Knowledge and attitudes of Japanese dental health care workers towards HIV-related disease.
The present study was undertaken to investigate knowledge of AIDS and HIV infection among Japanese dental health care workers, the source of that knowledge and attitudes of dental workers towards infected patients. The study population surveyed by means of a self-administered questionnaire consisted of 174 dental health workers at Nagasaki University Dental Hospital, including students and trainee hygienists. Most respondents (100% response) claimed their major source of AIDS knowledge to be derived from the media. Almost all considered their knowledge of AIDS and HIV infection to be more than moderate but still inadequate. The majority of respondents would be hesitant about performing dental treatment on HIV-positive patients. It was widely anticipated that dental patients infected with HIV would increase in the next few years and many were anxious about the increasing occupational risk of HIV infection. Only 22.4% of respondents had the same attitude towards treating HIV-positive and HIV-negative patients. Most also considered that they would be able to take care of the oral opportunistic diseases associated with HIV. Over 90.0% of respondents requested additional education about HIV, particularly information about the prevention and spread of the virus and cross-infection requirements. It is concluded that further training in the medical and psychological aspects of treating HIV-positive patients is indicated in Japan.


Predictive value of low BMD for 1-year fracture outcomes is similar for postmenopausal women ages 50-64 and 65 and Older: results from the National Osteoporosis Risk Assessment (NORA).
The relationship of low bone mass and fracture in younger postmenopausal women has not been extensively studied. In a large cohort of postmenopausal women > or =50 years of age, we found the relationship of BMD measured at peripheral sites and subsequent 1-year fracture risk to be similar between women <65 and those > or =65 years of age. Low bone mass and fractures are prevalent in older postmenopausal women. However, the frequency of low bone mass and fracture in younger postmenopausal women has not been studied extensively. There are very limited data regarding the association between BMD measurements and fractures in postmenopausal women who are between the ages of 50 and 64. In the National Osteoporosis Risk Assessment (NORA) we studied the frequency of low bone mass and its association with fracture in women 50-64 years of age in comparison with women > or =65 of age. NORA enrolled 200,160 postmenopausal women > or =50 years of age who had no prior diagnosis of osteoporosis. Baseline BMD was measured at the heel, forearm, or finger. A 1-year follow-up survey requesting incident fractures since baseline was completed by 163,935 women, 87,594 (53%) of whom were 50-64 years of age. The association between BMD and fracture was assessed using logistic regression, adjusted for important covariates. Thirty-one percent of women 50-64 years of age had low bone mass (T scores < or = -1.0) compared to 62% of women > or =65 years of age. During the first year of follow-up, 2440 women reported fractures of wrist/forearm, rib, spine, or hip, including 440 hip fractures. Nine hundred four women 50-64 years of age reported fractures, including 86 hip fractures, accounting for 37% of fractures and 20% of hip fractures reported in the entire NORA cohort. Relative risk for osteoporotic fracture was 1.5 for each SD decrease in BMD for both the younger and older groups of women. Low BMD in younger postmenopausal women 50-64 years of age showed a 1-year relative risk of fracture similar to that found in women > or =65 years of age.


A Theoretical Foundation for the Ethical Distribution of Authorship in Multidisciplinary Publications.
In academia, authorship on publications confers merit as well as responsibility. The respective disciplines adhere to their "typical" authorship practices: individuals may be named in alphabetical order (e.g., in economics, mathematics), ranked in decreasing level of contribution (e.g., biomedical sciences), or the leadership role may be listed last (e.g., laboratory sciences). However, there is no specific, generally accepted guidance regarding authorship distribution in multidisciplinary teams, something that can lead to significant tensions and even conflict. Using Scanlon's contractualism as a basis, I propose a conceptual foundation for the ethical distribution of authorship in multidisciplinary teams; it features four relevant principles: desert, just recognition, transparency, and collegiality. These principles can serve in the development of a practical framework to support ethical and nonarbitrary authorship distribution, which hopefully would help reduce confusion and conflict, promote agreement, and contribute to synergy in multidisciplinary collaborative research.


Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2.
Herpesviruses encode protein kinases. A subset of these proteins, represented by HSV-1 UL13, are conserved throughout all members of the Herpesviridae, and here, are designated CHPKs (conserved herpesvirus protein kinases). In addition to conserved gene products like CHPKs, herpesviruses encode genes specific to respective herpesviruses. When acting upon conserved viral gene products or cellular factors, CHPKs may play conserved roles in the life cycles of herpesviruses. CHPKs may also express unique functions within the infectious process of individual herpesviruses when specific viral gene products are targeted. CHPKs demonstrate specific activity in multiple herpesvirus infections, functioning in the regulation of viral gene expression in HSV-1, tissue tropism in VZV, and viral DNA synthesis, encapsidation and egress from the nucleus in HCMV. The HCMV CHPK, however, can partially substitute for the HSV-1 CHPK. Representative CHPKs from all Herpesviridae subfamilies can also facilitate the hyperphosphorylation of the cellular translation factor, EF-1delta. This indicates that CHPKs have conserved functions. Recent data have shown that both CHPKs and a cellular protein kinase, cdc2, phosphorylate the same amino acid residues of target proteins. Thus, CHPKs may mimic cdc2 function in infected cells.


A computational workflow for designing silicon donor qubits.
Developing devices that can reliably and accurately demonstrate the principles of superposition and entanglement is an on-going challenge for the quantum computing community. Modeling and simulation offer attractive means of testing early device designs and establishing expectations for operational performance. However, the complex integrated material systems required by quantum device designs are not captured by any single existing computational modeling method. We examine the development and analysis of a multi-staged computational workflow that can be used to design and characterize silicon donor qubit systems with modeling and simulation. Our approach integrates quantum chemistry calculations with electrostatic field solvers to perform detailed simulations of a phosphorus dopant in silicon. We show how atomistic details can be synthesized into an operational model for the logical gates that define quantum computation in this particular technology. The resulting computational workflow realizes a design tool for silicon donor qubits that can help verify and validate current and near-term experimental devices.


Enzymatic conjugation of erythrocyte glutathione with 1-chloro-2,4-dinitrobenzene: the fate of glutathione conjugate in erythrocytes and the effect of glutathione depletion on hemoglobin.
Erythrocyte glutathione (GSH) can be rapidly depleted by incubating the cells with 1-chloro-2,4-dinitrobenzene (CDNB), which forms 2,4-dinitrophenyl-S-glutathione with GSH through the reaction catalyzed by glutathione S-transferase. GSH-CDNB conjugate thus formed stays undegraded within the erythrocytes. This indicates that in the erythrocytes, mercapturic acid pathway is inoperative. Depletion of GSH in the intact erythrocytes by CDNB results in rapid oxidation of large amounts of hemoglobin to methemoglobin. When glutathione S-transferase-free hemolysate of erythrocytes is incubated with CDNB, the depletion of GSH as well as methemoglobin formation are minimal. Glutathione peroxidase and glutathione reductase activities of the erythrocytes are not affected by CDNB. These studies provide a specific enzymatic method for rapid removal of erythrocyte GSH and also indicate that GSH is vital in maintaining a reduced environment within the erythrocytes.


A method for the isolation and enrichment of purified bovine milk exosomes.
Exosomes are nanovesicles that play important roles in intercellular communication as they carry information to target cells. Isolation of high purity exosomes will aid in studying the exosomal cargo and quantity as well as how cell-specific messages are carried. We describe a new method incorporating size exclusion chromatography (SEC) to enrich milk-derived exosomes from extracellular vesicles (EVs). This involved the initial isolation of EVs from bovine milk via milk processing and ultracentrifugation; followed by a new method to enrich exosomes using SEC. This method was compared to buoyant density gradient centrifugation, a widely used method of enrichment. Exosomes were characterised by particle concentration and size (nanoparticle tracking analysis, NTA), morphology (transmission electron microscopy, TEM), presence of exosomal markers (immunoblotting) and protein concentration (bicinchoninic acid assay, BCA). Proteomic profiles of exosomal fractions were analyzed by mass spectrometry using Information Dependant Acquisition. Milk exosomal fractions were shown to contain exosomal markers flotillin-1 (FLOT-1) and tumor susceptibility gene-101 (TSG-101). The new method produced a higher yield of exosomes compared to buoyant density gradient centrifugation. Pooled exosomal fractions exhibited intact morphology by TEM. The use of SEC confirmed the fractionation of exosomes based on size while minimizing the interference with proteins. Tetraspanins CD9 and CD81 were observed via mass spectrometry in exosomal fractions. This new and efficient method confirmed the signatures for exosomes derived from unpasteurized bovine milk. Purification of exosomes is a foundational technique in the study of biomarkers for pathological conditions and effective drug delivery systems.


Darwin's historical sketch - an American predecessor: C.S. Rafinesque.
When early reviewers of Darwin's "On the origin of species" chided him for neglecting to mention predecessors to his theory of evolution, he added an "historical sketch" in later editions. Among the predecessors he cited was a French émigré to American named Constantine Samuel Rafinesque, who in the mid-1830s had written about the emergence of new species at a time when most naturalists (including Darwin initially) accepted the biblical story of creation and assumed the immutability of species. Rafinesque discovered and named thousands of new plants and animals in his American travels and flooded the taxonomic literature with reports, which seemed incomplete, confusing, and excessive to other naturalists. He alienated many who later dismissed his findings and excluded them from the biological literature. Soon after Rafinesque's death in 1840, Asa Gray, the young American botanist, wrote a damning critique of his work and suggested it be ignored. How Darwin learned of Rafinesque and his views on species is the focus of this essay, which also mentions briefly the two other American naturalists cited by Darwin in his sketch. Gray seems the likely informant through his correspondence with Darwin or his close associates.


Evidence of and recommendations for non-pharmacological interventions for common geriatric conditions: the SENATOR-ONTOP systematic review protocol.
Non-pharmacological therapies for common chronic medical conditions in older patients are underused in clinical practice. We propose a protocol for the assessment of the evidence of non-pharmacological interventions to prevent or treat relevant outcomes in several prevalent geriatric conditions in order to provide recommendations. The conditions of interest for which the evidence about efficacy of non-pharmacological interventions will be searched include delirium, falls, pressure sores, urinary incontinence, dementia, heart failure, orthostatic hypotension, sarcopaenia and stroke. For each condition, the following steps will be undertaken: (A) prioritising clinical questions; (B) retrieving the evidence (MEDLINE, the Cochrane Library, CINAHL and PsychINFO will be searched to identify systematic reviews); (C) assessing the methodological quality of the evidence (risk of bias according to the Cochrane method will be applied to the primary studies retrieved from the systematic reviews); (D) developing recommendations based on the evidence (Grading of Recommendations Assessment, Development and Evaluation (GRADE) items-risk of bias, imprecision, inconsistency, indirectness and publication bias-will be used to rate the overall evidence and develop recommendations). For each target condition, at least one systematic overview concerning the evidence of non-pharmacological interventions will be produced and published in peer-reviewed journals.


Decision making in young people at familial risk of depression.
Major depression is associated with abnormalities in reward processing at neural and behavioural levels. Neural abnormalities in reward have been described in young people at familial risk of depression but behavioural changes in reward-based decision making have been less studied in this group. We studied 63 young people (mean age 18.9 years) with a parent with a diagnosis of major depression but who had never been depressed themselves, that is with a positive family history of depression (the FH+ group). Participants performed the Cambridge Gambling Task (CGT), which provides several measures of decision making including deliberation time, quality of decision making, risk taking, risk adjustment and delay aversion. A control group of 49 age- and gender-matched young people with no history of mood disorder in a first-degree relative undertook the same task. Both FH+ participants and controls had low and equivalent scores on anxiety and depression self-rating scales. Compared to controls, the FH+ participants showed overall lower risk taking, although like controls they made more risky choices as the odds of a favourable outcome increased. No other measures of decision making differed between the two groups. Young people at increased familial risk of depression have altered risk taking that is not accounted for by current affective symptomatology. Lowered risk taking might represent an impairment in reward seeking, which is one of several changes in reward-based behaviours seen in acutely depressed patients; however, our findings suggest that decreased reward seeking could be part of a risk endophenotype for depression.


Analysis of accuracy of measurement of quadratic electro-optic coefficients in uniaxial crystals: a case study of KDP.
Taking KDP as an example of a uniaxial crystal, we analyze contributions to its quadratic electro-optic response with a view to explaining differences in published values of certain quadratic coefficients. In an eigenvalue theory of light propagation we show that the linear electro-optic coefficient contributes to the quadratic response, even under ideal laboratory conditions. In addition, the effect of imperfect crystal cutting and alignment is investigated by means of computer calculations based on the Jones calculus. It is found that, for relatively small inaccuracies, the calculated values of the quadratic coefficient g(xyxy) are approximately two orders of magnitude greater when measured with a static field than with a dynamic one. This finding could explain the observed spread in some results for KDP-type crystals.


Hypertension is a clinically important risk factor for critical illness and mortality in COVID-19: A meta-analysis.
As reported, hypertension may play an important role in adverse outcomes of coronavirus disease-2019 (COVID-19), but it still had many confounding factors. The aim of this study was to explore whether hypertension is an independent risk factor for critical COVID-19 and mortality. The Medline, PubMed, Embase, and Web of Science databases were systematically searched until November 2020. Combined odds ratios (ORs) with their 95% confidence interval (CIs) were calculated by using random-effect models, and the effect of covariates was analyzed using the subgroup analysis and meta-regression analysis. A total of 24 observational studies with 99,918 COVID-19 patients were included in the meta-analysis. The proportions of hypertension in critical COVID-19 were 37% (95% CI: 0.27 -0.47) when compared with 18% (95% CI: 0.14 -0.23) of noncritical COVID-19 patients, in those who died were 46% (95%CI: 0.37 -0.55) when compared with 22% (95% CI: 0.16 -0.28) of survivors. Pooled results based on the adjusted OR showed that patients with hypertension had a 1.82-fold higher risk for critical COVID-19 (aOR: 1.82; 95% CI: 1.19 - 2.77; P = 0.005) and a 2.17-fold higher risk for COVID-19 mortality (aOR: 2.17; 95% CI: 1.67 - 2.82; P < 0.001). Subgroup analysis results showed that male patients had a higher risk of developing to the critical condition than female patients (OR: 3.04; 95%CI: 2.06 - 4.49; P < 0.001) and age >60 years was associated with a significantly increased risk of COVID-19 mortality (OR: 3.12; 95% CI: 1.93 - 5.05; P < 0.001). Meta-regression analysis results also showed that age (Coef. = 2.3×10-2, P = 0.048) had a significant influence on the association between hypertension and COVID-19 mortality. Evidence from this meta-analysis suggested that hypertension was independently associated with a significantly increased risk of critical COVID-19 and inhospital mortality of COVID-19.


[The clinical picture and results of treating patients with ovarian fibromas (according to findings of the Prof. N.N. Petrov Research Institute of Oncology of the USSR Ministry of Health)].
The author presented a clinico-pathological analysis of the data concerning 41 patients with fibroma of the ovaries, treated at the N.N. Petrov Research Institute of Oncology of the USSR Ministry of Health from 1926 to 1974. A method of the "dynamic analysis" was used in studying 10-year survival rates which made 96.9%. Recurrences were observed among patients under a long-term follow-up, despite various scope of surgery employed. The author made a conclusion on the possibility to remove the adnexa only in women of childbearing age.


In vitro selection of ramR and soxR mutants overexpressing efflux systems by fluoroquinolones as well as cefoxitin in Klebsiella pneumoniae.
The relationship between efflux system overexpression and cross-resistance to cefoxitin, quinolones, and chloramphenicol has recently been reported in Klebsiella pneumoniae. In 3 previously published clinical isolates and 17 in vitro mutants selected with cefoxitin or fluoroquinolones, mutations in the potential regulator genes of the AcrAB efflux pump (acrR, ramR, ramA, marR, marA, soxR, soxS, and rob) were searched, and their impacts on efflux-related antibiotic cross-resistance were assessed. All mutants but 1, and 2 clinical isolates, overexpressed acrB. No mutation was detected in the regulator genes studied among the clinical isolates and 8 of the mutants. For the 9 remaining mutants, a mutation was found in the ramR gene in 8 of them and in the soxR gene in the last one, resulting in overexpression of ramA and soxS, respectively. Transformation of the ramR mutants and the soxR mutant with the wild-type ramR and soxR genes, respectively, abolished overexpression of acrB and ramA in the ramR mutants and of soxS in the soxR mutant, as well as antibiotic cross-resistance. Resistance due to efflux system overexpression was demonstrated for 4 new antibiotics: cefuroxime, cefotaxime, ceftazidime, and ertapenem. This study shows that the ramR and soxR genes control the expression of efflux systems in K. pneumoniae and suggests the existence of efflux pumps other than AcrAB and of other loci involved in the regulation of AcrAB expression.


Etching of Uncompensated Convex Corners with Sides along <n10> and <100> in 25 wt% TMAH at 80 °C.
This paper presents etching of convex corners with sides along <n10> and <100> crystallographic directions in a 25 wt% tetramethylammonium hydroxide (TMAH) water solution at 80 °C. We analyzed parallelograms as the mask patterns for anisotropic wet etching of Si (100). The sides of the parallelograms were designed along <n10> and <100> crystallographic directions (1 < n < 8). The acute corners of islands in the masking layer formed by <n10> and <100> crystallographic directions were smaller than 45°. All the crystallographic planes that appeared during etching in the experiment were determined. We found that the obtained types of 3D silicon shape sustain when n > 2. The convex corners were not distorted during etching. Therefore, no convex corner compensation is necessary. We fabricated three matrices of parallelograms with sides along crystallographic directions <310> and <100> as examples for possible applications. Additionally, the etching of matrices was simulated by the level set method. We obtained a good agreement between experiments and simulations.


[The history of neurectomy in horses with navicular disease].
The genetic predisposition to navicular disease is proven nowadays, but otherwise, etiology and pathogenesis are still unclear. Causal therapy isn't possible and because of the poor prognosis, neurectomy is still of bearing. This operation was performed already 200 years ago, but in the middle of the last century, critical voices have been raised in regard to the surgical procedure and its indication both for medical reasons and breeding. Clear instructions for exclusion of diseased animals from breeding are also older than one hundred years. These facts call for ethic considerations which concern both breeding and use of these animals. In earlier times, horses were used for basic human requirements mainly, but nowadays their employment occurs mainly for pleasure. Ethic reflections are our task, as our specialized knowledge forms their basis. Our philosophy has to be applicable in practice, what can be achieved best with utilitarianistic reasoning. The possibilities of our influence on the sport are limited, but in breeding our commitment has to be vigorous and unrestricted. Due to the development of immunogenetic studies, legal problems may arise in the near future as well.


Non-diverging analytical expression for the sensitivity of converging SPECT collimators.
Accurate analytical expressions for collimator resolution and sensitivity are important tools in the optimization of SPECT systems. However, presently known expressions for the sensitivity of converging collimators either diverge near the focal point or focal line(s), or are only valid on the collimator axis. As a result, these expressions are unsuitable to calculate volumetric sensitivity for e.g. short-focal length collimators that focus inside the object to enhance sensitivity. To also enable collimator optimization for these geometries, we here present non-diverging sensitivity formulas for astigmatic, cone beam and fan beam collimators that are applicable over the full collimator's field-of-view. The sensitivity was calculated by integrating previously derived collimator response functions over the full detector surface. Contrary to common approximations, the varying solid angle subtended by different detector pixels was fully taken into account which results in a closed-form non-diverging formula for the sensitivity. We validated these expressions using ray-tracing simulations of a fan beam and an astigmatic cone beam collimator and found close agreement between the simulations and the sensitivity expression. The largest differences with the simulation were found close to the collimator, where sensitivity depends on the exact placement of holes and septa, while our expression represents an average over all possible placements as is common practice for analytical sensitivity expressions. We checked that average differences between the analytical expression and simulations reduced to less than 1% of the maximum sensitivity when we averaged our simulations over different septa locations. Moreover, we found that our new expression reduced to the traditional diverging formula under certain assumptions. Therefore, the newly derived sensitivity expression may enable the optimization of converging collimators for a wide range of applications, in particular when the focus is close to, or in, the object of interest.


Cyclooxygenase-2-derived E prostaglandins down-regulate matrix metalloproteinase-1 expression in fibroblast-like synoviocytes via inhibition of extracellular signal-regulated kinase activation.
We examined the regulation of matrix metalloproteinase (MMP) production by mitogen-activated protein kinases and cyclooxygenases (COXs) in fibroblast-like synoviocytes (FLSCs). IL-1beta and TNF-alpha stimulated FLSC extracellular signal-regulated kinase (ERK) activation as well as MMP-1 and -13 release. Pharmacologic inhibitors of ERK inhibited MMP-1, but not MMP-13 expression. Whereas millimolar salicylates inhibited both ERK and MMP-1, nonsalicylate COX and selective COX-2 inhibitors enhanced stimulated MMP-1 release. Addition of exogenous PGE(1) or PGE(2) inhibited MMP-1, reversed the effects of COX inhibitors, and inhibited ERK activation, suggesting that COX-2 activity tonically inhibits MMP-1 production via ERK inhibition by E PGs. Exposure of FLSCs to nonselective COX and selective COX-2 inhibitors in the absence of stimulation resulted in up-regulation of MMP-1 expression in an ERK-dependent manner. Moreover, COX inhibition sufficient to reduce PGE levels increased ERK activity. Our data indicate that: 1) ERK activation mediates MMP-1 but not MMP-13 release from FLSCs, 2) COX-2-derived E PGs inhibit MMP-1 release from FLSCs via inhibition of ERK, and 3) COX inhibitors, by attenuating PGE inhibition of ERK, enhance the release of MMP-1 by FLSC.


Low-temperature, simple and fast integration technique of microfluidic chips by using a UV-curable adhesive.
In the fields of MicroElectroMechanical Systems (MEMS) and Lab On a Chip (LOC), a device is often fabricated using diverse substrates which are processed separately and finally assembled together using a bonding process to yield the final device. Here we describe and demonstrate a novel straightforward, rapid and low-temperature bonding technique for the assembly of complete microfluidic devices, at the chip level, by employing an intermediate layer of gluing material. This technique is applicable to a great variety of materials (e.g., glass, SU-8, parylene, UV-curable adhesive) as demonstrated here when using NOA 81 as gluing material. Bonding is firstly characterized in terms of homogeneity and thickness of the gluing layer. Following this, we verified the resistance of the adhesive layer to various organic solvents, acids, bases and conventional buffers. Finally, the assembled devices are successfully utilized for fluidic experiments.


Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration.
Cells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione-reductase-dependent routes are poor at supporting DNA replication in these organisms. We have studied proliferation of thioredoxin-reductase-1 (Txnrd1)-deficient hepatocytes in mice. During development and regeneration, normal mice and mice having Txnrd1-deficient hepatocytes exhibited similar liver growth rates. Proportions of hepatocytes that immunostained for PCNA, phosphohistone H3 or incorporated BrdU were also similar, indicating livers of either genotype had similar levels of proliferative, S and M phase hepatocytes, respectively. Replication was blocked by hydroxyurea, confirming that RNR activity was required by Txnrd1-deficient hepatocytes. Regenerative thymidine incorporation was similar in normal and Txnrd1-deficient livers, further indicating that DNA synthesis was unaffected. Using genetic chimeras in which a fluorescently marked subset of hepatocytes was Txnrd1-deficient while others were not, we found that the multigenerational contributions of both hepatocyte types to development and to liver regeneration were indistinguishable. We conclude that, in mouse hepatocytes, a Txnrd1-independent route for the supply of electrons to RNR can fully support DNA replication and normal proliferative growth.


Initial Bud Outgrowth Occurs Independent of Auxin Flow from Out of Buds.
Apical dominance is the process whereby the shoot tip inhibits the growth of axillary buds along the stem. It has been proposed that the shoot tip, which is the predominant source of the plant hormone auxin, prevents bud outgrowth by suppressing auxin canalization and export from axillary buds into the main stem. In this theory, auxin flow out of axillary buds is a prerequisite for bud outgrowth, and buds are triggered to grow by an enhanced proportional flow of auxin from the buds. A major challenge of directly testing this model is in being able to create a bud- or stem-specific change in auxin transport. Here we evaluate the relationship between specific changes in auxin efflux from axillary buds and bud outgrowth after shoot tip removal (decapitation) in the pea (Pisum sativum). The auxin transport inhibitor 1-N-naphthylphthalamic acid (NPA) and to a lesser extent, the auxin perception inhibitor p-chlorophenoxyisobutyric acid (PCIB), effectively blocked auxin efflux from axillary buds of intact and decapitated plants without affecting auxin flow in the main stem. Gene expression analyses indicate that NPA and PCIB regulate auxin-inducible, and biosynthesis and transport genes, in axillary buds within 3 h after application. These inhibitors had no effect on initial bud outgrowth after decapitation or cytokinin (benzyladenine; BA) treatment. Inhibitory effects of PCIB and NPA on axillary bud outgrowth only became apparent from 48 h after treatment. These findings demonstrate that the initiation of decapitation- and cytokinin-induced axillary bud outgrowth is independent of auxin canalization and export from the bud.


Integrated Immunization Information System in Indonesia: Prototype Design Using Quantitative and Qualitative Data.
As the volume of immunization records increases, problems with fragmented records arise, especially since the majority of records in developing countries, including Indonesia, remain paper based. Implementing an immunization information system (IIS) offers a solution to this problem. In this study, we designed an integrated IIS prototype in Indonesia using the design science research (DSR) methodology. The stages of the DSR methodology followed in this study included identifying problems and motivating and defining objectives for a solution, design and development, demonstration, evaluation, communication, and drawing conclusions and suggestions. Specifically, this study began with problem formulation and a literature review. We then applied quantitative (questionnaire with 305 members of the public) and qualitative (interviews with 15 health workers including nurses, midwives, and doctors) data collection approaches. The resulting high-fidelity prototype follows the 8 golden rules. There are 2 IIS designs, one for the public as immunization recipients and another for health workers. The functionalities include immunization history, schedule, recommendations, verification, certificates, reminders and recalls, coverage, monitoring, news, and reports of adverse events. Evaluation of the prototype was carried out through interviews and a questionnaire designed according to the System Usability Scale (SUS) and Post-Study System Usability Questionnaire (PSSUQ). The SUS value was 72.5 or "Good (Acceptable)," while the system usefulness, information quality, interface quality, and overall value on the PSSUQ were 2.65, 2.94, 2.48, and 2.71, respectively, which indicate it has an effective design. This provides a guide for health facilities, health regulators, and health application developers on how to implement an integrated IIS in Indonesia.


Dental plaque removal with a novel battery-powered toothbrush.
To compare the plaque removal efficacy of a positive control power toothbrush (Oral-B Ultra Plaque Remover) to an experimental power toothbrush (Crest SpinBrush) following a single use. This study was a randomized, controlled, examiner-blind, 2-period crossover design which examined plaque removal with the two toothbrushes following a single use in 38 completed subjects. Plaque was scored before and after brushing using the Turesky Modification of the Quigley-Hein Index. Baseline plaque scores were 1.89 and 1.91 for the experimental toothbrush and control toothbrush treatment groups, respectively. With respect to all surfaces examined, the experimental toothbrush delivered an adjusted (via analysis of covariance) mean difference between baseline and post-brushing plaque scores of 0.46 while the control toothbrush delivered an adjusted mean difference of 0.45. These results were not statistically significant (P=0.645). A 95% one-sided upper confidence limit on the Ultra Plaque Remover minus SpinBrush difference in amount of plaque removed was calculated as 9.4% of the Ultra Plaque Remover adjusted mean. A common criterion for what is known as an "at least as good as" test is that the 95% one-sided confidence limit on the product difference is below 10% of the control product mean. Using this criterion, the SpinBrush is at least as good as the Oral-B Ultra Plaque Remover. With respect to buccal and lingual surfaces, the experimental toothbrush delivered very similar results relative to the control toothbrush. These results were also not statistically significant (P> 0.564).


Association between insomnia patients' pre-treatment characteristics and their responses to distinctive treatment sequences.
It is common to provide insomnia patients a second treatment when the initial treatment fails, but little is known about optimal treatment sequences for different patient types. This study examined whether pre-treatment characteristics/traits predict optimal treatment sequences for insomnia patients. A community sample of 211 adults (132 women; Mage = 45.6 ± 14.9 years) with insomnia were recruited. Patients were first treated with behavioral therapy (BT) or zolpidem (Zol). Non-remitting BT recipients were randomized to a second treatment with either Zol or cognitive therapy; non-remitting Zol recipients underwent BT or Trazodone as a second treatment. Remission rates were assessed at the end of the first and second 6-week treatments. We then compared the remission rates of dichotomous groups formed on the basis of gender, age, pretreatment scores on SF36 and Multidimensional Fatigue Scale, the presence/absence of psychiatric/medical comorbidities or pain disorders, and mean subjective sleep duration and efficiency within and across treatment sequences. Lower remission rates were noted for those: with a pain disorder, poor mental health perceptions, high MFI fatigue scores, and lower sleep times and efficiencies. Patients with a pain disorder responded best to the BT-to-Zol sequence, whereas patients with more mental impairment, severe fatigue, short sleep, and low sleep efficiency responded poorly to treatment starting with BT. Pain, fatigue, poor mental health status, and subjective sleep duration and efficiency all affect response to different insomnia treatment sequences. Findings may guide clinicians in matching insomnia treatments to their patients. ClinicalTrials.gov Identifier: NCT01651442, Protocol version 4, April 20, 2011, registered June 26, 2012, https://clinicaltrials.gov/ct2/show/NCT01651442?rslt=With&type=Intr&cond=Insomnia&cntry=US&state=US%3ACO&city=Denver&age=12&draw=2&rank=1.


Surface-Functionalized Model Contact Lenses with a Bioinspired Proteoglycan 4 (PRG4)-Grafted Layer.
Ocular dryness and discomfort are the primary reasons for the discontinuation of contact lens wear. This is mainly due to poorly hydrated contact lens surfaces and increased friction, particularly at the end of the day and can potentially cause reduced vision or even inflammation. Proteoglycan 4 (PRG4) is a mucinous glycoprotein with boundary lubricating properties, naturally found in the eye, able to prevent tear film evaporation and protect the ocular surface during blinking. Aiming to improve the interfacial interactions between the ocular surface and the contact lens, the synthesis and characterization of surface-modified model contact lenses with PRG4 is described. Full-length recombinant human PRG4 (rhPRG4) was successfully grafted onto the surface of model conventional and silicone hydrogel (SiHy) contact lenses via its somatomedin B-like end-domain using N, N'-carbonyldiimidazole linking chemistry. Grafting was assessed by Fourier transform infrared spectroscopy-attenuated total reflectance, X-ray photoelectron spectroscopy, and radioactive (I131) labeling. Surface immobilization of rhPRG4 led to model conventional and SiHy materials with improved antifouling properties, without impacting optical transparency or causing any toxic effects to human corneal epithelial cells in vitro. The surface wettability and the boundary friction against human corneal tissue were found to be substrate-dependent, with only the rhPRG4-grafted model SiHy exhibiting a reduced contact angle and kinetic friction coefficient compared to the unmodified surfaces. Hence, clinical grade rhPRG4 can be an attractive candidate for the development of novel bioinspired SiHy contact lenses, providing improved comfort and overall lens performance.


RENAL nephrometry score: Predicting perioperative outcomes following open partial nephrectomy.
Partial nephrectomy has emerged as a standard treatment for small renal masses offering oncologic control equivalent to radical nephrectomy, with preservation of renal function and evidence for equivalent survival. In this study, we evaluated RENAL nephrometry score (RNS) in predicting perioperative outcomes in patients with partial nephrectomy. This was a prospective observational study conducted from February 2016 to August 2017 which included patients who underwent partial nephrectomy. The patients were divided into three groups depending on the complexity scores (low, moderate, and high). Tumors were assigned RNS and tumor-node-metastasis staging of the clinically malignant tumors was done. Blood loss, warm ischemia time (WIT), and surgical complications were assessed. A total of 20 patients underwent open partial nephrectomy during the study. There were 4 (20%) low, 11 (55%) moderate, and 5 (25%) high-complexity lesions. Blood loss was significantly different in three groups. All the cases in high-complexity group were performed with clamping the renal vessels with a mean WIT of 29 min. The overall complication rates were significantly different between the groups (P = 0.007); however, majority of the complications were low grade (Grades I and II) and were managed conservatively. In the present study, RNS was correlated with predicting surgical access route, need for clamping during partial nephrectomy, blood loss, decrease in glomerular filtration rate of operated kidneys, postoperative complications, and tumor grade.


Enforcing regulations on alcohol sales and use as universal environmental prevention.
The informal social control over alcohol consumption that was traditional in Southern European countries has weakened. At the same time there is an increase in binge drinking and drunkenness among young people in Spain. To mitigate this problem, regulations on alcohol and driving and restrictions on the sale and consumption of alcohol have been adopted. This paper documents the current regulations in the city of Barcelona and describes efforts to enforce them and their outcomes. Data from the municipal information systems on infringements reported for the period 2008-13 are provided. There is an increasing pressure of municipal services to enforce the rules in two areas: a) alcohol sales at night (retailers); and b) consumption in the public space (citizens). An increase in the controls of drink-driving has also taken place, and the proportion above legal limits has decreased. The largest relative increase occurred in the control of retailers. In Barcelona interventions are made to limit the supply and consumption of alcohol at low cost and during the night, and of driving under the influence of alcohol. There have been no documented episodes of massive drinking in public spaces (known as 'botellón') in the city. These actions, which complement other preventive efforts based on health education, can change the social perceptions of alcohol by minors in a direction less favorable to consumption, promoting environmental prevention.


Roadmaps for Guiding Chest Computed Tomography Interpretation involving Pneumonia.
CT scanning of the chest is one the most important imaging modalities available for pulmonary disease diagnosis. Lung segmentation plays a crucial step in the pipeline of computer-aided analysis and diagnosis. As deep learning models have achieved human-level accuracy in semantic segmentation of anatomical structures, we propose to use trained deep learning models to predict both healthy and infectious areas in chest CT slices. The semantic segmentation results are summarized and visualized using volume rendering technology in the form of roadmaps. The roadmaps consist of both location and volume information that can be used as a location guidance for inspecting suspected pulmonary lesions of chest CT and can possibly be combined into a rapid triage algorithm for treating acute pulmonary diseases.Clinical Relevance- This research applied trained semantic segmentation models in identifying normal lung and pneumonic infection areas to generate a roadmap for assisting medical doctors in browsing chest CT and prognostication.


The effect of a commercial probiotic product on the milk quality of dairy cows.
Probiotics intended to improve plant health and productivity of pastures grazed by dairy cow are becoming commercially available in Australia. Great Land (GL; Terragen Biotech Pty Ltd., Coolum Beach, QLD, Australia) is one such biologic soil conditioner and spray-on probiotic with a label claim of "acting to improve plant health and productivity." The objective of this study was to quantify the effect of GL on the milk quality of cows grazing pasture top-dressed with GL. Lactating dairy cows of mixed age and breed (primarily Holstein-Friesian), in their second lactation or greater, and at least 80 d in milk were enrolled and randomly allocated into 1 of 2 study groups: a treatment cow group (n = 98; cows grazed pasture that was top-dressed with GL according to the product label) and a control cow group (n = 114; cows grazed untreated pasture). As required, both groups were supplemented at the same rate with a mixed ration during the grazing period. Composite milk samples were collected weekly from each cow during the study and analyzed to determine milk components. Milk volumes were recorded at each milking using the herd management software of the study farm. Mean differences in the milk component variables were compared using mixed-effects linear regression models. After controlling for the effect of days in milk, cow lactation, and time since a cow entered the study, the treatment cows produced an average of 1.21 L/cow per day more milk (95% confidence interval: 0.34-2.08 L/cow per day) and more milk protein (0.03 kg/d; 95% confidence interval: 0.01-0.05 kg/d) than the control cows. Pasture cover and pasture consumption did not differ between the GL-treated and the untreated study paddocks grazed by the treatment or control cows. A limited amount of published data have examined the effect of probiotic pasture treatment on the milk quality of dairy cows. This study suggests that application of such products may be beneficial. The mechanisms associated with this type of outcome remain to be investigated.


Local symmetry breaking in SnO2 nanocrystals with cobalt doping and its effect on optical properties.
X-ray photoemission spectroscopy (XPS), X-ray diffraction (XRD) and transmission electron microscopy (TEM) have been used to study the structural and morphological characteristics of cobalt doped tin(iv) oxide (Sn1-xCoxO2; 0 ≤ x ≤ 0.04) nanocrystals synthesized by a chemical co-precipitation technique. Electronic structure analysis using X-ray photoemission spectroscopy (XPS) shows the formation of tin interstitials (Sni) and reduction of oxygen vacancies (VO) in the host lattice on Co doping and that the doped Co exists in mixed valence states of +2 and +3. Using XRD, the preferential position of the Sni and doped Co in the unit cell of the nanocrystals have been estimated. Rietveld refinement of XRD data shows that samples are of single phase and variation of lattice constants follows Vegard's law. XRD and TEM measurements show that the crystallite size of the nanocrystals decrease with increase in Co doping concentration. SAED patterns confirm the monocrystalline nature of the samples. The study of the lattice dynamics using Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy shows the existence of many disorder activated forbidden optical phonon modes, along with the corresponding classical modes, signifying Co induced local symmetry breaking in the nanocrystals. UV-Vis spectroscopy shows that the optical band gap has red shifted with increase in doping concentration. The study of Urbach energy confirms the increase in disorder in the nanocrystals with Co doping. Local symmetry breaking induced UV emission along with violet, blue and green luminescence has been observed from the PL study. The spectral contribution of UV emission decreases and green luminescence increases with increase in doping. Using PL, in conjunction with Raman spectroscopy, the type of oxygen vacancy induced in the nanocrystals on Co doping has been confirmed and the position of the defect levels in the forbidden zone (w.r.t. the optical band gap) has been studied.


Cardiovascular safety of febuxostat and allopurinol in patients with gout and cardiovascular comorbidities.
Comprehensive safety evaluation of new drugs for noncardiac indications is needed in the area of cardiovascular (CV) outcomes, particularly in populations with high CV risk such as gout. Febuxostat is a potent nonpurine selective inhibitor of xanthine oxidase approved for the treatment of gout. Long-term CV safety of febuxostat is being established in a randomized, allopurinol-controlled clinical study in patients with gout who have increased CV risk using an analytical approach that provides 90% power to meet a noninferiority margin of 1.3 for the hazard ratio (HR) (febuxostat relative to allopurinol). The primary CV end point for this trial is a composite of CV death, nonfatal myocardial infarction, nonfatal stroke, and unstable angina requiring urgent coronary revascularization. Approximately 7,500 men and women with gout and CV disease are being recruited and will be followed up for up to 5 years postrandomization. The statistical plan for the trial uses a design that evaluates the HR of febuxostat to allopurinol based on the primary CV composite end point when there are a maximum of 624 CV events. Interim analyses will be conducted when approximately 25%, 50%, and 75% of events have occurred. At each analysis, if the upper 1-sided confidence limit of the HR is <1.3, the study will be stopped, and the noninferiority of febuxostat relative to allopurinol with regard to CV risk will be declared. The CARES trial will define the CV safety profile of febuxostat and allopurinol in gout patients at high risk for CV events.


A ring to rule them all: a cyclic ketene acetal comonomer controls the nitroxide-mediated polymerization of methacrylates and confers tunable degradability.
2-Methylene-4-phenyl-1,3-dioxolane (MPDL) was successfully used as a controlling comonomer in NMP with oligo(ethylene glycol) methyl ether methacrylate (MeOEGMA) to prepare well-defined and degradable PEG-based P(MeOEGMA-co-MPDL) copolymers. The level of ester group incorporation is controlled, leading to reductions in molecular weight of up to 95% on hydrolysis. Neither the polymer nor its degradation products displayed cytoxicity. The method was also successfully applied to methyl methacrylate.


Exploring patterns of alcohol misuse in treatment-seeking UK veterans: A cross-sectional study.
To explore patterns of alcohol misuse in a sample of treatment-seeking veterans compared to the UK Armed Forces personnel population and the general public. Furthermore, the present study investigated which variables were associated with alcohol misuse in this sample, and in particular what factors were associated with increased or decreased severity of alcohol misuse. The present study investigated alcohol misuse in treatment-seeking veterans and compared it with the UK Armed Forces and the general public. In addition, it explored associations between sociodemographic, physical health and mental health variables and alcohol misuse. Results suggested that treatment-seeking veterans report different patterns of alcohol misuse compared to the UK Armed Forces and the general public. This group was more likely to report alcohol dependence and alcohol-related harm. They also reported higher levels of overall alcohol misuse than the general public. Mental health problems including PTSD, anxiety and depression, as well as anger, functional impairment and being single were all related to greater alcohol misuse. Being older and not in work were related to reduced alcohol misuse. These findings add further weight to the importance of ensuring appropriate support is provided to personnel leaving the Armed Forces. Treatment-seeking veterans have specific patterns of alcohol-related needs that should be addressed. Knowing more about the common alcohol-related problems in this group can help inform and improve mental health interventions. Findings on related variables will help in identifying those individuals who may be at most risk of alcohol-related problems.


Best Practices in Oncology Distress Management: Beyond the Screen.
The field of psychosocial oncology is a young discipline with a rapidly expanding evidence base. Over the past few decades, several lines of research have established that psychosocial problems, such as anxiety, depression, post-traumatic stress, fatigue, sexual dysfunction, and cognitive complaints, are common and consequential in patients with cancer. The word "distress" was chosen deliberately to capture a broad concept; consequently, distress screening is meant to function as an initial step in the more targeted evaluation of the source(s) of the patient's distress. In 2015, the American College of Surgeons' Commission on Cancer mandated psychosocial distress screening as part of their accreditation process. Similar screening requirements are in place internationally, including in Canada, where screening for distress is endorsed as the sixth vital sign and a standard of care that must be met by any Canadian health care organization providing cancer services that seeks to be accredited. Over the past few years, cancer centers around the world have been exploring optimum ways to implement and evaluate distress screening initiatives. This paper presents three approaches to distress screening implementation: (1) a model that incorporates the importance of shared values, perceived benefits, and relevant outcomes in the implementation of distress management protocols; (2) a Canadian knowledge translation application to distress screening, including triage considerations and interventions; and (3) a novel approach to distress management via the use of a mobile application to manage post-traumatic stress symptoms. In closing, future opportunities and challenges associated with the emergence of technology will be discussed.


A role for microtubule bundles in the morphogenesis of chicken erythrocytes.
The acquisition of cellular asymmetry is one of the post-mitotic events in development. The cells of the avian erythropoietic lineage acquire a simple invariant asymmetry as they mature. Erythrocytes develop in suspension from spherical through discoid to lentil-shaped (lentiform) cells, with a single rigorously specified microtubule bundle, the marginal band. We show here that developing erythrocytes can express highly asymmetric morphologies, including elongated cell bodies and long processes in response to two stimuli: mechanical manipulation (repeated washing) and exposure to cytochalasin D. These experiments suggest that erythrocytes pass through a developmental stage during which microtubules are able to exert elongating forces on the cell. That stage is one in which these cells normally change shape, from spherical to discoid. The results suggest that microtubules may both guide and drive the formation of the marginal band and the characteristic morphology of these cells.


Functional anatomy of the levator palpebrae superioris muscle and its connective tissue system.
The connective tissue system of the levator palpebrae superioris muscle (LPS) consists of the septa surrounding its muscle sheath, the superior transverse ligament (STL) commonly referred to as 'Whitnall's ligament' and the common sheath which is the fascia between the LPS and the superior rectus muscle (SRM). The anterior band-like component of the common sheath is called transverse superior fascial expansion (TSFE) of the SRM and LPS. It mainly extends from the connective tissue of the trochlea to the fascia of the lacrimal gland. A detailed description of the relation between the LPS and its connective tissue is presented. Furthermore, the course of the LPS in the orbit is described. The study was conducted to provide a morphological basis for biomechanical and clinical considerations regarding ptosis surgery. Postmortem dissections were performed in 16 orbits from eight cadavers. The microscopical anatomy was demonstrated in six formalin preserved orbits from six cadavers which had been sectioned in the frontal and sagittal plane and stained with haematoxylin and azophloxin. Surface coil magnetic resonance imaging in the sagittal and coronal plane was performed in five orbits from five normal volunteers using a T1 weighted spin echo sequence. The STL and the TSFE surround the LPS to form a fascial sleeve around the muscle which has attachments to the medial and lateral orbital wall. The TSFE, which is thicker than the STL, blends with Tenon's capsule. The STL and the fascial sheath of the LPS muscle are suspended from the orbital roof by a framework of radial connective tissue septa. MR images show that the TSFE is located between the anterior third of the superior rectus muscle and the segment of the LPS muscle where it changes its course from upwards to downwards. In this area, the LPS reaches its highest point in the orbit (culmination point). The culmination point is located a few millimetres posterior to the equator and superior to the globe. Whitnall's ligament can be considered to consist of two distinct parts--the TSFE inferior to the LPS and the STL superior to the LPS. Since the medial and lateral main attachments of Whitnall's ligament are situated inferior to the level of the culmination point of the LPS, the ligament itself is unlikely to suspend the levator muscle. However, a suspension of the LPS may be achieved by the radial connective tissue septa of the superior orbit. The TSFE in connection with the globe may have an additional supporting function. The elasticity of Whitnall's ligament and its connections with highly elastic structures including Tenon's capsule, may provide the morphological substrate for the previously proposed passive (that is, without orbicularis action) lowering of the lid during downward saccades.


Topology optimization design of flextensional actuators.
Flextensional actuators can be defined as a piezoceramic (or a stack of piezoceramics) connected to a flexible mechanical structure that converts and amplifies the output displacement of the piezoceramic. Essentially, the actuator performance depends on the distribution of stiffness and flexibility in the coupling structure and, therefore, on the coupling structure topology. In this work, we propose a general method for designing flextensional actuators with large output displacement (or generative force) by applying the topology optimization method. The goal is to design a flexible structure coupled to the piezoceramic that maximizes the output displacement (or force) in some specified direction. Static and low frequency applications are considered. To illustrate the implementation of the method, 2-D topologies of flextensional actuators are presented because of the lower computational cost; however, the method can be extended to 3-D topologies. By designing other types of coupling structures connected to the piezoceramic, new designs of flextensional actuators that produce output displacements or forces in different directions can be obtained, as shown. This method can be extended for designing flextensional hydrophones and sonars.


Echo-time dependence of the BOLD response transients - A window into brain functional physiology.
The blood oxygenation level-dependent (BOLD) fMRI response to neuronal activation results from a complex interplay of induced metabolic and vascular changes. Thus, its transients, such as initial overshoot and post-stimulus undershoot, provide a window into the dynamic relationships of the underlying physiological variables. In this study, we propose multi-echo fMRI as a tool to investigate the physiological underpinnings of the BOLD signal, in particular, and brain functional physiology, in general. In the human visual cortex at 3 T, we observed that the BOLD response is nonlinearly dependent on echo-time (TE) and the amount of nonlinearity varies during the entire time-course. Fitting a linear model to this nonlinear relationship resulted in a positive intercept at TE = 0 ms. The time-course of the intercept exhibited fast and slow modulations, distinctly different both from the BOLD response and cerebral blood flow (CBF). In order to shed light on the TE-dependence of the BOLD signal and the intercept time-course, we performed simulations based on a nonlinear two-compartmental BOLD signal model combined with the dynamic balloon model. The modeling suggests that the intercept time-course reflects a weighted sum of deoxyhemoglobin concentration and venous CBV signal changes. We demonstrate that only CBF-venous blood volume (CBV) uncoupling but not CBF-oxygen metabolism (CMRO2) uncoupling can fully account for our experimental observations. In particular, these results strongly argue for a slow evolution of the venous CBV together with stimulus-type-dependent CBF transients (the latter being tightly coupled with CMRO2) to be responsible for the BOLD signal adaptation during stimulation and for the post-stimulus undershoot. Thus, BOLD signal transients are composed of smoothed version of neuronal time-course as reflected in CBF and CMRO2 and secondary vascular processes due to biomechanics of venous blood vessels, and multi-echo fMRI in combination with modeling provides invaluable insights into these physiological processes.


[Inferior petrosal sinus catheterization: technical aspects].
Inferior petrosal sinus catheterization and sampling for corticotropin dosage helps to differentiate hypophisary and ectopic forms of Cushing syndrome. The aim of this paper is to describe the technique used in inferior petrosal sinus catheterization in our service, emphasizing the solution found for frequent difficulties, and verify the success rate achieved. Between September/2000 and September/2005, forty-two (eighty-four sinuses) patients were submitted to inferior petrosal sinus sampling. The difficulties for correct catheter positioning were identified and correlated with their solutions. Anatomical variations, similarity between IPS and emissary vein of the basilar plexus and unfavorable flow to the contrastation of the structures (retrograde catheterization) were the main problems. Using pre-shaped catheters, curved, steerable guide-wires, road-mapping and venography by contalateral injection, besides criteria to differentiate IPS from the emissary vein. Of the 84 sinuses approached, one was thrombosed, and 80 (96.4%) of 83 possible were selectively catheterized. No clinical complication occurred. IPSC can be safe and successfully performed in most cases. The identification of the emissary vein of the basilar plexus and use of venography by contralateral injection, improved the method performance.


Evaluation of arterial catheter management in very preterm neonates: peripheral artery versus umbilical artery.
To evaluate whether peripheral arterial catheter management is more effective than umbilical arterial management in very preterm neonates. Thirty-eight very preterm neonates born in Fukushima Medical University Hospital between October 2008 and March 2010 were evaluated. A peripheral arterial catheter was inserted in 19 neonates (peripheral group) and an umbilical arterial catheter in the remaining 19 neonates (umbilical group). The median gestational ages of the peripheral and umbilical groups were 195 and 185 days, respectively (p=0.04). The systolic and diastolic blood pressure (BP) was significantly higher in the peripheral group than in the umbilical group (p=0.03 and p=0.001). There was a significant relationship between BP at cannulation and urinary output after cannulation for 24 h in the peripheral group (r(s)=0.49, p=0.03); however, no such significant relationship was found in the umbilical group. We considered that peripheral artery catheters provide a well-functioning route for continuous BP monitoring, even in very preterm neonates. Because umbilical catheter placement might affect urinary output, we speculated that peripheral arterial catheter placement would be a more effective management strategy than umbilical arterial catheter placement in very preterm neonates. Further studies of larger populations are necessary to evaluate the effectiveness of arterial management including long-term follow-up studies.


Optimization of SARS-CoV-2 Spike Protein Expression in the Silkworm and Induction of Efficient Protective Immunity by Inoculation With Alum Adjuvants.
The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a spread of coronavirus disease 2019 (COVID-19) globally. In order to end the COVID-19 pandemic, an effective vaccine against SARS-CoV-2 must be produced at low cost and disseminated worldwide. The spike (S) protein of coronaviruses plays a pivotal role in the infection to host cells. Therefore, targeting the S protein is one of the most rational approaches in developing vaccines and therapeutic agents. In this study, we optimized the expression of secreted trimerized S protein of SARS-CoV-2 using a silkworm-baculovirus expression vector system and evaluated its immunogenicity in mice. The results showed that the S protein forming the trimeric structure was the most stable when the chicken cartilage matrix protein was used as the trimeric motif and could be purified in large amounts from the serum of silkworm larvae. The purified S protein efficiently induced antigen-specific antibodies in mouse serum without adjuvant, but its ability to induce neutralizing antibodies was low. After examining several adjuvants, the use of Alum adjuvant was the most effective in inducing strong neutralizing antibody induction. We also examined the adjuvant effect of paramylon from Euglena gracilis when administered with the S protein. Our results highlight the effectiveness and suitable construct design of the S protein produced in silkworms for the subunit vaccine development against SARS-CoV-2.


Treatment effect of "ryu-wei-ti-huang-wan" (a Chinese herbal prescription) on the sexual performance of male rats with streptozotocin-induced diabetes.
The treatment effect of "ryu-wei-ti-huang-wan', a Chinese prescription composed of extracts from six plants, on diabetic impotence was evaluated in the present study. Adult male Wistar rats were divided into three groups: (1) rats rendered diabetic with a single intraperitoneal injection of streptozotocin (60 mg/kg body weight); (2) rats with streptozotocin-induced diabetes treated with a ryu-wei-ti-huang-wan powder preparation at a dose of 30 mg powder/kg body weight twice a day, and (3) control rats. A male rat was caged with an adult ovariectomized female rat during the dark cycle. Infra-red-light-illuminated video recording was utilized to evaluate the sexual performance. The diabetic rats exhibited depressed mounting activity and no intromission or ejaculation. After ryu-wei-ti-huang-wan treatment either for 1 day or 2 weeks, the diabetic rats showed significant improvement in mounting performance with preservation of intromission and ejaculation. No significant difference in the blood sugar level was noted between the treatment and non-treatment groups. In conclusion, the diabetic rats showed impairment in sexual arousal, erectile as well as ejaculatory functions. Ryu-wei-ti-huang-wan was effective in preserving these functions with a rapid onset. It is evident that the extracts exert the therapeutic effects not through a lowering of blood sugar. These substances are potentially useful in the clinical treatment of male diabetic impotence.


PECULIARITIES OF IMMUNE STATUS IN THE PRESENCE OF SECONDARY IMMUNODEFICIENCY OF INFECTIOUS AND NON-INFECTIOUS ORIGIN IN WOMEN OF REPRODUCTIVE AGE.
The design of studies on the immune system does not have gender peculiarities, but the information about the higher frequency of pathology of the female reproductive system in the presence of immunodeficiency condition determines the purpose of this study, namely, to identify the features of immune status in the presence of secondary immunodeficiency of infectious (i.e., HIV infection, AIDS stage) and non-infectious origin (alcohol dependence syndrome) and their combination in women of reproductive age. The material for the study of cellular and humoral immunity was a lymphocyte suspension obtained by centrifugation of peripheral blood (taken within 12 hours after death) in women of reproductive age with HIV infection (AIDS stage), alcohol dependence syndrome and their combination. Immunological examination included the determination of quantitative indicators of cellular immunity using monoclonal antibodies: T-lymphocytes (CD3) and their main subpopulations of T-helper cells (CD4), cytotoxic lymphocytes (CD8), CD4/CD8 immunoregulatory index; as well as indicators of humoral immunity: B-lymphocytes (CD19) and immunoglobulins of the main classes (IgA, IgG, IgM). Additionally, interleukins IL-6 and IL-10 were studied to determine the parameters of the cytokine profile. The study indicates that the number of leukocytes and lymphocytes in the group of deceased women with alcohol dependence syndrome was 3.6±0.38x109/l and 0.82±0.35x109/l; in deceased women with HIV/AIDS, these indicators were reduced - 2.9±0.03x109/l and 0.39±0.04x109/l, respectively; and in deceased women with combined pathology (AIDS and alcohol dependence syndrome), they were reduced even more intensively - 2.7±0.04x109/l and 0.35±0.06x109/l (p<0.01). Compared to the control group - 5.22±0.4x109/l and 1.73±0.21x109/l - the number of leukocytes and lymphocytes was reduced in all study groups. In the group of deceased women with alcohol dependence syndrome, significant impairments in the proliferative activity of T-lymphocytes (CD3) and their subpopulation (CD4), as well as B lymphocytes (CD19) and natural killer cells (CD16) were found compared to the group of healthy individuals. Thus, in the control group, the percentage, and absolute values of CD3 were 60.37±4.2% and 1.04±0.05×106/l, and in women suffering from chronic alcoholism, they were statistically significantly lower - 49.1±3.1% and 0.42±0.08×106/l, respectively, p<0.01. The same tendency was found when comparing the values of T-helper cells (CD4) in the control group (44.2±2.9% and 0.76±0.13×106/l) and in deceased patients suffering from chronic alcoholism (33.7±4.6% and 0.28±0.23×106/l), p<0.01. Secondary immunodeficiencies of infectious and non-infectious origin in women (in particular, those formed in HIV/AIDS, alcohol dependence syndrome and their combination) are characterized by negative changes in the cellular and humoral components of the immune system, as evidenced by the presence of transient immunodeficiency, activation of cytolytic and auto aggressive reactions. As a result of these processes, systemic and organ pathology develops, in particular, weakening of the body's resistance to various infections and pathological changes in organs and tissues, which may be one of the links in the development of pathological processes in internal organs and tissues.


Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.
The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs.


Multi-omics analyses of cognitive traits and psychiatric disorders highlights brain-dependent mechanisms.
Integrating findings from genome-wide association studies with molecular datasets can develop insight into the underlying functional mechanisms responsible for trait-associated genetic variants. We have applied the principles of Mendelian randomization (MR) to investigate whether brain-derived gene expression (n = 1194) may be responsible for mediating the effect of genetic variants on eight cognitive and psychological outcomes (attention deficit hyperactivity disorder (ADHD), Alzheimer's disease, bipolar disorder, depression, intelligence, insomnia, neuroticism and schizophrenia). Transcriptome-wide analyses identified 83 genes associated with at least one outcome (PBonferroni < 6.72 × 10-6), with multiple-trait colocalization also implicating changes to brain-derived DNA methylation at nine of these loci. Comparing effects between outcomes identified evidence of enrichment which may reflect putative causal relationships, such as an inverse relationship between genetic liability towards schizophrenia risk and cognitive ability in later life. Repeating these analyses in whole blood (n = 31 684), we replicated 58.2% of brain-derived effects (based on P < 0.05). Finally, we undertook phenome-wide evaluations at associated loci to investigate pleiotropic effects with 700 complex traits. This highlighted pleiotropic loci such as FURIN (initially implicated in schizophrenia risk (P = 1.05 × 10-7)) which had evidence of an effect on 28 other outcomes, as well as genes which may have a more specific role in disease pathogenesis (e.g. SLC12A5 which only provided evidence of an effect on depression (P = 7.13 × 10-10)). Our results support the utility of whole blood as a valuable proxy for informing initial target identification but also suggest that gene discovery in a tissue-specific manner may be more informative. Finally, non-pleiotropic loci highlighted by our study may be of use for therapeutic translational endeavours.


Postlicensure safety surveillance for high-dose trivalent inactivated influenza vaccine in the Vaccine Adverse Event Reporting System, 1 July 2010-31 December 2010.
In December 2009, a new high-dose, trivalent, inactivated influenza vaccine (TIV-HD) was licensed for adults aged ≥65 years. We characterized clinical patterns of reports to the Vaccine Adverse Event Reporting System (VAERS) among older adults who received TIV-HD. We searched VAERS for reports involving persons aged ≥65 years who received TIV-HD or TIV (standard dose) from 1 July 2010 through 31 December 2010. Medical records were requested for serious reports (ie, those associated with death, hospitalization or prolonged hospitalization, life-threatening illness, or disability). Clinicians reviewed information and assigned a diagnostic category to each report. Empirical Bayesian data mining was used to identify disproportional reporting following TIV-HD in VAERS. Reporting rates were calculated for reports of Guillain-Barré syndrome and anaphylaxis. VAERS received 606 reports after TIV-HD in persons aged ≥65 years (8.2% of reports involved serious events). The number of reports yielded by searches using the terms "ocular hyperemia" and "vomiting" exceeded the data mining threshold; >80% of these reports were nonserious. Clinical review of serious reports found that a greater proportion involving gastrointestinal events were made after TIV-HD receipt (5 of 51 [9.8%]) than after TIV receipt (1 of 123 [0.8%]). Four persons who received TIV-HD had gastroenteritis, and 1 had multiple gastrointestinal symptoms; all recovered. A higher proportion of cardiac events were noted after receipt of TIV-HD (9 of 51 [17.6%]) than after receipt of TIV (6 of 123 [4.9%]). No concerning clinical pattern was apparent. The reporting rates of Guillain-Barré syndrome and anaphylaxis after TIV-HD receipt were 1.4 and 1.0 reports per million doses distributed, respectively. During the first year after US licensure of TIV-HD, no new serious safety concerns were identified in VAERS. Our analyses suggested a clinically important imbalance between the reported and expected number of gastrointestinal events after TIV-HD receipt. Future studies should assess this potential association.


Severity of panic disorder, adverse events in childhood, dissociation, self-stigma and comorbid personality disorders Part 1: Relationships between clinical, psychosocial and demographic factors in pharmacoresistant panic disorder patients.
Little is known about the relation between severity of panic disorder, adverse events in childhood, dissociation, self-stigma and comorbid personality disorders. The aim of this study is to look for the intercorrelations between these factors. The study explores the relation between clinical, demographic and social factors in panic disorder using cross sectional design. The inpatients with pharmacoresistant panic disorder with and without agoraphobia were included in the study. Participants were also assessed for comorbidity with other anxiety or personality disorder. The Clinical Global Impression (CGI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Dissociative Experiences Scale (DES), Internalized Stigma of Mental Illness (ISMI), Childhood Trauma Questionnaire-Short Form (CTQ-SF), Panic Disorder Severity Scale (PDSS) and demographic data were used as measurement tools. A total of 142 pharmacoresistant patients with panic disorder with or without agoraphobia were admitted for 6-week cognitive behavioral therapy inpatient program in psychotherapeutic department between November 2015 and July 2019. One hundred and five inpatients (33 males and 72 females) with mean age 37.8 + 12.1 years were included in the study. Sixty-nine patients suffer from additional comorbid anxiety disorder and 43 had comorbid personality disorder.


Physiological and morphological effects of genistein against the liver fluke, Fasciola hepatica.
A study has been carried out to determine the activity of genistein against adult liver fluke, Fasciola hepatica. Flukes were incubated in vitro in genistein at a concentration of 0.27 mg/ml (=1 mM). They ceased to move after 3 h, at which point the experiment was terminated and the specimens prepared for examination by scanning and transmission electron microscopy. Surface changes to the flukes comprised swelling and blebbing, especially in the posterior region of the flukes, and there was particular disruption to the spines, accompanied by some spine loss. Fine structural changes to the tegumental syncytium indicated an accelerated release of secretory bodies at the surface, but a reduction in their production within the cell bodies. Autophagic activity was evident in the tegumental cells, a phenomenon that was also observed in the gastrodermal cells. Disruption to the testis and vitelline follicles was severe, with an apparent block in the normal developmental sequence of the spermatogenic and vitelline cells, respectively. Shell protein production by the vitelline cells was also disrupted. In separate experiments, somatic muscle strips were exposed to concentrations of genistein ranging from 1 microm to 1 mm. There were statistically significant increases in the frequency and/or amplitude of muscle contractions at concentrations of 10 microm, 100 microm and 1 mm. The results suggest that genistein is capable of causing severe morphological and neuromuscular disruption to adult flukes in vitro over a short time-span.


Identification of Fusobacterium species by the electrophoretic migration of glutamate dehydrogenase and 2-oxoglutarate reductase in relation to their DNA base composition and peptidoglycan dibasic amino acids.
Rapid identification of Fusobacterium spp. is hampered by their inability to ferment carbohydrates and the availability of relatively few useful phenotypic characters. In an attempt to identify new diagnostic markers for species, we reported recently the potential utility of glutamate dehydrogenase (GDH) electrophoretic mobilities for distinguishing eight species of Fusobacterium. We have extended these observations to include all recognised members of the genus except F. prausnitzii and F. perfoetens, and our results show that they cluster into three broad electrophoretic groups. Some species, such as F. periodonticum, F. simiae and F. necrophorum, possessed GDH with similar electrophoretic mobilities. However, within such clusters, the electrophoretic migration of 2-oxoglutarate reductase (OGR) distinguished between species. Neither GDH or OGR mobility alone clearly differentiated all species, but their combined use provided unambiguous discrimination of all species except F. varium and F. mortiferum. The DNA base compositions of all species except F. naviforme (ATCC 25832) and F. sulci, were within the range 26-34 mol% G + C, suggesting the genus may be homogeneous. However, the peptidoglycan composition divided the genus into two major groups that contained either lanthionine or diaminopimelic acid; F. mortiferum peptidoglycan contained both dibasic amino acids.


Depression and anxiety in patients undergoing left ventricular assist device implantation.
Depression and anxiety are associated with a worse prognosis in heart failure patients. The aim of this study was to identify the prevalence of depression and anxiety in left ventricular assist device (LVAD) candidates and assess their effect on post-LVAD outcomes. Based on the pre-LVAD psychological assessment, the total cohort of 246 patients were divided into 4 groups: 1) no depression or anxiety (NDep&Anx group, n = 138); 2) isolated depression (Dep group, n = 42); 3) isolated anxiety (Anx group, n = 32), and 4) combined depression and anxiety (Dep&Anx group, n = 34). The Dep&Anx group was associated with higher prevalence of female gender (p = 0.03), higher body mass index (p = 0.03), elevated E/E' (p = 0.003), and increased Model For End-Stage Liver Disease (MELD) XI score (p = 0.04) prior to LVAD as compared to the other 3 subgroups. The prevalence of other major psychiatric disorders (p = 0.03) and narcotic dependence (p = 0.004) was higher in the Dep&Anx group. Post-LVAD implantation, heart rate and filling pressures were elevated and readmission rate was higher (p = 0.001) in the Dep&Anx group. There was no difference in survival between the groups (p = 0.40, Log-Rank test). Pre-existing anxiety and depression was associated with worse HF pre- and post-LVAD implantation and higher readmissions rate after LVAD implantation.


[Electron transport chain in a thermophilic methane-oxidizing culture of Methylococcus thermophilus].
The electron transport chain was studied in the obligate methane oxidizing culture of Methylococcus thermophilus during the oxidation of methanol (the source of carbon) which is an oxidized derivative of methane as well as during the oxidation of hydroxylamine which is an intermediate in the oxidation of ammonium (the source of nitrogen) by Mc. thermophilus cells. Cytochromes a, b and c are involved in electron transport. Cytochrome cco and cytochrome c554 have been isolated from the cell-free extract of Mc. thermophilus and purified. A scheme for electron transport operating in the oxidation of methanol and hydroxylamine is suggested on the basis of studying the characteristics of these cytochromes. Cytochrome a was shown to be a component of terminal oxidase. Cytochromes b are connected with membranes and also found in the composition of hydroxylamine oxidase. Cytochrome cco and, possibly, terminal oxidase (cytochromes a) are involved, in the oxidation of CH3OH by methanol dehydrogenase, in electron transport; cytochrome c554 as well as cytochrome b and c in the composition of hydroxylamine oxidase participate in electron transport in the oxidation of NH2OH by hydroxylamine oxidase. The characteristics of the electron transport system in Mc. thermophilus are discussed.


Phylogenetic and ecologic perspectives of a monkeypox outbreak, southern Sudan, 2005.
Identification of human monkeypox cases during 2005 in southern Sudan (now South Sudan) raised several questions about the natural history of monkeypox virus (MPXV) in Africa. The outbreak area, characterized by seasonally dry riverine grasslands, is not identified as environmentally suitable for MPXV transmission. We examined possible origins of this outbreak by performing phylogenetic analysis of genome sequences of MPXV isolates from the outbreak in Sudan and from differing localities. We also compared the environmental suitability of study localities for monkeypox transmission. Phylogenetically, the viruses isolated from Sudan outbreak specimens belong to a clade identified in the Congo Basin. This finding, added to the political instability of the area during the time of the outbreak, supports the hypothesis of importation by infected animals or humans entering Sudan from the Congo Basin, and person-to-person transmission of virus, rather than transmission of indigenous virus from infected animals to humans.


SERS immunoassay analysis of Escherichia coli and Staphylococcus aureus based on sandwich-structured complex probe and target-induced strand displacement.
A direct and ultra-sensitive surface-enhanced Raman scattering (SERS) immunoassay method is introduced for the detection of Escherichia coli and Staphylococcus aureus. This methodology is based on a sandwich-structured complex probe (SCP) mechanism, combined with target-induced strand displacement. Moreover, by leveraging the amplified SERS signal from gold nanoparticles (AuNPs) corresponding to an increase in bacterial count, we achieve quantitative determination. The SCP demonstrates remarkable specificity, sensitivity, and anti-interference capability in bacterial detection. The detection limits for both bacterial strains are as low as 10 CFU/mL. In our selectivity tests, all peak intensities had standard deviations (n = 3) below 6%. Recoveries in normal human serum were 101-110% for E. coli and 96-101% for S. aureus. In milk, the recoveries were 102-105% for E. coli and 100-105% for S. aureus, respectively, demonstrating a high level of accuracy and resistance to interference. In addition, the SCP offers a dual-detection capability, enabling simultaneous diagnosis of multiple targets, which greatly simplifies the testing procedure. The findings underscore that this immunoassay platform fulfills the demand for rapid and precise pathogenic bacterial diagnosis, holding substantial potential for practical applications.


Evaluation of cardiotoxicity of anthracycline-containing chemotherapy regimens in patients with bone and soft tissue sarcomas: A study of the FDA adverse event reporting system joint single-center real-world experience.
To assess the occurrence of cardiotoxicity in patients with tumors receiving anthracycline-based chemotherapy, especially for sarcomas. This study summarized the types and frequency of adverse events (AEs) for three anthracyclines from the FDA adverse event reporting system (FAERS) database. FAERS data from January 2004 to June 2022 were collected and analyzed. Disproportionality analyses, logistic regression, and descriptive analysis were used to compare the differences in cardiac disorders. A retrospective cohort study was conducted in a single center between December 2008 and May 2022. Our hospital-treated patients with bone and soft tissue sarcomas (BSTSs) with anthracycline-containing chemotherapy were analyzed. Serum markers, echocardiography, and electrocardiography have been used to evaluate cardiotoxic events. One hundred thousand and seventy-five AE reports were obtained for doxorubicin (ADM), epirubicin (EPI), and liposome doxorubicin (L-ADM) from the FAERS database. ADM (OR = 3.1, p < 0.001), EPI (OR = 1.5, p < 0.001), and sarcomas (OR = 1.8, p < 0.001) may increase the probability of cardiac disorders. Cardiac failure, cardiotoxicity, and cardiomyopathy were anthracyclines' top 3 frequent AEs. Among patients receiving ADM-containing therapy, those with ADM applied at doses ≥75 mg/m2 /cycle were more likely to develop cardiac disorders than the other subgroups (OR = 3.5, p < 0.001). Patients younger than 18 are more likely to benefit from dexrazoxane prevention of cardiac failure. Six hundred and eighty-three patients with BSTSs receiving anthracycline-based chemotherapy were analyzed in our center. Patients receiving ADM-containing chemotherapy were likelier to experience abnormalities in serum troponin-T and left ventricular ejection fraction (p < 0.05). 2.0% (6/300) of patients receiving ADM-containing chemotherapy required adjustment of the chemotherapy regimen because of cardiotoxicity, whereas none were in the EPI or L-ADM groups. Among patients receiving anthracycline-containing therapy, patients with BSTSs were more likely to develop cardiac disorders than other tumors. In addition, patients with BSTSs receiving ADM chemotherapy had a higher likelihood of cardiotoxic events than those receiving EPI or L-ADM.


Selenium nanoparticles act as an intestinal p53 inhibitor mitigating chemotherapy-induced diarrhea in mice.
Selenium, at high-dose levels approaching its toxicity, protects tissues from dose-limiting toxicities of many cancer chemotherapeutics without compromising their therapeutic effects on tumors, there by allowing the delivery of higher chemotherapeutic doses to achieve increased cure rate. In this regard, selenium nanoparticles (SeNPs), which show the lowest toxicity among extensively investigated selenium compounds including methylselenocysteine and selenomethionine, are more promising for application. The key issue remains to be resolved is whether low-toxicity SeNPs possess a selective protective mechanism. p53 or p53-regulated thrombospondin-1 has each been confirmed to be an appropriate target for therapeutic suppression to reduce side effects of anticancer therapy. The present study demonstrated that SeNPs transiently suppressed the expression of many intestinal p53-associated genes in healthy mice. SeNPs did not interfere with tumor-suppressive effect of nedaplatin, a cisplatin analogue; however, effectively reduced nedaplatin-evoked diarrhea. Nedaplatin-induced diarrhea was associated with activation of intestinal p53 and high expression of intestinal thrombospondin-1. The preventive effect of SeNPs on nedaplatin-induced diarrhea was correlated with a powerful concomitant suppression of p53 and thrombospondin-1. Moreover, the high-dose SeNPs used in the present study did not suppress growth nor caused liver and kidney injuries as well as alterations of hematological parameters in healthy mice. Overall, the present study reveals that chemotherapeutic selectivity conferred by SeNPs involves a dual suppression of two well-documented targets, the p53 and thrombospondin-1, providing mechanistic and pharmacologic insights on low-toxicity SeNPs as a potential chemoprotectant for mitigating chemotherapy-induced diarrhea.


Metacognitive beliefs and processes in clinical anxiety in children.
Recent research has explored the role of metacognitive beliefs and processes in clinical anxiety in youth. The aim of this study was to examine the relationship between metacognitions and anxiety in 7- to 12-year-old children with and without clinical anxiety disorders. A secondary aim of the study was to investigate the psychometric properties of the recently developed Metacognitions Questionnaire for Children (MCQ-C). The sample consisted of 83 children (60.2% female; Oceanian 71.1%), comprising 49 children with anxiety disorders and 34 nonclinical children. All children completed self-report measures of anxiety, emotional difficulties, and metacognitions. A subsample of 7- to 8-year-old participants was used to explore whether young children could wholly comprehend all items on the MCQ-C. Positive and negative metacognitive beliefs and cognitive monitoring were significantly correlated with anxiety and emotional difficulties. Clinical children endorsed significantly more negative and more positive metacognitive beliefs than nonclinical children. Each subscale of the MCQ-C had poor internal consistency. Support for the criterion and convergent validity of the MCQ-C was found. The results suggest that certain metacognitions play a role in clinical anxiety in children but that psychometrically and developmentally validated measures of these concepts in younger individuals are needed.


Reduced axonal transport in Parkinson's disease cybrid neurites is restored by light therapy.
It has been hypothesized that reduced axonal transport contributes to the degeneration of neuronal processes in Parkinson's disease (PD). Mitochondria supply the adenosine triphosphate (ATP) needed to support axonal transport and contribute to many other cellular functions essential for the survival of neuronal cells. Furthermore, mitochondria in PD tissues are metabolically and functionally compromised. To address this hypothesis, we measured the velocity of mitochondrial movement in human transmitochondrial cybrid "cytoplasmic hybrid" neuronal cells bearing mitochondrial DNA from patients with sporadic PD and disease-free age-matched volunteer controls (CNT). The absorption of low level, near-infrared laser light by components of the mitochondrial electron transport chain (mtETC) enhances mitochondrial metabolism, stimulates oxidative phosphorylation and improves redox capacity. PD and CNT cybrid neuronal cells were exposed to near-infrared laser light to determine if the velocity of mitochondrial movement can be restored by low level light therapy (LLLT). Axonal transport of labeled mitochondria was documented by time lapse microscopy in dopaminergic PD and CNT cybrid neuronal cells before and after illumination with an 810 nm diode laser (50 mW/cm2) for 40 seconds. Oxygen utilization and assembly of mtETC complexes were also determined. The velocity of mitochondrial movement in PD cybrid neuronal cells (0.175 +/- 0.005 SEM) was significantly reduced (p < 0.02) compared to mitochondrial movement in disease free CNT cybrid neuronal cells (0.232 +/- 0.017 SEM). For two hours after LLLT, the average velocity of mitochondrial movement in PD cybrid neurites was significantly (p < 0.003) increased (to 0.224 +/- 0.02 SEM) and restored to levels comparable to CNT. Mitochondrial movement in CNT cybrid neurites was unaltered by LLLT (0.232 +/- 0.017 SEM). Assembly of complexes in the mtETC was reduced and oxygen utilization was altered in PD cybrid neuronal cells. PD cybrid neuronal cell lines with the most dysfunctional mtETC assembly and oxygen utilization profiles were least responsive to LLLT. The results from this study support our proposal that axonal transport is reduced in sporadic PD and that a single, brief treatment with near-infrared light can restore axonal transport to control levels. These results are the first demonstration that LLLT can increase axonal transport in model human dopaminergic neuronal cells and they suggest that LLLT could be developed as a novel treatment to improve neuronal function in patients with PD.


A histochemical study of the mucous cells in the bucco-pharyngeal region of four Indian freshwater fishes in relation to their origin, development, occurrence and probable functions.
Observations on the origin, development and occurrence of mucous cells in the bucco-pharyngeal region of Labeo rohita (Ham.), Cirrhinus mrigala (Ham.), Catla catla (Ham.) and Clarias batrachus (Linn.) have been made histochemically, by PAS technique. The mucous cells have been found to develop from ordinary epithelial cells of the stratum Malpighii which is situated immediately above the basement membrane. The different stages in the development of mucous cells are: 1. Formation stage: Some of the epithelial cells get modified into mucous cells according to the need of the organ concerned. 2. Maturation stage: The spherical shaped mucous cells now become elongated and enlarged due to accumulation of mucin. They remain embedded in the stratified mucosa of the bucco-pharyngeal cavity. 3. Functional stage: In the course, these cells discharge their contents -- mucin into the bucco-pharyngeal cavity through an opening. 4. Degenerationstage: The mucous cells become empty soon after discharging their contents and eventually degenerate...


[Mechanisms of acute pulmonary edema during meningococcal shock in children (author;s transl)].
Meningococcic shocks may induce fatal acute pulmonary edemas. Ten children, who died in this condition, have been compared to 19 others, who during the treatment of the shock, developed right heart failure, without acute pulmonary edema (8 deaths, 11 survivals). The three groups of children could not be differentiated regarding their clinical status on admission, during the shock phase, or the treatments administered. Composition, volume and speed of administration of fluids were similar in the three groups. An increase in pulmonary capillary permeability could have occurred, and lead to the development of acute pulmonary failure, as presented by the children of the first group.


Primary care evaluation of the elderly for elective surgery.
The role of the primary physician in the preoperative evaluation of the elderly patient is critical. Due to the many associated changes of aging, careful assessment is required to reduce morbidity and mortality, and to identify treatable medical conditions which increase operative risk. Although increasing age is a major risk factor for surgery, the increased incidence of major diseases may be more important than age alone. Emergency surgery also involves considerably greater risk. It is important that the patient be involved in the decision-making process to the extent possible, and also that adequate postoperative and discharge planning be part of the preoperative management of the elderly person.


Sensitizing human cervical cancer cells In vitro to ionizing radiation with interferon beta or gamma.
Human cervical cancer is often associated with human papilloma virus (HPV). HPV products, such as the oncoproteins E6 and E7, are known to disrupt the function of TP53 (formerly known as p53). The protein encoded by the TP53 gene plays a central role in managing cellular damage. Interferons are known to down-regulate E6/E7 and may therefore restore TP53 function and influence radiation sensitivity. We investigated whether IFNB or IFNG, at various concentrations (2- 300 IU/ml) and for a range of durations of exposure (from 48 h before to 8 h after irradiation), were able to modify the radiation response of HeLa, C4-1, Me-180, C33-A and SiHa cells. In parallel to the clonogenic assays, we analyzed the effect on the mRNA that encodes IFNB and E6 by Northern blotting in the same experimental conditions. A significant change in the initial slope of the dose-response curve was observed more consistently with IFNB than with IFNG. No changes in the mRNA or protein level of TP53 and E6 could be detected. Thus other mechanisms of action need to be investigated to explain radiosensitization with recombinant IFNB in cells of human cervical cancer cell lines.