by spectroscopy.
Protein misfolding and aggregation are involved in a number of the so-called "conformational" diseases (e.g., transmissible spongiform encephalopathies and Alzheimer disease). The development of rational strategies to interfere with aggregation is a potential therapeutic approach that requires complete knowledge of the aggregation process. We studied the aggregation of ovalbumin in beta-sheet conformation using mainly the spectral changes in the spectra of two dyes (Congo Red and pinacyanol) caused by the aggregates. We assumed a linear model of polymerization that fit to the experimental data. The critical aggregation constant, concentration of half-aggregation, nucleation parameter, growth parameter, and number of aggregation and free energy changes (total and per residue) were determined as aggregation-related parameters. Beta-Ovalbumin aggregates in a cooperative way. Moreover, the differences between such parameters obtained with Congo Red and pinacyanol suggest that each dye interacts with the protein in its own way.


Frequency of cognitive impairment dramatically increases during the first 5 years of multiple sclerosis.
Previous studies have demonstrated that cognitive impairment is already present in patients suffering from a clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). However, little is known about the course of cognitive impairment after the occurrence of a CIS. In order to characterise the early evolution of cognitive impairment, the authors assessed during a 5-year follow-up period a group of 24 CIS patients with high risk of developing MS. Longitudinal neuropsychological assessment was performed at two time points (baseline and year 5) in patients and controls (baseline and year 1). At year 5, 54% of patients showed cognitive impairment against 29% at baseline. Multiple regression models showed that patients with a higher T(2) lesion load at baseline had a higher cognitive impairment at year 5. This longitudinal study performed in CIS patients showed that the frequency of cognitive impairment increases dramatically during the first 5 years following a CIS and that the cognitive status at year 5 was predictable by conventional MRI parameters recorded at baseline.


Solitary pedunculated multicystic viral plaque associated with canine papillomavirus 18 in a British Bulldog.
A pedunculated exophytic mass developed on the rump of a dog. Fine-needle aspiration revealed keratin debris suggestive of a follicular tumor. However, histology revealed a pigmented viral plaque that contained numerous keratin-filled cystic cavities. Canine papillomavirus 18 DNA sequences were detected in the lesion. Viral plaques are typically multiple sessile lesions of dogs. A viral plaque appearing as a solitary exophytic keratin-filled mass has not been reported previously, to our knowledge. The novel clinical findings in this case expand the ways that viral plaques may appear in dogs. In addition, the histologic findings represent a novel pathologic entity of dogs. Given that canine viral plaques can be progressive, and dogs typically develop numerous plaques, it is important to differentiate between a viral plaque and a hair follicle tumor.


Improving the prediction of malignancy in cytologically suspicious thyroid nodules.
Fine needle cytology aspirates (FNA) classified as THY4 are a heterogeneous group suspicious for malignancy [papillary thyroid cancer (PTC)], which is confirmed in 50-80% of cases after surgery. To better stratify THY4 FNA specimens for the relative risk of malignancy. We retrospectively analyzed 78 thyroid nodules classified as THY4 because of the presence of atypical cells, hypercellular trabeculae and/or intranuclear inclusions (ICI), in the absence of papillae. Two subgroups were identified: group 1 (38 nodules), showing ICI with (no.=17) or without (no.=21) trabeculae and cellular atypia, and group 2 (40 nodules), showing trabeculae and atypia but without ICI. PTC was detected at histology in 56/78 of the patients (71.8%). Malignancy occurred in 36/38 (94.7%) of the patients in group 1 and in 20/40 (50.0%) of the patients in group 2. Therefore, the positive predictive value (PPV) for PTC was 97.3% in the ICI+ specimens (group 1), with a sensitivity of 64.3% and specificity of 95.2%. When only ICI was present, without atypia and trabeculae, the PPV and specificity were similar (95.0 and 95.2%, respectively), but the sensitivity was decreased (48.7%). In specimens without ICI (group 2), the PPV was only 50.0%; however, combined with young age (<40 yr) and male gender, it reached a value similar to that of group1. In ICI+ specimens compared to ICI-, the risk of PTC is nearly doubled, since PPV increases from 50.0% to 97.3%. This observation suggests that surgery should be considered mandatory in all lesions classified THY4 at FNA, although the relevant difference in terms of cancer risk between ICI- vs ICI+ nodules might be an useful information for both the clinician and the patient.


The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic cell proliferation, induces angiogenesis in vitro and in vivo.
The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP), purified from bone marrow and constitutively synthesized in vivo, belongs to the family of negative regulators of hematopoiesis. It protects the stem cell compartment from the toxicity of anticancer drugs and irradiation and consequently contributes to a reduction in marrow failure. This current work provides experimental evidence for another novel biologic function of AcSDKP. We report that AcSDKP is a mediator of angiogenesis, as measured by its ability to modulate endothelial cell function in vitro and angiogenesis in vivo. AcSDKP at nanomolar concentrations stimulates in vitro endothelial cell migration and differentiation into capillary-like structures on Matrigel as well as enhances the secretion of an active form of matrix metalloproteinase-1 (MMP-1). In vivo, AcSDKP promotes a significant angiogenic response in the chicken embryo chorioallantoic membrane (CAM) and in the abdominal muscle of the rat. Moreover, it induces the formation of blood vessels in Matrigel plugs implanted subcutaneously in the rat. This is the first report demonstrating the ability of AcSDKP to interact directly with endothelial cells and to elicit an angiogenic response in vitro and in vivo.


Complications of endoscopic third ventriculostomy.
The purpose of this prospective investigation was to determine the rate of complications associated with endoscopic third ventriculostomy (ETV). Between March 1993 and October 2001, 193 ETVs were performed in 188 patients at a single institution. The age of the patients ranged from 1 month to 85 years (mean age 39 years). One procedure had to be abandoned because a severe venous hemorrhage blurred the surgeon's view; however, third ventriculostomy was successfully accomplished in that patient 14 days later. In addition, there were two cases in which significant venous hemorrhages could be controlled endoscopically by using irrigation. Postoperative imaging revealed three subdural collections, one tiny thalamic contusion, one cortical hemorrhage at the puncture site, and one severe subarachnoid hemorrhage (SAH). There were two deaths (1% mortality rate) related to the endoscopic procedure; causes of death were one SAH from a torn basilar perforating artery and one wound infection leading to meningitis and septic multiorgan failure. Three permanent deficits occurred (confusion, oculomotor palsy, and diabetes insipidus [1.6% permanent morbidity rate]). Transient deficits included four cases of meningitis, three cases of cerebrospinal fluid leak, two cases of herniation syndrome, two cases of confusion, one case in which there was a decrease of consciousness, two cases of oculomotor palsy, and one case in which there was loss of thirst (7.8% transient morbidity rate). Misplacement of the fenestration was the main reason for severe complications. During the course of the study, the complication rate dropped significantly (no incidences of mortality or permanent morbidity occurred during the last 100 procedures). All permanent and fatal complications occurred during the authors' very early experience, indicating that a steep learning curve was associated with the procedure. Endoscopic third ventriculostomy, if performed correctly, is a safe, simple, and effective treatment option for various forms of noncommunicating hydrocephalus.


[Vertebragenic dysphagia].
Dysphagia due to external compression by anterior hyperostosis of the cervical spine is rare. The diagnosis may be established by conventional X-ray of the spine, oesophagogram, CT or MRI. We operated on one patient with an exostosis on the axis and another patient with large anterior osteophytes from C3 to C7 in Forestiers's disease. Postoperatively the patients were asymptomatic. Painful dysphagia due to anterior hyperostosis of the cervical spine is an indication for surgery. The anterolateral extrapharyngeal approach from C3 to C7 and the transoral intrapharyngeal approach to the vertebra C2 are preferred. In cooperation between orthopaedics and ENT the surgical treatment has no major complications and gives good functional results.


Empowering older women: strategies to enhance their health and health care.
Older persons, especially older women, report that often their needs are not met in health care encounters. Lack of active participation by the patient is a major reason for this dissatisfaction. This article reviews research on older women's socialization that discourages them from challenging the status quo in interactions with others. It suggests ways that health care providers can empower female patients: They can encourage active participation during health care encounters, and they can help patients prepare for encounters so they can have their needs met.


Native glycosylation and binding of the antidepressant paroxetine in a low-resolution crystal structure of human myeloperoxidase.
Human myeloperoxidase (MPO) utilizes hydrogen peroxide to oxidize organic compounds and as such plays an essential role in cell-component synthesis, in metabolic and elimination pathways, and in the front-line defence against pathogens. Moreover, MPO is increasingly being reported to play a role in inflammation. The enzymatic activity of MPO has also been shown to depend on its glycosylation. Mammalian MPO crystal structures deposited in the Protein Data Bank (PDB) present only a partial identification of their glycosylation. Here, a newly obtained crystal structure of MPO containing four disulfide-linked dimers and showing an elaborate collection of glycans is reported. These are compared with the glycans identified in proteomics studies and from 18 human MPO structures available in the PDB. The crystal structure also contains bound paroxetine, a blocker of serotonin reuptake that has previously been identified as an irreversible inhibitor of MPO, in the presence of thiocyanate, a physiological substrate of MPO.


Environmental Specimen Bank in Ehime University (es-BANK), Japan for global monitoring.
During the last 40 years, The Center for Marine Environmental Studies (CMES), Ehime University collected a variety of environmental and biological material comprising about 1000 species and 100,000 samples from many developing and developed countries and also open seas and oceans all over the world. They were categorically archived, catalogued and stocked in our Environment Specimen Bank (es-BANK) facility equipped with a -25 degrees C cold room. We have already exchanged specimens with many scientific institutions and are also eager to widen our collaboration with other specimen banks. In our survey using the air, water, wildlife and human samples, we found that the major emission sources for the industrial chemicals like polychlorinated biphenyls (PCBs) are in the developed nations while those of organochlorine (OC) pesticides like dichlorodiphenyltrichloroethane and its metabolites (DDTs), hexachlorocyclohexane isomers (HCHs), etc. are located in developing countries. However, significant emission of modern environmental contaminants such as polybrominated diphenyl ethers (PBDEs) also seems to occur predominantly in countries with high economic growth rates. Apart from the modern incinerators and other industrial installations in developed nations, the compounds, like dioxins and related compounds (DRCs), were also found to be released in significant levels from the municipal solid waste dumping sites of developing countries. By evaluating the distribution patterns of various persistent toxic substances (PTSs) in our studies, we could conclude that DRCs and DDTs are regional contaminants, while PCBs, PBDEs, HCHs and hexachlorobenzene (HCB) are global contaminants. We also found that the pollution by PBDEs has been increasing in the last two decades while that of the legacy OCs has been decreasing.


Influence of internal biofilm growth on residual permeability loss in aerobic granular membrane bioreactors.
Membrane fouling results in flux decline or transmembrane pressure drop increase during membrane bioreactor (MBR) operation. Physical and chemical cleanings are essential to keep an MBR operating at an appropriate membrane flux. Considerable residual membrane permeability loss that cannot be removed by conventional cleaning requires membrane replacement. This study demonstrates that an internal biofilm can develop inside a hollow-fiber membrane and can probably account for up to 58.9 and 81.3% of total membrane resistance for aerobic granular MBR operated in sequencing batch reactor (SBR) mode or continuous-fed mode, respectively. The Arthrobacter sp. (accession no. AM900505 in GenBank) corresponded to internal biofilm development by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis and the agar-plating technique. This study also identifies a single strain, Arthrobacter sp., generates the internal biofilm. The Arthrobacter sp. is a rod-shaped bacterium with a size close to that of membrane pores, and can secrete excess bound proteins, hence can penetrate and attach itself inside the membrane and grow. Internal biofilm growth could contribute significantly to membrane resistance during long-term MBR operation.


A double blind controlled trial of methylprednisolone infusions in systemic lupus erythematosus using individualised outcome assessment.
Twenty one patients with severe systemic lupus erythematosus (SLE) were treated with three daily infusions of either 100 mg or 1 g of methylprednisolone on a randomised double blind basis. Nine patients with unsatisfactory outcome subsequently received the alternative therapy. Patients were rated for improvement on a four point scale using individualised criteria. On three occasions patients improved to 'ideal', on 12 there was 'useful' improvement, on 11 the patient remained static, and on four occasions there was deterioration. There was no significant difference between the clinical states after the two doses. The results suggest that any additional benefit of 1 g of methylprednisolone over 100 mg by repeated infusion in the treatment of active SLE is probably not enough to justify the potential hazards and cost involved.


Maternal age and adverse pregnancy outcome: a cohort study.
To examine the association between maternal age and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics. This was a retrospective study in women with singleton pregnancies attending the first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. Data on maternal characteristics, and medical and obstetric history were collected and pregnancy outcomes ascertained. Maternal age was studied, both as a continuous and as a categorical variable. Regression analysis was performed to examine the association between maternal age and adverse pregnancy outcome including pre-eclampsia, gestational hypertension, gestational diabetes mellitus (GDM), preterm delivery, small-for-gestational age (SGA) neonate, large-for-gestational age (LGA) neonate, miscarriage, stillbirth and elective and emergency Cesarean section. The study population included 76 158 singleton pregnancies with a live fetus at 11 + 0 to 13 + 6 weeks. After adjusting for potential maternal and pregnancy confounding variables, advanced maternal age (defined as ≥ 40 years) was associated with increased risk of miscarriage (odds ratio (OR), 2.32 (95% CI, 1.83-2.93); P < 0.001), pre-eclampsia (OR, 1.49 (95% CI, 1.22-1.82); P < 0.001), GDM (OR, 1.88 (95% CI, 1.55-2.29); P < 0.001), SGA (OR, 1.46 (95% CI, 1.27-1.69); P < 0.001) and Cesarean section (OR, 1.95 (95% CI, 1.77-2.14); P < 0.001), but not with stillbirth, gestational hypertension, spontaneous preterm delivery or LGA. Maternal age should be combined with other maternal characteristics and obstetric history when calculating an individualized adjusted risk for adverse pregnancy complications. Advanced maternal age is a risk factor for miscarriage, pre-eclampsia, SGA, GDM and Cesarean section, but not for stillbirth, gestational hypertension, spontaneous preterm delivery or LGA.


Influence of cerium content on the microstructure and thermal expansion properties of suction cast Al-Cu-Fe alloys.
Low-expansion alloys are of great importance and can be used for the development of new aerospace materials. Herein, we report diverse rare earth quasicrystal alloys fabricated by the vacuum suction casting process. The effects of the addition of cerium (Ce) on the microstructure, thermal expansion properties and microhardness of the Al-Cu-Fe alloy were systematically investigated. This study discovered the tiny Al-Cu-Fe-Ce microstructure. A uniform distribution could be achieved after Ce addition amount is elevated. At the Ce addition amount of 1 at%, the lowest alloy thermal expansion coefficient was obtained. The alloy exhibited the maximum microhardness under these conditions. The microhardness of alloys containing 1 at% of Ce was approximately 2.4 times higher than the microhardness exhibited by alloys devoid of Ce additives. The coefficient of thermal expansion decreases by approximately 20%. The use of the suction casting process and the addition of an appropriate amount of Ce can potentially help design and develop Al-Cu-Fe-Ce alloys.


Chronic obstructive pulmonary disease and β-blocker treatment in Asian patients with heart failure.
Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are increasingly frequent in Asia and commonly coexist in patients. However, the prevalence of COPD among Asian patients with HF and its impact on HF treatment are unclear. We compared clinical characteristics and treatment approaches between patients with or without a history of COPD, before and after 1:2 propensity matching (for age, sex, geographical region, income level, and ethnic group) in 5232 prospectively recruited patients with HF and reduced ejection fraction (HFrEF, <40%) from 11 Asian regions (Northeast Asia: South Korea, Japan, Taiwan, Hong Kong, and China; South Asia: India; Southeast Asia: Thailand, Malaysia, Philippines, Indonesia, and Singapore). Among the 5232 patients with HFrEF, a history of COPD was present in 8.3% (n = 434), with significant variation in geography (11.0% in Northeast Asia vs. 4.7% in South Asia), regional income level (9.7% in high income vs. 5.8% in low income), and ethnicity (17.0% in Filipinos vs. 5.2% in Indians) (all P < 0.05). Use of mineralocorticoid receptor antagonists and diuretics was similar between groups, while usage of all β-blockers was lower in the COPD group than in the non-COPD group in the overall (66.3% vs. 79.9%) and propensity-matched cohorts (66.3% vs. 81.7%) (all P < 0.05). A striking exception was the Japanese cohort in which β-blocker use was high in COPD and non-COPD patients (95.2% vs. 91.2%). The prevalence of COPD in HFrEF varied across Asia and was related to underuse of β-blockers, except in Japan.


Fabrication of hollow ZnO particles and its photocatalytic property by modifying of nano ZnS.
Large scale hollow ZnO spheres were prepared by a solvothermal method with the help of the solvent. And ZnS nanoparticles were successfully fabricated on the surface of ZnO via a hydrothermal process. These heterostructured ZnO/ZnS core/shell particles are around 1-2 microm in diameter, the ZnS shell formed on the surface of hollow ZnO sphere is comprise of the primary crystals about 30 nm in diameter. The products prepared were characterized by field emission scanning electron microscope (FE-SEM), X-ray powder diffraction (XRD), transmission electron microscope (TEM), and photo-luminescence spectroscope (PL). Theoretical calculation and experimental results have demonstrated that the combination of ZnO and ZnS (two wide band gap semiconductors) could yield a novel material with the photoexcitation threshold energy lower than the individual components. The electron transfers between ZnO core and ZnS shell, which strongly affect the photoluminescence and photocatalytic performances. The photocatalytic activities of the products were evaluated by methyl orange degradation as a probe reaction. The relationship of ZnO/ZnS core/shell particles as excellent photocatalyst could be anticipated.


The Moment Study: protocol for a mixed method observational cohort study of the Alternative Nicotine Delivery Systems (ANDS) initiation process among adult cigarette smokers.
Alternative Nicotine Delivery Systems (ANDS) such as e-cigarettes are battery-powered devices that aerosolize nicotine and other substances to simulate smoking without using tobacco. Little is known about the ANDS initiation process among adult smokers. The aims of this research are threefold to: (1) examine how ANDS use affects cigarette use; (2) examine how the immediate environmental and psychosocial contexts of cigarette and ANDS use vary within-and between-participants in general and by menthol preference and race; and, (3) examine participants' 'lived experience' of the subjective perceptions, meaning, influences and utility of cigarette and ANDS use. This study's mixed method, 6-week longitudinal design will produce a detailed description of the ANDS initiation process among adult smokers (N=100). Qualitative and quantitative data collection will include 3 weeks of: (1) ecological momentary assessment of patterns of cigarette/ANDS use, satisfaction, mood and craving; (2) geospatial assessment of participants' environment, including indoor and outdoor cigarette/ANDS norms and rules; (3) in-depth interviews about the meaning and utility of cigarette smoking and ANDS use; and, (4) saliva cotinine and exhaled carbon monoxide (CO) biomarkers. A diverse sample will be recruited with an equal number of menthol and non-menthol cigarette smokers. As the primary independent variable, we will investigate how ANDS use affects cigarette consumption. We will also examine how smoking-related and ANDS-related rules and norms surrounding product use influence cigarette and ANDS product use, and how the subjective effects of ANDS use affect ANDS perceptions, beliefs and use. This study was funded by the National Institute on Drug Abuse of the US National Institutes of Health (1R21DA036472), registered at ClinicalTrials.gov (NCT02261363), and approved by the Chesapeake IRB (Pro00008526). Findings will be disseminated to the scientific and lay community through presentations, reports and scientific publications. NCT02261363; Pre-results.


Delta beta thalassemia and hereditary persistence of fetal hemoglobin.
Delta beta Thalassemia and hereditary persistence of fetal hemoglobin (HPFH) constitute a heterogeneous group of disorders characterized by absent or reduced synthesis of adult hemoglobin (Hb A) and increased synthesis of fetal hemoglobin (Hb F). Coinheritance of these disorders with other beta chain hemoglobinopathies, such as beta thalassemia and the sickle cell (beta s) gene, can result in attenuation of the clinical severity of these hemoglobinopathies owing to the increased Hb F levels. The molecular basis of these disorders is quite heterogeneous and consists of both deletion and nondeletion types of mutations. The characterization of these molecular defects has provided new insights on the structure and function of important regulatory elements that are involved in the normal control of expression of the beta- and gamma-globin genes and in hemoglobin switching.


Metabolic engineering for the production of chitooligosaccharides: advances and perspectives.
Chitin oligosaccharides (CTOs) and its related compounds chitosan oligosaccharides (CSOs), collectively known as chitooligosaccharides (COs), exhibit numerous biological activities in applications in the nutraceutical, cosmetics, agriculture, and pharmaceutical industries. COs are currently produced by acid hydrolysis of chitin or chitosan, or enzymatic techniques with uncontrollable polymerization. Microbial fermentation by recombinant Escherichia coli, as an alternative method for the production of COs, shows new potential because it can produce a well-defined COs mixture and is an environmentally friendly process. In addition, Bacillus subtilis, a nonpathogenic, endotoxin-free, GRAS status bacterium, presents a new opportunity as a platform to produce COs. Here, we review the applications of COs and differences between CTOs and CSOs, summarize the current preparation approaches of COs, and discuss the future research potentials and challenges in the production of well-defined COs in B. subtilis by metabolic engineering.


Validation study of canine urine cortisol measurement with the Immulite 2000 Xpi cortisol immunoassay.
We report here validation of the Immulite 2000 Xpi cortisol immunoassay (Siemens; with kit lot numbers <550) for measurement of urine cortisol in dogs, with characterization of the precision (CV), accuracy (spiking-recovery [SR] bias), and observed total error (TEo = bias + 2CV) across the reportable range. Linearity assessed by simple linear regression was excellent. Imprecision, SR bias, and TEo increased markedly with decreasing urine cortisol concentration. Interlaboratory comparison studies determined range-based (RB) bias and average bias (AB). The 3 biases (SR, RB, and AB) and resulting TEo differed markedly. At 38.6 and 552 nmol/L (1.4 and 20 μg/dL), between-run CVs were 10% and 4.5%, respectively, and TEoRB were ~30% and 20%, respectively, similar to observations in serum in another validation study. These analytical performance parameters should be considered for urine cortisol:creatinine ratio (UCCR) result interpretation, given that, for any hypothetical errorless urine creatinine measurement, the error % on UCCR mirrors the error % on urine cortisol. Importantly, there is no commonly used interpretation threshold for UCCR, given that UCCR varies greatly depending on measurement methods and threshold computation. To date, there is no manufacturer-provided quality control material (QCM) with target values for urine cortisol with an Immulite; for Liquicheck QCM (Bio-Rad), between-run imprecision was ~5% for both QCM levels. Acceptable QC rules are heavily dependent on the desired total allowable error (TEa) for the QCM system, itself limited by the desired clinical TEa.


Real-world unexpected outcomes predict city-level mood states and risk-taking behavior.
Fluctuations in mood states are driven by unpredictable outcomes in daily life but also appear to drive consequential behaviors such as risk-taking. However, our understanding of the relationships between unexpected outcomes, mood, and risk-taking behavior has relied primarily upon constrained and artificial laboratory settings. Here we examine, using naturalistic datasets, how real-world unexpected outcomes predict mood state changes observable at the level of a city, in turn predicting changes in gambling behavior. By analyzing day-to-day mood language extracted from 5.2 million location-specific and public Twitter posts or 'tweets', we examine how real-world 'prediction errors'-local outcomes that deviate positively from expectations-predict day-to-day mood states observable at the level of a city. These mood states in turn predicted increased per-person lottery gambling rates, revealing how interplay between prediction errors, moods, and risky decision-making unfolds in the real world. Our results underscore how social media and naturalistic datasets can uniquely allow us to understand consequential psychological phenomena.


Prenylflavonoids from Glycyrrhiza uralensis and their protein tyrosine phosphatase-1B inhibitory activities.
Two new 2-arylbenzofurans, glycybenzofuran (1) and cyclolicocoumarone (2), together with 10 known flavonoids including licocoumarone (3), glycyrrhisoflavone (4), glisoflavone (5), cycloglycyrrhisoflavone (6), isoliquiritigenin (7), licoflavone A (8), apigenin (9), isokaempferide (10), glycycoumarin (11), and isoglycycoumarin (12), were isolated from the roots of Glycyrrhiza uralensis and their structures were determined by extensive spectroscopic analyses. Compounds 1 and 5 showed significant protein tyrosine phosphatase-1B (PTP1B) inhibitory activity in vitro with the IC50 values of 25.5 and 27.9 microM, respectively. The structure-activity relationship indicated that the presence of prenyl group and ortho-hydroxy group is important for exhibiting the activity. Kinetic analysis indicated that compound 1 inhibits PTP1B by a competitive mode, whereas compound 5 by a mixed mode.


Psychometric Properties of the QoL-ME: A Visual and Personalized Quality of Life Assessment App for People With Severe Mental Health Problems.
Background: Quality of Life (QoL) assessment in people with severe mental health problems may benefit from improved personalization and accessibility. Therefore, an innovative, digital, visual, and personalized QoL assessment app for people with severe mental health problems was recently developed: the QoL-ME. The aim of this study was to evaluate the psychometric quality of the QoL-ME by assessing its reliability, validity, and responsiveness. Methods: To examine the reliability of the QoL-ME, the internal consistency of its subscales was assessed using Cronbach's Alpha. Correlations between the QoL-ME and the MANSA were computed to appraise the construct validity of the QoL-ME. Internal responsiveness was evaluated using the standardized response mean and external responsiveness was investigated using hierarchical regression. Results: Cronbach's Alpha's of the subscales of the QoL-ME ranged between 0.5 and 0.84. In accordance with expectations, the language-based core version of the QoL-ME correlated strongly (r = between 0.55 and 0.76) with the MANSA, whilst the picture-based additional modules of the QoL-ME correlated moderately (r = 0.3) with the MANSA. The standardized response mean was 0.23 and the regression model revealed a coefficient β of -0.01. Conclusions: The QoL-ME has adequate psychometric properties. In comparison with similar pictorial instruments, both the QoL-ME's reliability and validity can be considered as sufficient. The results indicate that the responsiveness of the QoL-ME is insufficient. Additional research is needed to evaluate and potentially modify the instrument to improve its responsiveness.


Cell culture modeling of genotype-directed sensitivity to selective kinase inhibitors: targeting the anaplastic lymphoma kinase (ALK).
Selective kinase inhibitors have emerged as an important class of cancer therapeutics. The clinical success of drugs such as imatinib, erlotinib, and lapatinib, together with findings demonstrating the important relationship between specific tumor genotypes and clinical response to these agents, also has brought to the forefront the concept of "personalized cancer medicine." The potential broader significance of this relationship has been further highlighted in preclinical studies using tumor-derived cell lines as a model system that can faithfully recapitulate the association of specific genotypes with drug sensitivity, suggesting the utility of cancer cell lines to identify novel candidate biomarkers for predicting clinically responsive patient subsets for newly developed anticancer agents. The case of the anaplastic lymphoma kinase (ALK) nicely exemplifies this, and cell line profiling has revealed that ALK mutations present in a subset of anaplastic large cell lymphomas (ALCLs), non-small cell lung cancers (NSCLCs), and neuroblastomas appear to sensitize cancer cells to treatment with selective ALK kinase inhibitors. Such findings suggest that genotype-based stratification of cancer patients for treatment with selective kinase inhibitors, even across multiple diseases of distinct tissue origin, may be essential for maximizing their clinical benefit.


Pairing symmetry conversion by spin-active interfaces in magnetic normal-metal-superconductor junctions.
We study the proximity-induced superconducting correlations in a normal metal connected to a superconductor when the interface between them is spin active and the normal metal is ballistic or diffusive. Remarkably, for any interface spin polarization there is a critical interface resistance, above which the conventional even-frequency proximity component vanishes completely at the chemical potential, while the odd-frequency component remains finite. We propose a way to unambiguously observe the odd-frequency component.


Overexpression of miR-34c inhibits high glucose-induced apoptosis in podocytes by targeting Notch signaling pathways.
Recent findings have shown that microRNAs play critical roles in the pathogenesis of diabetic nephropathy. miR-34c has been found to inhibit fibrosis and the epithelial-mesenchymal transition of kidney cells. However, the role of miR-34c in diabetic nephropathy has not been well studied. The current study was designed to investigate the role and potential underlying mechanism of miR-34c in regulating diabetic nephropathy. After treating podocytes with high glucose (HG) in vitro, we found that miR-34c was downregulated and that overexpression of miR-34c inhibited HG-induced podocyte apoptosis. The direct interaction between miR-34c and the 3'-untranslated region (UTR) of Notch1 and Jagged1 was validated by dual-luciferase reporter assay. Moreover, Notch1 and Jagged1 as putative targets of miR-34c were downregulated by miR-34c overexpression in HG-treated podocytes. Overexpression of miR-34c inhibited HG-induced Notch signaling pathway activation, as indicated by decreased expression of the Notch intracellular domain (NICD) and downstream genes including Hes1 and Hey1. Furthermore, miR-34c overexpression increased the expression of the anti-apoptotic gene Bcl-2, and decreased the expression of the pro-apoptotic protein Bax and cleaved Caspase-3. Additionally, the phosphorylation of p53 was also downregulated by miR-34c overexpression. Taken together, our findings suggest that miR-34c overexpression inhibits the Notch signaling pathway by targeting Notch1 and Jaggged1 in HG-treated podocytes, representing a novel and potential therapeutic target for the treatment of diabetic nephropathy.


Dermatological manifestation can be an early sign in Covid-19: Report of three cases with a novel manifestation masquerading Steven Johnson syndrome.
Various dermatological manifestations have been observed in patients with Coronavirus disease (COVID-19) infection ranging from maculopapular rashes, urticaria, chickenpox-type lesions, chilblain-like, distal-limb ischemia, and livedo racemosa. While most of these cutaneous findings are self-resolving, they may aid in the timely diagnosis of this infection. We are reporting three patients presenting with dermatological features resembling (i) varicella zoster, (ii) herpes labialis, and (iii) Steven Johnson Syndrome (SJS) who were subsequently diagnosed with Covid-19 infection. The skin lesions disappeared after successful treatment of Covid-19.


Ethical and Practical Concerns about IRB Restrictions on the Use of Research Data.
In response to researcher noncompliance with ethical and regulatory provisions governing research with humans, protocol deviations, and unanticipated problems with research, institutional review boards (IRBs) or institutions sometimes impose restrictions on the use of research data, although specific cases in which this happens are unlikely to be known publicly. We review IRB policies at top research institutions in the United States about restrictions on the use of research data and describe potential reasons for restricting the use of such data in the context of ensuring compliance with human subjects research standards. We also discuss ethical considerations related to restricting the use of research data and argue that IRBs have limited regulatory authority to take such actions. Finally, we offer recommendations regarding decision-making about restricting the use of research data and call for additional guidance in this area.


[When to look for cancer in case of unintentional weight loss ?]
The definition of unintentional weight loss (UWL) is heterogeneous and most commonly used as a UWL of >5% over the past 6 months. The differential diagnosis of UWL is very broad and encompasses non-medical causes, somatic illnesses, and psychiatric conditions. One of the feared diagnoses remains the presence of an underlying cancer. It is observed that UWL is more associated with certain types of cancer, in particular digestive. The primary workup for UWL should begin with a history and a detailed physical examination searching for associated symptoms or signs. The age, sex and smoking status are factors to be considered in particular. Management of UWL does not meet established recommendations and should be guided by relevant signs and symptoms. Future studies are necessary, in particular to clarify the place of imaging in the diagnostic process.


'Prolonged coasting': an effective method for preventing severe ovarian hyperstimulation syndrome in patients undergoing in-vitro fertilization.
Over a 4 year period ending 1 January 1995, 51 women scheduled for in-vitro fertilization (IVF) and embryo transfer were inadvertently severely overstimulated with menotrophins, as evidenced by the development of > 29 ovarian follicles in association with peak plasma oestradiol concentrations of > 6000 pg/ml. Accordingly, these women were at great risk of developing life-endangering complications associated with severe ovarian hyperstimulation syndrome (OHSS). Treatment involved withholding the administration of both menotrophins and human chorionic gonadotrophin for a number of days, while continuing gonadotrophin-releasing hormone agonist until the plasma oestradiol concentration fell to < 3000 pg/ml ('prolonged coasting'). The mean number of oocytes retrieved was 21.0, while the mean number of embryos transferred per procedure was 5.4. There were 21 clinical pregnancies (i.e. pregnancy rate of 41% per oocyte retrieval), 19 of which resulted in live births (i.e. a live birth rate of 37% per oocyte retrieval). Two pregnancies miscarried and there were four multiple gestations (three sets of twins and one set of triplets). None of the women developed severe OHSS. Prolonged coasting is an effective method of preventing the occurrence of severe OHSS without necessitating the cancellation of the IVF cycle or compromising success rates.


Preference and ability to perform blood-versus oral-fluid-based HIV self-testing in adolescents and young adults in Bangkok.
Introduction: Adolescents and young adults (AYA) have limited access to HIV screening tests despite the risk of acquiring HIV infection. This study aims to understand AYA preferences and their ability to perform HIV self-tests (HIVST).Methods: A cross-sectional study looked at AYA preferences when offered a choice between blood-based (INSTI®) and oral fluid-based (OraQuick®) HIVST. Adolescents and young adult participants between 18 and 24 years-old who report inconsistent condom use or had a history of sexually transmitted diseases were enrolled. Participants were offered a choice between blood-based and/or oral fluid-based HIVSTs with explanations of the differences between two types. Then, written and short video instructions according to the chosen type were given before participants performed a test. The study seeks to understand test preference, ability to perform and interpret test results.Results: From March to April 2021, 87 AYA were enrolled with a median age of 20 years (interquartile range (IQR) 18-22). Of the participants, 54 (62.1%) were men who have sex with men (MSM), 25 (28.7%) were cisgender men or women and 8 (9.2%) were transgender women (TGW). There were 37 (42.5%) first-time HIV testers and 32 (36.8%) HIV PrEP users. There were 57 participants (65.6%, 95% CI 54.6%-75.4%) that preferred blood-based HIVSTs. Reasons for preferring blood-based testing were the rapid results (77.2%) and higher accuracy (66.7%). The ability to perform and interpret HIVST results were 89.5% and 98% among INSTI users and 93.3% and 100.0% among OraQuick® users. None was HIV-positive. Moreover, 13.8% of the participants initiated same-day pre-exposure prophylaxis (PrEP).Conclusions: Thai AYA preferred blood-based over oral fluid-based HIVSTs. Most AYAs were able to perform the HIVSTs and interpret results. Supervision and post-test counselling of HIVSTs should be implemented to ensure AYA gain benefits from HIVSTs.


Performance evaluation of biofil toilet waste digester technologies in Ghana: the efficacy of effluent treatment options.
The study was carried out to assess the efficacy of a standard Biofil toilet digester with regard to its effluent quality and to evaluate the performance of new effluent polishing options being developed by BiofilCom. Influent and effluent were collected from 18 standard Biofil digesters connected to full-flush toilets. Effluent from five pilot installations with improved effluent polishing options were also taken for analyses. Ten other Biofil installations were selected to assess the impact of digester effluent discharge on the surrounding soil. Pollutant concentrations in the Biofil effluent exceeded both Ghana EPA and WHO standards for discharge though pollutant removal efficiencies were high: 84% for biochemical oxygen demand, 86.1% for chemical oxygen demand and 82.4% for total suspended solids. Escherichia coli and total coliform levels were significantly reduced by 63% and 95.6%, respectively, and nutrients were the least removed from effluents. Generally, effluents from the majority of the pilot polishing options met most of the discharge standards. E. coli were present in the soil at all study sites, except one. Biofil digester effluent is discharged subsurface but comparing their effluent quality with standards for discharge into water courses is relevant especially in areas of frequent flooding and high water tables.


Predator-prey model with disease infection in both populations.
A predator-prey model with disease infection in both populations is proposed to account for the possibility of a contagious disease crossing species barrier from prey to predator. We obtain several threshold parameters from local analysis of various equilibria of the proposed system as well as coupled conditions on these threshold parameters which determine the stability of these equilibria. One of the coupled conditions, in the form of an ecological threshold number for the predator-prey ecosystem, always determines the coexistence of predators and prey. The other condition, in the form of a disease basic reproduction number, dictates whether the disease will become endemic in the ecosystem. Under one combination of these coupled conditions, a highly infectious disease could drive the predators to extinction when predators and prey would have coexisted without the disease. For another combination of the conditions, the predation of the more vulnerable infected prey could cause the disease to be eradicated in the ecosystem, in some case even approaching a disease-free periodic solution, when the disease would have otherwise remained endemic in the prey population in the absence of predation. This indicates that the presence of disease in both predators and prey could either promote or impair coexistence, and its precise impact needs to be explored specifically in each particular situation. By considering disease infection in both populations, our model also yields more complex dynamics, allowing for the possibility of bistability and periodic oscillation, in either disease-free or endemic states, in the ecosystem for which the conditions are obtained analytically and with the help of numerical simulations.


Agrobacterium-mediated transient expression via root absorption in flowering Chinese cabbage.
Because most transient transformation techniques are inadequate for functional genomics research in roots, we aimed to develop a simple and efficient Agrobacterium-mediated transient transformation system that utilized root absorption for research in flowering Chinese cabbage. Both semi-quantitative and fluorescent quantitative RT-PCR confirmed that the target gene BcAMT1;3 was more highly expressed in plants that were infected with the transformed Agrobacterium strain (EHA105-p35S-BcAMT1;3) than in control plants that were infected with the control strain (EHA105-p35S). Furthermore, GUS staining analysis conformed the availability of this transient transformation system. In addition, we found that the highest transformation efficiency was achieved using an Agrobacterium cell density of OD600 = 0.3 for 3-6 h, without hyperosmotic pretreatment, and under these conditions, the peak transformation efficiency was observed at 2 and 4 d after infection. The transformation method developed by the present study is simple and convenient, since no special equipment is required, and since the method causes no damage, the plants can be used for subsequent experiments.


Stimulus-Responsive Plasmonic Chiral Signals of Gold Nanorods Organized on DNA Origami.
In response to environmental variations, living cells need to arrange the conformational changes of macromolecules to achieve the specific biofunctions. Inspired by natural molecular machines, artificial macromolecular assemblies with controllable nanostructures and environmentally responsive functions can be designed. By assembling macromolecular nanostructures with noble metal nanoparticles, environmental information could be significantly amplified and modulated. However, manufacturing dynamic plasmonic nanostructures that are efficiently responsive to different stimuli is still a challenging task. Here we demonstrate a stimulus-responsive plasmonic nanosystem based on DNA origami-organized gold nanorods (GNRs). L-shaped GNR dimers were assembled on rhombus-shaped DNA origami templates. The geometry and chiral signals of the GNR nanoarchitectures respond to multiple stimuli, including glutathione reduction, restriction enzyme action, pH change, or photoirradiation. While the glutathione reduction or restriction enzyme caused irreversible changes in the plasmonic circular dichroism (CD) signals, both pH and light irradiation triggered reversible changes in the plasmonic CD. Our system transduces external stimuli into conformational changes and circular dichroism responses in near-infrared (NIR) wavelengths. By this approach, programmable optical reporters for essential biological signals can be fabricated.


Retention equilibrium and mass transfer characteristics in reversed-phase liquid chromatography using methanol-water mixtures.
Pulse response experiments (i.e., elution chromatography) were made in reversed-phase liquid chromatography (RPLC) using a C18 silica gel column and methanol-water mixtures of different compositions (phi). The moment analysis of the elution peak profiles measured in the RPLC system provided some items of information about four parameters characterizing the retention equilibrium and the mass transfer kinetics in the column, i.e., adsorption equilibrium constant, isosteric heat of adsorption, surface diffusion coefficient and activation energy of surface diffusion. Characteristics of the chromatographic behavior were studied by analyzing the dependence of the four parameters on phi and the correlation between them. It was found that surface diffusion was one of the important processes of molecular migration having a significant contribution to the mass transfer kinetics in the column. Both the adsorption equilibrium constant and the surface diffusion coefficient varied depending on phi. The direction of their changes was approximately opposite, suggesting that the mass transfer in the manner of surface diffusion was restricted owing to the retention of the sample molecules on the stationary phase.


Angiotensin converting enzyme response to hypoxia in man: its role in altitude acclimatization.
The response of serum angiotensin converting enzyme (ACE) activity to three grades of hypoxia was studied in two groups of human subjects. Hypoxic gas mixtures having oxygen concentrations of 14, 12.6 and 10.4% were breathed successively for a period of 10 min at each concentration. Venous blood was sampled at the end of each of the three periods and arterial oxygen saturation was recorded throughout the experiment. The subjects were selected as being 'good' or 'poor' acclimatizers according to their history of acute mountain sickness. There were five subjects in each group. Hypoxia resulted in a reduction in ACE activity in both groups, the reduction being linear with respect to arterial oxygen saturation. The reduction in ACE activity was greater in the good acclimatizer group as shown by a significantly greater slope of the response line of ACE activity to arterial oxygen saturation. The significance of this finding in relation to the mechanism underlying acute mountain sickness is discussed.


Pharmacological characterization of cloned chicken neuropeptide Y receptors Y1 and Y5.
The neuropeptide Y (NPY) receptor subtypes Y1 and Y5 are involved in the regulation of feeding and several other physiological functions in mammals. To increase our understanding of the origin and mechanisms of the complex NPY system, we report here the cloning and pharmacological characterization of receptors Y1 and Y5 in the first non-mammal, chicken (Gallus gallus). The receptors display 80-83% and 64-72% amino acid sequence identity, respectively, with their mammalian orthologues. The three endogenous ligands NPY, peptide YY (PYY) and pancreatic polypeptide (PP) have similar affinities as in mammals, i.e. NPY and PYY have subnanomolar affinity for both receptors whereas chicken PP bound with nanomolar affinity to Y5 but not to Y1. A notable difference to mammalian receptor subtypes is that the Y1 antagonist SR120819A does not bind chicken Y1, whereas BIBP3226 does. The Y5 antagonist CGP71863A binds to the chicken Y5 receptor. Anatomically, both Y1 and Y5 have high mRNA expression levels in the infundibular nucleus which is the homologous structure of the hypothalamic arcuate nucleus in mammals. These results suggest that some of the selective Y1 and Y5 antagonists developed in mammals can be used to study appetite regulation in chicken.


Amantadine resistance in relation to the evolution of influenza A(H3N2) viruses in Iran.
The aminoadamantanes, amantadine and rimantadine, have been used to prevent and treat influenza A virus infections for many years. Several reports have shown an increased level of resistance to these drugs, particularly among influenza A(H3N2) subtype viruses, during recent years. We observed an increase in amantadine resistance, due to a Ser31Asn mutation in the M2 channel protein, among A(H3N2) viruses circulating in Iran during 2005-2007. Sequence analyses of the haemagglutinin and neuraminidase genes as well as the M gene of these viruses revealed that the emergence of resistance was in general consistent with the progressive worldwide evolution of H3N2 viruses.


Different therapeutic effects of distinct KISS1 fragments on breast cancer in vitro and in vivo.
Breast cancer is the most frequently diagnosed cancer in women. In these studies, a metastasis suppressor gene, KISS1 and its truncated fragment, were overexpressed in the breast cancer cell line MDA-MB-231. In addition, KISS1 expression was downregulated in MDA-MB-157 cell line using a KISS1-specific siRNA. The effects of KISS1 on breast cancer cells both in vivo and in vitro were then identified. Our results indicate that KISS1 can induce apoptosis and inhibit mobility of breast cancer cells. Moreover, the expression of KISS1 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher compared to that of mice bearing tumors that did not express KISS1. We also confirm that KISS1 could decrease the number of circulating tumor cells (CTCs). The plasma levels of metastin and the number of CTCs were significantly positively correlated. Furthermore, we found that KISS1 can inactivate p-MEK and p-ERK. Overall, these studies demonstrate the antitumor activity of KISS1 in the breast cancer cell lines and provide insight into relevant mechanisms that may lead to novel treatments for breast cancer.


Empirical comparison of web-based antimicrobial peptide prediction tools.
Antimicrobial peptides (AMPs) are innate immune molecules that exhibit activities against a range of microbes, including bacteria, fungi, viruses and protozoa. Recent increases in microbial resistance against current drugs has led to a concomitant increase in the need for novel antimicrobial agents. Over the last decade, a number of AMP prediction tools have been designed and made freely available online. These AMP prediction tools show potential to discriminate AMPs from non-AMPs, but the relative quality of the predictions produced by the various tools is difficult to quantify. We compiled two sets of AMP and non-AMP peptides, separated into three categories-antimicrobial, antibacterial and bacteriocins. Using these benchmark data sets, we carried out a systematic evaluation of ten publicly available AMP prediction methods. Among the six general AMP prediction tools-ADAM, CAMPR3(RF), CAMPR3(SVM), MLAMP, DBAASP and MLAMP-we find that CAMPR3(RF) provides a statistically significant improvement in performance, as measured by the area under the receiver operating characteristic (ROC) curve, relative to the other five methods. Surprisingly, for antibacterial prediction, the original AntiBP method significantly outperforms its successor, AntiBP2 based on one benchmark dataset. The two bacteriocin prediction tools, BAGEL3 and BACTIBASE, both provide very good performance and BAGEL3 outperforms its predecessor, BACTIBASE, on the larger of the two benchmarks. firstname.lastname@example.com or email@example.com. Supplementary data are available at Bioinformatics online.


Familial moyamoya disease associated with Graves' disease in a mother and daughter. Two case reports.
A mother and daughter presented with a rare combination of moyamoya disease and Graves' disease. A 19-year-old woman experienced numbness in her right hand due to cerebral infarction during therapy for Graves' disease. Cerebral angiography demonstrated stenoses of the bilateral internal carotid arteries and net-like abnormal collateral vessels indicative of moyamoya disease. Her 52-year-old mother with a history of Graves' disease presented with left hemiparesis due to intracerebral hemorrhage; she recovered after hematoma evacuation. Postoperative angiography demonstrated stenoses of the bilateral internal carotid arteries and net-like abnormal collateral vessels indicative of moyamoya disease. Another otherwise healthy daughter manifested slight stenosis of the left internal carotid artery. After cerebral revascularization surgery the patients were able to return to their normal daily lives. These familial cases of moyamoya disease and Graves' disease indicate hereditary involvement in both diseases.


Effects of water intake on the responses of haemorheological variables to resistance exercise.
To examine the effects of drinking an amount of water equal to weight loss on the responses of blood rheological variables, eleven healthy male subjects performed three resistance exercise trials. The aim of the first session was to determine the amount of weight loss following a resistance exercise trial at 80% of one repletion maximum (1RM). In the second and third sessions subjects performed the same resistance exercise protocol without and with drinking an amount of water equal to that recorded for body weight loss. Three venous blood samples were taken before exercise, immediately after exercise, and at the end of 30-min recovery and were analysed for haematocrit (Hct), haemoglobin (Hb), blood cells count and the main determinant of blood rheology. Haematocrit, plasma viscosity, fibrinogen, albumin, and total protein were significantly increased in response to resistance exercise and returned to pre-exercise level following 30-min of recovery. The changes in blood rheological variables in response to resistance exercise occurred similarly in both control and water trials with no significant difference being observed between trials. Plasma volume loss through sweating and respiratory tract during resistance exercise could have contributed to the decrease in plasma volume, though, this contribution was negligible. Therefore, it is concluded that the increases in blood rheological variables in response to resistance exercise are mainly due to plasma shifts from intravascular space to extravascular spaces rather than plasma volume loss through sweating and respiratory tract.


Amino acid sequence of an intrinsic inhibitor of mitochondrial ATPase from yeast.
The amino acid sequence of an intrinsic inhibitor of mitochondrial ATPase isolated from yeast was completed by using solid-phase sequencing and conventional procedures. The inhibitor was found to be composed of 63 amino acid residues, to lack tryptophan, cysteine, and tyrosine, and to have a molecular weight of about 7,383. The inhibitor was characterized as a basic protein with 16 basic and 13 acidic amino acid residues, and several clusters of basic residues were noted. Some comments are made on the hydrophobic amino acids and the presence of repeated sequences.


SNAP-25 and synaptotagmin involvement in the final Ca(2+)-dependent triggering of neurotransmitter exocytosis.
In neurons, depolarization induces Ca2+ influx leading to fusion of synaptic vesicles docked at the active zone for neurotransmitter release. While a number of proteins have now been identified and postulated to participate in the assembly and subsequent disengagement of a vesicle docking complex for fusion, the mechanism that ultimately triggers neuroexocytosis remains elusive. Using a cell-free, lysed synaptosomal membrane preparation, we show that Ca2+ alone is sufficient to trigger secretion of glutamate and furthermore that Ca(2+)-signaled exocytosis is effectively blocked by antibodies and peptides to SNAP-25, a key constituent of the vesicle docking complex. In addition, Ca2+ inhibits the ability of synaptotagmin, a synaptic vesicle protein proposed as a calcium sensor and triggering device, to associate with this docking complex. These results support a model in which Ca(2+)-dependent triggering of neurotransmission at central synapses acts after ATP-dependent potentiation of the docking-fusion complex for membrane fusion.


United States geographic bacteria susceptibility patterns. 1995 ASCP Susceptibility Testing Group.
Drug resistance in microbial pathogens once considered "conquered" is now recognized as a major emerging health-care issue in many parts of the United States. There is a very real possibility this problem will continue to spread throughout our country, heralding the beginning of the "post-antibiotic era." A significant issue in dealing with this rapidly developing problem is a lack of national data presented in a reasonably rapid manner that highlights the geographic distribution of increasing resistance to antimicrobial agents. In the Fall of 1994, the Microbiology Council of the American Society of Clinical Pathologists (ASCP) adopted a proposal to present geographic susceptibility and resistance patterns for selected pathogens on at least an annual basis. The American Journal of Clinical Pathology subsequently agreed to publish this information as a service to its readers. The following report is the first of these annual surveys. All laboratories submitting this information expended considerable effort to voluntarily compile the information. These data are sent to the AJCP in the spirit that all our cooperation will be needed to begin developing solutions for combating the problem of growing drug resistance in microbial pathogens. All were enthusiastic participants in this project and are to be commended, along with the ASCP, for supporting this project! We plan to continue this annual survey as long as the interest continues, and the need persists. It is clear the future of infectious diseases and clinical microbiology is filled with challenge. Only time will tell if we are able and ready to meet this new threat to our medical well-being with cooperation, energy, sufficient resources, and creative solutions.


Study of endometrial tissue in dysfunctional uterine bleeding.
Dysfunctional uterine bleeding (DUB) is defined as heavy and or irregular menstruation in the absence of recognizable pelvic pathology, pregnancy or general bleeding disorder. Hyperplastic endometrium is abnormal histology finding found in DUB. Out of three type of hyperplasia, atypical type is associated with co-existent ca endometrium and the chance of progression to ca endometrium is very high. Thus this study was conducted to see the incidence of hyperplasia of endometrium in cases of DUB and to see the risk factors for endometrial hyperplasia. It was a prospective study carried out in span of two years (2010 JULY- 2013 Jan) in Nepal Medical College and Teaching Hospital. Hundred cases DUB who under went D&C or hysterectomy were included to study the age range, the relation of parity, patient symptom, contraceptive method and medical disease with the type of endometrial histology. It was found that DUB was common in perimenopusal age (49%) and the incidence increase with the increase of parity. Abnormal endometrial finding (hyperplasia) was found in 31% of the cases. Atypical and complex hyperplasia were associated with irregular menstruation and one third of the hyperplastic patient had hypertension (32.26%). Thus perimenopausal age, irregular menstruation and hypertension are risk factors for hyperplasia. So it is mandatory to do endometrial sampling in cases of perimenopausal age with irregular menstruation withor without hypertension.


Classifying vulnerability to sleep deprivation using baseline measures of psychomotor vigilance.
To identify measures derived from baseline psychomotor vigilance task (PVT) performance that can reliably predict vulnerability to sleep deprivation. Subjects underwent total sleep deprivation and completed a 10-min PVT every 1-2 h in a controlled laboratory setting. Participants were categorized as vulnerable or resistant to sleep deprivation, based on a median split of lapses that occurred following sleep deprivation. Standard reaction time, drift diffusion model (DDM), and wavelet metrics were derived from PVT response times collected at baseline. A support vector machine model that incorporated maximum relevance and minimum redundancy feature selection and wrapper-based heuristics was used to classify subjects as vulnerable or resistant using rested data. Two academic sleep laboratories. Independent samples of 135 (69 women, age 18 to 25 y), and 45 (3 women, age 22 to 32 y) healthy adults. In both datasets, DDM measures, number of consecutive reaction times that differ by more than 250 ms, and two wavelet features were selected by the model as features predictive of vulnerability to sleep deprivation. Using the best set of features selected in each dataset, classification accuracy was 77% and 82% using fivefold stratified cross-validation, respectively. In both datasets, DDM measures, number of consecutive reaction times that differ by more than 250 ms, and two wavelet features were selected by the model as features predictive of vulnerability to sleep deprivation. Using the best set of features selected in each dataset, classification accuracy was 77% and 82% using fivefold stratified cross-validation, respectively. Despite differences in experimental conditions across studies, drift diffusion model parameters associated reliably with individual differences in performance during total sleep deprivation. These results demonstrate the utility of drift diffusion modeling of baseline performance in estimating vulnerability to psychomotor vigilance decline following sleep deprivation.


Why does three times per week hemodialysis provide inadequate dialysis for children?
The duration of chronic conventional dialysis is a risk factor in children, both in terms of growth retardation and cardiovascular morbidity and mortality. Therefore, we need to develop alternative strategies, such as preemptive kidney transplantation and/or more intensive dialysis prescription. Indeed, conventional hemodialysis could be improved in all children by the use of high permeable membrane and ultrapure dialysis fluids (having very low endotoxin levels); by the addition of a convective dialysis dose to the urea diffusion dialysis dose (Kt/Vurea), i.e., hemodiafiltration; moreover, by the preservation of cardiovascular morphology and function (optimized blood pressure control); and also by the prescription of more frequent/longer dialysis sessions.


Effect of Dispersed Reinforcement on Ultrasonic Pulse Velocity in Stabilized Soil.
One of the fundamental techniques for road subgrades is soil stabilization. Considering the high emission of carbon dioxide during the production of binders, novel techniques to reduce the binder are being studied. Thus, we investigated dispersed reinforcement in stabilized soils. A study was conducted to determine the ultrasonic pulse velocity in nine mixtures of soil, cement, and polypropylene fibers and then correlate the results with other destructive tests. The results show a decrease in wave velocity in mixes with fiber addition by up to 18.5%. The result is dependent on the curing time and whether the samples were stored in a water tank. Immersion in water increases the obtained results by about 6.3%. Based on the analysis, for mixtures with fibers, boundary velocities of waves above which lower values of modulus of elasticity were obtained were determined. Depending on the mix and the module analyzed, the limits range from 2194 m/s to 2498 m/s.


Mortality and cancer incidence in carriers of constitutional t(11;22)(q23;q11) translocations: A prospective study.
The constitutional t(11;22)(q23;q11) translocation is the only recurrent non-Robertsonian translocation known in humans. Carriers are phenotypically normal and are usually referred for cytogenetic testing because of multiple miscarriages, infertility, or having aneuploidy in offspring. A breast cancer predisposition has been suggested, but previous studies have been small and had methodological shortcomings. We therefore conducted a long-term prospective study of cancer and mortality risk in carriers. We followed 65 male and 101 female carriers of t(11;22)(q23;q11) diagnosed in cytogenetic laboratories in Britain during 1976-2005 for cancer and deaths for an average of 21.4 years per subject. Standardised mortality (SMR) and incidence (SIR) ratios were calculated comparing the numbers of observed events with those expected from national age-, sex-, country- and calendar-period-specific population rates. Cancer incidence was borderline significantly raised for cancer overall (SIR = 1.56, 95% CI: 0.98-2.36, n = 22), and significantly raised for invasive breast cancer (SIR = 2.74, 95% CI: 1.18-5.40, n = 8) and in situ breast cancer (SIR = 13.0, 95% CI: 3.55-33.4, n = 4). Breast cancer risks were particularly increased at ages <50 (SIR = 4.37, 95% CI: 1.42-10.2 for invasive, SIR = 22.8, 95% CI: 2.76-82.5 for in situ). Mortality was borderline significantly raised for breast cancer (SMR = 4.82, 95% CI: 0.99-14.1) but not significantly raised for other cancers or causes. Individuals diagnosed with t(11;22)(q23;q11) appear to be at several-fold increased breast cancer risk, with the greatest risks at premenopausal ages. Further research is required to understand the genetic mechanism involving 11q23 and 22q11 and there may be a need for enhanced breast cancer surveillance among female carriers.


Evaluation of kangaroo pericardium as an alternative substitute for reconstructive cardiac surgery.
Bioprosthetic materials (human, bovine and porcine) are used in various cardio-thoracic repair and replacement procedures because of excellent performance and low thrombogenicity. These bioprosthetic substitutes fail due to degeneration and calcification. This study examines the morphology, tensile properties and calcification potential of kangaroo pericardium in vitro and in vivo. Bovine (control tissue) and kangaroo pericardium, fixed in 0.625% buffered glutaraldehyde, were examined by light and scanning electron microscopy. A standard method was used for biaxial testing. Pericardial strips (10 x 5 mm) were implanted subcutaneously into male Wistar rats and retrieved after 4, 6 and 8 weeks and examined by Von Kossa's stain technique and atomic absorption spectrophotometry. Histology revealed serosa and fibrosa cell layers in both tissues. Electron microscopy showed a densely arranged collagen matrix in kangaroo pericardium. Kangaroo pericardium calcified significantly less than bovine pericardium at 4 weeks (0.80+/-0.28 versus 21.60+/-4.80 microg/mg) at 6 weeks (0.48+/-0.08 versus 32.80+/-14.4 microg/mg) and at 8 weeks (2.40+/-1.20 versus 30.40+/-17.20 microg/mg), respectively. Kangaroo pericardium has a densely arranged collagen matrix with a higher extensibility and significantly lower calcification potential. Therefore, kangaroo pericardium could be used as an alternative substitute in cardiac surgery because of its low calcification potential.


[Chlamydial infection in mass abortions in goats].
Etiologic and clinical-and-epizootiologic studies were carried out of a chlamydial infection in goat flocks where abortions took place on a mass scale. Discovered were two foci of chlamydial abortion. Two strains of Chlamydia psittaci were isolated from aborted fetuses and from placentas on two farms. The strains were identified both antigenically and morphologically. The serologic investigation of a total of 167 goats on 6 farms with abortions revealed that in the course of two enzootics as many as 93.67 per cent of the goats that miscarried had complement-fixing titers ranging from 1:32 to 1:1024, the average geometric titer being 84. In the contacts and the goats that gave birth normally the average geometric titers were 11.3 and 9.8, respectively. In four of the enzootics with abortions 82.14 per cent of the goats were serologically negative, and the average geometric titer was less than 2.


Deposition of mercury species in the Ny-Alesund area (79 degrees N) and their transfer during snowmelt.
Arctic snowpacks are often considered as temporary reservoirs for atmospheric mercury (Hg) deposited during springtime deposition events (AMDEs). The fate of deposited species is of utmost importance because melt leads to the transfer of contaminants to snowmelt-fed ecosystems. Here, we examined the deposition, fate, and transfer of mercury species (total Hg (THg) and methylmercury (MeHg)) in an arctic environment from the beginning of mass deposition of Hg during AMDEs to the full melt of the snow. Following these events, important amounts of THg were deposited onto the snow surface with concentrations reaching 373 ng.L(-1) and estimated deposition fluxes of 200-2160 ng.m(-2). Most of the deposited Hg was re-emitted to the atmosphere via photochemical reactions. However, a fraction remained stored in the snow and we estimated that the spring melt contributed to an input of 1.5-3.6 kg.year(-1) of THg to the fjord (i.e., 8-21% of the fjord's THg content). A monitoring of MeHg in snow using a new technique (DGT sensors) is also presented.


Multiple-dose activated charcoal in an accidental vancomycin overdose.
Multiple-dose activated charcoal may enhance the enterocapillary clearance of vancomycin. A 17-day-old female neonate born with congenital meningomyelocele and Arnold-Chiari malformation was iatrogenically overdosed with a 500 mg intravenous bolus of vancomycin during a shunt operation. The Red Man's Syndrome developed within minutes, characterized by sudden hypotension, skin rash and cyanosis. Serum vancomycin level at one hour after the injection was 165.7 micrograms/mL, as measured by an enzyme immunoassay method (EMIT). Multiple dose activated charcoal, 1 g/kg, was first given five hours after injection, and continued every four hours for 12 doses. The half-life of vancomycin during charcoal administration was calculated to be 9.4 h or less than the reported 13.4-33.7 h half-life in normal neonates. The neonate's renal function tests and brainstem auditory responses remained normal. Gastrointestinal dialysis with multiple-dose activated charcoal without cathartics appeared to shorten the elimination half-life of vancomycin.


How to estimate multislice CT effective dose more correctly.
The purpose of this paper is to provide data concerning differences in multislice CT effective dose estimation when using various methods and techniques, determine the reasons for these differences, and submit proposals for improving the estimation accuracy. All the experiments (chest and head exam settings) were conducted using 64-slice CT scanners from various manufacturers. Effective dose estimates have been obtained on the basis of the conventional dose-length product method, absorbed dose distribution curves, and using anthropomorphic phantoms with thermoluminescent dosimeters as a model method. Using the conventional dose-length product method leads to underestimation of effective doses (approximately 16 and 19% for head and chest studies, respectively, on average for all scanners) due to partly neglecting scattered in-patient radiation. Additional differences in dose estimates occur when using the "new" ICRP 103 instead of the "old" ICRP 60 Publication recommendations (13% for chest and 23% for head studies on average). It seems reasonable to calibrate scanners with weighted CT dose index values taking into account complete scattered radiation effects. Dose conversion factors for different studies and patient age must be recalculated in conformity with ICRP Publication 103 recommendations. With implementation of the presented proposals, the discrepancy in effective dose evaluation will not exceed a few percent as compared to anthropomorphic phantom measurements.


FPL 64176 modification of Ca(V)1.2 L-type calcium channels: dissociation of effects on ionic current and gating current.
FPL 64176 (FPL) is a nondihydropyridine compound that dramatically increases macroscopic inward current through L-type calcium channels and slows activation and deactivation. To understand the mechanism by which channel behavior is altered, we compared the effects of the drug on the kinetics and voltage dependence of ionic currents and gating currents. Currents from a homogeneous population of channels were obtained using cloned rabbit Ca(V)1.2 (alpha1C, cardiac L-type) channels stably expressed in baby hamster kidney cells together with beta1a and alpha2delta1 subunits. We found a striking dissociation between effects of FPL on ionic currents, which were modified strongly, and on gating currents, which were not detectably altered. Inward ionic currents were enhanced approximately 5-fold for a voltage step from -90 mV to +10 mV. Kinetics of activation and deactivation were slowed dramatically at most voltages. Curiously, however, at very hyperpolarized voltages (< -250 mV), deactivation was actually faster in FPL than in control. Gating currents were measured using a variety of inorganic ions to block ionic current and also without blockers, by recording gating current at the reversal potential for ionic current (+50 mV). Despite the slowed kinetics of ionic currents, FPL had no discernible effect on the fundamental movements of gating charge that drive channel gating. Instead, FPL somehow affects the coupling of charge movement to opening and closing of the pore. An intriguing possibility is that the drug causes an inactivated state to become conducting without otherwise affecting gating transitions.


Clinical relevance of pharmacokinetic and pharmacodynamic properties of edoxaban when treating patients with atrial fibrillation and heart failure.
Atrial fibrillation (AF) is an independent risk factor for stroke. It is most prevalent in the elderly and frequently coexists with heart failure (HF). The joint occurrence of AF and HF further worsens prognosis. The prevention of thromboembolism is crucial in the management of AF. In recent years, new oral anticoagulants (NOACs) have been licensed for the prevention of stroke and systemic embolism in patients with AF. Areas covered: This article reviews the key published studies on the pharmacology, clinical efficacy and safety of edoxaban, the latest NOAC to receive approval for the AF indication. This potent and selective inhibitor of factor Xa shows predictable pharmacokinetic and pharmacodynamic profiles. Its efficacy and safety have been demonstrated in the pivotal, phase III, warfarin-controlled ENGAGE AF-TIMI 48 trial in 21,105 AF patients. Expert opinion: NOACs will likely improve the management of AF, with or without HF. Edoxaban has a favorable pharmacokinetic profile that supports its use in special patient populations, including patients aged ≥75 years, with HF, renal impairment, poor adherence, and on polypharmacy. Proven strategies of edoxaban dose-reduction for optimal use in the presence of moderate renal impairment, and/or use of strong P-gp inhibitors are available.


Assessing patient safety culture of internal medicine house staff in an academic teaching hospital.
Patient safety culture (PSC) examines how individuals perceive an organization's commitment and proficiency in health and safety management. The primary objective of this study was to assess hospital PSC from the perspective of internal medicine house staff, and to compare the results by postgraduate year (PGY) of training and to national hospital benchmark data. The authors modified and used a version of the Hospital Survey on Patient Safety Culture (HSOPSC), which has 12 PSC dimensions. Each dimension uses a 5-level Likert scale of agreement ("Strongly disagree" to "Strongly agree") or frequency ("Never" to "Always"). The survey was distributed to 68 PGY-2 and PGY-3 internal medicine house staff at an academic medical center between December 2006 and February 2007. Composite scores were created for each respondent by calculating the proportion of positive responses for each domain. Domain score means were compared between PGYs and to survey data from hospitals that administered the HSOPSC (ie, benchmark data). The overall response rate was 85.3% (58/68). House staff scored lower on 6 and 4 of the 12 PSC dimensions, when compared with the overall national hospital and medicine unit benchmarks, respectively (P < .05). PGY-3 staff scored lower than PGY-2 staff in 2 dimensions (P < .05). PGY-2 and PGY-3 internal medicine house staff at our institution were in agreement on most of the PSC dimensions. Overall, house staff PSC was significantly lower than national hospital benchmark data for half of the dimensions. The results of this study will be used to establish internal PSC benchmarks and to identify targets for interventions to further improve PSC.


Commentary: development of perception-action systems and general principles of pattern formation.
Our commentary on this special issue devoted to Developmental Biodynamics: Brain, Body, and Behavior Connections is divided into 3 main sections. The first section is an overview of the individual contributions. 5 major themes are identified: (1) inappropriateness of computational treatments of development and the need for more biologically and physically relevant treatments; (2) significance of tailoring muscular to nonmuscular forces in developing movement coordination; (3) importance of spontaneous movements as exploratory and formative mechanisms; (4) influences of action capabilities on the development of perception capabilities, and vice versa; (5) applications of methods and techniques of nonlinear dynamics to developmental processes. In the second section, we provide a synopsis of current ways of thinking about prototypical developmental processes, namely, pattern formation and pattern differentiation, in various classes of physical and biological systems. It is suggested that efforts to understand the progressive formation and differentiation of patterns in terms of very general principles provide a valuable resource of concepts and methods for students of child development. In the third section, hypotheses about the development of perception-action systems are generated from juxtaposing the themes and conjectures of this special issue with general principles of pattern formation. The hypotheses suggest the possibility of a pattern formation or dynamics approach to child development as an alternative to the conventional approaches emphasizing maturation (nativist), specific learning experiences (empiricist), cognitive stages (Piagetian), and strategies of encoding and retrieval (information processing).


Intelligent systems in medical diagnosis.
From an intelligent system for a computer supported medical diagnosis it is expected to achieve high accuracy and ability to draw conclusions from a small data sets. Medical practice could takes many years to generate a large database. A new mathematical method that is able to learn on a small data set is presented.


Regulation of ncd by the oligomeric state of tubulin.
We have compared the interaction of ncd (non-claret disjunctional), a kinesin related protein, with microtubules and tubulin heterodimer. Ultracentrifugation experiments revealed that the ncd motor domain, residues 335-700 (ncd335), does not induce tubulin polymerization but stabilizes pre-formed microtubules with a maximum effect at a 1:1 ncd335:tubulin ratio. Ncd335 binding to tubulin or microtubules was estimated by following the change in fluorescence polarization of an exogenous dye attached to Cys670 of ncd335. Ncd335 binding to tubulin (containing GTP or GDP-bound) is characterized by a 2:1 stoichiometry, a higher affinity and an increased sensitivity towards salt, ADP, ATP and AMPPNP, as compared with ncd335 binding to microtubules. Maximum ATPases were 0.06-0.08 sec(-1) and 1.8-2.0 sec(-1) for the ncd335-tubulin and ncd335-microtubules complexes, respectively. Only the polymerized complex is fully functional, suggesting the presence of additional contacts between adjacent protofilaments. Moreover, the data reveal that the oligomeric state of microtubules is a potent regulator for the activity of kinesin related proteins.


[Clinical studies of recombinant human erythropoietin in patients on long-term dialysis].
Recombinant human erythropoietin (r-HuEPO) was administered in 68 dialyzed patients (32 on acetate hemodialysis, 24 bicarbonate hemodialysis and 12 on hemo-filtration). The mean initial Hb 52.7 +/- 8.0g/L, Ht 19.4 +/- 2.2%, serum ferritin > 100ng/L. Each patients received r-HuEPO intravenously, at the dose of 300U/Kg/w for 6.2 +/- 4.3 months. Target range: Hb 100-120g/L, Ht 30-35%. After r-HuEPO treatment, blood transfusion was not needed for any of the patients, anemia was ameliorated with increase of Hb and Ht levels. It was found that the minimum effective dose of the r-HrEPO was 150-300U/Kg/w. We conclude that r-HuEPO is effective as treatment for the anemia of dialyzed patients. However, hypertension, clotted dialyzers and dialysis access thromboses were been developed in some patients after correction of anemia. There is now a general consensus that these side effects may be minimized if r-HuEPO is initially given in small doses with increments to avoid a too rapid correction of the anemia.


Reversible sensorineural hearing loss in Lyme disease.
We report a case of bilateral sensorineural hearing loss of two years duration which appears to have been due to late Borrelia burgdorferi infection. The 39-year-old woman presented with bilateral deafness and multiple other neurological complaints some six months after developing a 'target' lesion on the lower leg after walking in the New Forest. 'Serology' for Borrelia burgdorferi became positive and the patient made a complete recovery from both her deafness and her other neurological problems after a five-week course of oral antibiotic therapy.


Listening to the Shenzhen Primary Healthcare Context to Adapt the mhGAP-IG.v2 for the Assessment of Depression: Qualitative Workshops with Primary Healthcare Leaders.
In Shenzhen, despite recent primary and mental healthcare reform, Primary healthcare doctors (PHC) have limited access to diagnostic tools and a significant mental health treatment gap presides. The World Health Organization's (WHO) mental health gap intervention guide (mhGAP-IG.v2) offers a non-specialist and evidence-based guide for the assessment of depression however requires adaptation to the context of use. Bilingual (Mandarin and English) qualitative research was undertaken with 30 PHC leaders from Shenzhen to compare their assessment approach for depression against the mhGAP-IG.v2 in order to identify context-specific modifications for a local guide. Local assessment differentiators included: a need for culturally sensitive translation of depression symptoms; a preference for a broad, non-hierarchical symptom presentation (including somatic, behavioural and anxiety items); national prioritisation of suicide patients; the integration of family into the cycle of care; limited primary care awareness of a depressive episode in Bipolar Disorder; and China's specialist-led diagnostic approach. Contextual modification of mhGAP-IG.v2 is recommended to take account of China's unique cultural and primary health system response to depression. Ongoing mental health training is required to develop professional confidence in the recognition of mental disorders.


Ionization and Fragmentation of DCOOD Induced by Synchrotron Radiation at the Oxygen 1s Edge: The Role of Dimer Formation.
The ionization and photofragmentation of molecules in the core region has been widely investigated for monomers and dimers of organic molecules in the gas phase. In this study, we used synchrotron radiation to excite electrons of the oxygen K-edge in an effusive molecular beam of doubly deuterated formic acid. We used time-of-flight mass spectrometry and employed the spectroscopic techniques photoelectron-photoion coincidence and photoelectron photoion-photoion coincidence to obtain spectra of single and double coincidences at different pressures. Our results indicate the presence of ions and ion pairs that have charge-to-mass ratio higher than the monomer DCOOD, as the (DCOOD)·D(+), and pairs (DCO(+), DCO(+)) and (CO(+), DCO(+)). Comparing the spectra obtained for different pressures we can ascertain that these ions are formed by the fragmentation of DCOOD dimers.


Semantic Context-Aware Image Style Transfer.
To provide semantic image style transfer results which are consistent with human perception, transferring styles of semantic regions of the style image to their corresponding semantic regions of the content image is necessary. However, when the object categories between the content and style images are not the same, it is difficult to match semantic regions between two images for semantic image style transfer. To solve the semantic matching problem and guide the semantic image style transfer based on matched regions, we propose a novel semantic context-aware image style transfer method by performing semantic context matching followed by a hierarchical local-to-global network architecture. The semantic context matching aims to obtain the corresponding regions between the content and style images by using context correlations of different object categories. Based on the matching results, we retrieve semantic context pairs where each pair is composed of two semantically matched regions from the content and style images. To achieve semantic context-aware style transfer, a hierarchical local-to-global network architecture, which contains two sub-networks including the local context network and the global context network, is proposed. The former focuses on style transfer for each semantic context pair from the style image to the content image, and generates a local style transfer image storing the detailed style feature representations for corresponding semantic regions. The latter aims to derive the stylized image by considering the content, the style, and the intermediate local style transfer images, so that inconsistency between different corresponding semantic regions can be addressed and solved. The experimental results show that the stylized results using our method are more consistent with human perception compared with the state-of-the-art methods.