Young's interference experiment for generating light with non-uniform coherence states.
Up to now, methods for generating non-uniformly correlated light have been of two kinds: one is based on the use of specially designed random phase screens, and the other relies on the coherent-mode superposition, both being very complex experimental procedures. In this Letter, we show both theoretically and experimentally that in Young's interference experiment with light having a sufficiently large transverse coherence width, as compared with the width of the slits, the initially uniformly correlated partially coherent light converts to a non-uniformly correlated light. Such a non-uniform correlation is induced by the interference of light fields originating from the two slits. Our results point to the possibility of using diffraction by specially tailored deterministic aperture arrays for generating light with exotic coherence states.


Percutaneous drainage of pelvic lymphatic fluid collections in the renal transplant patient.
Seventeen renal transplant patients with pelvic lymphatic fluid collections were treated with percutaneous drainage. Eleven of 16 patients with lymphoceles (69%) were successfully managed without surgery, although seven of these patients required repeat catheter insertions, and three patients developed local infections. The patient with an ovarian cystadenoma was treated with surgery. The mean duration of catheter insertion was ten days for initial drainage and 16 days for repeat drainage. Elevated serum creatinines decreased in 14 of the patients with lymphoceles (88%), including all five patients without pelvocaliectasis, but never returned to baseline in six instances. This observation may reflect the inadequate therapy of frequently encountered concurrent renal parenchymal abnormalities (rejection, cyclosporine toxicity, acute tubular necrosis). While percutaneous management of lymphoceles is technically easy and usually ultimately effective, the interventional radiologist should be prepared for long duration of catheter insertions, repeat interventions, and variable clinical courses. Differentiation of lymphoceles from other fluid collections, such as cystic ovarian neoplasms, may be difficult.


Searching for new biomarkers of renal diseases through proteomics.
Technological advances have resulted in a renaissance of proteomic studies directed at finding markers of disease progression, diagnosis, or responsiveness to therapy. Renal diseases are ideally suited for such research, given that urine is an easily accessible biofluid and its protein content is derived mainly from the kidney. Current renal prognostic markers have limited value, and renal biopsy remains the sole method for establishing a diagnosis. Mass spectrometry instruments, which can detect thousands of proteins at nanomolar (or even femtomolar) concentrations, may be expected to allow the discovery of improved markers of progression, diagnosis, or treatment responsiveness. In this review we describe the strengths and limitations of proteomic methods and the drawbacks of existing biomarkers, and provide an overview of opportunities in the field. We also highlight several proteomic studies of biomarkers of renal diseases selected from the plethora of studies performed. It is clear that the field of proteomics has not yet fulfilled its promise. However, ongoing efforts to standardize sample collection and preparation, improve study designs, perform multicenter validations, and create joint industry-regulatory bodies offer promise for the recognition of novel molecules that could change clinical nephrology forever.


Impaired distensibility of the left ventricle after stiffening of the right ventricle.
Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.


Calcineurin/NFAT signaling in lymphoid malignancies.
Deregulated calcium signaling is observed at different stages of tumorigenic processes. An important signaling pathway activated in response to calcium involves the protein phosphatase calcineurin and NFAT transcriptional factors. We review here recent data that indicate an important role of the calcineurin/NFAT pathway in lymphoma/leukemogenesis and discuss the potential therapeutic implications of these findings.


Perceived Competence in the Face of Death before and after Nursing Studies: An Intrasubject Longitudinal Study.
Perceived competence is a subject's perception of being able to interact effectively with the environment. Perceived Competence in the face of death in Nursing degree programs in which the presence of the subject of death and bereavement is key becomes more topical and relevant. The objective of this study is to determine whether this competence is improved through Nursing Studies. This study was designed as paired repeated intrasubject measures, initial measurement at the beginning of the first year and second measurement in the fourth year of the Nursing degree. One hundred and seventeen nursing students were assessed. Significant improvement is evidenced in three of the four dimensions of Perceived Competence in the face of death (Accompaniment and Communication: 25.70/29.34; Self-Confidence: 9.64/12.78; Management of Self-Fear: 13.18/14.66). These results show notable differences with their cross-sectional predecessors, suggesting the need for further studies in this field to consolidate a still developing body of knowledge.


Peel bond strengths of five impression material tray adhesives.
The peel bond strengths of five impression materials and their tray adhesives to a perforated and non-perforated test surface were measured and the results were compared using a one-way ANOVA and Student Newman Keuls Multiple Range Test at p less than or equal to .05 level of significance. The auto-mix addition reaction silicone material Extrude produced the greatest peel bond strengths on both the non-perforated test surface (10.88 kg/cm2), and on the perforated test surface (15.88 kg/cm2). These bond strengths were greater than those obtained from the polysulphide and polyether materials used in the study. Using the perforated test surface significantly increased the peel bond strength for all the materials tested. It was concluded that in order to achieve the maximum adhesive bond, impression trays should be perforated. The greatest peel bond strengths were obtained using Extrude medium-body impression material.


Effects of omeprazole, famotidine, and ranitidine on the enzyme activities of carbonic anhydrase from bovine stomach in vitro and rat erythrocytes in vivo.
In this study, the effects of omeprazole, famotidine, and ranitidine on bovine stomach carbonic anhydrase (EC 220.127.116.11.) isoenzymes have been investigated in vitro. Bovine stomach carbonic anhydrase (CA) was purified from four different cell localisations of bovine stomach using affinity chromatography by Sepharose 4B-L-tyrosine sulphanilamide. The inhibition or activation effects of three different medical drugs on CA isoenzymes were determined using esterase activity and the CO(2)-hydratase method by plotting activity % vs. [medical drug]. The K(i) values for omeprazole, famotidine, and ranitidine were determined in all localization CA, respectively. The I(50) values of the drugs exhibiting an inhibition effect were found by means of these graphs. It was observed that omeprazole, famotidine, and ranitidine showed inhibition of bovine stomach CA activity. In addition, in vivo studies were performed for these medical drugs in Sprague-Dawley rats. It was demonstrated that CA in erythrocytes was significantly inhibited by these drugs to 3 h.


Two Patients with Complex Rearrangements Suggestive of Germline Chromoanagenesis.
Chromoanagenesis, a phenomenon characterized by complex chromosomal rearrangement and reorganization events localized to a limited number of genomic regions, includes the subcategories chromothripsis, chromoanasynthesis, and chromoplexy. Although definitions of these terms are evolving, constitutional chromoanagenesis events have been reported in a limited number of patients with variable phenotypes. We report on 2 cases with complex genomic events characterized by multiple copy number gains and losses confined to a single chromosome region, which are suggestive of constitutional chromoanagenesis. Case 1 is a 43-year-old male with intellectual disability and recently developed generalized tonic-clonic seizures. Chromosomal microarray analysis identified a complex rearrangement involving chromosome region 14q31.1q32.2, consisting of 16 breakpoints ranging in size from 0.2 to 6.2 Mb, with 5 segments of normal copy number present between these alterations. Interestingly, this case represents the oldest known patient with a complex rearrangement indicative of constitutional chromoanagenesis. Case 2 is a 2-year-old female with developmental delay, speech delay, low muscle tone, and seizures. Chromosomal microarray analysis identified a complex rearrangement consisting of 28 breakpoints localized to 18q21.32q23. The size of the copy number alterations ranged from 0.042 to 5.1 Mb, flanked by 12 small segments of normal copy number. These cases add to a growing body of literature demonstrating complex chromosomal rearrangements as a disease mechanism for congenital anomalies.


Different lengths of times for progressions in adolescent substance involvement.
The present study examined Lengths Of Times for important transitions in substance involvement from Initiation to Regular use (LOTIR), first Problem from drug use (LOTIP), and first experience of Dependence (LOTID) for alcohol, tobacco, cannabis, cocaine, and opiates. Data were from a longitudinal study of 590 children (22.2% female) at different levels of risk for substance use disorders based on their fathers' substance use-related diagnoses. Participants' substance involvement was assessed at four ages: 10-12, and follow-ups at two, five, and eight years later. Results suggested that faster transitions were more due to drug-related constructs (including possible social milieus of different drug classes and interactions between drug class and neurophysiology) than intrapersonal constructs. The shortest transition times (and greatest addictive liabilities) were for opiates followed respectively by cocaine, cannabis, tobacco, and alcohol. Females had shorter transition times, though gender differences were small. Some evidence was found for a familial influence on transition times above what was accounted for by differences between substances.


Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade.
The classic sterol regulatory cis element (sre-1) in the LDL receptor promoter mediates sterol regulatory element binding protein (SREBP)-binding and the effects of insulin and platelet derived growth factor (PDGF). To elucidate whether SREBP-1a and SREBP-2 play a direct role in insulin and PDGF action, stable cell lines of HepG2 deficient in either SREBP-1 or SREBP-2 were used. Transfection of these cells with the wild-type promoter fragment of the low density lipoprotein (LDL) receptor gene showed that the effects of insulin and PDGF were significantly reduced in both, SREBP-1- as well as SREBP-2-deficient cells. Insulin and PDGF action could be reconstituted again in these deficient cell lines by reintroducing SREBP-1a or SREBP-2. Preincubation of cells with either the phosphatidylinositol (PI)-3 kinase inhibitor wortmannin or the mitogen-activated protein (MAP) kinase cascade inhibitor PD 98059 showed that the latter abolished the stimulatory effects of insulin and PDGF on LDL receptor promoter activity completely, whereas wortmannin had no effect. Overexpression of upstream activators of the MAP kinases, like MEKK1 or MEK1, stimulated LDL receptor promoter activity several fold in an sre-1 related manner. These effects could be enhanced by coexpression of the transcriptional active N-terminal domains of SREBP-1a and SREBP-2. Using the heterologous Gal-4 system, we could show that intracellular activation of the MAP kinase cascade by ectopic expression of MEKK1 or MEK1 has a direct stimulatory effect on the transcriptional activity of SREBP-1a and SREBP-2. Experimental evidence for a direct link between MAP kinases and SREBPs was obtained due to the MAP kinases ERK1 and ERK2 phosphorylating recombinant GST-fusion proteins of SREBP-1a and SREBP-2, in vitro. We conclude that SREBP-1a and SREBP-2 mediate different regulatory effects converging at sre-1 and that they appear to be linked to the MAP kinase cascade, possibly being direct substrates of ERK1 and ERK2.


A High-Quality, Chromosome-Level Genome Provides Insights Into Determinate Flowering Time and Color of Cotton Rose (Hibiscus mutabilis).
Hibiscus mutabilis (cotton rose) is a deciduous shrub or small tree of the Malvaceae family. Here, we report a chromosome-scale assembly of the H. mutabilis genome based on a combination of single-molecule sequencing and Hi-C technology. We obtained an optimized assembly of 2.68 Gb with a scaffold N50 length of 54.7 Mb. An integrated strategy of homology-based, de novo, and transcriptome-based gene predictions identified 118,222 protein-coding genes. Repetitive DNA sequences made up 58.55% of the genome, and LTR retrotransposons were the most common repetitive sequence type, accounting for 53.15% of the genome. Through the use of Hi-C data, we constructed a chromosome-scale assembly in which Nanopore scaffolds were assembled into 46 pseudomolecule sequences. We identified important genes involved in anthocyanin biosynthesis and documented copy number variation in floral regulators. Phylogenetic analysis indicated that H. mutabilis was closely related to H. syriacus, from which it diverged approximately 15.3 million years ago. The availability of cotton rose genome data increases our understanding of the species' genetic evolution and will support further biological research and breeding in cotton rose, as well as other Malvaceae species.


Cellular Senescence in Sarcopenia: Possible Mechanisms and Therapeutic Potential.
Aging promotes most degenerative pathologies in mammals, which are characterized by progressive decline of function at molecular, cellular, tissue, and organismal levels and account for a host of health care expenditures in both developing and developed nations. Sarcopenia is a prominent age-related disorder in musculoskeletal system. Defined as gradual and generalized chronic skeletal muscle disorder, sarcopenia involves accelerated loss of muscle mass, strength and function, which is associated with increased adverse functional outcomes and evolutionally refers to muscle wasting accompanied by other geriatric syndromes. More efforts have been made to clarify mechanisms underlying sarcopenia and new findings suggest that it may be feasible to delay age-related sarcopenia by modulating fundamental mechanisms such as cellular senescence. Cellular senescence refers to the essentially irreversible growth arrest mainly regulated by p53/p21CIP1 and p16INK4a/pRB pathways as organism ages, possibly detrimentally contributing to sarcopenia via muscle stem cells (MuSCs) dysfunction and the senescence-associated secretory phenotype (SASP) while cellular senescence may have beneficial functions in counteracting cancer progression, tissue regeneration and wound healing. By now diverse studies in mice and humans have established that targeting cellular senescence is a powerful strategy to alleviating sarcopenia. However, the mechanisms through which senescent cells contribute to sarcopenia progression need to be further researched. We review the possible mechanisms involved in muscle stem cells (MuSCs) dysfunction and the SASP resulting from cellular senescence, their associations with sarcopenia, current emerging therapeutic opportunities based on targeting cellular senescence relevant to sarcopenia, and potential paths to developing clinical interventions genetically or pharmacologically.


Molecular-dynamics simulation of model polymer nanocomposite rheology and comparison with experiment.
The shear-rate dependence of viscosity is studied for model polymer melts containing various concentrations of spherical filler particles by molecular-dynamics simulations, and the results are compared with the experimental results for calcium-carbonate-filled polypropylene. Although there are some significant differences in scale between the simulated model polymer composite and the system used in the experiments, some important qualitative similarities in shear behavior are observed. The trends in the steady-state shear viscosities of the simulated polymer-filler system agree with those seen in the experimental results; shear viscosities, zero-shear viscosities, and the rate of shear thinning are all seen to increase with filler content in both the experimental and simulated systems. We observe a significant difference between the filler volume fraction dependence of the zero-shear viscosity of the simulated system and that of the experimental system that can be attributed to a large difference in the ratio of the filler particle radius to the radius of gyration of the polymer molecules. In the simulated system, the filler particles are so small that they only have a weak effect on the viscosity of the composite at low filler volume fraction, but in the experimental system, the viscosity of the composite increases rapidly with increasing filler volume fraction. Our results indicate that there exists a value of the ratio of the filler particle radius to the polymer radius of gyration such that the zero-shear-rate viscosity of the composite becomes approximately independent of the filler particle volume fraction.


[Bladder suspension by retropubic endoscopy. Techniques and preliminary results (24 cases)].
The authors propose an original technical based on the concept of bladder neck support by a sling (Goebell-Stoeckel) to treat urinary stress incontinence, without cystocele, in young women. The technical modifications concern: the incision: retropubic endoscopy facilitated by a dissection balloon and combined with a short vaginal incision. The use of synthetic material for the sling: expanded polytetrafluoroethylene (Gore-Tex) attached to Cooper's ligaments by a suture tied extracorporeally. The long-term objective is to achieve results comparable to those of open surgery with a lower morbidity. From 1992 to 1994, 24 patients were treated according to this technique by the same operator. The mean age was 48 years. In every case, this operation constituted the first procedure for incontinence, and only one patient had a history of previous pelvic surgery (Caesarean section). Incontinence was classified as stage 3 according to the Ingelmann Sundberg classification in 46% of cases. 35% of patients present uninhibited contractions, and 35% presented urethral hypotonia. Two intraoperative complications and immediate postoperative complications were only minor. The mean operating time was 2 hours 45 minutes. With experience, it gradually decreased, as did the hospital stay, which was an average of 4.3 days. With a short mean follow-up (1 year 7 days), the results were good in 71% of cases, satisfactory in 8% of cases (1 case of urgency, 1 case of persistent retention), with a failure in 5 cases (21%); 1 case of true incontinence confirmed by clinical examination and 4 cases of minor incontinence during occasional violent effort.


The Osteoclasp. A dynamic compression device for internal fixation of bone.
The Osteoclasp, a dynamic compression device for internal stainless steel fixation of bone, has been presented. The historical background of its creation and early experimentation for research and development of the Osteoclasp have been reviewed. Physical properties and dimensions of the Osteoclasp, in combination with instrumentation for implantation, has been presented to educate the reader on proper selection and implantation of the Osteoclasp. Specific indications and contraindications for the Osteoclasp have been discussed. Using proper surgical technique, the Osteoclasp will provide constant dynamic compression across an incomplete fracture to enhance bone healing through primary bone repair. Several case histories illustrate the various uses of the Osteoclasp in the lower extremity. Specific illustrations of improper technique will serve to amplify the necessity of appropriate selection of the Osteoclasp for internal fixation and illustration of proper surgical technique. The Osteoclasp has been, and will continue to be, a viable technique for bone fixation. New surgical techniques and bone fixation devices will continue to evolve and further enhance primary bone healing.


Practical aspects of clinical trials on chemoprevention of prostate cancer.
In addition to the normal aspects of organizing clinical trials, the launch of a chemoprevention trial on prostate cancer needs extra effort. The sample size and duration of follow-up is so extensive that such a trial should be organized as an intergroup study, preferably worldwide. For that a central data center and data management is mandatory. Because healthy individuals are involved, refusal, loss to follow-up and inadequate adherence may be substantial. The choice of the study endpoint presence of prostate cancer or death due to prostate cancer will lead to completely different sample sizes and length of follow-up. Of criteria leading to the diagnosis of prostate cancer (PSA, DRE and transrectal ultrasound), at least two are rather subjective. The drug involved might affect the criteria for diagnosis. Because of the high incidence of clinically nonsignificant prostate cancer of men over 55, a large number of nonrelevant prostate cancers will be detected in both arms. Due to the long follow-up and alterations in the state of the art of detection and therapy of prostate cancer, the completion of such a study might be hampered. If the average price per patient involved in a clinical trial is currently between USD 1, 000 and 2,000, one may calculate that for 30,000 men, USD 20-40 million are needed, not including the hospital visits, examinations and biopsies. Economic considerations thus play a major role in organizing trials on the chemoprevention of prostate cancer.


[Spatial distribution characteristics and ecological effects of carbon and nitrogen of soil in Huolin River catchment wetland].
This paper studied the spatial distribution characteristics and ecological effects of organic carbon and nitrogen in soils of Huolin River catchment wetland in horizontal and vertical levels. The results showed that the differences of horizontal and vertical distribution of organic carbon and nitrogen were very obvious, and of all the factors such as the period of wetting and drying cycles, leaching, plant and flood etc., the period of wetting and drying cycles was contents the critical one, which caused the differences. Soil organic carbon was significantly correlated with soil nitrogen (r = 0.977). The ratio of carbon and nitrogen (C/N) changed along with the humidity gradient, and soil pH values obviously influenced the concentration of organic carbon and nitrogen. The correlation of C/N values and organic carbon and nitrogen contents in wetland soil and in grassland soil were remarkably different, and the ecological effects mainly included production effect and clarification effect.


The mechanism of SP1/p300 complex promotes proliferation of multiple myeloma cells through regulating IQGAP1 transcription.
Our previous research had firstly shown that MM cells overexpressed IQGAP1 gene and activated Ras/Raf/MEK/ERK pathway. But the mechanism of IQGAP1 overexpression and IQGAP1 gene transcription regulation remains uncertain. The mechanism of IQGAP1 overexpression and transcriptional regulation of IQGAP1 gene in myeloma cells was explored in the study. Through bioinformatics analysis and prediction we predicted and screened transcription factor Sp1 as a possible upstream regulator of IQGAP1.The proliferation, cell cycle and downstream ERK1/2 and p-ERK1/2 proteins were detected after siRNA-IQGAP1 was transfected to myeloma cells. The expression of Sp1, p300, IQGAP1, p-ERK1/2 and ERK1/2 were detected after Sp1 and p300 were inhibited or overexpressed respectively. The dual-luciferase reporter system was used to detect the activity of IQGAP1 gene promoter. CHIP was used to detect the binding of the Sp1 and IQGAP1 promoter regions.CO-IP was used to explore the interaction between Sp1 and p300.The mRNA expression levels of Sp1,p300 and IQGAP1 of the myeloma patients were detected, and the correlation analysis of their mRNA expression levels were carried out. The results showed IQGAP1-siRNA inhibits cell proliferation, cell cycle, IQGAP1 expression and phosphorylation of ERK1/2 protein. Inhibition of Sp1 or p300 down-regulated ERK1/2 and IQGAP1 expression; overexpression of Sp1 or p300 up-regulated ERK1/2 and IQGAP1 expression; Sp1 and p300 had a positive regulation effect on IQGAP1.Over expression of Sp1 or p300 significantly increased activity of IQGAP1 gene promoter. The transcription factor Sp1 plays a regulatory role in the IQGAP1 promoter region. There is an interaction between Sp1 and p300 in myeloma cells. The mRNA expression levels of Sp1, IQGAP1 and p300 in MM samples showed a positive correlation. In summary IQGAP1 is required for cell proliferation in MM cells, and the transcription of Sp1/p300 complex regulates expression of IQGAP1 gene.


Uterine mixed embryonal rhabdomyosarcoma and fetal rhabdomyoma.
A polypoid uterine tumor, occurring in a 31-year-old woman, with histopathologic features of both embryonal rhabdomyosarcoma and fetal rhabdomyoma is reported. The clinical and pathologic differences between pure fetal rhabdomyoma and embryonal rhabdomyosarcoma are detailed and theories concerning the histogenesis of such a mixed, or intermediate, tumor are discussed. Most likely, this neoplasm represents one example in a spectrum of tumors with varying proportions of immature and mature skeletal muscle elements. Its good prognosis is in keeping with that of uterine (cervical) embryonal rhabdomyosarcomas in general, although the presence of mature skeletal muscle elements may signify an even better prognostic group of tumors.


Ultraflat Au nanoplates as a new building block for molecular electronics.
We demonstrate the charge transport properties of a self-assembled organic monolayer on Au nanoplates with conductive probe atomic force microscopy (CP-AFM). Atomically flat Au nanoplates, a few hundred micrometers on each side, that have only (111) surfaces, were synthesized using the chemical vapor transport method; these nanoplates were employed as the substrates for hexadecanethiol (HDT) self-assembled monolayers (SAMs). Atomic-scale high-resolution images show (√3 x √3) R30° molecular periodicity, indicating a well-ordered structure of the HDT on the Au nanoplates. We observed reduced friction and adhesion forces on the HDT SAMs on Au nanoplates, compared with Si substrates, which is consistent with the lubricating nature of HDT SAMs. The electrical properties, such as I-V characteristics and current as a function of load, were measured using CP-AFM. We obtained a tunneling decay constant (β) of 0.57 Å(-1), including through-bond (βtb = 0.99 Å(-1)) and through-space (βts = 1.36 Å(-1)) decay constants for the two-pathway model. This indicates that the charge transport properties of HDT SAMs on Au nanoplates are consistent with those on a Au (111) film, suggesting that SAMs on nanoplates can provide a new building block for molecular electronics.


The patient who would not tell his name.
The case of a patient who refused to give the analyst his name for over a year and a half is presented. Analysis of his resistances and transference reactions points to the fact that he unconsciously wanted to be raped. Analysis of other secrets revealed a strong wish to tease and torment the analyst and to hold back incestuous, murderous, and other sexual and aggressive fantasies.


The epidemiology of iodine-deficiency disorders in relation to goitrogenic factors and thyroid-stimulating-hormone regulation.
In children aged 5-7 y from goiter-endemic areas in Ubangi, Zaire, and Ntcheu, Malawi, mean serum thyroxin (T4) concentrations were 53 +/- 49 vs 81 +/- 33 nmol/L (P < 0.05), and thyroid-stimulating hormone (TSH) values were 24.3 +/- 9.6 vs 4.5 +/- 3.3 mU/L respectively (P < 0.01); mean urinary iodine concentrations were 0.14 +/- 0.02 vs 0.09 +/- 0.02 mumol/L, and mean thiocyanate concentrations were 0.33 +/- 0.05 vs 0.17 +/- 0.05 nmol/L, respectively (P < 0.05). Mean serum selenium concentrations were 0.343 +/- 0.176 mumol/L in Ubangi and 0.437 +/- 0.178 mumol/L in Ntcheu (P < 0.05). In two groups of 11 adolescent girls from Ubangi, the mean values for excretion of urinary iodine were 1.31 +/- 0.14 and 0.58 +/- 0.17 mumol/L (P < 0.05) after a meal of cassava or a control meal of rice, respectively. In euthyroid subjects from Ubangi, mean serum TSH for a given serum T4 was approximately twice as high for children aged < 15 y than for those aged 16-25 y. The high frequency of myxedematous cretins observed in Ubangi very probably result from both severe iodine and selenium deficiency together with thiocyanate overload.


Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model.
This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with "temperament," including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor.


Emerging roles of Kruppel-like factor 6 and Kruppel-like factor 6 splice variant 1 in ovarian cancer progression and treatment.
Epithelial ovarian cancer is one of the most lethal gynecologic cancers and the fifth most frequent cause of female cancer deaths in the United States. Despite dramatic treatment successes in other cancers through the use of molecular agents targeted against genetically defined events driving cancer development and progression, very few insights into epithelial ovarian cancer have been translated from the laboratory to the clinic. If advances are to be made in the early diagnosis, prevention, and treatment of this disease, it will be critical to characterize the common and private (personalized) genetic defects underlying the development and spread of epithelial ovarian cancer. The tumor suppressor Kruppel-like factor 6 and its alternatively spliced, oncogenic isoform, Kruppel-like factor 6 splice variant 1, are members of the Kruppel-like zinc finger transcription factor family of proteins, which have diverse roles in cellular differentiation, development, proliferation, growth-related signal transduction, and apoptosis. Inactivation of Kruppel-like factor 6 and overexpression of Kruppel-like factor 6 splice variant 1 have been associated with the progression of a number of human cancers and even with patient survival. This article summarizes our recent findings demonstrating that a majority of epithelial ovarian cancer tumors have Kruppel-like factor 6 allelic loss and decreased expression coupled with increased expression of Kruppel-like factor 6 splice variant 1. The targeted reduction of Kruppel-like factor 6 in ovarian cancer cell lines results in marked increases in cell proliferation, invasion, tumor growth, angiogenesis, and intraperitoneal dissemination in vivo. In contrast, the inhibition of Kruppel-like factor 6 splice variant 1 decreases cellular proliferation, invasion, angiogenesis, and tumorigenicity; this provides the rationale for its potential therapeutic application. These results and our recent demonstration that the inhibition of Kruppel-like factor 6 splice variant 1 can dramatically prolong survival in a preclinical mouse model of ovarian cancer are reviewed and discussed.


Enhancement of antigen-specific Treg vaccination in vivo.
The conversion of naive T cells into Treg can be achieved in vivo by delivery of antigen under subimmunogenic conditions. Here we have examined several drugs for their ability to enhance the conversion process in vivo and have found that the rapamycin analog everolimus potently enhances Treg conversion by interfering with T-cell costimulation, reducing cell division and thereby activation of DNA methyltransferase 1 as well as by reducing T-cell activation through the ATP-gated P2×7 receptor controlling Ca2(+) influx. The resulting Tregs exhibit increased stability of Foxp3 expression even when generated in TGFβ-containing media in vitro. Thus the mammalian target of rapamycin (mTOR) inhibitor everolimus in addition to inhibiting immune responses enhances Treg conversion by several distinct pathways. The converted Tregs can be further expanded by injection of IL-2/IL-2ab complexes. These complexes also increase the number of CD25(+)Foxp3(-) cells that, however, do not represent cytokine secreting effector cells but anergic cells, some of which can secrete IL-10 and can themselves be considered regulatory T cells as well. The combined use of everolimus and IL-2/IL-2ab complexes in vivo makes it feasible to achieve highly effective antigen-driven conversion of naive T cells into Treg and their expansion in vivo and thereby the described protocols constitute important tools to achieve immunological tolerance by Treg vaccination.


Growth and Aflatoxin Production by Aspergillus parasiticus NRRL 2999 in the Presence of Lactic Acid and at Different Initial pH values.
Twenty-five milliliters of glucose-yeast-salts medium containing 0, 0.5, 0.75, 1.0, 1.5 and 2.0% lactic acid with an initial pH of 3.5 or 4.5 were inoculated with 1 ml of a spore suspension containing 106 conidia of Aspergillus parasiticus NRRL 2999 and incubated at 28°C for 10 d. The pH of the medium, weight of mycelium and aflatoxin production were determined after 3, 7, and 10 d of incubation. Amounts of aflatoxin produced were determined using reversed-phase high-performance liquid chromatography. Cultures grown in the presence of 0.5 and 0.75% lactic acid at an initial pH of 4.5 produced more aflatoxin B1 than did the other cultures at the end of 3 d of incubation. This was not true for aflatoxin G1; with increasing concentrations of lactic acid, cultures produced decreasing amounts of aflatoxin G1. Also, cultures growing in the medium with an initial pH of 3.5 produced more aflatoxin B1 in the presence of lactic acid at the end of 3 d of incubation than did control cultures. Cultures growing in the presence of 0.5 and 0.75% lactic acid produced the most aflatoxin. Maximum amounts of aflatoxin G1 were produced after 7 d of incubation, with cultures growing in the presence of 0.5 and 0.75% lactic acid producing the most. Lactic acid did not inhibit growth (mycelium weight) of cultures in the medium with initial pH values of 3.5 or 4.5 except there was a slight decrease in mycelial weight when the medium contained 0.5% lactic acid and had an initial pH value of 3.5.


Anti-inflammatory properties of enamel matrix derivative in human blood.
Enamel matrix derivative (EMD), extracted from porcine tooth buds, has been shown to promote periodontal healing in patients with severe periodontitis. This involves modulation of the inflammatory response followed by the onset of periodontal regeneration. Based on these observations, we examined the ability of EMD to modulate the release of a pro-inflammatory cytokine [tumor necrosis factor (TNF)-alpha], an anti-inflammatory cytokine (interleukin-10) and a chemokine (interleukin- 8) in whole human blood challenged by bacterial cell wall components. Whole blood from healthy donors was challenged by lipopolysaccharide or peptidoglycan and incubated with different concentrations of EMD or a cAMP analogue 8-(4-chlorophenyl)thio-cAMP (8-CPT-cAMP). TNF-alpha, interleukin-8 and interleukin-10 were analysed from plasma by enzyme-linked immunosorbent assay (ELISA) while cAMP levels of peripheral blood mononuclear cell lysates were analysed by enzyme immunoassay (EIA). We found that EMD attenuated the release of TNF-alpha and interleukin-8 in whole blood from healthy donors challenged by lipopolysaccharide or peptidoglycan, while the release of interleukin-10 was unchanged. Enamel matrix derivative also produced a four-fold increase in the cAMP levels of peripheral blood mononuclear cell lysates. Like EMD, 8-CPT-cAMP attenuated the formation of TNF-alpha, but not of interleukin-10, in blood challenged by lipopolysaccharide. Enamel matrix derivative limits the release of pro-inflammatory cytokines induced by lipopolysaccharide or peptidoglycan in human blood, suggesting that it has anti-inflammatory properties. We propose that this effect of EMD is, at least partly, secondary to an increase in the intracellular levels of cAMP in peripheral blood mononuclear cells.


Pericardial diverticulum with unusual symptomatology.
A healthy 37 yr old female presented with recurrent right-sided chest pain which spontaneously disappeared. On a chest roentgenogram a lesion in the right cardiophrenic angle was found. Magnetic resonance imaging suggested a cystic structure. During thoracotomy a pericardial diverticulum was found. The pain was probably caused by intermittent volvulus of the diverticulum.


Cognitive failure in end of life.
Cognitive failure is known to be common in patients with advanced illness and can lead to significant distress for the persons affected and their environment. To get an insight on the most recent advances concerning cognitive failure at the end of life, a literature review has been performed focusing on the syndrome in general palliative care as well as on palliative care in patients with dementia. Cognitive impairment is diagnosed in varying commonness in up to 56% of patients. Reviewed research focused in part on diagnosing distress of patients being cognitively impaired. Signs and behaviours for distress were identified and observed in a high number of patients. Additionally, with focus on the caretakers distress, it could be demonstrated that for example general anxiety disorders were significantly more common when a delirium was perceived. Goals of care for the patients with end-stage dementia can be defined as quality of life, dignity and comfort. Prognostication of the disease trajectory in patients with end-stage disease remains difficult even when the reviewed research shows growing evidence on the risk factors and causes for death of these patients. An overall improvement in professional care independent of the place of care for patients with cognitive impairment and dementia is still claimed by professionals and primary caretakers. In addition to further research, the lack of palliative care expertise can possibly be resolved by more specific, supportive and educational initiatives.


Is a Price Increase Policy Enough for Adolescent Smokers?: Factors Affecting the Effectiveness of Increasing Cigarette Prices Among Korean Adolescent Smokers.
Cigarette pricing policy is one tool for controlling smoking behavior on a national scale. It is unclear, however, what effects such policy has on adolescents and which characteristic subgroups of adolescents are more or less sensitive to cigarette pricing policy. Our data came from the 2013 Korea Youth Risk Behavior Web-based Survey. The dependent variable was whether or not a participant was classified as a "persistent smokers," defined as a smoker who would continue smoking despite any price increase. Other variables of interest were smoking days (quantity), previous attempts to stop smoking, and previous education on smoking cessation. The statistical analysis was performed using weighted data and the SURVEYFREQ and SURVEYLOGISTIC procedures in SAS 9.3. Among 7094 adolescent smokers (5349 males and 1745 females), 19.9% of males and 25.1% of females reported as persistent smokers. Compared with light smokers, heavy smokers are more likely to be persistent smokers (male: odds ratio [OR] = 2.45, 95% confidence interval [CI] = 2.04-2.95, P value < .001; female: OR = 3.23, 95% CI = 2.44-4.27, P value < .001). When we stratified the data by household income, previous attempts to stop smoking, and previous education on smoking cessation, that trend remained statistically significant. Because heavier smokers with higher risk of health-related consequences were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional cessation policy is needed along with pricing policy for adolescents with heavier smoking behavior in Korea. This study shows that heavy smokers are more likely to be persistent smokers despite the cigarette price increase policy, compared with light smokers in Korean adolescents. Because heavier smokers were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional tobacco control policies should be evaluated and effective ones implemented in addition to cigarette prices to reduce smoking among regular adolescent smokers.


Randomized, placebo-controlled, phase III surgical adjuvant clinical trial of megestrol acetate (Megace) in selected patients with malignant melanoma.
A randomized, double-blind, placebo-controlled phase III clinical trial was performed to assess megestrol acetate (Megace) as a postsurgical adjuvant therapy for patients with locally advanced malignant melanoma. Patients whose tumors were greater than 1.7 mm thick and had no regional lymph node involvement and patients with regional lymph node involvement were randomized to receive either 160 mg twice per day oral suspension of megestrol acetate or placebo. Treatment was administered for a maximum of 2 years or until disease progression. The study accrued 262 eligible patients. All but two patients were followed until death or a minimum of 4.5 years. Disease progression was documented in 156 patients. Neither progression-free survival (PFS) nor overall survival (OS) was found to differ between the treatments. The median PFS was 2.4 years in the megestrol acetate arm and 2.3 years in the placebo arm. Multivariate analysis revealed a significantly decreased PFS for patients with four or more positive regional lymph nodes and metachronous nodal disease. Median OS was 5.3 years in the megestrol acetate arm and 3.9 years in the placebo arm. Multivariate analysis revealed that OS was significantly decreased for patients 70 years of age or older with four or more positive lymph nodes. Adjuvant therapy with megestrol acetate oral suspension administered at a dose of 160 mg twice a day for 2 years was not found to be effective in prolonging PFS or OS in patients with surgically resected, locally advanced melanoma.


Strength and aerobic training attenuate muscle wasting and improve resistance to the development of disability with aging.
By the age of 50 yrs old, humans become aware that they are losing muscle strength (mass) and endurance (mitochondria). A frequent symptom of neuromuscular disorders is muscle weakness (Walton, 1988). We define the aging-associated muscle wasting as a progressive neuromuscular syndrome that will lower the quality of life in the elderly by (1) decreasing the ability to lift loads (progressing to difficulty arising from a chair), and (2) decreasing endurance (leading to an inability to perform the activities of daily living, which increases health care costs). Campion (1994) states that the most successful outcome would be for the very elderly to take control of the last stage of their life and make it worth living. To obtain this goal, prevention of muscle wasting is an absolute requirement. Muscle mass and motor unit number, activation, and synchronization are highly related to strength; both decrease with aging (Rodgers and Evans, 1993). Resistance-training is the best way to increase muscle mass, neural coordination, and strength. Mitochondrial concentration is highly related to endurance capacity in young and old (Holloszy and Coyle, 1984). Both muscle contractile and mitochondrial protein decrease with aging in sedentary humans (reviewed by Rodgers and Evans, 1993). Endurance training, which is the best exercise to increase/maintain mitochondrial concentration with aging, has generally resulted in relatively small functional benefits to nursing home patients (Fiatarone et al., 1994).(ABSTRACT TRUNCATED AT 250 WORDS)


Contribution to the knowledge of Afrotropical Dryinidae, Embolemidae and Sclerogibbidae (Hymenoptera), with description of new species from Central African Republic and Uganda.
An updated checklist of Dryinidae, Embolemidae and Sclerogibbidae from Central African Republic and Uganda is presented. The following new species of Dryinidae are described: from Central African Republic: Anteon dzanganum sp. n. (Anteoninae); from Uganda: Anteon granulatum sp. n., Anteon kibalense sp. n., Anteon makererense sp. n., Anteon mubfs sp. n. (Anteoninae); Bocchus kibalensis sp. n. (Bocchinae); Dryinus kibalus sp. n. (Dryininae); Gonatopus kanyawarus sp. n. (Gonatopodinae). The following species have been recorded for the first time from Central African Republic: Embolemidae: Ampulicomorpha madecassa Olmi, 1999a; Embolemus capensis Olmi, 1997; Dryinidae: Aphelopus mediocarinatus (Benoit, 1951d), Aphelopus testaceus Olmi, 1991, Aphelopus wittei Benoit, 1951c (Aphelopinae); Anteon cautum Olmi, 1994a, Anteon evertsi Olmi, 1989, Anteon gutturnium (Benoit, 1951b), Anteon inflatrix Benoit, 1951b, Anteon kivuanum (Benoit, 1951c), Anteon semajanna Olmi, Copeland & Guglielmino, 2015, Anteon zairense Benoit, 1951d (Anteoninae); Pseudodryinus townesi (Olmi, 1984) (Dryininae); Echthrodelphax tauricus Ponomarenko, 1970, Gonatopus camerounensis Olmi, 2011, Gonatopus kolyadai Olmi, 2007b, Neodryinus antiquus Benoit, 1954, Neodryinus tussaci Olmi, 2004b (Gonatopodinae); Sclerogibbidae: Probethylus callani Richards, 1939b; Sclerogibba algerica Benoit, 1963, Sclerogibba rapax Olmi, 2005a. The following species have been recorded for the first time from Uganda: Embolemidae: Ampulicomorpha magna Olmi, 1996; Dryinidae: Anteon cautum Olmi, 1994a, Anteon fisheri Olmi, 2003, Anteon hoyoi Olmi, 1984, Anteon kivuanum (Benoit, 1951c), Anteon townesi Olmi, 1984, Anteon zairense Benoit, 1951d (Anteoninae); Bocchus bini Olmi, 1984 (Bocchinae); Dryinus saussurei (Ceballos, 1936) (Dryininae); Echthrodelphax migratorius Benoit, 1954, Neodryinus tussaci Olmi, 2004b (Gonatopodinae). The following further species has been recorded for the first time from Mali: Sclerogibba algerica Benoit, 1963 (Sclerogibbidae); from Ivory Coast: Adryinus oweni Olmi, 1984 (Gonatopodinae); from Cameroon and South Africa: Gonatopus operosus Olmi, 1993 (Gonatopodinae); from Democratic Republic of the Congo and Zambia: Neodryinus antiquus Benoit, 1954 (Gonatopodinae); from South Africa: Anteon striatum Olmi, 2005b (Anteoninae). Including the above new records, 23 species of Dryinidae (previously six), two species of Embolemidae (previously none) and three species of Sclerogibbidae (previously two) are now known from Central African Republic. For Uganda, 39 species of Dryinidae (previously 23), one species of Embolemidae (previously none) and four species of Sclerogibbidae (previously four) are now known. Additional new faunistic records are provided for Cameroon, Democratic Republic of the Congo, Ivory Coast, Mali, South Africa and Zambia.


Adaptation of exercise-induced stress in well-trained healthy young men.
What is the central question of this study? Exercise is known to induce stress-related physiological responses, such as changes in intestinal barrier function. Our aim was to determine the test-retest repeatability of these responses in well-trained individuals. What is the main finding and its importance? Responses to strenuous exercise, as indicated by stress-related markers such as intestinal integrity markers and myokines, showed high test-retest variation. Even in well-trained young men an adapted response is seen after a single repetition after 1 week. This finding has implications for the design of studies aimed at evaluating physiological responses to exercise. Strenuous exercise induces different stress-related physiological changes, potentially including changes in intestinal barrier function. In the Protégé Study (ISRCTN14236739; www.isrctn.com), we determined the test-retest repeatability in responses to exercise in well-trained individuals. Eleven well-trained men (27 ± 4 years old) completed an exercise protocol that consisted of intensive cycling intervals, followed by an overnight fast and an additional 90 min cycling phase at 50% of maximal workload the next morning. The day before (rest), and immediately after the exercise protocol (exercise) a lactulose and rhamnose solution was ingested. Markers of energy metabolism, lactulose-to-rhamnose ratio, several cytokines and potential stress-related markers were measured at rest and during exercise. In addition, untargeted urine metabolite profiles were obtained. The complete procedure (Test) was repeated 1 week later (Retest) to assess repeatability. Metabolic effect parameters with regard to energy metabolism and urine metabolomics were similar for both the Test and Retest period, underlining comparable exercise load. Following exercise, intestinal permeability (1 h plasma lactulose-to-rhamnose ratio) and the serum interleukin-6, interleukin-10, fibroblast growth factor-21 and muscle creatine kinase concentrations were significantly increased compared with rest only during the first test and not when the test was repeated. Responses to strenuous exercise in well-trained young men, as indicated by intestinal markers and myokines, show adaptation in Test-Retest outcome. This might be attributable to a carry-over effect of the defense mechanisms triggered during the Test. This finding has implications for the design of studies aimed at evaluating physiological responses to exercise.


Childhood trauma and posttraumatic stress disorder in patients with psychosis: clinical challenges and emerging treatments.
To review the current literature on childhood trauma and emerging treatments for posttraumatic stress disorder (PTSD), one of its most prevalent consequences, in patients with psychotic disorders. Of patients with psychosis, 40-50% report either childhood sexual abuse or childhood physical abuse, and 11-46% fulfil a diagnosis of PTSD. About one-third of patients report childhood emotional abuse in the absence of other forms of childhood trauma. More robust evidence is mounting to support the role of childhood trauma in the aetiology of psychosis, but more research is needed to understand the underlying mechanisms. Patients with a history of childhood trauma and/or PTSD have a more severe clinical profile compared with those without these experiences, worse overall functioning, and lower remission rates. Research suggests that instruments assessing childhood trauma and PTSD developed for the general population are also appropriate for use among people with psychosis, and trauma-focussed treatments can be used safely and effectively in this group. Childhood trauma and its consequences are highly prevalent among patients with psychosis and severely affect the course and outcome. Treatment approaches appropriate for this population need to be further evaluated and implemented into routine practice.


Use of a rotary bioartificial liver in the differentiation of human liver stem cells.
The use of bioartificial livers (BALs) for the expansion of human adult liver stem cells and the production of growth factors could be a potential strategy for cell-based extracorporeal liver support. The present study aimed to assessing the differentiation of human adult liver stem cells in a rotary BAL. Liver stem cells were seeded into a polysulphone membrane filter at a density of 3 x 10(8) cells, and the filter was connected to a rotary bioreactor perfusion system (37 degrees C, 50 mL/min, 48 h). Viability, cell differentiation, and metabolic performances were evaluated at 24 and 48 h. Hepatocyte growth factor production from human adult liver stem cells, mature hepatocytes, and mesenchymal stem cells in adhesion and in the rotary BAL conditions was compared. Liver stem cells cultured in the rotary BAL produced the highest amounts of albumin (p = 0.002) and ammonia-induced urea (p = 0.0001), and had an increased cytochrome P450 expression in respect to liver stem cells in adhesion. Remarkably, liver stem cells in the rotary BAL produced very high amounts of hepatocyte growth factor (p = 0.005) in respect to hepatocytes and mesenchymal stem cells. Moreover, the cells lost their stem cell markers and acquired several markers of mature hepatocytes. In conclusion, the rotary BAL favored liver stem cell differentiation into mature hepatocyte-like cells.


Effects on RNA interference in gene expression (RNAi) in cultured mammalian cells of mismatches and the introduction of chemical modifications at the 3'-ends of siRNAs.
The highly specific posttranscriptional silencing of gene expression induced by double-stranded RNA (dsRNA) is known as RNA interference (RNAi) and has been demonstrated in plants, nematodes, Drosophila, and protozoa, as well as in mammalian cells. The suppression of expression of specific genes by chemically synthesized 21-nucleotide (21-nt) RNA duplexes has been achieved in various lines of mammalian cells, and this technique might prove to be a valuable tool in efforts to analyze biologic functions of genes in mammalian cells. In order to investigate the utility of potential modifications that can be introduced into small interfering RNAs (siRNAs) and also to study their functional anatomy, we synthesized different types of siRNA targeted to mRNA of Jun dimerization protein 2 (JDP2). Our detailed analysis demonstrated that siRNAs with only one mismatch, relative to the target, on the antisense strand had reduced RNAi effect, whereas the corresponding mutation on the sense strand did not interfere with the RNAi. Moreover, one 2-hydroxyethylphosphate (hp) substitution at the 3'-end of the antisense strand but not of the sense strand also prevented RNAi, whereas a related modification at the 3'-end of either strand, using 2'-O,4'-C-ethylene thymidine (eT), which is a component of ethylene-bridge nucleic acids (ENA), completely abolished RNAi. These results support the hypothesis that the two strands have different functions in RNAi in cultured mammalian cells and indicate that their chemical modification of siRNAs at the 3'-end of the sense strand exclusively is possible, without loss of RNAi activity, depending on the type of modification. Because modification at the 3'-end of the antisense strand by hp or eT abolished the RNAi effect, it appears possible that the 3'-end is recognized by the RNA-induced silencing complex (RISC).


Prescription sleep aid use among adults: United States, 2005-2010.
Data from the National Health and Nutrition Examination Survey, 2005-2010. About 4% of U.S. adults aged 20 and over used prescription sleep aids in the past month. The percentage of adults using a prescription sleep aid increased with age and education. More adult women (5.0%) used prescription sleep aids than adult men (3.1%). Non-Hispanic white adults were more likely to use sleep aids (4.7%) than non-Hispanic black (2.5%) and Mexican-American (2.0%) adults. Prescription sleep aid use varied by sleep duration and was highest among adults who sleep less than 5 hours (6.0%) or sleep 9 or more hours (5.3%). One in six adults with a diagnosed sleep disorder and one in eight adults with trouble sleeping reported using sleep aids.


Heterogeneous nuclear ribonucleoprotein complexes and proteins in Drosophila melanogaster.
Pre-mRNAs cotranscriptionally associate with a small group of proteins to form heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. We have previously identified two genes in Drosophila melanogaster, Hrb98DE and Hrb87F (i.e., genes at 98DE and 87F encoding putative hnRNA binding proteins), which encode five protein species homologous to the mammalian A-B hnRNP proteins. The studies presented herein show that antibodies against the RNP domains of Hrb98DE reacted with 10 to 15 distinct spots of 38 to 40 kDa in the basic region of two-dimensional gels. These nuclear proteins bound single-stranded nucleic acids and were extracted from Drosophila tissue culture cells as 40 to 80S hnRNP complexes in association with 300 to 800 nucleotide fragments of RNA. The peak of poly(A)+ RNA sequences was coincident with the peak of HRB proteins in sucrose gradients, strongly suggesting that the HRB complexes identified are Drosophila hnRNP complexes. The repertoire of HRB proteins did not change significantly during embryogenesis and was similar to that observed in Drosophila tissue culture cells. Analyses with peptide-specific antisera demonstrated that the major proteins in the hnRNP complex were encoded by the two genes previously identified. Although the Drosophila HRB proteins are only approximately 60% identical throughout the RNP domains to the mammalian A-B hnRNP proteins, features of the basic pre-mRNA packaging mechanism appear to be highly conserved between D. melanogaster and mammals.


Effect of bridgehead substitution on the fluorescence quenching of 2,3-diazabicyclo[2.2.2]oct-2-enes by solvents and antioxidants.
Azoalkanes of the 2,3-diazabicyclo[2.2.2]-oct-2-ene type have been introduced as probes for antioxidants in homogeneous solution as well as in liposomes and micelles. The bimolecular fluorescence quenching of the bridgehead dichloro-substituted 1,4-dichloro-2,3-diazabicyclo[2.2.2]-oct-2-ene (3) was compared with that of the parent compound 2,3-diazabicyclo[2.2.2]-oct-2-ene (1) and the bridgehead-dialkylated compound 4-methyl-1-isopropyl-2,3-diazabicyclo[2.2.2]-oct-2-ene (2). Compound 3 showed a more efficient fluorescence quenching in C-H containing solvents (e.g., in n-hexane: 30 ns for 3 versus 340 ns for 1 and 770 ns for 2), but a less efficient quenching in aqueous solution (e.g., in deaerated H(2)O: 485 ns for 3 versus 420 ns for 1 and 340 ns for 2), and also by molecular oxygen (k(q)/10(9) M(-1) s(-1) = 0.32 for versus 2.5 for 1 and 1.9 for 2). Towards low-molecular weight antioxidants, compound 3 showed a significantly higher reactivity (e.g., for reduced glutathione: k(q)/10(9) M(-1) s(-1) = 1.8 for 3 versus 0.82 for 1 and 0.39 for 2), at the expense of a lower differentiation between the investigated antioxidants (lower selectivity). The increased reactivity of 3 and lower, as well as qualitatively different, selectivity is attributed to a combination of factors, most importantly the slightly increased excitation energy of 3 and its lower excited-state nucleophilicity. The latter was independently corroborated, besides its longer fluorescence lifetime in aqueous solution, through the trends in quenching rate constants of the azoalkanes 1-3 towards electron-deficient versus electron-rich lactone antioxidants of the benzofuranone type. While common inorganic buffer constituents caused no fluorescence quenching, significant quenching was observed, as a curiosity, for hydrogencarbonate (k(q)/10(6) M(-1) s(-1) = 1.7 for 3 versus 2.4 for 1 and 0.45 for 2), with a fully manifested kinetic deuterium isotope effect (k(q)(H(2)O)/k(q)(D(2)O) = 12) for 3.


Mood Disturbances in Alzheimer's Disease.
Our aim in this chapter is to review and synthesize the extensive literature on disturbances of mood, including both major depression and other less severe, less well-characterized depressive states, that are frequent in Alzheimer's Disease. We use a dimensional conceptual approach, as it allows a systematic perspective on studies regarding depressive features in dementia, many of which are based on varying assumptions. Evidence is presented regarding epidemiology, symptomatology, course, impact on cognition, risk factors, etiopathology, aids in diagnosis, and treatment.


Optimizing non-Pb radiation shielding materials using bilayers.
The objective of this study was to demonstrate that the weight of non-Pb radiation shielding materials can be minimized by structuring the material as a bilayer composed of different metal-powder-embedded elastomer layers. Measurements and Monte Carlo (MC) calculations were performed to study the attenuation properties of several non-Pb metal bilayers over the x-ray energy range 30-150 keV. Metals for the layers were chosen on the basis of low cost, nontoxicity, and complementary photoelectric absorption characteristics. The EGSnrc user code cavity.cpp was used to calculate the resultant x-ray fluence spectra after attenuation by these metal layers. Air kerma attenuation was measured using commercially manufactured metal/elastomer test layers. These layers were irradiated using the primary standard calibration beams at the Institute for National Measurement Standards in Ottawa, Canada utilizing the six x-ray beam qualities recommended in the German Standard DIN 6857. Both the measurements and the calculations were designed to approximate surface irradiation as well as penetrating radiation at 10 mm depth in soft tissue. The MC modeling point and the position of the measurement detector for surface irradiation were both directly against the downstream face of the attenuating material, as recommended in DIN 6857. The low-Z upstream/high-Z downstream ordering of the metal bilayers provided substantially more attenuation than the reverse order. Optimal percentages of each metal in each bilayer were determined for each x-ray radiation beam quality. Depending on the x-ray quality, appropriate choices of two complementary metal-embedded elastomer layers can decrease the weight of radiation shielding garments by up to 25% compared to Pb-based elastomer garments while providing equivalent attenuation.


Cystic neoplasms of the pancreas: results of 114 cases.
To identify clinical, radiographic, and histopathologic characteristics associated with cancer in cystic pancreatic neoplasms and to evaluate our preoperative diagnostic accuracy to predict cancer in such cysts. Retrospective case series of 114 patients with cystic lesions of the pancreas who underwent resection between 1992 and 2006. Eighty-nine patients (78%) had benign or premalignant cysts; 25 patients (22%) had malignant cysts (carcinoma in situ and/or an invasive cancer). The factors most predictive of malignancy were age (P = 0.03), presence of symptoms (P = 0.02), and a dilated pancreatic duct (P = 0.01). Of the symptoms recorded, weight loss (P = 0.01) and jaundice (P = 0.02) had the strongest correlation with malignancy. We correctly predicted the pathological diagnosis (benign vs malignant) for only 39 (67%) of the 58 patients where a preoperative diagnosis was clearly evident. Endoscopic ultrasound did not seem to improve our ability to preoperatively differentiate benign from malignant cysts (P > 0.05). This series confirms that age, the presence of symptoms, and a dilated pancreatic duct on imaging are significantly associated with cancer in pancreatic cysts, and it highlights our inability to consistently make the preoperative diagnosis of cancer. Until more accurate markers of malignancy are available, an aggressive approach to management seems justified.


Current treatment of psoriasis with biologics.
Psoriasis is a chronic inflammatory skin disease with a significant number of patients suffering from additional joint involvement and other co-morbidities. The precise pathomechanisms of this disease are still unknown. But based on recent findings a picture emerges putting a new subset of inflammatory T cells, so-called Th17 T cells, into the centre of psoriasis pathogenesis. These cells secrete interleukin (IL)-17 and a further set of so-called Th17 cytokines such as IL-21 and IL-22, the latter of which appears to significantly contribute to the epidermal changes observed in this disease. Differentiation and maintenance of Th17 cells depends on IL-23 and transforming growth factor (TGF)-beta, secreted by activated monocytes or macrophages within the dermal compartment. In recent years, a plethora of new treatment approaches was introduced using antibodies or small molecule inhibitors specifically targeting inflammatory cytokines, cellular receptors or signalling mechanisms. Based on current results from large clinical trials, a more individualized treatment for affected patients may be achieved in the near future. In this review, we summarize the current knowledge about treatment of psoriasis with biological agents targeting inflammatory mechanisms.


Beyond implantable first generation cardiac prostheses for treatment of end-stage cardiac patients with clinical results in a multicenter.
After 30 years of research and development effort for both ventricular assist device (VAD) and total artificial heart (TAH) in the United States, they have been demonstrating effectiveness in the bridge to transplantation and destination therapy. Smaller size, long-term durable second generation and third generation blood pumps are now being tested in animals and moving to clinical applications. These are now combined with genetic engineering, tissue engineering and regenerative medical therapy techniques to provide newer treatment methodologies for end-stage cardiac patients. In Japan, heart transplantation was restarted in 1999, but to date only 13 transplants have been performed. Shortage in donor hearts is hindering the prevalence of heart transplantation. Over a dozen of end-stage cardiac patients are waiting for heart transplantation in hospital with a paracorporeal pneumatic VAD. Although implantable VADs have been imported from the USA, they have not acquired a wide clinical use yet because of their large size and high cost. There is a great need for development of a compact, low cost, totally implantable VAD and TAH in Japan to improve the quality of life of end-stage cardiac patients. This paper reviews the current status of the first generation pulsatile VAD and TAH as a bridge to transplantation and destination therapy around the world, followed with a review of the second and third generation blood pumps beyond the limitations of the first generation systems. Future recommendations are also discussed to improve the systems in Japan.


Inoculation of peritoneal dialysate fluid into blood culture bottles improves culture rates.
The aim of the study was to determine if direct inoculation of peritoneal fluid into Bactec blood culture bottles would improve the positive bacteriological yield compared with conventional techniques in continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis. All patients presenting with suspected peritonitis had peritoneal fluid injected directly into aerobic and anaerobic Bactec blood culture bottles as well as into sterile culture tubes. Thirty-seven paired samples were analysed. Twenty conventional cultures (54%) were positive compared with 33 (89%) done according to the Bactec system (P < 0.002). In only 1 case did the former technique prove superior. Direct inoculation of peritoneal fluid into Bactec blood culture bottles is therefore superior to conventional methods and has obvious therapeutic implications.


Argan Oil as a Rich Source of Linoleic Fatty Acid for Dietetic Structured Lipids Production.
Argan oil is rich in long-chain unsaturated fatty acids (FA), mostly oleic and linoleic, and natural antioxidants. This study addresses the production of low-calorie structured lipids by acidolysis reaction, in a solvent-free system, between caprylic (C8:0; system I) or capric (C10:0; system II) acids and argan oil, used as triacylglycerol (TAG) source. Three commercial immobilized lipases were tested: Novozym® 435, Lipozyme® TL IM, and Lipozyme® RM IM. Higher incorporation degree (ID) was achieved when C10:0 was used as acyl donor, for all the lipases tested. Lipozyme® RM IM yielded the highest ID for both systems (28.9 ± 0.05 mol.% C10:0, and 11.4 ± 2.2 mol.% C8:0), being the only catalyst able to incorporate C8:0 under the reaction conditions for biocatalyst screening (molar ratio 2:1 FA/TAG and 55 °C). The optimal conditions for Lipozyme® RM IM in system II were found by response surface methodology (66 °C; molar ratio FA/TAG of 4:1), enabling to reach an ID of 40.9 mol.% of C10:0. Operational stability of Lipozyme® RM IM in system II was also evaluated under optimal conditions, after eight consecutive 24 h-batches, with biocatalyst rehydration between cycles. The biocatalyst presented a half-life time of 103 h.


Cefpodoxime proxetil in the treatment of lower respiratory tract infections.
Cefpodoxime proxetil is the orally absorbed ester of cefpodoxime, a new third generation cephalosporin. In the gastrointestinal tract, cefpodoxime proxetil is hydrolysed to cefpodoxime, which has potent antibacterial activity against the major bacterial pathogens involved in lower respiratory tract infections: Haemophilus influenzae, Moraxella (Branhamella) catarrhalis (including beta-lactamase-producing strains), and Streptococcus pneumoniae (including amoxicillin-resistant strains). Six randomised comparative studies in patients with lower respiratory tract infections, 5 of which were large (enrollment of more than 200 patients) and double-blind, examined the efficacy and safety of cefpodoxime proxetil. Cefpodoxime proxetil (at a dosage equivalent to 200mg of cefpodoxime) administered twice daily for 5 to 10 days was similar in clinical and bacteriological efficacy to the following: amoxicillin 500mg 3 times daily in the treatment of community-acquired pneumonia; intramuscular ceftriaxone Ig once daily in the treatment of pulmonary infections in hospitalised patients; and to amoxicillin/clavulanic acid 500/125mg 3 times daily in the treatment of acute exacerbations of chronic bronchitis (AECB). Additionally, a dosage equivalent to 100mg or 200mg of cefpodoxime twice daily was similar in clinical and bacteriological efficacy to amoxicillin 250mg 3 times daily in the treatment of bronchitis (acute or AECB). The adverse events noted with cefpodoxime proxetil administration were similar to those associated with other beta-lactam antibacterials and most commonly involved the gastrointestinal tract and skin or mucous membranes. Thus, cefpodoxime proxetil is a useful addition to the antibacterials available for the treatment of infections of the lower respiratory tract.


Lateralization of Executive Function: Working Memory Advantage for Same Hemifield Stimuli in the Monkey.
Working memory capacity, the amount of information that may be maintained in mind over a period of seconds, is extremely limited, to a handful of items. Some evidence exists that the number of visual items that may be maintained in working memory is independent for the two hemifields. To test this idea, we trained monkeys to perform visual working memory tasks that required maintenance in memory of the locations and/or shapes of 3-5 visual stimuli. We then tested whether systematic performance differences were present for stimuli concentrated in the same hemifield, vs. distributed across hemifields. We found little evidence to support the expectation that working memory capacity is independent in the two hemifields. Instead, when an advantage of stimulus arrangement was present, it involved multiple stimuli presented in the same hemifield. This conclusion was consistent across variations of the task, performance levels, and apparent strategies adopted by individual subjects. This result suggests that factors such as grouping that favor processing of stimuli in relative proximity may counteract the benefits of independent processing in the two hemispheres. Our results reveal an important property of working memory and place constraints on models of working memory capacity.


Evaluation of Socially-Aware Robot Navigation.
As mobile robots are increasingly introduced into our daily lives, it grows ever more imperative that these robots navigate with and among people in a safe and socially acceptable manner, particularly in shared spaces. While research on enabling socially-aware robot navigation has expanded over the years, there are no agreed-upon evaluation protocols or benchmarks to allow for the systematic development and evaluation of socially-aware navigation. As an effort to aid more productive development and progress comparisons, in this paper we review the evaluation methods, scenarios, datasets, and metrics commonly used in previous socially-aware navigation research, discuss the limitations of existing evaluation protocols, and highlight research opportunities for advancing socially-aware robot navigation.


Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study.
During the 2009 pandemic of an emerging influenza A virus (IAV; H1N1pdm09), data from several European countries indicated that the spread of the virus might have been interrupted by the annual autumn rhinovirus epidemic. We aimed to investigate viral interference between rhinovirus and IAV with use of clinical data and an experimental model. We did a clinical data analysis and experimental infection study to investigate the co-occurrence of rhinovirus and IAV in respiratory specimens from adults (≥21 years) tested with a multiplex PCR panel at Yale-New Haven Hospital (CT, USA) over three consecutive winter seasons (Nov 1 to March 1, 2016-17, 2017-18, and 2018-19). We compared observed versus expected co-detections using data extracted from the Epic Systems electronic medical record system. To assess how rhinovirus infection affects subsequent IAV infection, we inoculated differentiated primary human airway epithelial cultures with rhinovirus (HRV-01A; multiplicity of infection [MOI] 0·1) or did mock infection. On day 3 post-infection, we inoculated the same cultures with IAV (H1N1 green fluorescent protein [GFP] reporter virus or H1N1pdm09; MOI 0·1). We used reverse transcription quantitative PCR or microscopy to quantify host cell mRNAs for interferon-stimulated genes (ISGs) on day 3 after rhinovirus or mock infection and IAV RNA on days 4, 5, or 6 after rhinovirus or mock infection. We also did sequential infection studies in the presence of BX795 (6 μM), to inhibit the interferon response. We compared ISG expression and IAV RNA and expression of GFP by IAV reporter virus. Between July 1, 2016, and June 30, 2019, examination of 8284 respiratory samples positive for either rhinovirus (n=3821) or IAV (n=4463) by any test method was used to establish Nov 1 to March 1 as the period of peak virus co-circulation. After filtering for samples within this time frame meeting the inclusion criteria (n=13 707), there were 989 (7·2%) rhinovirus and 922 (6·7%) IAV detections, with a significantly lower than expected odds of co-detection (odds ratio 0·16, 95% CI 0·09-0·28). Rhinovirus infection of cell cultures induced ISG expression and protected against IAV infection 3 days later, resulting in an approximate 50 000-fold decrease in IAV H1N1pdm09 viral RNA on day 5 post-rhinovirus inoculation. Blocking the interferon response restored IAV replication following rhinovirus infection. These findings show that one respiratory virus can block infection with another through stimulation of antiviral defences in the airway mucosa, supporting the idea that interference from rhinovirus disrupted the 2009 IAV pandemic in Europe. These results indicate that viral interference can potentially affect the course of an epidemic, and this possibility should be considered when designing interventions for seasonal influenza epidemics and the ongoing COVID-19 pandemic. National Institutes of Health, National Institute of General Medical Sciences, and the Yale Department of Laboratory Medicine.


Treatment of laryngopharyngeal reflux.
Proton-pump inhibitors form the cornerstone of antireflux therapy for laryngopharyngeal reflux. In this article, we provide algorithms to guide the management of minor, major, and life-threatening cases.


The use of core genome multilocus sequence typing to determine the duration of vancomycin-resistant Enterococcus faecium outbreaks.
The prevalence of vancomycin-resistant Enterococcus faecium has increased rapidly, and in Denmark, we are facing an endemic outbreak situation in hospitals. The aim of this study was to use whole-genome sequencing (WGS) and core genome multilocus sequencing typing (cgMLST) to determine the duration of VREfm outbreaks and thereby evaluate the effect of our infection control strategies. We included all VREfm isolates from six hospitals in the Capital Region of Denmark that were sequenced between 2012 and 2020. Ward data were collected from our laboratory information system. A ward outbreak was defined as two patient samples from the same ward within a period of 30 days belonging to the same cgMLST cluster. cgMLST complex types were determined using Ridom SeqSphere v7.2.3, where a maximum of 20 allelic differences between isolates defines a cluster. We included 1690 patient isolates between 2012 and 2020. Our collection consisted of 45 unique clusters and 227 ward outbreaks. The median duration of outbreaks was 20 days. We reported a median outbreak duration of VREfm outbreaks based on WGS data to be 20 days, and thus concluded that our infection control precautions are adequate.


Survival with Cemiplimab in Recurrent Cervical Cancer.
Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).


High-throughput yeast two-hybrid screening.
Charting the interactions among proteins is essential for understanding biological processes. While a number of complementary technologies for detecting protein interactions are available, the yeast two-hybrid system is one of the few that have been successfully scaled up. Two-hybrid screens have been used to construct extensive protein interaction maps for humans and several model organisms, and these maps have proven invaluable for studies on a variety of biological systems. These maps, however, have not come close to covering all proteins or interactions detectable by yeast two-hybrid. This is due in part to the difficulty of using library screening methods to sample all possible binary combinations of proteins. Ideally, every binary pair of proteins would be tested individually to ensure that every detectable interaction is identified. For organisms with large proteomes, however, this is not economically feasible and instead efficient pooling schemes must be implemented. The high-throughput two-hybrid screening methods presented here are designed to efficiently maximize coverage for selected sets of proteins or entire proteomes. We present two high-throughput screening protocols. Both methods are designed to identify interactors for any number of bait proteins expressed as DNA-binding domain (BD) fusions. The choice of which protocol to use depends largely on the nature of the available library of proteins fused to an activation domain (AD). The first protocol is appropriate for screening a library of AD clones, such as a cDNA library, a domain library, or a large pool of AD clones. By contrast, the second protocol is appropriate for screening a large array of individual sequence-verified AD clones. This protocol screens small pools of AD clones from the array in a two-phase scheme. Although the methods presented were developed using the LexA version of the yeast two-hybrid system, we include notes as appropriate to accommodate users of other versions.


Autophagy in the stress-induced myocardium.
Cardiovascular disease is a leading cause of death worldwide, particularly in Western societies. During an ischaemic insult, ventricular pressure from the heart is diminished as a result of cardiac myocyte death by necrosis and apoptosis. Autophagy is a process whereby cells catabolise intracellular proteins in order to generate ATP in times of stress such as nutrient starvation and hypoxia. Emerging evidence suggests that autophagy plays a positive role in cardiac myocyte survival during periods of cellular stress performing an important damage limitation function. By promoting cell survival, cardiac myocyte loss is reduced thereby minimising the potential of heart failure. In contrast, it has been reported that autophagy can also be a form of cell death. By considering the various animal models of autophagy, we examine the role of the Signal Transducers and Activator of Transcription (STAT) proteins in the autophagic response. Additionally we review the role of the tumour suppressor, p53 and its family member p73 and their potential role in the autophagic response.


The Role of Knee Positioning and Range-of-Motion on the Closed-Stance Forehand Tennis Swing.
This paper discusses the role of knee positioning and range-of- motion on the closed-stance forehand tennis swing. The analyses of tennis swing mechanics were performed using a computer model comprised of a full-body model of a human and an inertial model of a racket. The model was driven by subject forehand swings (16 female college-level subjects) recorded with a high-speed digital motion analysis system. The study discovered that both initial knee positioning and range-of-motion were positively related to racket velocity and characteristic of more skilled players. The direct effects of knee positioning and range-of-motion on racket movement are minimal, however there are several indirect biomechanical effects on the forehand motion such as movement of the body mass center, work of the knee, hip and back joints, and the angular range-of-motion of the hips and torso. Some of these indirect effects were related to racket velocity and characteristic of more skilled players. Factors that influenced knee positioning and range-of-motion include years of playing, amount of coaching, and body style. Efforts to both increase and restrict the knee movements of the subjects resulted in substantially lower racket velocities (and other detrimental biomechanical effects) implying that there may be optimal knee positions and range-of-motion for a given subject. The most skilled subject exhibited a high degree of consistency of knee positioning and range-of-motion. This subject adjusted for varying ball height through modified initial knee positioning while maintaining fairly constant ranges-of-motion. Key pointsInitial knee positioning and range-of-motion were positively related to racket velocity and characteristic of more skilled players for the closed stance forehand motion.Knee positioning and range-of-motion had several indirect biomechanical effects on the forehand motion such as movement of the body mass center, work of the knee, hip and back joints, and the angular range-of-motion of the hips and torso.Efforts to both increase and restrict the knee movements resulted in substantially lower racket velocities implying that there may be optimal knee positions and range-of-motion for a given subject.The most skilled subject exhibited a high degree of consistency of knee positioning and range-of-motion. This subject adjusted for varying ball height through modified initial knee positioning while maintaining fairly constant ranges-of-motion.


Microvascular Ageing Links Metabolic Disease to Age-Related Disorders: The Role of Oxidative Stress and Inflammation in Promoting Microvascular Dysfunction.
Longer life span and increased prevalence of chronic, noncommunicable, inflammatory diseases fuel cardiovascular mortality. The microcirculation is central in the cross talk between ageing, inflammation, cardiovascular, and metabolic diseases. Microvascular dysfunction, characterized by alteration in the microvascular endothelial function and wall structure, is described in an increasing number of chronic age-associated diseases, suggesting that it might be a marker of ageing superior to chronological age. The aim of this review is to thoroughly explore the connections between microvascular dysfunction, ageing, and metabolic disorders by detailing the major role played by inflammation and oxidative stress in their evolution. Older age, hypertension, nutrient abundance, and hyperglycemia concur in the induction of a persistent low-grade inflammatory response, defined as meta-inflammation or inflammageing. This increases the local generation of reactive oxygen species that further impairs endothelial function and amplifies the local inflammatory response. Mitochondrial dysfunction is a hallmark of many age-related diseases. The alterations of mitochondrial function promote irreversible modification in microvascular structure. The interest in the hypothesis of chronic inflammation at the center of the ageing process lies in its therapeutic implications. Inhibition of specific inflammatory pathways has been shown to lower the risk of many age-related diseases, including cardiovascular disease. However, the whole architecture of the inflammatory response underpinning the ageing process and its impact on the burden of age-related diseases remain to be fully elucidated. Additional studies are needed to unravel the connection between these biological pathways and to address their therapeutic power in terms of cardiovascular prevention.


[Paget's disease mimicking metastatic prostate cancer on bone scan image : a case report].
A 61-year-old man was referred to our hospital complaining of elevated serum prostate-specific antigen (PSA) (5.1 ng/ml). Histopathologic diagnosis with trans-rectal prostate biopsy specimen was adenocarcinoma, Gleason score 4+5 = 9. Bone scintigraphy revealed an abnormal uptake on left coxal bone. The patient was diagnosed with prostate cancer with bone metastasis. He received androgen deprivation therapy for two years. Serum PSA decreased to an undetected level. However, the abnormal activity of left coxal bone lesion was not changed on bone scintigraphy. Coxal bone biopsy was performed. The bone lesion was histopathologically diagnosed as Paget's disease of bone.


Surgical Treatment of Neuroendocrine Tumors of the Terminal Ileum or Cecum: Ileocecectomy Versus Right Hemicolectomy.
Simple ileocecectomy and right hemicolectomy are two potential operative approaches to treat patients with neuroendocrine neoplasm in the terminal ileum and/or cecum (IC-NENs). We sought to define the long-term outcome of patients undergoing ileocecectomy versus right hemicolectomy for IC-NENs, as well as characterize number of nodes evaluated and lymph node metastasis (LNM) associated with each procedure. Patients who underwent curative-intent resections for IC-NENs between 2000 and 2016 were identified from a multi-institutional database. The clinicopathologic characteristics, surgical procedures, and the overall (OS) and recurrence-free survival (RFS) were compared among patients who underwent formal right hemicolectomy versus ileocecectomy only. Among 127 patients with IC-NENs, median size of the largest tumor size was 2.0 (IQR 1.2-2.9) cm; 35 (27.6%) patients had multiple lesions. At the time of surgery, 93 (73.2%) patients underwent a right hemicolectomy, whereas 34 (26.8%) had ileocecectomy only. Every patient had a lymph node dissection (LND) with a median number of 16 (IQR 12-22) nodes evaluated. A majority (n = 110, 86.6%) of patients had LNM with a median number of 3 (IQR 2-5) LNM. Patients who underwent hemicolectomy had more lymph nodes evaluated versus patients who had an ileocecectomy only (median, 18 vs. 14, p = 0.004). Patients who underwent formal right hemicolectomy versus ileocecectomy had a similar OS (median OS, 101.9 vs. 144.5 months, p = 0.44) and RFS (median RFS, 70.3 vs. not attained, p = 0.80), respectively. Ileocecectomy had similar long-term outcomes versus right hemicolectomy in treatment of IC-NENs despite a difference in the lymph node harvest.


Comparative UAV and Field Phenotyping to Assess Yield and Nitrogen Use Efficiency in Hybrid and Conventional Barley.
With the commercialization and increasing availability of Unmanned Aerial Vehicles (UAVs) multiple rotor copters have expanded rapidly in plant phenotyping studies with their ability to provide clear, high resolution images. As such, the traditional bottleneck of plant phenotyping has shifted from data collection to data processing. Fortunately, the necessarily controlled and repetitive design of plant phenotyping allows for the development of semi-automatic computer processing tools that may sufficiently reduce the time spent in data extraction. Here we present a comparison of UAV and field based high throughput plant phenotyping (HTPP) using the free, open-source image analysis software FIJI (Fiji is just ImageJ) using RGB (conventional digital cameras), multispectral and thermal aerial imagery in combination with a matching suite of ground sensors in a study of two hybrids and one conventional barely variety with ten different nitrogen treatments, combining different fertilization levels and application schedules. A detailed correlation network for physiological traits and exploration of the data comparing between treatments and varieties provided insights into crop performance under different management scenarios. Multivariate regression models explained 77.8, 71.6, and 82.7% of the variance in yield from aerial, ground, and combined data sets, respectively.


An integrated approach to emergency psychiatric care.
Increased demands for psychiatric emergency services led to a crisis in New York City emergency rooms. The New York State Comprehensive Psychiatric Emergency Program was developed as a systemic response to the crisis. The model includes four integrated components designed to enhance the entire mental health system.


Water conservation benefits of urban heat mitigation.
Many cities globally are seeking strategies to counter the consequences of both a hotter and drier climate. While urban heat mitigation strategies have been shown to have beneficial effects on health, energy consumption, and greenhouse gas emissions, their implications for water conservation have not been widely examined. Here we use a suite of satellite-supported regional climate simulations in California to show that broad implementation of cool roofs, a heat mitigation strategy, not only results in significant cooling, but can also meaningfully decrease outdoor water consumption by reducing evaporative and irrigation water demands. Irrigation water consumption across the major metropolitan areas is reduced by up to 9% and irrigation water savings per capita range from 1.8 to 15.4 gallons per day across 18 counties examined. Total water savings are found to be the highest in Los Angeles county, reaching about 83 million gallons per day. Cool roofs are a valuable solution for addressing the adaptation and mitigation challenges faced by multiple sectors in California.


Protective antigen detection using horizontally stacked hexagonal ZnO platelets.
Anthrax toxin detection before bacteremia, when toxin concentration is low, improves the chances of efficient treatment and cure. We present a novel technique for ultrasensitive detection of a protective antigen (PA(83)) of anthrax using an array of zinc oxide nanorods in conjunction with a FITC-labeled PA affinity peptide. The nanorods are composed of horizontally stacked hexagonal platelets which are uniformly spaced and grown unidirectionally upon a glass substrate via a new and simple technique. Images taken under UV emission demonstrate fluorescence sensitivity to PA as a function of antigen concentration, and a negative control using bovine serum albumin produced no fluorescence signal. The fluorescence signal of the PA-peptide complex is also significantly reduced in the absence of the nanorods, suggesting that the presence of ZnO nanorods inhibits the self-quenching properties of the fluorophore. A lower limit of detection for the assay system for PA is estimated at 150 aM, which demonstrates the possibility of using ZnO nanorods in biological sensor systems.


X-Ray absorption spectroscopy quantitative analysis of biomimetic copper(II) complexes with tridentate nitrogen ligands mimicking the tris(imidazole) array of protein centres.
In this study copper(ii) complexes with the tridentate nitrogen ligand bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-BB) are considered as model compounds for the Cu-tris(imidazole) array found in several copper proteins. 2-BB chelates copper(ii) forming two six-membered rings and the complexes contain methanol, nitrite, azide and water as ancillary ligands; both the coordination numbers and stereochemistries differ in these complexes. Their key structural features were investigated by using full multiple-scattering theoretical analysis of the copper K-edge X-ray absorption spectrum with the MXAN code. We showed that using cluster sizes large enough to include all atoms of the ligand, the analysis of the XANES region can give both a structural model of the metal centre and map the structure of the 2-BB complexes. Complex [Cu(2-BB)(N(3))](+) provided a critical test through the comparison of the XANES simulation results with crystallographic data, thus permitting the extension of the method to the complex [Cu(2-BB)(H(2)O)(n)](+) (n = 1 or 2), for which crystallographic data are not available but is expected to bear a five-coordinated Cu(3N)(2O) core (n = 2). The structural data of [Cu(2-BB)(MeOH)(ClO(4))](+) and [Cu(2-BB)(NO(2))](+), both with a Cu(3N)(2O) core but with a different stereochemistry, were used as the starting parameters for two independent simulations of the XANES region of the [Cu(2-BB)(H(2)O)(2)](+) cation. The two structural models generated by simulation converge towards a structure for the aqua-cation with a lower coordination number. New calculations, where four-coordinated Cu(3N)(O) cores were considered as the starting structures, validated that the structure of the aqua-complex in the powder state has a copper(ii) centre with a four-coordinated Cu(3N)(O) core and a molecular formula [Cu(2-BB)(H(2)O)](ClO(4)).(H(2)O). A water solvation molecule, presumed to be disordered from the simulations with the two Cu(3N)(2O) cores, is present. The successful treatment of this Cu-2-BB complex system allows the extension of the method to other biomimetic compounds when a structural characterization is lacking.