Dietary vitamin D intake, cardiovascular disease and cardiometabolic risk factors: a sex-based analysis from the ATTICA cohort study.
The present study aimed to evaluate the association between dietary vitamin D intake and 10-year first fatal/nonfatal cardiovascular disease (CVD), conventional CVD risk factors and surrogate markers related to inflammation, coagulation, insulin resistance, liver and renal function. The ATTICA study was conducted during 2001-2012 including 1514 men and 1528 women (aged >18 years) from the greater Athens area, Greece. Dietary assessment was based on a validated semi-quantitative food frequency questionnaire. Daily intake of vitamin D was calculated using a standardised food database. Follow-up (2011-2012) was achieved in 2020 participants (n = 317 cases). Ranking from first to third vitamin D tertile, CVD events were 24%, 17% and 12% for men (P = 0.002) and 14%, 10% and 11% for women (P = 0.59). Inverse associations between vitamin D and CVD in total sample [hazard ratio (HR) = 0.76 95% confidence interval (CI) = 0.60-0.97] and in men (HR = 0.66 95% CI = 0.49-0.89) were observed, and lost after adjusting for inflammation/coagulation markers; for women, no significant trends were observed. Regarding 10-year onset of conventional risk factors, inverse associations of vitamin D with hypertension in men (HR = 0.62 95% CI = 0.39-0.99) and transition to metabolically unhealthy status in women (HR = 0.69 95% CI = 0.51-0.93) were observed. Significant inverse associations for C-reactive protein, interleukin-6 and fibrinogen in both sexes, whereas these were revealed only in women for insulin resistance. Contradicting the neutral/modest associations in vitamin-D supplementation trials, increased food-generated vitamin D may protect against hard and intermediate CVD endpoints, implying different paths between sexes.


Making annual indexes of health.
A discrete-state, continuous-time Markov model of health states and state transition probabilities is outlined as the basis of a health index that would reflect the annual health distribution and expected health changes of a population. The final index is an additive one, summing expected durations of the various health states over the entire population sample. The weights attached to the expected durations are derived from the instantaneous incidence rates, or intensity functions, that define the transition probabilities. A general procedure for collecting data during overlapping 6-week periods from numerous population subsamples is described.


Hemofiltration and double high flux dialysis: risks and benefits.
Convective therapies such as hemofiltration, hemodiafiltration and double high flux dialysis have been shown to improve treatment delivered and treatment tolerance when compared to conventional dialysis therapies. The risk associated with these treatments is primarily in the quality of the substitution fluid. Technological advances now permit on-line produced substitution fluid, thereby significantly reducing the cost associated with hemofiltration and hemodiafiltration. The quality of the substitution fluid is only assured when the quality of the RO water used is within the guidelines set by the Association for the Advancement of Medical Instrumentation (AAMI). Therefore, the success of the application of this therapy is dependent on the water treatment protocols in the dialysis units. The success of this modality as a treatment for chronic renal failure is dependent on identifying those patient groups who will benefit most from this more efficient but more expensive treatment.


Program sustainability of a community-based intervention to prevent falls among older Australians.
Multi-strategy interventions have been demonstrated to prevent falls among older people, but studies have not explored their sustainability. This paper investigates program sustainability of Stay on Your Feet (SOYF), an Australian multi-strategy falls prevention program (1992-1996) that achieved a significant reduction in falls-related hospital admissions. A series of surveys assessed recall, involvement and current falls prevention activities, 5 years post-SOYF, in multiple original SOYF stakeholder groups within the study area [general practitioners (GPs), pharmacists, community health (CH) staff, shire councils (SCs) and access committees (ACs)]. Focus groups explored possible behavioural changes in the target group. Surveys were mailed, except to CH staff and ACs, who participated in guided group sessions and were contacted via the telephone, respectively. Response rates were: GPs, 67% (139/209); pharmacists, 79% (53/67); CH staff, 63% (129/204); SCs, 90% (9/10); ACs, 80% (8/10). There were 73 older people in eight focus groups. Of 117 GPs who were practising during SOYF, 80% recalled SOYF and 74% of these reported an influence on their practice. Of 46 pharmacists operating a business during SOYF, 45% had heard of SOYF and 79% of these reported being 'somewhat' influenced. Of 76 community health staff (59%) in the area at that time, 99% had heard of SOYF and 82% reported involvement. Four SCs retained a SOYF resource, but none thought current activities were related. Seven ACs reported involvement, but no activities were sustained. Thirty-five focus group participants (48%) remembered SOYF and reported a variety of SOYF-initiated behaviour changes. Program sustainability was clearly demonstrated among health practitioners. Further research is required to assess long-term effect sustainability.


[Vertical ridge augmentation using a microplate in conjunction with a Gore-Tex membrane. A case report].
Oral implantology is considered an acceptable treatment modality to replace missing teeth when a recipient site with a sufficient horizontal and vertical bone volume exists. Guided bone regeneration is based on the principle of selective exclusion of non osteogenic cells from the bony defect by a barrier membrane. Several supporting systems of the barrier membrane have been successfully used to treat non space-mantaining de-fects. A 35-year-old female affected by a partial edentulism in the molar area of the right mandible showed 8 mm of bone height of the residual ridge above the alveolar canal. A vertical ridge augmentation was performed using a Gore-Tex membrane in conjunction with a microplate and an irradiated freeze-dried cortico-cancellous allograft. Six months after the surgical procedure a 11.5 mm by 5 mm threaded implant was placed into the regenerated bone. After three months of healing, the implant was uncovered and considered integrated. Before the implant placement, a biopsy of the regenerated bone was arried out by a triphine. The histological examination of the bony core showed the attainment of biological goals of guided bone regeneration. The surgical technique followes in this case report has been effective in regenerating a vertical bone volume sufficient for implant treatment.


Dendritic gold nanowire growth observed in liquid with transmission electron microscopy.
The growth of nanoscale gold dendrites was studied in situ in a thin liquid film with transmission electron microscopy (TEM) using a liquid cell with silicon nitride (SiN) windows. Gold nanoparticle seeds were covered by a thin liquid layer containing precursor solution. Dendrite nucleation was induced by the electron beam leading to an initial burst of growth. The growth then settled at tip velocities between 0.1 and 2.0 nm/s for different dendrites. Tip velocities fluctuated as different dendrite geometries grew from the tips. Those dendrites showing granularities in their structure experienced the largest growth speed. Comparison of the observed velocities with diffusion-limited growth rates suggests that dendrite growth in thin films at this scale is limited by diffusion. The described method may find application in research on the mechanisms behind dendrite growth and also to study other types of anisotropic growth of nanomaterials driven by crystal and twin geometries.


Neuromyelitis optica and opticospinal multiple sclerosis: Mechanisms and pathogenesis.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. In Asians, MS is rare; however, when it appears, the selective and severe involvement of the optic nerves and spinal cord is characteristic. This form, termed opticospinal MS (OSMS), has similar features to the relapsing form of NMO in Western populations. Recently, a specific IgG against NMO, designated NMO-IgG, was discovered, and the relevant antigen was found to be aquaporin-4 (AQP4), one of the major water channel proteins in the CNS. Because NMO-IgG has been reported to be present in 30-60% of OSMS patients, OSMS in Asians has been suggested to be the same entity as NMO. The sensitivity of NMO-IgG/anti-AQP4 antibody for NMO varies from 30% to 80%, while the specificity is 90-100%. Pathological studies on NMO have revealed perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions, where myelin basic protein (MBP) staining was relatively preserved. IgG from NMO-IgG-seropositive NMO patients induces astrocyte death in culture in the presence of complements, and reproduces astrocyte loss in vivo when MBP-specific T cells are co-transferred to cause experimental autoimmune encephalomyelitis. It is thus postulated that the complement-activating anti-AQP4 antibody plays a pivotal role in the development of NMO lesions through astrocyte necrosis, and that demyelination is a secondary event. However, in autopsied cases of NMO, we and others found that some demonstrated selective AQP4 loss while others showed preservation of AQP4, even in the acute lesions. We also found that, in some MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. In the CSF, proinflammatory cytokines such as IL-17, IL-8, IFNγ, and G-CSF are markedly elevated in OSMS patients, irrespective of the presence or absence of anti-AQP4 antibody. In OSMS and NMO patients, T cells reactive to myelin proteins show intra- and inter-molecular epitope spreading, suggesting that T cells are already stimulated with myelin antigens in vivo. These findings suggest that mechanism of NMO and OSMS in Asians is heterogeneous, anti-AQP4 antibody-related and -unrelated, and that not only anti-AQP4 antibody but also myelin-autoreactive Th17 or Th1 cells may also play a role in triggering CNS inflammation. Possible mechanisms for NMO and OSMS are discussed in this review.


Exercise training and energy restriction decrease neutrophil phagocytic activity in judoists.
To investigate the effects of weight reduction as the result of exercise training and energy restriction on neutrophil function. Eighteen male competitive college judoists participated in the study. In a whole blood assay, oxidative burst activity, phagocytic activity, expressions of Fc gamma receptor 3 (CD16), and complement receptor 3 (CD11b) of neutrophils were measured on a per cell basis by flow cytometry at day 20, 5, and 1 before and at day 7 after the competition. The rate of neutrophil producing reactive oxygen species decreased before the competition, whereas the oxidative burst activity per cell increased significantly in all subjects, which resulted in a significant increase of the total oxidative burst activity. However, there were no significant effect of energy restriction on oxidative burst activity. The rate of neutrophils incorporating opsonized zymosan decreased significantly with energy restriction. The total phagocytic activity of 10,000 neutrophils and the phagocytic activity per cell also decreased significantly by severe energy restriction. The surface antigen expressions of CD11b and CD16 were unaffected by weight reduction. The results suggest that with respect to the management of health conditions, weight reduction for judoists should be composed of exercise training and energy restriction should be moderate.


HLA-DPA1 gene is a potential predictor with prognostic values in multiple myeloma.
Multiple myeloma (MM) is an incurable hematological tumor, which is closely related to hypoxic bone marrow microenvironment. However, the underlying mechanisms are still far from fully understood. We took integrated bioinformatics analysis with expression profile GSE110113 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database, and screened out major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) as a hub gene related to hypoxia in MM. Differentially expressed genes (DEGs) were filtrated with R package "limma". Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed using "clusterProfiler" package in R. Then, protein-protein interaction (PPI) network was established. Hub genes were screened out according to Maximal Clique Centrality (MCC). PrognoScan evaluated all the significant hub genes for survival analysis. ScanGEO was used for visualization of gene expression in different clinical studies. P and Cox p value < 0.05 was considered to be statistical significance. HLA-DPA1 was finally picked out as a hub gene in MM related to hypoxia. MM patients with down-regulated expression of HLA-DPA1 has statistically significantly shorter disease specific survival (DSS) (COX p = 0.005411). Based on the clinical data of GSE47552 dataset, HLA-DPA1 expression showed significantly lower in MM patients than that in healthy donors (HDs) (p = 0.017). We identified HLA-DPA1 as a hub gene in MM related to hypoxia. HLA-DPA1 down-regulated expression was associated with MM patients' poor outcome. Further functional and mechanistic studies are need to investigate HLA-DPA1 as potential therapeutic target.


Task alters category representations in prefrontal but not high-level visual cortex.
A central question in neuroscience is how cognitive tasks affect category representations across the human brain. Regions in lateral occipito-temporal cortex (LOTC), ventral temporal cortex (VTC), and ventro-lateral prefrontal cortex (VLFPC) constitute the extended "what" pathway, which is considered instrumental for visual category processing. However, it is unknown (1) whether distributed responses across LOTC, VTC, and VLPFC explicitly represent category, task, or some combination of both, and (2) in what way representations across these subdivisions of the extended 'what' pathway may differ. To fill these gaps in knowledge, we scanned 12 participants using fMRI to test the effect of category and task on distributed responses across LOTC, VTC, and VLPFC. Results reveal that task and category modulate responses in both high-level visual regions, as well as prefrontal cortex. However, we found fundamentally different types of representations across the brain. Distributed responses in high-level visual regions are more strongly driven by category than task, and exhibit task-independent category representations. In contrast, distributed responses in prefrontal cortex are more strongly driven by task than category, and contain task-dependent category representations. Together, these findings of differential representations across the brain support a new idea that LOTC and VTC maintain stable category representations allowing efficient processing of visual information, while prefrontal cortex contains flexible representations in which category information may emerge only when relevant to the task.


New insights into the mechanisms of innate immune receptor signalling in fibrosis.
Recent advances in our understanding of innate immunity and inflammation have direct bearing on how we understand autoimmunity, and fibrosis, and how innate immune sensors might stimulate both of these key features of several fibrotic diseases. Toll-like receptors (TLRs) are the major receptors for recognizing pathogen associated molecular patterns present on bacterial cell walls, such as LPS, and nucleic acids (RNA and DNA). Several intracellular pathways mediate TLR effects and initiate various pro-inflammatory programs. Mechanisms for control of inflammation, matrix remodeling, and ultimately fibrosis are also activated. Transforming growth factor-beta (TGF-β), Interleukin-1 (IL-1), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-13 (IL-13), and interferon (IFNs) appear particularly important in regulating pro-fibrotic aspects of innate immune activation. These mechanisms appear important in fibrotic disease affecting multiple organ-systems, including lung, liver, kidney, and skin. These observations provide new paradigms for understanding the relationship between immunity/inflammation and fibrosis, however, the precise ligand and mechanism linking innate immune sensor(s) to fibrosis remain uncertain in most illnesses.


Intravenous digital subtraction angiography with iohexol.
Iohexol is a nonionic water-soluble iodinated contrast medium with chemical and physical properties similar to those of metrizamide. A randomized double-blind study was performed in 40 patients undergoing intravenous digital subtraction angiography for suspected carotid and vertebral disease to compare the radiographic imaging quality and side effects of iohexol with those of Renografin-76 (diatrizoate meglumine and diatrizoate sodium). The use of iohexol yielded a higher percentage of "excellent" images with a lesser incidence of image degradation due to swallowing and motion. Iohexol was also associated with milder and less frequent patient discomfort. No clinically significant changes in laboratory data parameters were observed with either contrast medium.


Effects of exercise on monocrotaline-induced changes in right heart function and pulmonary artery remodeling in rats.
Pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) is an experimental protocol of right heart failure. We analyzed the role of exercise training on the right ventricle structure and function, pulmonary artery remodeling, and GSK-3β expression. Rats were divided among the following groups: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), and trained monocrotaline (TM). Rats underwent exercise training for a period of 5 weeks, with 3 weeks post-MCT injection. Rats in the SM and TM groups presented with an increase in right ventricle hypertrophy indexes and lung congestion. The right ventricular end diastolic pressure (RVEDP), right ventricular systolic pressure (RVSP), and its minimum and maximal pressure derivates were increased in the SM and TM groups. The right ventricle interstitial volume pulmonary artery thickness and p-GSK-3β/GSK-3β were increased in the MCT groups as compared with the control groups. The TM group had a reduction in interstitial volume, p-GSK-3β/GSK-3β ratio, pulmonary artery thickness, RVEDP, and an increase in intramyocardial vessels volume as compared with the SM group. The overall results have shown that the exercise protocol used promoted positive changes in right ventricle and pulmonary artery remodeling. These observations also suggest that structural remodeling may be influenced by signaling proteins, such as GSK-3β.


A Typology of Familicide Perpetrators in Australia.
The murder of family members is one of the most difficult crimes to understand. This study uses Shye's action systems framework combined with multivariate data analysis to test the hypothesis that different forms of familicide will reflect the four states an action system can take, namely: Integrative, Expressive, Conservative and Adaptive. A multidimensional scaling analysis (MDS) was performed on 54 crime scene variables describing 104 cases of intra-familial homicide. The analysis revealed four distinct modes of functioning, which provided tentative support for Shye's action system. Each of the four modes had distinct associations with perpetrator characteristics. The Expressive and Integrative modes were associated with Cluster B personality traits, and criminal and substance use histories. The Adaptive mode was associated with trauma histories, mood disorders, and personality disorder traits. The Conservative theme was associated with trauma histories and psychotic disorders. Implications of findings for risk assessment and intervention are discussed.


Rotavirus infection in foals.
Fecal samples from 86 foals with diarrhea were examined by electron microscopy during a 2.5 year period. Of these, 26 (30%) were positive for rotavirus. All of the cases were found in epizootic areas. The disease was produced in an experimental foal by inoculation via stomach tube of a bacteria-free fecal filtrate containing rotavirus. Examination of postmortem tissues from the duodenum and jejunum of 2 naturally infected foals and an experimentally infected foal revealed replicating virus in the intestinal epithelial cells. A limited survey of complement-fixing antibody to rotavirus in horses from Kentucky, Virginia, and France indicated that all horses had antibody to the virus. The sole exception was 1 foal from which blood samples were collected prior to suckling. These results were presumptive evidence that rotavirus is a major cause of diarrhea in foals, and the presence of antibody in horses from diverse areas is evidence for the ubiquitousness of this infection.


Application of RNA polymerase beta-subunit gene (rpoB) sequences for the molecular differentiation of Legionella species.
The nucleotide sequences of the partial rpoB gene were determined from 38 Legionella species, including 15 serogroups of Legionella pneumophila. These sequences were then used to infer the phylogenetic relationships among the Legionella species in order to establish a molecular differentiation method appropriate for them. The sequences (300 bp) and the phylogenetic tree of rpoB were compared to those from analyses using 16S rRNA gene and mip sequences. The trees inferred from these three gene sequences revealed significant differences. This sequence incongruence between the rpoB tree and the other trees might have originated from the high frequency of synonymous base substitutions and/or from horizontal gene transfer among the Legionella species. The nucleotide variation of rpoB enabled more evident differentiation among the Legionella species than was achievable by the 16S rRNA gene and even by mip in some cases. Two subspecies of L. pneumophila (L. pneumophila subsp. pneumophila and subsp. fraseri) were clearly distinguished by rpoB but not by 16S rRNA gene and mip analysis. One hundred and five strains isolated from patient tissues and environments in Korea and Japan could be identified by comparison of rpoB sequence similarity and phylogenetic trees. These results suggest that the partial sequences of rpoB determined in this study might be applicable to the molecular differentiation of Legionella species.


The Botrytis cinerea early secretome.
The extracellular proteome, or secretome, of phytopathogenic fungi is presumed to be a key element of their infection strategy. Especially interesting constituents of this set are those proteins secreted at the beginning of the infection, during the germination of conidia on the plant surfaces or wounds, since they may play essential roles in the establishment of a successful infection. We have germinated Botrytis cinerea conidia in conditions that resemble the plant environment, a synthetic medium enriched with low molecular weight plant compounds, and we have collected the proteins secreted during the first 16 h by a double precipitation protocol. 2-D electrophoresis of the precipitated secretome showed a spot pattern similar for all conditions evaluated and for the control medium without plant extract. The proteins in 16 of these spots were identified by PMF and corresponded to 11 different polypeptides. Alternative determination of secretome composition by LC-MS/MS of tryptic fragments rendered a much larger number, 105 proteins, which included all previously identified by PMF. All proteins were functionally classified according to their putative function in the infection process. Key features of the early secretome include a large number of proteases, the abundance of proteins involved in the degradation of plant defensive barriers, and plenty of proteins with unknown function.


Enhancing maize productivity by mitigating alkaline soil challenges through acidified biochar and wastewater irrigation.
In alkaline soil conditions, the availability of essential nutrients for plant growth becomes limited, posing a significant challenge for achieving optimal maize growth and yield. Exploring the impact of biochar and waste irrigation on soil alkalinity and maize production in arid regions has received limited attention. This study aimed to evaluate the effects of three levels of acidified biochar (0, 5, and 10 Mg ha-1) in two growing seasons of maize-spring and autumn. The treatments were applied following a randomized complete block design with three replications. Biochar was applied only in the autumn season, and its residual effects were evaluated in the spring season. The study found that using acidifying biochar at a rate of 10 Mg ha-1 significantly increased maize yield by 35.8% compared to no application and by 16.4% compared to a rate of 5 Mg ha-1. In the autumn, applying acidified biochar at 10 Mg ha-1 reduced soil pH by 3.65% and 6.41% compared to 0 and 5 Mg ha-1. In the spring, the same application led to a decrease in soil pH by 5.84% and 7.37% compared to the lower rates. Additionally, using 10 Mg ha-1 of acidifying biochar increased soil phosphorus concentration by 87.6% and soil potassium concentration by 38.0% compared to not using biochar, and by 46.2% and 35.0% compared to the 5 Mg ha-1 application. These findings suggest that the reduction of soil pH by applying biochar at a rate of 10 Mg ha-1 facilitated an increase in nutrient availability in the soil, consequently leading to higher maize yield. Notably, no significant differences were observed in maize productivity and soil properties between the spring and autumn seasons. Therefore, this study paves the way for further exploration into the long-term effects of acidifying biochar on maize productivity and soil properties in similar agroecological contexts.


Kinetically assembled binary nanoparticle networks.
Embedding percolating networks of nanoparticles (NPs) within polymers is a promising approach for mechanically reinforcing polymers and for introducing novel electronic, transport, and catalytic properties into otherwise inert polymers. While such networks may be obtained through kinetic assembly of unary system of NPs, the ensuing structures exhibit limited morphologies. Here, we investigate the possibility of increasing the diversity of NP networks through kinetic assembly of multiple species of NPs. Using lattice Monte Carlo simulations we show that networks obtained from co-assembly of two NP species of different sizes exhibit significantly more diverse morphology than those assembled from a single species. In particular, we achieved considerable variations in the particle spatial distribution, proportions of intra- and interspecies contacts, fractal dimension, and pore sizes of the networks by simply modulating the stoichiometry of the two species and their intra and inter-species affinities. We classified these distinct morphologies into "integrated", "coated", "leaved", and "blocked" phases, and provide relevant phase diagrams for achieving them. Our findings are relevant to controlled and predictable assembly of particle networks for creating multifunctional composites with improved properties.


A novel cuproptosis-related gene prognostic signature in colon adenocarcinoma.
Cuproptosis is the latest cell death type caused by enhanced mitochondrial-dependent energy metabolism. This study plans to establish a survival prognosis model for colon adenocarcinoma (COAD) patients based on cuproptosis-related genes (CRGs). We investigated the genetic alterations of CRGs in COAD based on The Cancer Genome Atlas database and validated in the GSE41328 dataset. Our results showed that LIPT1, PDHA1, GLS, and CDKN2A had significantly higher expression in COAD tissues than in normal tissues, while FDX1, DLD, and MTF1 had significantly lower expression in COAD tissues than in normal tissues (|(log2(fold change))| > 2, p < 0.05). DLD (hazard ratio (HR): 0.658; 95% confidence interval (CI): 0.445, 0.974; p = 0.037) and CDKN2A (HR: 1.785; 95% CI: 1.200, 2.654; p = 0.004) expressions were linked with overall survival throughout a log-rank test. CRG prognostic scores exhibited an area under the curve of 0.737, 0.646, and 0.633 at 1, 3, and 5 years. Patients with a high-risk factor suffered from poor prognosis (HR = 1.514; 95% CI: 1.022, 2.243; p = 0.0386). An independent validation dataset (GSE41328 (N = 20)) confirmed the above results. The CRGs' signature may be used as a prognostic predictor for COAD patients, providing unique insights into anticancer therapy.


UP1 extends life of primary porcine fetal fibroblasts in culture.
Genetic modification of somatic cell nuclei and subsequent nuclear transfer has opened an opportunity to create gene-targeted animals. However, somatic cells have a limited life span in culture and it is not possible to introduce precise genetic changes in both alleles in this narrow time window. To increase the life span of somatic cell in culture, both genetic and chemical approaches have been tried with varying success. Here, we report the effect of two anti-oxidants, glutathione and n-t-butyl hydroxylamine, and of the expression of UP1, a shortened derivative of heterogeneous nuclear riboprotein (hnRNP)A1, on the life extension of primary porcine fibroblasts in culture. Under our experimental conditions, the use of anti-oxidants did not result in any prolongation of the life span. In contrast, UP1 expression increased the life span significantly. While most control cells stopped growing by PDL 20, and none survived beyond PDL 35, 100% of UP1-expressing clones reached PDL50, and 40% made it to PDL65. The five UP1-expressing clones were karyotyped at PDL 50. While all of them had a range of numerical chromosomal abnormalities, two clones retained 30-40% normal cells, all the cells in other three clones had abnormal chromosome numbers. Thus, expression of UP1 may be useful in extending the life span of somatic cells in culture. This, in turn, will facilitate the process of gene targeting in this cell type.


Battling the hematological malignancies: the 200 years' war.
The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti-folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients) and drug development costs become more expensive, and the significant negative long-term effects of current therapy on both children and adults. These challenges will be gradually overcome, if we (a) develop new models of cooperation among academia, industry, and government, (b) continue the growth of international participation in cancer research (more keen minds to the task), and (c) convince the governments of the world, including that of the U.S., that an investment in minimizing the effects of cancer is as important as defending against other threats to the welfare and longevity of their citizens.


Outpatient treatment trial of mild and severe hypertension.
Not much is known about the feasibility or the advantages of treatment of subjects with only mild hypertension. There are also many unresolved problems in the outpatient management of hypertension of any severity. In this study an analysis is made of the results of a controlled treatment trial of 56 subjects with mild hypertension, 26 of whom were treated with active drug and 30 initially with placebo, and a treatment programme involving 81 patients with moderate or severe hypertension, all of whom received treatment with active drug. The drugs used in this study were bethanidine, debrisoquine, and guanethidine.Follow-up for 12 months or more was achieved in 87% of individuals admitted to the study with mild hypertension and in 80% with severe hypertension. Many subjects with only mildly raised blood pressure were found to have cardiac enlargement on chest x-ray (up to 45%) and left ventricular hypertrophy on electrocardiogram (up to 51%). Rapid rates of rise of blood pressure were observed in many placebo-treated subjects; but good blood pressure control was achieved in 63 out of 104 patients (61%) receiving active drug in both the mild and the severe hypertension groups. The drugs used showed approximately equal effectiveness in controlling blood pressure.


Turbo-FLASH based arterial spin labeled perfusion MRI at 7 T.
Motivations of arterial spin labeling (ASL) at ultrahigh magnetic fields include prolonged blood T1 and greater signal-to-noise ratio (SNR). However, increased B0 and B1 inhomogeneities and increased specific absorption ratio (SAR) challenge practical ASL implementations. In this study, Turbo-FLASH (Fast Low Angle Shot) based pulsed and pseudo-continuous ASL sequences were performed at 7T, by taking advantage of the relatively low SAR and short TE of Turbo-FLASH that minimizes susceptibility artifacts. Consistent with theoretical predictions, the experimental data showed that Turbo-FLASH based ASL yielded approximately 4 times SNR gain at 7T compared to 3T. High quality perfusion images were obtained with an in-plane spatial resolution of 0.85×1.7 mm(2). A further functional MRI study of motor cortex activation precisely located the primary motor cortex to the precentral gyrus, with the same high spatial resolution. Finally, functional connectivity between left and right motor cortices as well as supplemental motor area were demonstrated using resting state perfusion images. Turbo-FLASH based ASL is a promising approach for perfusion imaging at 7T, which could provide novel approaches to high spatiotemporal resolution fMRI and to investigate the functional connectivity of brain networks at ultrahigh field.


Arthroplasty of the elbow joint using vascularized iliac bone graft for reconstruction of massive bone defect of the distal humerus.
The authors present a case of a 39-year-old man with an enormous bone defect of the distal humerus secondary to an infected nonunion, who was successfully reconstructed using a vascularized iliac bone graft. The use of a vascularized iliac bone graft may be an option for reconstructing such massive defects of the metaphyseal area of the humerus.


Pressure-induced ocular torsion.
We describe 3 patients within whom ocular torsion could be induced by application of positive air pressure to one external ear canal. In all cases, the superior pole of the eye rotated away from the stimulated ear when positive pressure was applied. The amplitude of torsion ranged from 3 degrees to 16 degrees. Exploratory tympanotomy was performed in all 3 patients. In 2 patients, round-window fistulas were found and repaired. In the third patient, no fistula was noted but the oval- and round-window areas were patched. There was no resolution of symptoms after surgery in any patient. Based on these cases, patients presenting with pressure-induced ocular torsion are unlikely to have resolution of their symptoms, even when a perilymphatic fistula is confirmed and repaired. We hypothesize that pressure-induced ocular torsion is caused by an irreversible juxtaposition of the utricle and stapes footplate.


Molecular cloning of steroid hydroxylases.
Recombinant plasmids specific for bovine adrenocortical cytochromes P-450scc and P-45011 beta have been identified and characterized. Using these cDNA inserts as probes, it is found that tissue specificity of gene expression for these two proteins is as expected. Cytochrome P-450scc mRNA is found in adrenocortical and corpus luteum RNA while cytochrome P-45011 beta mRNA is found only in adrenocortical RNA. Neither mRNA was detected in heart, liver or kidney RNA. Cytochrome P-450scc mRNA is found to be 1.9 kb in length while cytochrome P-45011 beta mRNA is found to be 4 kb in length. Treatment of bovine adrenocortical cells with ACTH or other modulators results in increased levels of cytochrome P-450scc and cytochrome P-45011 beta mRNAs. Cytochrome P-450scc is found to be encoded by a limited number or even a single gene.


The SalGI restriction endonuclease. Enzyme specificity.
We have analysed the kinetics of DNA cleavage in the reaction between the SalGI restriction endonuclease and plasmid pMB9. This reaction is subject to competitive inhibition by DNA sequences outside the SalGI recognition site; we have determined the Km and Vmax. for the reaction of this enzyme at its recognition site and the KI for its interaction at other DNA sequences. We conclude that the specificity of DNA cleavage by the enzyme is only partly determined by the discrimination it shows for binding at its recognition sequence compared with binding to other DNA sequences.


Flowing-gas diode pumped alkali lasers: theoretical analysis of transonic vs supersonic and subsonic devices.
We examine transonic diode pumped alkali laser (DPAL) devices as a simpler alternative to supersonic devices, suggested by B.D. Barmashenko and S. Rosenwaks [Appl. Phys. Lett. 102, 141108 (2013)], where complex hardware, including supersonic nozzle, diffuser and high power mechanical pump, is required for continuous closed cycle operation. Three-dimensional computational fluid dynamics modeling of transonic (Mach number M ~0.9) Cs and K DPALs, taking into account the kinetic processes in the lasing medium is reported. The performance of these lasers is compared with that of supersonic (M ~2.5) and subsonic (M ~0.2) DPALs. For Cs DPAL the maximum achievable power of transonic device is lower than that of supersonic, with the same resonator and Cs density at the laser section inlet, by only ~3% implying that supersonic operation mode has only small advantage over transonic. On the other hand, for subsonic laser the maximum power is by 7% lower than in transonic, showing larger advantage of transonic over subsonic operation mode. The power achieved in supersonic and transonic K DPALs is higher than in subsonic by ~80% and ~20%, respectively, showing a considerable advantage of supersonic device over transonic and of transonic over subsonic.


Impact of high UV fluences on the mechanical and sensing properties of polymer optical fibers for high strain measurements.
PMMA-based fibers are widely studied for strain measurements and show repeatable results for Fiber Bragg Gratings (FBGs) inscribed using 325 nm laser and 248 nm laser. However, there is no available material mechanical behavior characterization of the UV source impact on the fiber properties. In this manuscript, fibers are irradiated with high fluence of 325 nm and 248 nm lasers and the fibers properties are investigated using dynamic mechanical analysis and tensile strain for potential use of these fibers past the yield point. It is demonstrated that the UV sources shifted the ultimate tensile strength and changed the strain hardening behavior. Tensile strain measurements show excellent repeatability for gratings inscribed with these two sources with similar sensitivity of 1.305 nm/mɛ for FBG inscribe with 325 nm laser, and 1.345 nm/mɛ for grating written with 248 nm laser in the range 0 to 1.5 % elongation. Furthermore, tests far beyond the yield point (up to 2.8 % elongation) show that grating inscribed with lower UV wavelength exhibit hysteresis. Finally, we demonstrate that 248 nm laser fluence shall be chosen carefully whereas even high 325 nm laser fluence do not critically impact the sensor properties.


Synthesis of Highly Biocompatible and Temperature-Responsive Physical Gels for Cryopreservation and 3D Cell Culture.
There is considerable interest in the cryopreservation in 3D cell culture, as structurally preserving intact cells and tissues is critical in utilizing these systems to promote cell differentiation and tissue organization. Temperature-responsive physical gels and zwitterionic polymers are useful materials as 3D scaffolds for cell culture which may also provide cryoprotection to the composite cells. Nevertheless, there has been a lack of relevant data for polymer systems that have both of these properties. In this study, highly biocompatible triblock copolymers were examined for their effectiveness both as gelators and as cryo-protectants. The triblock copolymers were synthesized with 2-methacryloyloxyethyl phosphorylcholine (MPC) and di(ethylene glycol) methyl ether methacrylate (DEGMA) via atom transfer radical polymerization (PDEGMA113-b-PMPC243-b-PDEGMA113). ABA triblock copolymers composed of hydrophilic "B" block and temperature responsive "A" block could form physical gels above their lower critical solution temperatures (LCST). PDEGMA113-b-PMPC243-b-PDEGMA113 triblock copolymer exhibited the LCST derived from DEGMA and assembled in micellar structures forming physical gels above the LCST. The mechanical properties of the physical gels were evaluated by rheological tests, and the low toxicity of PDEGMA113-b-PMPC243-b-PDEGMA113 was confirmed by MTT assay. Interestingly, the triblock copolymer showed ice recrystallization inhibition (IRI) activity which was determined to be suitable for the cryopreservation of several cell lines. In vitro studies were conducted to demonstrate the cryo-protectant properties and the formation of two and three-dimensional (2D/3D) cell culture scaffolds with high biocompatibility. This stimuli-responsive gelator polymers can therefore be useful for cryopreservation of different cells models, and a promising material for 3D cell culture.


Superoxide production of human polymorphonuclear leukocytes stimulated by leukotriene B4.
Leukotriene B4 stimulated a transient production of superoxide anions (O2-) by human polymorphonuclear leukocytes which continued for only about 1 min. The production was dependent on Ca2+ in the suspending medium and no production was observed without the addition of calcium. The concentrations of leukotriene B4 and calcium for the half-maximal production were about 1 microM and 200 microM, respectively. 8-(N,N,-Diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an intracellular calcium antagonist, did not inhibit the O2- production stimulated by leukotriene B4 in the presence of calcium, while N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin inhibitor, did. When leukotriene B4 was added to the cells treated with cytochalasin B, the production of O2- was biphasic: an initial rapid phase, followed by a slow one. The slow phase was also dependent on Ca2+ concentrations but it could be induced even without the addition of Ca2+ to the medium. The cells treated with both cytochalasin B and TMB-8 in Ca2+-free medium showed a negligible production of superoxide on addition of leukotriene B4, but the production appeared upon addition of CaCl2. These findings suggest that the superoxide production stimulated by leukotriene B4 is associated with the influx of Ca2+.


Beta-Lactam vs. Fluoroquinolone Monotherapy for Pseudomonas aeruginosa Infection: A Systematic Review and Meta-Analysis.
Pseudomonas aeruginosa (PA) is a leading cause of healthcare-associated infections. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs) and fluoroquinolones (FQs), given either together in combination therapy or alone in monotherapy. A systematic review and meta-analysis were performed to evaluate the therapeutic efficacy of BL agents versus FQ agents as active, definitive monotherapy in PA infections in adults. Comprehensive literature searches of the Medline and Scopus electronic databases, alongside hand searches of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar, were performed without a time restriction to identify studies published in English comparing BL and FQ agents given as monotherapy for PA infection in hospitalized adults for which mortality, bacteriological eradication, or clinical response was evaluated. One reviewer screened search results based on pre-defined selection criteria. Two reviewers independently assessed included studies for methodological quality using NIH assessment tools. Two fixed-effects meta-analyses were performed. A total of 368 articles were screened, and six studies involving 338 total patients were included in the meta-analysis. Upon evaluation of methodological quality, two studies were rated good, three fair, and one poor. A meta-analysis of three studies demonstrates FQ monotherapy is associated with significantly improved survival compared to BL monotherapy for patients with PA bacteremia (OR, 3.65; 95% CI, 1.27-10.44; p = 0.02). A meta-analysis of three studies demonstrates FQ monotherapy is associated with equivalent bacteriological eradication compared to BL monotherapy for PA pneumonia or skin and soft tissue infection (RD, 0.07; 95% CI, -0.09 to 0.24; p = 0.39). The meta-analyses demonstrate FQ monotherapy significantly improves survival in PA bacteremia and is associated with similar rates of bacteriological eradication in pneumonia and skin and soft tissue infection caused by PA compared to BL monotherapy. However, more research is needed to make meaningful clinical recommendations.


Comparison of different media for preservation and transport of viable rickettsiae.
Rickettsiae tend to have a rapid decrease of viability outside living cells. Therefore, the transport of samples containing viable rickettsiae for culturing in cell culture for diagnostic purposes is challenging. The viability of rickettsiae in different transport media (commercially available transport medium COPAN "UTM-RT transport medium for viruses, chlamydia, mycoplasma, and ureaplasma," minimal essential medium (MEM) with and without 10% foetal calf serum) at various time points at 4 °C and at ambient temperature (22 °C) was compared. Rickettsia honei was used as model organism. After 2 weeks of storage at room temperature, no viable rickettsiae were detectable any more while storage at 4 °C kept rickettsiae viable for up to 4 weeks. The commercially available COPAN medium showed similarly good or slightly better stabilizing effects on rickettsiae compared with MEM + 10% foetal calf serum, pure MEM demonstrated the poorest results. It is important to transport and store media with potentially rickettsiae-containing samples at 4 °C to prevent inactivation. MEM + 10% foetal calf serum can be used if no commercial medium is available with similarly good results.


Iodine Intake through Processed Food: Case Studies from Egypt, Indonesia, the Philippines, the Russian Federation and Ukraine, 2010-2015.
The current performance indicator for universal salt iodisation (USI) is the percentage of households using adequately iodised salt. However, the proportion of dietary salt from household salt is decreasing with the increase in consumption of processed foods and condiments globally. This paper reports on case studies supported by the Global Alliance for Improved Nutrition (GAIN)-UNICEF USI Partnership Project to investigate processed food industry use of adequately iodised salt in contrasting national contexts. Studies were conducted in Egypt, Indonesia, the Philippines, the Russian Federation, and Ukraine. In all cases, the potential iodine intake from iodised salt in selected food products was modelled according to the formula: quantity of salt per unit of food product × minimum regulated iodine level of salt at production × average daily per capita consumption of the product. The percent of adult recommended nutrient intake for iodine potentially provided by the average daily intake of bread and frequently consumed foods and condiments was from 10% to 80% at the individual product level. The potential contribution to iodine intake from the use of iodised salt in the processed food industry is of growing significance. National USI strategies should encourage co-operative industry engagement and include regulatory monitoring of iodised salt use in the food industry in order to achieve optimal population iodine status.


Immunological quantitation of levels of tissue inhibitor of metalloproteinase-1 in human colon cancer.
Treatment of rodent cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate activates protein kinase C, leading to increased expression of several genes, including a gene originally designated TPA-S1 or phorbin (M. D. Johnson, G. M. Housey, P. T. Kirschmeier, and I. B. Weinstein, Mol. Cell Biol., 7: 2821-2829, 1987). Sequence analysis of this cloned gene indicated homology with human erythroid-potentiating activity and tissue inhibitor of metalloproteinase (TIMP-1). Elevated levels of phorbin mRNA have been observed in human colon tumors (J. G. Guillem, M. F. Levey, L. L. Hsieh, M. D. Johnson, P. LoGerfo, K. A. Forde, and I. B. Weinstein, Mol. Carcinogen., 3: 68-74, 1990) and this increase correlated with the extent of invasion. To further investigate this phenomenon at the protein level, monoclonal antibodies were developed against the recombinant form of TIMP-1. A competitive enzyme-linked immunosorbent assay was developed for quantitation of the TIMP-1 protein in tissue extracts. Elevated levels of TIMP-1 protein were found in 31 human colon tumors, compared to paired samples of adjacent normal mucosa. In a subset of samples, previously analyzed for phorbin mRNA levels (n = 25), there was a good correlation between the abundance of TIMP-1 protein and phorbin mRNA. Immunoaffinity column purification of tumor extracts followed by Western blot analysis was used to confirm the enzyme-linked immunosorbent assay data. These results provide evidence that phorbin and TIMP-1 represent the same gene. In addition, the immunoassays we have developed may be useful in further studies on the role of TIMP-1 in human colon cancer.


PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
While reversible histone modifications are linked to an ever-expanding range of biological functions, the demethylases for histone H4 lysine 20 and their potential regulatory roles remain unknown. Here we report that the PHD and Jumonji C (JmjC) domain-containing protein, PHF8, while using multiple substrates, including H3K9me1/2 and H3K27me2, also functions as an H4K20me1 demethylase. PHF8 is recruited to promoters by its PHD domain based on interaction with H3K4me2/3 and controls G1-S transition in conjunction with E2F1, HCF-1 (also known as HCFC1) and SET1A (also known as SETD1A), at least in part, by removing the repressive H4K20me1 mark from a subset of E2F1-regulated gene promoters. Phosphorylation-dependent PHF8 dismissal from chromatin in prophase is apparently required for the accumulation of H4K20me1 during early mitosis, which might represent a component of the condensin II loading process. Accordingly, the HEAT repeat clusters in two non-structural maintenance of chromosomes (SMC) condensin II subunits, N-CAPD3 and N-CAPG2 (also known as NCAPD3 and NCAPG2, respectively), are capable of recognizing H4K20me1, and ChIP-Seq analysis demonstrates a significant overlap of condensin II and H4K20me1 sites in mitotic HeLa cells. Thus, the identification and characterization of an H4K20me1 demethylase, PHF8, has revealed an intimate link between this enzyme and two distinct events in cell cycle progression.


Survey of needle-stick injuries in paediatric health personnel of 5 university hospitals in Tehran.
To study the prevalence and correlates of needle-stick injury in the health personnel of the Paediatric Department of five university-affiliated hospitals in Tehran, from April till June 2009. Cross-sectional questionnaire survey. Physicians undergoing paediatric training and nurses working in the paediatric departments filled up a pre-designed questionnaire. Relevant variables were compared between doctors and nurses. Three-hundred fifty-five health personnel were enrolled. Of these 49.3% had incurred needle stick injury at least once, 36.7% doctors and 54.9% nurses (p=0.002). Nurses fared better than the doctors as regards knowledge about hazards of improper needle disposal. Correct answers from doctors and nurses respectively were: 45.6% vs. 59.3% about needle separation and 41.9% vs. 81.2% about recapping, (p=0.02 and <0.001). Doctors 11.1% and Nurses 37.7% believed injections to be better than oral medication for children, (p<0.001), however, 68.9% of doctors and 46.6% of nurses believed that parents preferred injections to oral medicines for their children, (p<0.001). Only 26.6% knew about auto-disable syringes. Vaccinated against Hepatitis B was present in 92.7%. Doctors 58.7% and 55.3% nurses knew HBV to be the most common needle transmitted infection, (p=0.56). Needle-stick injuries are common among Paediatric health care personnel and their knowledge about prevention strategies is suboptimal. Most, health personnel are immunized against Hepatitis B.


Enterovibrio baiacu sp. nov.
We report here the novel species to encompass the isolate A649T (=CBAS 716T = CBRVS P1061T) obtained from viscera of the healthy pufferfish Sphoeroides spengleri (Family Tetraodontidae). Genomic taxonomy analysis demonstrates that the novel strain A649T had < 95% average amino acid identity/average nucleotide identity (AAI/ANI) and < 70% similarity of genome-to-genome distance (GGDH) towards its closest neighbors which places A649T into a new Enterovibrio species (Enterovibrio baiacu sp nov.). In silico phenotyping disclosed several features that may be used to differentiate related Enterovibrio species. The nearly complete genome assembly of strain A649T consisted of 5.4 Mbp and 4826 coding genes.


Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis.
Insomnia is a multi-factorial disorder with conventional treatment options that are not satisfactory for many patients. This metaanalysis analyzed the safety and efficacy of daridorexant. An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively. Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one. Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia. The registration number is CRD42022335233. www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).


Pulsed-field gel electrophoresis analysis of virus assemblages present in a hypersaline environment.
A method for analyzing virus assemblages in aquatic environments was developed and used for studying the highest-salinity ponds (from 13.4 to 35% salinity) from a multi-pond solar saltern in Alicante, Spain. The protocol consisted of a series of concentration and purification steps including tangential flow filtration and ultracentrifugation, followed by the preparation of total viral nucleic acids that were subsequently separated by pulsed-field gel electrophoresis. For every sample analyzed, a characteristic DNA pattern was obtained, whose complexity was related to viral diversity. The comparison of our results with a similar analysis carried out with marine virus assemblages shows that, as expected, the viral diversity corresponding to the analyzed hypersaline environment is considerably lower than that of a marine environment.


Teaching treatment planning. A problem-solving model.
An effective physical therapist must be able to identify a patient's problems and the cause of the problems and to plan specific treatments with a sound rationale. This article presents a model used as a teaching tool for treatment planning may be used in both academic and clinical settings. Questions that are used in completing the model and examples of the model's application are presented. Teaching the problem-solving model and its use in one physical therapy curriculum are discussed.


Acceleration mechanism of abrasive particle in ultrasonic polishing under synergistic physical vibration and cavitation: Numerical study.
Ultrasonic technology is widely applied in the engineering ceramic polishing processes without the limitation of material properties and ideally integrated into computer numerical control system. Ultrasonic-induced cavitation and mechanical vibration effect could accelerate the motion of solid abrasives. The individual behaviors of microjet/shockwave of ultrasonic cavitation in gases and liquids, and micro-abrasives with simple harmonic vibrations in solids and liquids has been extensively studied. To conduct a systematic and integrated study of abrasives behavior in the polishing contact region involving abrasive, surround-workpiece wall, ultrasonic physical vibration, and ultrasonic cavitation impact, a novel model integrating the free abrasive motion velocity and fixed abrasive indentation depth under multi-scale contact was proposed according to Hertzian contact theory, Greenwood-Williamson model, indentation deformation theory, the basic equations of cavitation bubble dynamics, cavitation impact control equations, and Newton's law of motion equation. The effects of ultrasonic amplitude, ultrasonic frequency, preloading force and particle size on the proposed model were investigated by theoretical analysis and numerical simulations. Ultrasonic physical vibration mainly influences the dynamic gap and further influence the number of different abrasives. Furthermore, the indentation depth of fixed abrasive depends mainly on the abrasive geometry. As the contact gap and abrasive size decrease, the indentation depth gradually decreases. Under the synergistic effect of cavitation-induced shock wave and microjet, the velocity of free abrasive in this paper is generally 0-150 m/s, and the kinetic energy of free abrasive increases roughly linearly with increasing frequency and approximately as a quadratic function with increasing particle size. Increasing the preloading force leads to a reduction in the abrasive kinetic energy. Besides, the kinetic energy induced by the shock wave has a cliff-like increment at an amplitude of 0.7-0.8 μm. It is revealed that the abrasive kinetic energy is suppressed by the cavitation bubble expansion and collapse at smaller ultrasonic pressure amplitude and surround-wall distance. This research provides a theoretical reference for the modeling of potential defects and material removal on the workpiece surface caused by abrasive motion during polishing, and reduces the trial cost for parameter optimization in actual polishing processing.


Glycosaminoglycan production by murine melanoma variants in vivo and in vitro.
Glycosaminoglycan (GAG) synthesis of B-16 melanoma metastatic variants was examined in vivo and in vitro to begin to assess the relationship between the presence of these polymers and the process of primary invasion and metastasis. The variants that were examined for GAG production included the F-1 line that exhibits low metastatic potential, the F-10 line selected for high metastatic potential, and the BL6 line selected for high invasiveness. The F-1 cell line was routinely less invasive than the F-10 and BL6 lines when injected s.c. into the legs of irradiated Swiss Webster mice. All cell lines formed palpable tumors after s.c. injection, but histological sections revealed early and extensive invasion in only F-10 and BL6 tumors. The F-1 tumors were surrounded by a connective tissue capsule and did not begin to invade into host tissue until this structure disappeared approximately 16 days after injection of tumor cells. Some consistent alterations in GAG synthesis, particularly the release of hyaluronic acid and heparan sulfate, were observed among the cell lines in vivo and in vitro, although differences observed in vitro were small and variable. In vivo all tumors were surrounded by a hyaluronic acid-rich zone that was concentrated at the tumor-stromal interface and was transitory. Hyaluronate occurred as a diffuse band around BL6 and F-10 tumors but was confined to a capsule surrounding the less aggressive F-1 tumor. In vitro the BL6 and F-10 cell lines released larger amounts of heparan sulfate and hyaluronic acid than did the F-1 cell line. Differences in release of chondroitin sulfate by the cell lines were not observed. Differences in trypsin-releasable GAG, presumably associated with the glycocalyx, were also not apparent. These results link the release in vitro and organization in vivo of hyaluronic acid and heparan sulfate to invasion and metastasis.


Anti-lipopolysaccharide and anti-tumor necrosis factor/cachectin antibodies for the treatment of gram-negative bacteremia and septic shock.
Endotoxin is composed of lipid A, the toxic moiety, of the core region, a conserved structure among Gram-negative bacteria, and of the O-side chains, a highly variable part responsible for the antigenic specificity. The concept of cross-protection afforded by antiserum raised against the core region of endotoxin is supported by the following data: experimentally antiserum protected against infections caused by a wide range of Gram-negative bacteria or endotoxins; in patients with Gram-negative bacteremia, survival was associated with high levels of anti-core antibodies, and mortality was reduced by the prophylactic or therapeutic use of immune serum or plasma. However, the proof that protection is afforded by cross-protective anti-core antibodies is still lacking. Furthermore, many experimental studies and clinical studies trials have shown controversial results. Ongoing experimental studies and recently completed clinical trials, using either polyclonal or monoclonal anti-core antibodies should help clarify the issues both of the clinical efficacy and of the mechanism of protection. Tumor necrosis factor/cachectin has been unequivocally shown, both in experimental animal models and in humans to be a pivotal mediator of the clinical and humoral manifestations of shock induced by endotoxin or by whole Gram-negative bacteria. In humans, TNF was been transiently detected in the blood of volunteers challenged with endotoxin, in a small proportion of patients with Gram-negative sepsis, but in the vast majority of patients with established septic shock. However, in patients the magnitude and the evolution of the blood concentration of TNF differed from that observed in animal models or in human volunteers after an acute challenge with either Gram-negative bacteria or endotoxin, probably reflecting differences in infectious stimuli. In children with meningococemia and in adults with Gram-negative septic shock, TNF was associated with the patient's outcome. Anti-TNF monoclonal antibodies are presently undergoing clinical investigation in patients with septic shock. However, one should keep in mind that TNF serves both beneficial and detrimental functions depending upon its concentration in body fluids.


TriMEDB: a database to integrate transcribed markers and facilitate genetic studies of the tribe Triticeae.
The recent rapid accumulation of sequence resources of various crop species ensures an improvement in the genetics approach, including quantitative trait loci (QTL) analysis as well as the holistic population analysis and association mapping of natural variations. Because the tribe Triticeae includes important cereals such as wheat and barley, integration of information on the genetic markers in these crops should effectively accelerate map-based genetic studies on Triticeae species and lead to the discovery of key loci involved in plant productivity, which can contribute to sustainable food production. Therefore, informatics applications and a semantic knowledgebase of genome-wide markers are required for the integration of information on and further development of genetic markers in wheat and barley in order to advance conventional marker-assisted genetic analyses and population genomics of Triticeae species. The Triticeae mapped expressed sequence tag (EST) database (TriMEDB) provides information, along with various annotations, regarding mapped cDNA markers that are related to barley and their homologues in wheat. The current version of TriMEDB provides map-location data for barley and wheat ESTs that were retrieved from 3 published barley linkage maps (the barley single nucleotide polymorphism database of the Scottish Crop Research Institute, the barley transcript map of Leibniz Institute of Plant Genetics and Crop Plant Research, and HarvEST barley ver. 1.63) and 1 diploid wheat map. These data were imported to CMap to allow the visualization of the map positions of the ESTs and interrelationships of these ESTs with public gene models and representative cDNA sequences. The retrieved cDNA sequences corresponding to each EST marker were assigned to the rice genome to predict an exon-intron structure. Furthermore, to generate a unique set of EST markers in Triticeae plants among the public domain, 3472 markers were assembled to form 2737 unique marker groups as contigs. These contigs were applied for pairwise comparison among linkage maps obtained from different EST map resources. TriMEDB provides information regarding transcribed genetic markers and functions as a semantic knowledgebase offering an informatics facility for the acceleration of QTL analysis and for population genetics studies of Triticeae.


A key requirement for CD300f in innate immune responses of eosinophils in colitis.
Eosinophils are traditionally studied in the context of type 2 immune responses. However, recent studies highlight key innate immune functions for eosinophils especially in colonic inflammation. Surprisingly, molecular pathways regulating innate immune activities of eosinophil are largely unknown. We have recently shown that the CD300f is highly expressed by colonic eosinophils. Nonetheless, the role of CD300f in governing innate immune eosinophil activities is ill-defined. RNA sequencing of 162 pediatric Crohn's disease patients revealed upregulation of multiple Cd300 family members, which correlated with the presence of severe ulcerations and inflammation. Increased expression of CD300 family receptors was also observed in active ulcerative colitis (UC) and in mice following induction of experimental colitis. Specifically, the expression of CD300f was dynamically regulated in monocytes and eosinophils. Dextran sodium sulfate (DSS)-treated Cd300f-/- mice exhibit attenuated disease activity and histopathology in comparison with DSS-treated wild type (WT). Decreased disease activity in Cd300f-/- mice was accompanied with reduced inflammatory cell infiltration and nearly abolished production of pro-inflammatory cytokines. Monocyte depletion and chimeric bone marrow transfer experiments revealed a cell-specific requirement for CD300f in innate immune activation of eosinophils. Collectively, we uncover a new pathway regulating innate immune activities of eosinophils, a finding with significant implications in eosinophil-associated gastrointestinal diseases.


[Spanish version of Adonis Complex Questionnaire. A questionnaire to test the muscle dimorphism and vigorexy].
To validate the Spanish version of Adonis Complex Questionnaire in bodybuilders. Participants included 99 bodybuilders who train regularly (age: 25.45±5.19 y; BMI=24.53±1.89). In order to test the discriminant and concurrent validity the Exercise Dependence Scale-Revised (EDS-R) and the Eating Attitudes Test (EAT-26) were used. The scale's psychometric properties were obtained through a concurrent validity process, factorial analysis of principal components, internal consistency, and test-retest reliability. The internal consistency of this questionnaire was high (Cronbach's Alpha= 0.880) in total scale. The intraclass correlation coefficient (ICC) to test the temporal consistency of the questionnaire was 0.707 (95% IC=0.336- 0.871). The questionnaire obtained concurrent validity with the EDS-R (r=0.613, p<0.001), and EAT-26 (r=0.422, p<0.001). The results have shown a three-factor structure Factor 1: psychosocial effect of physical appearance, Factor 2: control of physical appearance, Factor 3: concern about physical appearance which explain 65.29% of variance. The Adonis Complex Questionnaire shows a proper psychometric properties and it is a valid and reliable measure of vigorexy and muscle dimorphism in bodybuilders.


Relationships between immunogen structure and antisera specificity in the narcotic alkaloid series.
We report the production and comparative specificities of antisera raised to different immunogens containing codeine, morphine, and oxycodone. Antisera raised to bovine serum albumin (BSA) conjugates of codeine-6-hemisuccinate, ethylmorphine-6-hemisuccinate, or oxycodone-6-carboxymethyloxime had greatest recognition of structural changes around the piperidine ring nitrogen atom and th 14-position. N-carboxypropylnormorphine-BSA, N-carboxypropylnorcodeine-BSA, and norcodeine-BSA (directly coupled) conjugates elicited antisera that recognized structural changes at the 3- and 6-positions best, but also clearly discerned changes in the 14-substituent. Attachment of codeine to BSA via the 8-position gave a conjugate that elicited antisera with specificity characteristics similar to those of the antiserum to N-carboxypropylnorcodeine-BSA. Thus clear relationships existed between immunogen structure and antiserum specificity. The utility of these antisera was illustrated by the application of antiserum to codeine-6-hemisuccinate-BSA and solvent extraction to a study of codeine disposition in the dog. The specific antisera of N-carboxypropylnormorphine-BSA and to norcodeine-BSA were applied directly to an examination of the distribution of codeine and metabolically produced morphine in the milk and plasma of a nursing mother.


Empowering qualities and skills for leaders in neurosurgery.
Neurosurgeons may have multiple roles including clinician, educator, researcher, and administrator. Leaders in neurosurgery have the added responsibilities of setting a vision, communicating the vision, implementing a plan to achieve it, and gaining commitment from the team and other stakeholders. For success in the current era of U.S. health care, neurosurgical leaders must deliver despite challenges such as reduced resources, increased protocolized care, automation, and depersonalization. In this work, we describe five empowering strategies that can help leaders perform best. The steps include deepening self-awareness, leading with honesty, developing emotional intelligence, improving coaching skills, and becoming a better influencer. Leaders that take these steps to invest in their leadership skills will reap broad benefits.


Using Biometric Sensor Data to Monitor Cancer Patients During Radiotherapy: Protocol for the OncoWatch Feasibility Study.
Patients with head and neck cancer (HNC) experience severe side effects during radiotherapy (RT). Ongoing technological advances in wearable biometric sensors allow for the collection of objective data (eg, physical activity and heart rate), which might, in the future, help detect and counter side effects before they become severe. A smartwatch such as the Apple Watch allows for objective data monitoring outside the hospital with minimal effort from the patient. To determine whether such tools can be implemented in the oncological setting, feasibility studies are needed. This protocol describes the design of the OncoWatch 1.0 feasibility study that assesses the adherence of patients with HNC to an Apple Watch during RT. A prospective, single-cohort trial will be conducted at the Department of Oncology, Rigshospitalet (Copenhagen, Denmark). Patients aged ≥18 years intended for primary or postoperative curatively intended RT for HNC will be recruited. Consenting patients will be asked to wear an Apple Watch on the wrist during and until 2 weeks after RT. The study will include 10 patients. Data on adherence, data acquisition, and biometric data will be collected. Demographic data, objective toxicity scores, and hospitalizations will be documented. The primary outcome is to determine if it is feasible for the patients to wear a smartwatch continuously (minimum 12 hours/day) during RT. Furthermore, we will explore how the heart rate and physical activity change over the treatment course. The study will assess the feasibility of using the Apple Watch for home monitoring of patients with HNC. Our findings may provide novel insights into the patient's activity levels and variations in heart rate during the treatment course. The knowledge obtained from this study will be essential for further investigating how biometric data can be used as part of symptom monitoring for patients with HNC. ClinicalTrials.gov NCT04613232; https://clinicaltrials.gov/ct2/show/NCT04613232. PRR1-10.2196/26096.


Relative Contribution of Risk Factors for Early-Onset Myopia in Young Asian Children.
To investigate the associations of near work, outdoor activity, and anthropometric risk factors with early-onset myopia in Singaporean preschool children. Pregnant women who attended their first-trimester clinic at two major maternity units were recruited for the GUSTO birth cohort (n = 1236). Cycloplegic autorefraction and axial length (AL) were obtained in 3-year-old children (n = 572). Parents completed detailed questionnaires on parental myopia, near work, and outdoor activities when the child was 2 years of age. Height and weight were measured in the children at various time points from birth to 3 years of age. Among the cohort of 572 children, 35 children (6.1%) had early-onset myopia. In multivariable regression models, compared to children whose parents were not myopic, those with two myopic parents were more likely to have a more myopic spherical equivalent (SE) (regression coefficient: -0.36; 95% confidence interval [CI]: -0.61 to -0.11) and longer AL (regression coefficient: 0.24; 95% CI: 0.10-0.39) and more likely to have myopia (odds ratio [OR] = 4.8; 95% CI: 1.4-16.6). Neither near work nor outdoor activity was associated with SE, AL, and myopia. Taller children were found to have longer AL at birth and at 12, 24, and 36 months, but there were no associations with SE. Genetic factors may have a greater contribution to early development of refractive error compared to environmental factors.


[Intensive culture of fresh water fish].
Recently, eel recirculation systems have provoked increasing attention in intensive fish culture, especially concerning animal welfare. "Aquaculture", "Intensive Culture", and "Recirculation Systems" are often confused with each other. This study, first of all, differentiates among these terms. The economic relevance of aquaculture in the Federal Republic of Germany is demonstrated by figures. A tendency towards intensive methods can only be seen in trout and eel culture. The problems of recirculation systems are explained comprehensively. Particular emphasis is laid on the conflict between theoretical suitability of intensive fish production and the absence of commercially working systems. At present, intensive fish culture does not pose a serious animal welfare problem in Germany. However, it is necessary to define the biological requirements of fish concerning their optimal accommodation in aquaculture facilities. According to the Law for the Protection of Animals, these requirements have to be laid down in an ordinance. Only then control is possible as to whether aquaculture systems fulfill fish welfare demands.


Clinical efficacy of nebulized drugs.
There is a mandatory need for effortless drug administration to young children since the prevalence among them of recurrent wheezing is a 15-20%. It is becoming increasingly evident that many of these children respond dramatically well to beta2-agonists and topical steroids; accordingly this sub-group of children should be treated as asthmatics. The dose of topical steroids is critical as opposed to that of beta2-agonists which are often administered in doses well above the minimal effective dose. Budesonide suspension has proven its efficacy in adults in a study of 21 patients with asthma treated with budesonide suspension delivered from a nebulizer activated during inspiration versus metered dose inhalation (MDI) via a large-volume spacer. Nebulized in this manner the suspension exhibited a dose-dependent effect, apparently equipotent to the MDI administration as evaluated from daily peak expiratory flow measurements and symptom scoring. Continuous nebulization of budesonide in 18 schoolchildren with bronchial asthma similarly showed a dose-dependent improvement of lung function and symptom score, though in a 1:2 potency ratio as compared to MDI administration, probably due to loss of nebulized aerosol during expiration. In a subsequent study of 23 young children unresponsive to beta2-agonist therapy, nebulized budesonide was without demonstrable effect. Recently, a study of 31 young children with steroid-dependent asthma demonstrated a significant improvement from continuous nebulization of budesonide 1mg twice daily. In conclusion, the efficacy of nebulized budesonide has been convincingly demonstrated in patients with reversible symptoms of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)


Evolutionary origin and sequence signatures of the heterodimeric ABCG5/ABCG8 transporter.
ATP-binding cassette (ABC) systems, characterized by ABC-type nucleotide-binding domains (NBDs), play crucial roles in various aspects of human physiology. Human ABCG5 and ABCG8 form a heterodimeric transporter that functions in the efflux of sterols. We used sequence similarity search, multiple sequence alignment, phylogenetic analysis, and structure comparison to study the evolutionary origin and sequence signatures of ABCG5 and ABCG8. Orthologs of ABCG5 and ABCG8, supported by phylogenetic analysis and signature residues, were identified in bilaterian animals, Filasterea, Fungi, and Amoebozoa. Such a phylogenetic distribution suggests that ABCG5 and ABCG8 could have originated in the last common ancestor of Amorphea (the unikonts), the eukaryotic group including Amoebozoa and Opisthokonta. ABCG5 and ABCG8 were missing in genomes of various lineages such as snakes, jawless vertebrates, non-vertebrate chordates, echinoderms, and basal metazoan groups. Amino-acid changes in key positions in ABCG8 Walker A motif and/or ABCG5 C-loop were observed in most tetrapod organisms, likely resulted in the loss of ATPase activity at one nucleotide-binding site. ABCG5 and ABCG8 in Ecdysozoa (such as insects) exhibit elevated evolutionary rates and accumulate various changes in their NBD functional motifs. Alignment inspection revealed several residue positions that show different amino-acid usages in ABCG5/ABCG8 compared to other ABCG subfamily proteins. These residues were mapped to the structural cores of transmembrane domains (TMDs), the NBD-TMD interface, and the interface between TMDs. They serve as sequence signatures to differentiate ABCG5/ABCG8 from other ABCG subfamily proteins, and some of them may contribute to substrate specificity of the ABCG5/ABCG8 transporter.


A critical evaluation of fasted state simulating gastric fluid (FaSSGF) that contains sodium lauryl sulfate and proposal of a modified recipe.
The aim of this work is to evaluate one of the most commonly used fasted state simulating gastric fluids (FaSSGFs), which contains sodium lauryl sulfate (SLS) (FaSSGF(SLS)), and propose a more appropriate surfactant concentration. Surface tension studies clearly show that the critical micelle concentration (CMC) of SLS in the relevant media (a media whose pH and sodium chloride concentration are representative of physiological conditions) is significantly lower (p<0.05) than 8.67 mM, which is the SLS concentration in FaSSGF(SLS). The CMC of SLS in the relevant media was determined to be 1.75 mM. Based on this a modified recipe is proposed in which the concentration of SLS is sufficient to achieve a surface tension similar to that in vivo without causing artificial micellar solubilization. Solubility, intrinsic dissolution, and GastroPlus modeling studies are presented to support and give rationale for the modified recipe. In addition, a comparison between the modified recipe and other FaSSGFs reported in the literature is made.


The relation between myocardial blush grade and myocardial contrast echocardiography: which one is a better predictor of myocardial damage?
Background. Myocardial blush grade (MBG) and myocardial contrast echocardiography (MCE) are both indices for myocardial perfusion in patients with ST-elevation acute myocardial infarction (STEMI). We aimed to compare MBG with MCE in the infarct-related artery segment for assessing infarct size in patients with STEMI treated with primary percutaneous coronary intervention (PCI).Methods. 43 patients underwent successful (postprocedural TIMI flow 3) primary PCI for STEMI. MBG was assessed at the end of the PCI procedure and MCE was assessed 1.7+/-1.8 days after PCI. Enzymatic infarct size was estimated by measurementof enzyme activities by using lactate dehydrogenase (LDH) as the referenceenzyme. Cumulative enzyme release (LDHQ(48)) from at least five serial measurements up to 48 hours after symptom onset was calculated. Also peak creatine kinase, CK-MB and peak LDH were measured.Results. MBG 0/1, 2 and 3 were observed in 14, 12 and 17 patients, respectively, and was compared with tertiles of MCE. We found a parallel correlation between both MBG and MCE and LDHQ(48). However, there was no correlation between MCE and MBG. Patients with both normal MCE and a normal MBG had least myocardial damage and those with both impaired MCE and an impaired MBG had most myocardial damage.Conclusion. Both MBG and MCE are good predictors of infarct size in STEMI patients treated with PCI. However, these markers are not mutually related, possibly due to time-related changes in myocardial perfusion. Combining these two markers may yield a more accurate prediction of final myocardial damage. (Neth Heart J 2010;18:25-30.).


A review of methods to determine the functional arterial parameters stiffness and resistance.
In treatment of hypertension not only the pressure response is of interest, but also the effect on arterial parameters, for example, stiffness and resistance, is essential. We therefore reviewed what quantitative information on arterial stiffness can be obtained from pressure wave analysis. Using data from published large cohort studies, we derived relations between stiffness and the pressure-derived variables systolic pressure, pulse pressure, augmentation index (AIx), return time of reflected wave and reflection magnitude. All pressure-derived variables give limited information on arterial function in terms of stiffness and resistance, except AIx (in low stiffness range only). Input impedance as a comprehensive description of the arterial system is too complex to derive and interpret in practice, but is accurately described by three parameters: systemic vascular resistance, total arterial stiffness, and aortic characteristic impedance (outflow tract size and proximal aortic stiffness). These parameters predict aortic pressure well in terms of magnitude and shape: with measured flow the predicted (p) and measured (m) systolic, Ps, and diastolic, Pd pressures relate as Ps,p=0.997 Ps,m-1.63 and Pd,p=1.03 Pd,m-3.12 mmHg (n=17). Therefore, methods should be developed to determine, preferably noninvasively, these three arterial parameters. Variables derived from pressure wave shape alone (e.g. inflection point, AIx among others), and wave separation (e.g. reflection magnitude), while predicting cardiovascular events, give little information on arterial function. We propose to develop new, and improve existing, noninvasive methods to determine systemic vascular resistance, total arterial stiffness, and aortic characteristic impedance. This will allow quantifying the response of arterial function to treatment.


Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2.
Two types of acyl-CoA synthetase (ACS), designated ACS1 and ACS2, are structurally similar isozymes with different tissue distributions. The two enzymes are organized into the following five regions: an NH2 terminus; two luciferase-like regions; a linker connecting the luciferase-like regions; a COOH terminus. Under the control of a lac promoter, rat ACS1 and ACS2 were overproduced in Escherichia coli and purified to homogeneity. The specific activities of the purified ACS1 and ACS2 were 26.2 mumol.min-1.mg-1 and 7.4 mumol.min-1.mg-1, respectively, and the most efficiently utilized saturated fatty acids were those with 10-18 carbon atoms. Among unsaturated fatty acids with 16-22 carbon atoms, the most preferred substrates were palmitoleate, oleate and linoleate for ACS1, and, for ACS2, oleate, arachidonate, eicosapentaenoate and docosahexaenoate. To determine the functionally important regions in the ACS isozymes, we constructed five ACS1 mutants lacking each of the five regions. Introduction of these mutants into E. coli revealed that all five regions in ACS1 are required for functional expression of the enzyme in E. coli; deletion of any one of the five regions almost completely abolished the enzyme activity.


A multi-stage approach to clustering and imputation of gene expression profiles.
Microarray experiments have revolutionized the study of gene expression with their ability to generate large amounts of data. This article describes an alternative to existing approaches to clustering of gene expression profiles; the key idea is to cluster in stages using a hierarchy of distance measures. This method is motivated by the way in which the human mind sorts and so groups many items. The distance measures arise from the orthogonal breakup of Euclidean distance, giving us a set of independent measures of different attributes of the gene expression profile. Interpretation of these distances is closely related to the statistical design of the microarray experiment. This clustering method not only accommodates missing data but also leads to an associated imputation method. The performance of the clustering and imputation methods was tested on a simulated dataset, a yeast cell cycle dataset and a central nervous system development dataset. Based on the Rand and adjusted Rand indices, the clustering method is more consistent with the biological classification of the data than commonly used clustering methods. The imputation method, at varying levels of missingness, outperforms most imputation methods, based on root mean squared error (RMSE). Code in R is available on request from the authors.


[Structural changes in the marker chromosome of rhesus macaques subjected to irradiation].
Using 48 Macaca rhesus undergone acute single does and prolonged small dose daily irradiation, a long-term preservation of reconstructions in the pair of marker nucleolus-forming chromosomes has been shown. The animals were examined in different periods from irradiation, ranging from 3 months to 16.5 years. The frequency of retained reconstructions in the long arms of chromosomes was reliably above the frequency of alterations in the short arms. Reconstructions in the long arms of the marker chromosome were seen in the heterochromatin area after differential chromosome staining. Alterations in the functionally active area of the short arms of the marker chromosome retained extremely rarely being observed only in monkeys that survived through long-term small-dose irradiation.


Challenges Posed by Transnational Commercial Surrogacy: The Jurisprudence of the European Court of Human Rights.
There is little consensus between European States regarding the legal treatment of surrogacy in general and of transnational commercial surrogacy in particular. Against this background, the jurisprudence of the European Court of Human Rights (ECtHR) in this matter is of particular significance since it provides some common ground for the legal treatment of transnational commercial surrogacy in Europe. For this reason, the present paper will outline the development of the jurisprudence of the ECtHR on transnational commercial surrogacy, giving particular attention to the Mennesson and Labassee decisions, the Paradiso/Campanelli case, and the 2019 Advisory Opinion. On this basis, it will conclude by underlining the importance of the best interests of the child principle in the jurisprudence of the ECtHR on transnational commercial surrogacy.


Breast cancer seeking agents: basic approach.
The knowledge of biochemical and physiological mechanisms involved in tissue localization is important so as to understand the information given by diagnostic nuclear medicine imaging, and eventually to design new radiopharmaceuticals. The cellular mechanisms which permit a high cancer uptake involve the perfusion and metabolism around the tumour tissue, the interference with normal function, the altered perfusion and/or metabolism within the tumour. All these phenomena can contribute to a high concentration of particular radiotracers in cancer and can create a favourable tumour/background ratio uptake sufficient for cancer imaging. Those molecules might be also powerful tools for reaching an advanced understanding of neoplastic and even "normal" cell biology. During these last years, some radiotracer specifically designed for different applications proved to be promising radiopharmaceuticals for breast cancer imaging. This is the case of monoclonal antibodies (Mabs) developed in the past against membrane cancer antigens. Other tracers, originally proposed for the study of vascular perfusion (cardiovascular tracers), have also revealed a capacity to be taken up by cancer cells. The radiopharmaceuticals mostly used as tumour seeking agents today (Radiothallium, Sestamibi, Tetrophosmin) were generated with other applications in mind. In this paper we review the mechanisms of uptake of the most relevant agents currently proposed for breast cancer imaging, including 18F-fluorodeoxyglucose (FDG). The radiotracers will be examined on the basis of the available scientific evidence regarding their cellular uptake and release. Moreover, we report our preliminary studies on the cellular uptake and release of these and other compounds recently introduced in clinical trials.


Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus.
The emergence and global spread of the pandemic H1N1 2009 influenza virus have raised questions regarding the protective effect of available seasonal vaccines and the efficacy of a newly produced matched vaccine. Ferrets were immunized with the 2008-2009 formulations of commercially available live attenuated (FluMist; MedImmune) or split-inactivated (Fluviral; GlaxoSmithKline) vaccines, a commercial swine vaccine (FluSure; Pfizer), or a laboratory-produced matched inactivated whole-virus vaccine (A/Mexico/InDRE4487/2009). Adaptive immune responses were monitored, and the animals were challenged with A/Mexico/InDRE4487/2009 after 5 weeks. Only animals that received the swine or matched vaccines developed detectable hemagglutination-inhibiting antibodies against the challenge virus, whereas a T cell response was exclusively detected in animals vaccinated with FluMist. After challenge, all animals had high levels of virus replication in the upper respiratory tract. However, preexisting anti-pandemic H1N1 2009 antibodies resulted in reduced clinical signs and improved survival. Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10. The present study demonstrates that a single dose of matched inactivated vaccine confers partial protection against a pandemic H1N1 2009 virus, and it suggests that a higher dose or prime-boost regimen may be required. The consequences of mismatched immunity to influenza merit further investigation.


Polymerase chain reaction-based genotype classification among human Blastocystis hominis populations isolated from different countries.
Since the genotype of human Blastocystis hominis isolates is highly polymorphic, PCR-based genotype classification using known sequenced-tagged site (STS) primers would allow the identification or classification of different genotypes. Five populations of human B. hominis isolates obtained from Japan, Pakistan, Bangladesh, Germany, and Thailand were subjected to genotype analysis by using seven kinds of STS primers. Ninety-nine out of 102 isolates were identified as one of the known genotypes, while one isolate from Thailand showed two distinct genotypes and two isolates from Japan were negative with all the STS primers. The most dominant genotype among four populations, except for all four isolates from Thailand, was subtype 3 and it varied from 41.7% to 92.3%. The second most common genotype among four populations was either subtype 1 (7.7-25.0%) or subtype 4 (10.0-22.9%). Subtype 2, subtype 5, and/or subtype 7 were only rarely detected among the isolates from Japan and Germany, while subtype 6 was not detected. The phylogenetic position of the two isolates which were negative with all STS primers, was inferred from the small subunit rRNA (SSU rRNA) genes with the known sequence data of 20 Blastocystis isolates. Since the two isolates were positioned in an additional clade in the phylogenetic tree, this suggested they were a new genotype. These results demonstrated that PCR-based genotype classification is a powerful tool with which to analyse genotypes of Blastocystis isolates obtained from clinical samples. In addition, two groups of the isolates from 15 symptomatic and 11 asymptomatic patients in Bangladesh were compared with the PCR-based subtype classification. Since both groups were only classified into two distinct genotypes of subtype 1 or subtype 3 and no statistically significant difference was observed between the two groups, in this study it could not be shown that the specific genotype correlated with the pathogenic potential of B. hominis.


Segmenting hippocampal subfields from 3T MRI with multi-modality images.
Hippocampal subfields play important roles in many brain activities. However, due to the small structural size, low signal contrast, and insufficient image resolution of 3T MR, automatic hippocampal subfields segmentation is less explored. In this paper, we propose an automatic learning-based hippocampal subfields segmentation method using 3T multi-modality MR images, including structural MRI (T1, T2) and resting state fMRI (rs-fMRI). The appearance features and relationship features are both extracted to capture the appearance patterns in structural MR images and also the connectivity patterns in rs-fMRI, respectively. In the training stage, these extracted features are adopted to train a structured random forest classifier, which is further iteratively refined in an auto-context model by adopting the context features and the updated relationship features. In the testing stage, the extracted features are fed into the trained classifiers to predict the segmentation for each hippocampal subfield, and the predicted segmentation is iteratively refined by the trained auto-context model. To our best knowledge, this is the first work that addresses the challenging automatic hippocampal subfields segmentation using relationship features from rs-fMRI, which is designed to capture the connectivity patterns of different hippocampal subfields. The proposed method is validated on two datasets and the segmentation results are quantitatively compared with manual labels using the leave-one-out strategy, which shows the effectiveness of our method. From experiments, we find a) multi-modality features can significantly increase subfields segmentation performance compared to those only using one modality; b) automatic segmentation results using 3T multi-modality MR images could be partially comparable to those using 7T T1 MRI.