Reliability and validity of the Child Perception Questionnaire 8 ~ 10 (CPQ8~10) in China: an instrument for measuring oral health-related quality of life among 8-10-year-old children.
Children aged 8-10 are in a critical stage of growth and development, facing complex and specific oral health problems. In China, there is no specific assessment questionnaire for this age group. The Child Perception Questionnare 8 ~ 10 (CPQ8~10) has been widely used in many countries, with good reliability and validity. This study aimed to translate the CPQ8~10 into Chinese and assess its reliability and validity, and ascertain its applicability for 8-10-year-old children in China. Brislin's translation model was used in developing the Chinese version of CPQ8~10. Internal consistency, retest reliability, criterion validity, and confirmatory factor analysis were performed to evaluate the reliability and validity of the Chinese version of the CPQ8~10 among 494 8 ~ 10-year-old children in China. A Chinese version of the CPQ8~10, aligned with Chinese culture and social features, was developed. The criterion validity was 0.719 (P < 0.001). The item-level content validity index (I-CVI) and scale-level content validity index (S-CVI) for the Chinese version of the CPQ8~10 were 0.80 ~ 1.00 and 0.968, respectively. Factor analysis revealed a logical relationship among the items in the Chinese version of the CPQ8~10. The Cronbach's α coefficient, retest reliability, and Guttman split-half reliability coefficient for the Chinese version of the CPQ8~10 were 0.819, 0.830, and 0.849, respectively. The Chinese version of the CPQ8~10 exhibited a structure consistent with the original questionnaire, displaying good reliability and validity. This study facilitates the application of CPQ8~10 in China. The Chinese version of the CPQ8~10 is a brief and suitable tool to evaluate oral health-related quality of life of 8 ~ 10-year-old children.


Reduced oxygen uptake during steady state exercise after 21-day mountain climbing expedition to 6,194 m.
We investigated the effect of a 21-day climbing expedition to 6,194 m on the oxygen uptake (V022) and leg blood flow (LBF) responses to submaximal exercise in five healthy, fit men during two-leg kicking exercise a 0-W and 50-W. Tests were completed 1 week before and 3 days after altitued acclimatization. The adaptation of VO2 at exercise onset was described by the time to 63% of the new steady state. Steady state VO2 during 50-W exercise was less post-climb (1290+/- 29 mL/min, mean +/- SE) than pre-climb (1413+/- 63 mL/min, P <.05). VO2 adapted more slowly at the onset of 50-W exercise post climb. There were no differences in the steady state LBF during the 50-W exercise, the increase above baseline, or the adaptation post-climb. Respiratory exchange ratio was greater at 50-W post-climb compared to pre-climb. Reduced steady state V02 during exercise after exposure to high altitude is consistent with an increase in metabolic efficiency.


Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice.
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid metabolism and is currently being pursued as a therapeutic agent for insulin resistance and type 2 diabetes. However, the cellular mechanisms by which FGF21 modifies insulin action in vivo are unclear. To address this question, we assessed insulin action in regular chow- and high-fat diet (HFD)-fed wild-type mice chronically infused with FGF21 or vehicle. Here, we show that FGF21 administration results in improvements in both hepatic and peripheral insulin sensitivity in both regular chow- and HFD-fed mice. This improvement in insulin responsiveness in FGF21-treated HFD-fed mice was associated with decreased hepatocellular and myocellular diacylglycerol content and reduced protein kinase Cε activation in liver and protein kinase Cθ in skeletal muscle. In contrast, there were no effects of FGF21 on liver or muscle ceramide content. These effects may be attributed, in part, to increased energy expenditure in the liver and white adipose tissue. Taken together, these data provide a mechanism by which FGF21 protects mice from lipid-induced liver and muscle insulin resistance and support its development as a novel therapy for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes.


Association between Klinefelter syndrome and focal nodular hyperplasia.
Focal nodular hyperplasia is a benign lesion of the liver, predominantly affecting women. Its etiology is unknown. Elevated levels of estrogens have been invoked to play a role in the disease. Klinefelter syndrome is the most common sex chromosome disorder, characterized by 47, XXY karyotype, resulting in male hypogonadism and sex hormone imbalance. We present a case of a 25-year-old man affected by Klinefelter syndrome, admitted to our hospital for aspecific dyspeptic symptoms. During admission he underwent: blood test for the liver function and sexual hormonal status, ultrasonography, echo color power Doppler and computerized tomography scan of the liver, and liver biopsy. A hypergonadotropic hypogonadism was present. Imaging of the liver showed an hepatic lesion that liver biopsy confirmed to be a focal nodular hyperplasia. Although the association could be casual, the sex hormone imbalance present in Klinefelter syndrome may suggest a role in the development of this benign liver lesion.


Self-Regulated Dynamical Criticality in Human ECoG.
Mounting experimental and theoretical results indicate that neural systems are poised near a critical state. In human subjects, however, most evidence comes from functional MRI studies, an indirect measurement of neuronal activity with poor temporal resolution. Electrocorticography (ECoG) provides a unique window into human brain activity: each electrode records, with high temporal resolution, the activity resulting from the sum of the local field potentials of ∼10(5) neurons. We show that the human brain ECoG recordings display features of self-regulated dynamical criticality: dynamical modes of activation drift around the critical stability threshold, moving in and out of the unstable region and equilibrating the global dynamical state at a very fast time scale. Moreover, the analysis also reveals differences between the resting state and a motor task, associated with increased stability of a fraction of the dynamical modes.


Evaluation of effects of methamphetamine repeated dosing on proliferation and apoptosis of rat germ cells.
Methamphetamine (MAMP) is a central nervous system stimulant that is increasingly abused especially by teenagers and young adults, a group in its reproductive age. MAMP effects on the male reproductive system are not clear. In this experimental study, we evaluated the effects of MAMP administration on proliferation and apoptosis in seminiferous tubules of rat testis. Methamphetamine hydrochloride was synthesized by iodination of norephedrine hydrochloride and reduction to methamphetamine. Mature male rats were randomly divided into four groups (n=7) and were injected intraperitoneally with MAMP (1, 5 or 10 mg/kg) or saline at the same time, once daily for 14 consecutive days. Twenty four hs after the last injection, perfused testis were fixed, sectioned and stained by TUNEL labeling or proliferating cell nuclear antigen (PCNA) immunostaining. Apoptotis and proliferation indices were calculated and ratios of proliferation/apoptosis in the seminiferous tubules were obtained. Cell proliferation and the ratio of proliferation to apoptosis decreased significantly in all experimental groups compared to the control group. Conversely, apoptosis was increased in these groups. Such differences were observed in both spermatogonia and primary spermatocytes. In the control group, more than 95% of spermatogonia were PCNA-positive. However, 10 mg/kg of MAMP caused a reduction to approximately 75% PCNA staining in spermatogonia. In some tubules of the experimental groups, more than 10 TUNEL-positive germ cells were seen, although in the control group, the tubules with 3 TUNEL-positive germ cells were rarely observed and the majority of tubules were without such cells. There were significant differences in the indices between the 1 mg/kg group and the higher dose groups, but there was no such difference between the 5 mg/kg and 10 mg/kg groups. In some tubules of the experimental groups, significant gaps in the epithelium between the spermatogonia layer and other cell layers were observed. These results show that repeated administration of MAMP, especially at higher doses, may cause a decrease in cellular proliferation, induce apoptosis and change the proliferation/apoptosis ratio in testis. This might explain the MAMP effect on the spermatogenesis process. It is suggested that studies on the consequence of MAMP consumption on male fertility is warranted.


Room temperature O transfer from N2O to CO mediated by the nearest Cd(i) ions in MFI zeolite cavities.
The dominant oxidation state of cadmium is +ii. Although extensive investigations into the +ii oxidation state have been carried out, the chemistry of CdI is still largely underdeveloped. Here, we report a new functionality of cadmium created by the zeolite lattice: room temperature O transfer from N2O to CO mediated by the nearest monovalent cadmium ions in MFI zeolite. Thermal activation of CdII ion-exchanged MFI zeolite in vacuo affords the diamagnetic [CdI-CdI]2+ species with a short CdI-CdI σ bond (2.67 Å). This species generates two CdI˙ sites under UV irradiation through homolytic cleavage of the CdI-CdI σ bond, and the thus-formed nearest CdI˙ sites abstract an O atom from N2O to generate the [CdII-Ob-CdII]2+ core, where Ob means bridged oxygen. This bridging atomic oxygen species is transferred to CO at room temperature, through which CO oxidation and regeneration of the CdI-CdI σ bond then proceed. This is the first example pertaining to the reversible redox reactivity of the nearest monovalent cadmium ions toward stable small molecules. In situ spectroscopic characterization captured all the intermediates in the reaction processes, and these data allowed us to calibrate the density-functional-theory cluster calculations, by means of which we were able to show that the charge compensation requirement at the nearest two Al sites arrayed circumferentially in the 10-membered ring of MFI zeolite creates such novel functionalities of cadmium. The unprecedented reactivity of CdI and its origin are discussed.


Implementation of care practices to prevent and repair perineal trauma in childbirth.
To implement care practices for perineal trauma prevention and repairing in normal birth. Quasi-experimental study conducted at Hospital da Mulher Mãe-Luzia, in Macapá, AP, Brazil. Seventy-four (74) nurses and obstetricians and 70 post-partum women were interviewed and the records of 555 patients were analyzed. The study was conducted in three stages: pre-audit and baseline audit (phase 1); educational intervention and implementation of best practices (phase 2); post-implementation audit (phase 3). Data was analyzed by comparison of the results of phases 1 and 3. Following the educational intervention, a lower number of health professionals encouraged directed pushing, performed episiotomies and repaired first-degree lacerations; more women reported lithotomy position; more patient records indicated the use of Vicryl™ to suture the perineal mucosa and skin. The educational intervention improved birth care and perineal outcomes. Nevertheless, gaps were identified in the implementation of evidence, as well as inappropriate perineal care management.


An internal control for routine diagnostic PCR: design, properties, and effect on clinical performance.
We constructed internal controls (ICs) to provide assurance that clinical specimens are successfully amplified and detected. The IC nucleic acids contain primer binding regions identical to those of the target sequence and contain a unique probe binding region that differentiates the IC from amplified target nucleic acid. Because only 20 copies of the IC are introduced into each test sample, a positive IC signal indicates that amplification was sufficient to generate a positive signal from targets present at the limit of test sensitivity. The COBAS AMPLICOR Chlamydia trachomatis, Neisseria gonorrhoeae, Mycobacterium tuberculosis, and human hepatitis C virus tests exhibited inhibition rates ranging from 5 to 9%. Approximately 64% of these inhibitory specimens were not inhibitory when a second aliquot was tested. Because repeatedly inhibitory specimens were not reported as false negative and because additional infected specimens were detected during retesting, test sensitivities were 1 to 6% greater than they would have been if the IC had not been used.


[Cellular immunity indices of ovarian cancer patients].
The dynamics of functional indexes of T-cell immunity was studied in 47 patients with extended ovarian tumor. The said parameters were found to be adversely affected in primary patients as a result of surgery and chemotherapy. They came back to normal during remission but were badly deranged in relapsing patients.


Use of the Stromal Vascular Fraction in Intermediate-Deep Acute Burns: A Case With Its Own Control.
We present a case of symmetrical thermal intermediate-deep burns treated in a case-control fashion with the stromal vascular fraction (SVF) obtained with the MyStem™ device and a scaffold of hyaluronic acid. After enzymatic debridement and SVF harvesting and application, we observed quicker healing (as assessed by wound area histogram planimetry) in the case area as opposed to the control one, which eventually underwent skin grafting. At the 3 months follow-up, the Vancouver Scar Scale was 9 for the case side and 10 for the control side, with a tendency to hypertrophic scarring in both areas, while patient satisfaction Visual Analogue Scale was 7 for the case side and 2 for the control side. CD31 expression, a marker of neoangiogenesis, was significantly higher in the case area as compared to the control one. SVF could potentially represent a valid alternative to the current standard of care, with a decreased need of invasive surgery and consequent improved patients' quality of life.


Decreased binding of antibiotics to lipopolysaccharides from polymyxin-resistant strains of Escherichia coli and Salmonella typhimurium.
The interactions of polycationic antibiotics with lipopolysaccharide (LPS) isolated from parental and polymyxin-resistant strains of Salmonella typhimurium and Escherichia coli were measured by using a cationic spin probe. Electron spin resonance spectra indicated that increasing concentrations of cations competitively displaced probe from LPS aggregates. Polymyxin B and other cations displaced less probe from LPS of polymyxin-resistant strains than from LPS of the parental strains, whereas the same amount or more probe was displaced from isolates of the mutants by the structurally similar antibiotic, EM 49 (octapeptin). In general, the differential affinities of these antibiotics for LPS correlated with their antibiotic activity in vivo, suggesting that resistance results from a decrease in antibiotic permeability across the outer membrane due to alterations in the LPS which affect antibiotic binding. The alterations in the structure of LPS from the polymyxin-resistant mutants of E. coli were characterized using 31P nuclear magnetic resonance spectroscopy. The results suggested that esterification of the core-lipid A phosphates is responsible for increased resistance to polymyxin B and that this alteration is different from that previously proposed for the S. typhimurium strains. In both cases, however, resistance was the result of modifications that result in a less acidic lipid A.


[STIGMA AND HIV / AIDS AMONG PUERTO RICAN PARENTS / MOTHERS AND ADOLESCENTS].
Communication between parents and adolescents about sexuality is important for the healthy development of young people. Stigmatizing attitudes towards HIV/AIDS may adversely impact this communication. The aim of this study was to identify stigmatizing attitudes towards HIV/AIDS among Puerto Rican parents and adolescents. This effort is part of the Cuídalos Project which aimed to test a web-based intervention to increase communication about sexuality and health among parents and adolescents through an experimental design with 458 parent/adolescent (13-17 years of age) dyads. For the purposes of this article we report descriptive statistics on HIV/AIDS stigma attitudes gathered as part of our baseline measurement. Both parents and adolescents manifested stigmatizing attitudes towards HIV/AIDS. In light of these results it is necessary to continue developing interventions to reduce stigma among this population. Parents can be an invaluable asset to reduce stigma among adolescents and to help prevent sexual risk behaviors and new infection.


Experimental study on the effect of caffeine hydrogel on the expression of TGF -β1, α-SMA and collagen in hypertrophic scar of rabbit ears.
This study evaluated the effects of topical use of caffeine hydrogel on hypertrophic scar in a rabbit ear wound model. Nine rabbits were randomly divided into three groups: control group, caffeine hydrogel group and matrix group. Punched defects were established on each rabbit's ear which resulted in a hypertrophic scar. When the wound epithelialization and scar hyperplasia could be seen, control group did not do any treatment, while caffeine hydrogel group and matrix group were treated with caffeine hydrogel and hydrogel matrix, respectively. After 3 weeks of administration, the general morphological changes of scar were observed, and the scar tissue of rabbit ears was stained with HE and Masson. The relative expressions of TGF β-1, α-SMA, type Ⅰ collagen and type Ⅲ collagen in scar tissue were detected by Western blot. In all three groups, findings showed that caffeine hydrogel can inhibit scar growth by reducing the expression of TGF β-1, reducing the proliferation of fibroblasts, improving collagen arrangement and reducing collagen deposition. The overall study shows efficacy and mechanism of caffeine. It concluded that caffeine could be an effective therapeutic agent for hypertrophic scars.


Environmental and anthropogenic factors associated with the likelihood of detecting Salmonella in agricultural watersheds.
Surface water is one of the primary sources of irrigation water for produce production; therefore, its contamination by foodborne pathogens, such as Salmonella, may substantially impact public health. In this study, we determined the presence of Salmonella in surface water and characterized the relationship between Salmonella detection and environmental and anthropogenic factors. From April 2019 to February 2020, 120 samples from 30 sites were collected monthly in four watersheds located in two different central Chile agricultural regions (N = 1080). Water samples from rivers, canals, streams, and ponds linked to each watershed were obtained. Surface water (10 L) was filtrated in situ, and samples were analyzed for the presence of Salmonella. Salmonella was detected every month in all watersheds, with a mean detection percentage of 28% (0%-90%) across sampling sites, regardless of the season. Overall, similar detection percentages were observed for both regions: 29.1% for Metropolitan and 27.0% for Maule. Salmonella was most often detected in summer (39.8% of all summer samples tested positive) and least often in winter (14.4% of winter samples). Random forest analysis showed that season, water source, and month, followed by latitude and river, were the most influential factors associated with Salmonella detection. The influences of water pH and temperature (categorized as environmental factors) and factors associated with human activity (categorized as anthropogenic factors) registered at the sampling site were weakly or not associated with Salmonella detection. In conclusion, Salmonella was detected in surface water potentially used for irrigation, and its presence was linked to season and water source factors. Interventions are necessary to prevent contamination of produce, such as water treatment before irrigation.


[Papillomas of the urinary bladder induced by N-nitroso-N-methylurea in rats].
N-nitroso-N-methylurea (a total dosage--6 mg per animal), administered by a catheter in the urinary bladder cavity in female rats, following 9--56 weeks induced in 16 of 23 rats tumors of the vesical mucous membrane (mostly transitional cell papillomas).


Occurrence and stability of lone pair-π stacking interactions between ribose and nucleobases in functional RNAs.
The specific folding pattern and function of RNA molecules lies in various weak interactions, in addition to the strong base-base pairing and stacking. One of these relatively weak interactions, characterized by the stacking of the O4' atom of a ribose on top of the heterocycle ring of a nucleobase, has been known to occur but has largely been ignored in the description of RNA structures. We identified 2015 ribose-base stacking interactions in a high-resolution set of non-redundant RNA crystal structures. They are widespread in structured RNA molecules and are located in structural motifs other than regular stems. Over 50% of them involve an adenine, as we found ribose-adenine contacts to be recurring elements in A-minor motifs. Fewer than 50% of the interactions involve a ribose and a base of neighboring residues, while approximately 30% of them involve a ribose and a nucleobase at least four residues apart. Some of them establish inter-domain or inter-molecular contacts and often implicate functionally relevant nucleotides. In vacuo ribose-nucleobase stacking interaction energies were calculated by quantum mechanics methods. Finally, we found that lone pair-π stacking interactions also occur between ribose and aromatic amino acids in RNA-protein complexes.


How does carbon dioxide permeate cell membranes? A discussion of concepts, results and methods.
We review briefly how the thinking about the permeation of gases, especially CO2, across cell and artificial lipid membranes has evolved during the last 100 years. We then describe how the recent finding of a drastic effect of cholesterol on CO2 permeability of both biological and artificial membranes fundamentally alters the long-standing idea that CO2-as well as other gases-permeates all membranes with great ease. This requires revision of the widely accepted paradigm that membranes never offer a serious diffusion resistance to CO2 or other gases. Earlier observations of "CO2-impermeable membranes" can now be explained by the high cholesterol content of some membranes. Thus, cholesterol is a membrane component that nature can use to adapt membrane CO2 permeability to the functional needs of the cell. Since cholesterol serves many other cellular functions, it cannot be reduced indefinitely. We show, however, that cells that possess a high metabolic rate and/or a high rate of O2 and CO2 exchange, do require very high CO2 permeabilities that may not be achievable merely by reduction of membrane cholesterol. The article then discusses the alternative possibility of raising the CO2 permeability of a membrane by incorporating protein CO2 channels. The highly controversial issue of gas and CO2 channels is systematically and critically reviewed. It is concluded that a majority of the results considered to be reliable, is in favor of the concept of existence and functional relevance of protein gas channels. The effect of intracellular carbonic anhydrase, which has recently been proposed as an alternative mechanism to a membrane CO2 channel, is analysed quantitatively and the idea considered untenable. After a brief review of the knowledge on permeation of O2 and NO through membranes, we present a summary of the (18)O method used to measure the CO2 permeability of membranes and discuss quantitatively critical questions that may be addressed to this method.


Otitis media at Canyon Day, Ariz. A 16-year follow-up in Apache Indians.
A 16-year follow-up survey of native Americans living in Canyon Day, Ariz, did not show improvement in the 9.3% rate of clinically significant otitis media. However, the manifestations were more benign, especially in children, and included the spectrum of otitis media. A genetically determined eustachian tube difference may explain the high rate of occurrence of otitis media in these Apache Indians. Improvements in living conditions and health care may explain the change to less severe manifestations.


A virosomal immunization strategy against cervical cancer and pre-malignant cervical disease.
In this study, we demonstrate that fusion-active virosomes, containing recombinant human papillomavirus type 16 (HPV16) E7 protein antigen, are capable of inducing a robust class I MHC-restricted cytotoxic T-lymphocyte (CTL) response against HPV-transformed tumour cells in a murine model system. Virosomes are reconstituted viral envelopes, which do not contain the genetic material of the native virus. During the reconstitution process, protein antigens can be encapsulated within the virosomes. In the present study, we used virosomes derived from influenza virus. These virosomes retain the cell binding and membrane fusion characteristics of native influenza virus, and have the capacity to deliver encapsulated antigens to the cytosol of antigen-presenting cells through fusion from within acidic endosomes. After immunization of mice with virosomes containing encapsulated HPV16 E7 protein, the animals developed a strong E7-specific CTL response as assessed by 51Cr release measurements and MHC tetramer staining of spleen cells. Immunization with E7-containing virosomes also resulted in E7-specific antibody responses. In tumour challenge experiments, immunization of mice with E7-containing virosomes prevented tumour outgrowth in >70% of the animals. Thus, influenza-derived virosomes with encapsulated HPV E7 protein antigen act as an excellent vaccine delivery system for induction of cellular immunity against HPV-transformed cells and represent a promising immunotherapeutic vaccine for the treatment of (precursor lesions of) cervical cancer.


Influence of host weight, sex and reproductive status on helminth parasites of the wild rabbit, Oryctolagus cuniculus, in Navarra, Spain.
A study was carried out in Navarra (northern Spain) on the influence of the weight, sex and reproductive status (lactant, pregnant or lactant + pregnant females and testicular weight for males) of the wild rabbit (Oryctolagus cuniculus) on two cestodes species: Andrya cuniculi and Mosgovoyia ctenoides and four intestinal nematodes: Graphidium strigosum, Trichostrongylus retortaeformis, Nematodiroides zembrae and Dermatoxys hispaniensis. A significantly higher prevalence of A. cuniculi was detected in lactant + pregnant females compared with non-breeding females. Trichostrongylus retortaeformis and N. zembrae showed a significantly higher mean intensity in lactant and lactant + pregnant females than in non-reproductive females. Trichostrongylus retortaeformis presented a higher mean intensity in females than in males, and the mean intensity of the same parasite species was significantly lower in active and inactive males compared with lactant and lactant + pregnant females. There were no significant differences between sexes in the prevalence of helminth parasites. No significant correlation was detected between host weight and the intensity (of infection) of helminths studied. No significant differences in the prevalence and mean intensity of the two cestode species were observed in the three weight categories studied (kittens, juveniles and adults). The prevalence of G. strigosum and mean intensity of T. retortaeformis were significantly higher in older heavier animals than in juveniles.


Understanding the Action of RARγ Agonists on Human Osteochondroma Explants.
Osteochondromas are cartilage-capped growths located proximate to the physis that can cause skeletal deformities, pain, limited motion, and neurovascular impingement. Previous studies have demonstrated retinoic acid receptor gamma (RARγ) agonists to inhibit ectopic endochondral ossification, therefore we hypothesize that RARγ agonists can target on established osteochondromas. The purpose of this study was to examine the action of RARγ agonist in human osteochondromas. Osteochondroma specimens were obtained during surgery, subjected to explant culture and were treated with RARγ agonists or vehicles. Gene expression analysis confirmed the up-regulation of RARγ target genes in the explants treated with NRX 204647 and Palovarotene and revealed strong inhibition of cartilage matrix and increased extracellular matrix proteases gene expression. In addition, immunohistochemical staining for the neoepitope of protease-cleaved aggrecan indicated that RARγ agonist treatment stimulated cartilage matrix degradation. Interestingly, cell survival studies demonstrated that RARγ agonist treatment stimulated cell death. Moreover, RNA sequencing analysis indicates changes in multiple molecular pathways due to RARγ agonists treatment, showing similarly to human growth plate chondrocytes. Together, these findings suggest that RARγ agonist may exert anti-tumor function on osteochondromas by inhibiting matrix synthesis, promoting cartilage matrix degradation and stimulating cell death.


A global analysis of CNVs in Chinese indigenous fine-wool sheep populations using whole-genome resequencing.
Copy number variation (CNV) is an important source of genetic variation that has a significant influence on phenotypic diversity, economically important traits and the evolution of livestock species. In this study, the genome-wide CNV distribution characteristics of 32 fine-wool sheep from three breeds were analyzed using resequencing. A total of 1,747,604 CNVs were detected in this study, and 7228 CNV regions (CNVR) were obtained after merging overlapping CNVs; these regions accounted for 2.17% of the sheep reference genome. The average length of the CNVRs was 4307.17 bp. "Deletion" events took place more frequently than "duplication" or "both" events. The CNVRs obtained overlapped with previously reported sheep CNVRs to variable extents (4.39-55.46%). Functional enrichment analysis showed that the CNVR-harboring genes were mainly involved in sensory perception systems, nutrient metabolism processes, and growth and development processes. Furthermore, 1855 of the CNVRs were associated with 166 quantitative trait loci (QTL), including milk QTLs, carcass QTLs, and health-related QTLs, among others. In addition, the 32 fine-wool sheep were divided into horned and polled groups to analyze for the selective sweep of CNVRs, and it was found that the relaxin family peptide receptor 2 (RXFP2) gene was strongly influenced by selection. In summary, we constructed a genomic CNV map for Chinese indigenous fine-wool sheep using resequencing, thereby providing a valuable genetic variation resource for sheep genome research, which will contribute to the study of complex traits in sheep.


Induction of heat shock protein 47 synthesis by TGF-beta and IL-1 beta via enhancement of the heat shock element binding activity of heat shock transcription factor 1.
With most immunological reactions, tissue fibrosis, collagen overproduction caused by immune cytokines, is inevitably associated. Among the various immune cytokines, heat shock protein 47 (HSP47) is a procollagen-specific molecular chaperon and is essential for secretion of procollagen from cells. Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts. As for IL-1beta, its effect on HSP47 has not been elucidated. In the present study, using human embryonic lung fibroblast cells, we first disclosed that both TGF-beta and IL-1beta induced HSP47 synthesis. We then revealed that the binding of the heat shock element (HSE) by heat shock transcription factor 1 (HSF1) was enhanced by both cytokines. We further demonstrated that trimer formation of HSF1, which is essential for its binding to HSE, was induced by these cytokines. The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines. Collectively, TGF- beta and IL-1beta were found to induce trimer formation of HSF1 which in turn bound to HSE of HSP47, resulting in the enhancement of HSP47 expression. Thus, HSP47 could well be a good candidate for molecular targeting in controlling tissue fibrosis, given that both principal fibrinogenetic cytokines (TGF-beta, IL-1beta) are commonly involved in its induction through HSF1 trimerization.


[Alcohol-induced changes of porphyrin metabolism (author's transl)].
Alcohol is a agenrphyrinogenic agent which may cause disturbances in porphyrin metabolism in healthy persons as well as biochemical and clinical manifestations of acute and chronic hepatic porphyrias. After excessive alcohol infestion in man a secondary hepatic coproporphyrinuria develops transiently, which persists in alcoholic liver disease. The alcohol-liver-porphyrinuria syndrome ranges first among the secondary hepatic disturbances of porphyrin metabolism. In acute hepatic porphyrias (acute intermittent porphyria, porphyria varigata and hereditary coproporphyria) alcohol induces delta-aminolevulinic acid synthase because in these porphyrias the control mechanisms of porphyrinogen and heme synthesis in liver are disturbed ("molecular regulatory diseases"). On the contrary, in chronic hepatic porphyrias, which are already associated with liver damage ("membrane diseases"), alcohol potentiates the disturbance of the decarboxylation of uro- and heptacarboxyporphyrinogen, which is followed by a hepatic accumulation of uro- and heptacarboxyporphyrin and their sometimes extreme urinary excretion. Alcohol may transform a symptomatic coproporphyrinuria into chronic hepatic porphyria. One can deduct from experimental and clinical studies that in liver alcohol inhibits the enzymes coproporphyrinogen oxidase, delta-aminolevulinic acid dehydratase and uroporphyrinogen decarboxylase and induces delta-aminolevulinic acid synthase. Abstinence from alcohol is an important measure in the therapy and prophylaxis of all hepatic porphyrias.


Variation in habitat preference and population structure among three species of the Lake Malawi cichlid genus Protomelas.
Several studies have demonstrated strong population structuring over small distances in the rocky-shore mbuna cichlid fishes from Lake Malawi, suggesting the potential for allopatric speciation. However, many endemic Lake Malawi cichlids are neither mbuna, nor confined to rocky shores. Using microsatellites, we investigated the population structure in three species of the non-mbuna genus Protomelas. The rocky-shore P. taeniolatus showed high levels of population structure even over distances of less than 1 km, while the sandy-shore species P. similis showed no significant structure over distances up to 21 km. Protomelas fenestratus, which is generally found at the interface between rocks and sand, also showed low levels of population structure. Our results suggest that the model of allopatric speciation based on habitat fragmentation within the current lake basin may be equally applicable to rocky-shore non-mbuna as to mbuna, but that an alternative model is required to explain speciation among sandy-shore species as well as the deep-water and pelagic species.


Lumbar discography.
A comprehensive review of the literature dealing with lumbar discography was conducted. The purpose of the review is to update the North American Spine Society position statement published in 1994 that addressed criticisms of lumbar discography, to identify indications for Lumbar discography remains a controversial diagnostic procedure. There are concerns about its safety and clinical value, although many support its use in specific applications. Articles dealing with lumbar discography were reviewed and are summarized in this report. Most of the recent literature supports the use of discography in selected patients. Although not to be taken lightly, many of the serious complications and high complication rates reported before 1970 have decreased since then because of improvement in injection technique, imaging and contrast materials. Most of the current literature supports the use of discography in select situations. Indications for discography include, but are not limited to: (1) Further evaluation of demonstrably abnormal discs to help assess the extent of abnormality or correlation of the abnormality with the clinical symptoms. Such symptoms may include recurrent pain from a previously operated disc and lateral disc herniation. (2) Patients with persistent, severe symptoms in whom other diagnostic tests have failed to reveal clear confirmation of a suspected disc as the source of pain. (3) Assessment of patients who have failed to respond to surgical intervention to determine if there is painful pseudarthrosis or a symptomatic disc in a posteriorly fused segment and to help evaluate possible recurrent disc herniation. (4) Assessment of discs before fusion to determine if the discs within the proposed fusion segment are symptomatic and to determine if discs adjacent to this segment are normal. (5) Assessment of candidates for minimally invasive surgical intervention to confirm a contained disc herniation or to investigate dye distribution pattern before chemonucleolysis or percutaneous procedures. Lumbar discography should be performed by those well experienced with the procedure and in sterile conditions with a double-needle technique and fluoroscopic imaging for proper needle placement. Information assessed and recorded should include the volume of contrast injected, pain response, with particular emphasis on its locations and similarity to clinical symptoms, and the pattern of dye distribution. Frequently, discography is followed by axial computed tomography scanning to obtain more information about the condition of the disc.


Effectiveness of embolization of the internal iliac or uterine arteries in the treatment of massive obstetrical and gynecological hemorrhages.
This study evaluated the effectiveness of embolization of internal iliac artery or uterine artery in the treatment of massive obstetrical and gynecological hemorrhages, including postpartum hemorrhages. A total of 21 patients with massive obstetrical and/or gynecological hemorrhages underwent the modified Seldinger procedure. The catheter was inserted into the femoral artery on one side. Then, internal iliac artery angiography was performed to identify lesions in the areas supplied by internal iliac artery, and the bleeding site. Gelatin sponge particles were injected to embolize the bleeding artery. A second angiography was performed to determine whether embolization was successful. Clinical success was achieved in 20 patients after a single embolization procedure. Hysterectomy was performed in one woman with pernicious placenta previa due to persistent massive bleeding 24 hours after the removal of uterine packing. In the remaining 20 patients, the uterus was preserved. All 21 patients were cured and discharged. Embolization of internal iliac artery or uterine artery is an effective method to treat massive obstetrical and gynecological hemorrhages, including postpartum hemorrhages, and provides a new option to preserve the uterus.


[Surgical treatment of postbulbar ulcers, complicated by penetration into pancreatic head].
The results of surgical treatment of 293 patients with postbulbar duodenal ulcers (PBU) have been analysed. It was established that PBU in the majority of cases are associated with several complications of the ulcer, the main of which being penetration of the ulcer into the pancreatic head. Comparing the results of resections of the stomach and organ-saving procedures in PBU, the author suggests that organ-saving methods in combination with vagotomy have some advantages over resectional methods.


A differential host response to viral infection defines a subset of earlier-onset diverticulitis patients.
Diverticulitis is the chronic inflammation of diverticula. Whether the pathophysiology of earlier-onset patients differs from later-onset patients is unknown. We profiled the colonic transcriptomes of these two patient populations to gain insight into the molecular underpinnings of diverticulitis. We conducted deep RNA sequencing (RNA-seq) on colonic segments surgically resected from earlier-onset (<42 years old, n=13) and later-onset (>65 years old, n=13) diverticulitis patients. We used bioinformatic approaches to cluster the patients based on the relationship of differentially expressed genes and to inform on the molecular pathways that segregated the clusters. Principal component analysis identified three patient clusters; diverticulitis later-onset (DVT-LO), diverticulitis mixed-onset (DVT-MO), and diverticulitis earlier-onset (DVT-EO). The patients comprising DVT-EO, which was the majority of earlier-onset patients, displayed increased expression of anti-viral response genes. This finding was confirmed using an independent weighted co-expression network analysis (WGCNA) of differentially expressed genes. We found that the majority of patients with earlier-onset disease contained elevated expression of host genes involved in the anti-viral response. Thus, susceptibility to a viral pathogen may offer one explanation why some individuals develop diverticulitis at an earlier age.


Physicochemical and pharmacokinetic characterization of a spray-dried cefpodoxime proxetil nanosuspension.
Cefpodoxime proxetil (CP) is a prodrug, the third generation cephem-type broad-spectrum antibiotic administered orally. However, CP was found to be a poorly water-soluble drug with low bioavailability when orally administered. In the present investigation, the spray-dried cefpodoxime proxetil nanosuspension (SDN) was prepared. The physicochemical properties were characterized by rheological evaluation, particle size measurement and its distribution, dynamics of reconstitution, in-vitro dissolution testing, surface morphology, surface area and pore size measurements. The pharmacokinetic study of SDN, in comparison to a marketed cefpodoxime proxetil for oral suspension (MS), was also performed in rabbits after a single oral dose. It was found that SDN exhibited a significant decrease in t(max), a 1.60-fold higher area under curve (AUC) and 2.33-fold higher maximum plasma concentration (C(max)) than MS.


Sildenafil-associated hepatoxicity: a review of the literature.
Sildenafil citrate (Viagra®) is a vasoactive agent available worldwide since 1998 for the treatment of male erectile dysfunction. It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. When sildenafil is orally administered, it is rapidly absorbed with a maximum plasma concentration achieved within 1 h and has a terminal half-life of between 3 to 6 h. The drug is extensively and rapidly metabolized by the liver, primarily by the CYP3A4 enzyme. Although the drug is well tolerated, specific adverse events have been observed, like flushing, headaches, dyspepsia, and visual disturbances. Liver toxicity related to sildenafil consumption has been considered a very rare event. However, in the last decade, some cases of sildenafil-associated hepatotoxicity have been reported. Furthermore, some hepatic intoxications have been reported after the intake of "natural" or "herbal" aphrodisiac supplements sold through Internet, sex shops, social media, and by word-of-mouth found to contain sildenafil and other phosphodiesterase type 5 (PDE-5) inhibitors. Studies investigating a possible link between sildenafil use and liver damage are limited, and the underlying mechanism responsible for hepatotoxicity is still missing. Studies in animals evidence that the hematopoietic function of the liver may have severely been affected as a result of a probable toxic effect of sildenafil. Here, the studies reporting liver toxicity by sildenafil in humans and in animals are reported and discussed.


Controllable construction of isoquinolinedione and isocoumarin scaffolds via RhIII-catalyzed C-H annulation of N-tosylbenzamides with diazo compounds.
A highly efficient protocol for the synthesis of isoquinolinediones by RhIII-catalyzed C-H activation/annulation/decarboxylation of N-tosylbenzamides with diazo compounds is reported. The switchable synthesis of isocoumarins was also achieved successfully via C-H activation/annulation with slight modification of the reaction conditions. Importantly, the synthetic utility of this new reaction was further demonstrated in an atom-economical and operationally convenient total synthesis of a TDP2 inhibitor derivative from commercially available starting materials.


Effect of diet change on insulin action: difference between muscles and adipocytes.
To investigate the difference of insulin action between skeletal muscle and adipose tissue in response to dietary manipulation, we studied the effect of high-sucrose (HS) and high-fat (HF) diet on insulin action by measuring insulin binding and insulin action both in soleus muscles and adipocytes. HS feeding led to a 14 and 28% decrease, and HF feeding led to a 25 and 36% decrease in insulin binding both to soleus muscles and adipocytes, respectively (P less than 0.01). In HF-fed rats, both rates of glucose uptake and intracellular glucose metabolism were impaired by 30-40% in soleus muscles (P less than 0.01), and adipocyte glucose uptake was also decreased by 30% in the submaximally insulin-stimulated state (P less than 0.05). On the other hand, in HS-fed rats with prominent hyperinsulinemia, glucose uptake was 2.3- to 2.7-fold increased in adipocytes (P less than 0.01). However, both rates of glucose uptake and intracellular glucose metabolism were not increased in soleus muscles from HS-fed rats. Steady-state plasma glucose (SSPG) level was unchanged in HS-fed rats during somatostatin, glucose, and insulin infusion, whereas the SSPG level of HF-fed rats was twice as much as that in controls (P less than 0.01). These results indicate that long-term regulation of glucose metabolism by ambient insulin in skeletal muscle may be different from that in adipocytes and that insulin action in muscle, rather than in adipocyte, may reflect insulin action of whole body.


Engineering and functionalization of biomaterials via surface modification.
It is imperative to control the interactions between biomaterials and living tissues to optimize their therapeutic effects and disease diagnostics. Because most biomaterials do not have the perfect surface properties and desirable functions, surface modification plays an important role in tailoring the surface of biomaterials to allow better adaptation to the physiological surroundings and deliver the required clinical performance. This paper reviews recent progress pertaining to the surface treatment of implantable macro-scale biomaterials for orthopedic and dental applications as well as micro- and nano-biomaterials for disease diagnosis and drug/gene delivery. Recent advances in surface modification techniques encompassing adsorption, deposition, ion implantation, covalent binding, and conversion have spurred more expeditious development of new-generation biomaterials.


Motor nerve transfers to restore extrinsic median nerve function: case report.
Active pronation is important for many activities of daily living. Loss of median nerve function including pronation is a rare sequela of humerus fracture. Tendon transfers to restore pronation are reserved for the obstetrical brachial plexus palsy patient. Transfer of expendable motor nerves is a treatment modality that can be used to restore active pronation. Nerve transfers are advantageous in that they do not require prolonged immobilization postoperatively, avoid operating within the zone of injury, reinnervate muscles in their native location prior to degeneration of the motor end plates, and result in minimal donor deficit. We report a case of lost median nerve function after a humerus fracture. Pronation was restored with transfer of the extensor carpi radialis brevis branch of the radial nerve to the pronator teres branch of the median nerve. Anterior interosseous nerve function was restored with transfer of the supinator branch to the anterior interosseous nerve. Clinically evident motor function was seen at 4 months postoperatively and continued to improve for the following 18 months. The patient has 4+/5 pronator teres, 4+/5 flexor pollicis longus, and 4-/5 index finger flexor digitorum profundus function. The transfer of the extensor carpi radialis brevis branch of the radial nerve to the pronator teres and supinator branch of the radial nerve to the anterior interosseous nerve is a novel, previously unreported method to restore extrinsic median nerve function.


Influence of Occlusal Bite Forces on Teeth with Altered Periodontal Support: A Three-Dimensional Finite Element Stress Analysis.
Masticatory forces generate various degrees of stress and strain in the periodontium of teeth which determine the clinical functions and load-bearing capacity of the teeth. There are few in vitro studies that have analyzed stress generated due to combined forces acting on the teeth. Thus, the objective of the present study was to do a comparative analysis of the influence of various stresses on the periodontal ligament and alveolar bone of maxillary central incisor with normal bone height and reduced bone height under simulated standard masticatory using finite element stress analysis. A 3D model of the tooth was obtained with the help of ANSYS software. These models were subjected to various oblique forces, i.e., 100N and 235.9N, applied at 45° angle on the lingual surface of the maxillary central incisor and stress values were recorded in three dimensions. The results from FE analysis were analyzed using 3D Von Mises Criteria. It was observed that in healthy periodontium; it was observed that among the periodontal structure studied, the maximum stress levels were exerted on root followed by cortical bone, cancellous bone, and PDL, irrespective of the force, as compared to the diseased periodontium, in which the bone height was reduced, the maximum stresses were on root followed by cortical bone, PDL, and cancellous bone. The main factor governing the success of any periodontal procedure depends on the height of the remaining bone and the amount of force exerted on to the tooth and the stress generated within the tooth. The finite element method could be of substantial importance in this respect as it can assess the stresses of various occlusal forces on the periodontal ligament, root, cortical bone, and cancellous bone of teeth in a periodontally healthy and diseased state.


The Convergence Between Cultural Psychology and Developmental Science: Acculturation as an Exemplar.
The present article proposes an integration between cultural psychology and developmental science. Such an integration would draw on the cultural-psychology principle of culture-psyche interactions, as well as on the developmental-science principle of person↔context relations. Our proposed integration centers on acculturation, which is inherently both cultural and developmental. Specifically, we propose that acculturation is governed by specific transactions between the individual and the cultural context, and that different types of international migrants (e.g., legal immigrants, undocumented immigrants, refugees, asylum seekers, crisis migrants) encounter quite different culture-psyche interactions and person↔context relations. We outline the ways in which various acculturation-related phenomena, such as acculturation operating at macro-level versus micro-level time scales, can be viewed through cultural and developmental lenses. The article concludes with future directions in research on acculturation as an intersection of cultural and developmental processes.


Non-invasive recording of His bundle potential in man. Simplified method.
In 6 cases with sinus rhythm and one with atrial fibrillation, the bipolar surface electrocardiograms were taken through band pass filters simultaneously with the intracavitary His bundle electrogram, and averaged using a signal processer. By these relatively simplified procedures 'blips' considered to be derived from His bundle potentials between PR segments could be recorded. It was found that 'blips' originating from the His bundle were recorded most distinctly when a cathode was applied to the posterior mid-line and an anode to the sternum, both at the level of the fourth intercostal space. In some instances it was possible to record 'blips' probably derived from the bundle-branches. To identify the onset of ventricular potentials it was necessary to refer to the surface electrocardiograms taken with a usual time constant. The interval from the onset of 'blip' to the onset of ventricular activity (BV) agreed perfectly with the directly recorded His bundle to ventricle conduction time (HV) in 6 out of 7 cases investigated, and in the remaining case this interval was found to be only 1 ms longer than the HV.


The diffusion capsule, a novel device for the addition of a solute at a constant rate to a liquid medium. Its application to metabolic regulation.
The diffusion capsule consists of a cylindrical container that can be completely filled with a solution and sealed with a small semi-permeable membrane at one end. In use, the capsule is immersed in an agitated liquid. Experiments on concentrated solutions in the capsule showed that, contrary to diffusion theory, the rate of diffusion of solute (sugars or amino acids) out of the capsule remained virtually constant until about 65% of the solute had diffused out of the capsule. Thus the device has been used to maintain constant material feed rates for periods exceeding 30h. The capsule is a simple and compact substitute for a pump and is superior to a pump for small feed rates in many applications. The capsule greatly extends the scope of the shake-flask culture technique for micro-organisms in that substrate-limited growth, possibly the aspect of greatest interest, is readily achieved simply by dropping in the flask a capsule containing the substrate. Diffusion feed should facilitate study of the metabolism of toxic substrates: also it is likely to provide an improved means for supplying a pulse of tracer to a culture.


Near missed diagnosis of extensive aortic dissection in a young patient presenting with non-specific symptoms.
Acute aortic dissection is a frequently fatal condition that rarely involves young individuals. It has an estimated worldwide prevalence of 0.5-2.95 per 100,000 persons per year, with a mean incidence at around age 60. Of all the aortic dissections, less than 10% involve patients younger than 40 years of age. We present the case of a forty-yearold male who presented in the emergency department with non-specific complaints of nausea and lightheadedness. The patient being hemodynamically and clinically stable was discharged after supportive treatment. However after 5 hours the patient presented again in the emergency department with a neck pain, hypotension and sweating. CT angiography revealed a massive aortic dissection involving ascending, arch and descending aorta up to the bifurcation of iliac arteries. The patient was immediately taken for surgery for the replacement of ascending aorta and resuspension of aortic valve. The patient tolerated surgery well and was discharged after being clinically and haemodynamically stable.


[Regarding the special feature of "the frontline of nanoparticle research": progress of the Study Group on Fibrous and Particulate Substances (SGFPS)].
Among the symposia organized by various study groups in the Japanese Society of Hygiene (JSH), the Study Group on Fibrous and Particulate Substances (SGFPS) presented a symposium entitled "The frontline of nanoparticle research" chaired by Professor Takemi Otsuki (Kawasaki Medical School, Japan) and Dr. Seishiro Hirano (National Institute for Environmental Studies, Japan) on 26 March, 2012, as a part of the program of the 82nd Annual Meeting of JSH in Kyoto, Japan. Special features consist of three presentations given at the above-mentioned symposium. In this article, we introduce the progress of the Study Group on Fibrous and Particulate Substances (SGFPS) from the initial symposium entitled "Asbestos: Science and Society" held at the 76th Annual Meeting of JSH at Ube, Japan to the last above-mentioned symposium in Kyoto. The health-related issues caused by exposure to fibrous materials such as asbestos and also particulated substances such as nanoparticles will be lasting in the future and researchers including our study group have to make their best efforts to resolve these problems and to reduce health impairments due to exposure to environmental fibrous and particulated substances.


Liquid hot water treatment of rice straw enhances anaerobic degradation and inhibits methane production during in vitro ruminal fermentation.
Liquid hot water (LHW) treatment can be used to disrupt the fiber structure of rice straw. This in vitro ruminal batch culture study investigated the effect of LHW treatment on feed degradation, methane (CH4) production, and microbial populations. Rice straw was treated by LHW, and in vitro ruminal fermentation was performed using an automatic system with 72 h of incubation. Scanning electron microscopy showed that LHW treatment disrupted the physical structure of rice straw. Liquid hot water treatment decreased neutral detergent fiber and hemicellulose contents of the rice straw and increased neutral detergent solubles, water-soluble carbohydrates, and arabinose contents. Liquid hot water treatment increased dry matter degradation and volatile fatty acid concentration and decreased the acetate:propionate ratio, CH4 production, hydrogen accumulation, neutral detergent fiber degradation, and populations of protozoa, fungi, and cellulolytic bacteria. In summary, LHW treatment disrupted the cellulose-hemicellulose-lignin structure matrix of rice straw, leading to increased substrate degradability and decreased CH4 production. Therefore, the LHW treatment is a potential strategy to improve the nutritive value of forage such as rice straw and decrease the CH4 emissions in ruminants.


Efficacy of sodium hypochlorite and peroxyacetic acid to reduce murine norovirus 1, B40-8, Listeria monocytogenes, and Escherichia coli O157:H7 on shredded iceberg lettuce and in residual wash water.
The efficiency of sodium hypochlorite (NaOCl) and peroxyacetic acid (PAA) to reduce murine norovirus 1 (MNV-1), a surrogate for human norovirus, and Bacteroides fragilis HSP40-infecting phage B40-8 on shredded iceberg lettuce was investigated. The levels of removal of viruses MNV-1 and B40-8 were compared with the reductions observed for bacterial pathogens Listeria monocytogenes and Escherichia coli O157:H7. Two inoculation levels, one with a high organic load and the other containing a 10-fold lower number of pathogens and organic matter, showed that the effectiveness of NaOCl was greatly influenced by the presence of organic material, which was not observed for PAA. Moreover, the present study showed that 200 mg/liter NaOCl or 250 mg/liter PAA is needed to obtain an additional reduction of 1 log (compared with tap water) of MNV-1 on shredded iceberg lettuce, whereas only 250 mg/liter PAA achieved this for bacterial pathogens. None of the treatments resulted in a supplementary 1-log PFU/g reduction of B40-8 compared with tap water. B40-8 could therefore be useful as an indicator of decontamination processes of shredded iceberg lettuce based on NaOCl or PAA. Neither MNV-1, B40-8, nor bacterial pathogens could be detected in residual wash water after shredded iceberg lettuce was treated with NaOCl and PAA, whereas considerable numbers of all these microorganisms were found in residual wash water consisting solely of tap water. This study illustrates the usefulness of PAA and NaOCl in preventing cross-contamination during the washing process rather than in causing a reduction of the number of pathogens present on lettuce.


No association between genetic polymorphisms in NAD(P)H oxidase p22phox and paraoxonase 1 and colorectal cancer risk.
Impaired metabolism of ingested toxic or carcinogenic compounds is a postulated mechanism underlying colorectal cancer (CRC). Furthermore, it is suggested that reactive oxygen species (ROS) may play a role in human cancer development. Polymorphic variations in NAD(P)H oxidase p22phox and paraoxonase 1 (PON1) enzyme activities may alter superoxide production or the rate of chemical metabolism, respectively, and this may influence the risk for CRC. Therefore, this study was designed to determine whether the distribution of polymorphisms in NAD(P)H oxidase p22phox and PON1 genes was different in sporadic CRCpatients versus healthy controls. The study participants (365 cases and 354 controls) were all of Caucasian origin. NAD(P)H oxidase p22phox H72Y, and PON1 L55M and Q192R polymorphisms were genotyped by polymerase chain reaction, eventually followed by restriction-fragment-length-polymorphism analyses. Comparison of CRC patients and controls revealed no significant differences in genotype distributions or allele frequencies for polymorphisms in the NAD(P)H oxidase p22phox and PON1 genes. Investigation of potential associations between the variant NAD(P)H oxidase p22phox or PON1 alleles and the clinical characteristics, tumour location or tumour stage, also did not reveal statistically significant associations. Variant genotypes of NAD(P)H oxidase p22phox and PON1 do not contribute to the susceptibility to CRC.


High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays.
Autoantibodies are a hallmark of autoimmune diseases such as lupus and have the potential to be used as biomarkers for diverse diseases, including immunodeficiency, infectious disease, and cancer. More precise detection of antibodies to specific targets is needed to improve diagnosis of such diseases. Here, we report the development of reusable peptide microarrays, based on giant magnetoresistive (GMR) nanosensors optimized for sensitively detecting magnetic nanoparticle labels, for the detection of antibodies with a resolution of a single post-translationally modified amino acid. We have also developed a chemical regeneration scheme to perform multiplex assays with a high level of reproducibility, resulting in greatly reduced experimental costs. In addition, we show that peptides synthesized directly on the nanosensors are approximately two times more sensitive than directly spotted peptides. Reusable peptide nanosensor microarrays enable precise detection of autoantibodies with high resolution and sensitivity and show promise for investigating antibody-mediated immune responses to autoantigens, vaccines, and pathogen-derived antigens as well as other fundamental peptide-protein interactions.


Genome comparison of the epiphytic bacteria Erwinia billingiae and E. tasmaniensis with the pear pathogen E. pyrifoliae.
The genus Erwinia includes plant-associated pathogenic and non-pathogenic Enterobacteria. Important pathogens such as Erwinia amylovora, the causative agent of fire blight and E. pyrifoliae causing bacterial shoot blight of pear in Asia belong to this genus. The species E. tasmaniensis and E. billingiae are epiphytic bacteria and may represent antagonists for biocontrol of fire blight. The presence of genes that are putatively involved in virulence in E. amylovora and E. pyrifoliae is of special interest for these species in consequence. Here we provide the complete genome sequences of the pathogenic E. pyrifoliae strain Ep1/96 with a size of 4.1 Mb and of the non-pathogenic species E. billingiae strain Eb661 with a size of 5.4 Mb, de novo determined by conventional Sanger sequencing and next generation sequencing techniques. Genome comparison reveals large inversions resulting from homologous recombination events. Furthermore, comparison of deduced proteins highlights a relation of E. billingiae strain Eb661 to E. tasmaniensis strain Et1/99 and a distance to E. pyrifoliae for the overall gene content as well as for the presence of encoded proteins representing virulence factors for the pathogenic species. Pathogenicity of E. pyrifoliae is supposed to have evolved by accumulation of potential virulence factors. E. pyrifoliae carries factors for type III secretion and cell invasion. Other genes described as virulence factors for E. amylovora are involved in the production of exopolysaccharides, the utilization of plant metabolites such as sorbitol and sucrose. Some virulence-associated genes of the pathogenic species are present in E. tasmaniensis but mostly absent in E. billingiae. The data of the genome analyses correspond to the pathogenic lifestyle of E. pyrifoliae and underlines the epiphytic localization of E. tasmaniensis and E. billingiae as a saprophyte.


Human papillomavirus vaccination: the policy debate over the prevention of cervical cancer--a commentary.
The human papillomavirus (HPV) family causes a variety of benign, premalignant, and malignant lesions in men and women. HPV types 16 and 18 are responsible for causing 70% of all cases of cervical cancer each year. Recently, a vaccine that can prevent cervical cancer by protecting women from infection with the most common types of HPV has been made available. Following Food and Drug Administration approval and endorsement by the Centers for Disease Control and Prevention, it is the right and the duty of the state legislatures to implement vaccination programs. This vaccine, a vaccine for a sexually transmitted disease, has stirred a fierce debate. Religion and sexuality have dominated the discussion, and political calculations are inherent to the process; nonetheless, epidemiological analyses are also essential to the decision to mandate the HPV vaccine. HPV vaccine program implementation processes are at many stages in many states, and programs vary widely. Some provide information to families, whereas others allot a range of funding for voluntary vaccination. Virginia is, thus far, the only state to have enacted a mandate. This article discusses the various programs in place, the proposed legislation, and the debate surrounding the political process.


It's not ageing, stupid: why population ageing won't bankrupt health systems.
An ageing population is often viewed as a factor that will increase healthcare expenditures (HCE) to unsustainable levels. With nearly half the disease burden in high-income countries arising in older people, there are concerns that caring for a burgeoning older population that is sick and dependent on support will not be possible. The aim of this narrative review is to examine how population ageing is likely to affect future HCE growth. We find that despite the increasing share of older people over the next few decades, the changing age-mix will not be a significant driver of HCE growth. While older people, on average, incur higher per person healthcare spending than younger people, the proportions of the population at the oldest and most costly age groups increase very slowly over time. In the European Union, we estimate the changing age-mix to result in the increase of the average annual growth in per person health spending by no more than 0.6 additional percentage points per year between 2015 and 2050. Therefore, price growth and technological advancements, independent of population ageing, will be the main contributors to future HCE growth.


Exogenous application of jasmonic acid induces volatile emissions in rice and enhances parasitism of Nilaparvata lugens eggs by the parasitoid Anagrus nilaparvatae.
Jasmonate signaling pathway plays an important role in induced plant defense against herbivores and pathogens, including the emission of volatiles that serve as attractants for natural enemies of herbivores. We studied the volatiles emitted from rice plants that were wounded and treated with jasmonic acid (JA) and their effects on the host-searching behavior of the rice brown planthopper, Nilaparvata lugens (Stål), and its mymarid egg parasitoid Anagrus nilaparvatae Pang et Wang. Female adults of N. lugens significantly preferred to settle on JA-treated rice plants immediately after release. The parasitoid A. nilaparvatae showed a similar preference and was more attracted to the volatiles emitted from JA-treated rice plants than to volatiles from control plants. This was also evident from greenhouse and field experiments in which parasitism of N. lugens eggs by A. nilaparvatae on plants that were surrounded by JA-treated plants was more than twofold higher than on control plants. Analyses of volatiles collected from rice plants showed that JA treatment dramatically increased the release of volatiles, which included aliphatic aldehydes and alcohols, monoterpenes, sesquiterpenes, methyl salicylate, n-heptadecane, and several as yet unidentified compounds. These results confirm an involvement of the JA pathway in induced defense in rice plants and demonstrate that the egg parasitoid A. nilaparvatae exploits plant-provided cues to locate hosts. We explain the use of induced plant volatiles by the egg parasitoid by a reliable association between planthopper feeding damage and egg presence.


Comparative analysis of genetic diversity between Qinghai-Tibetan wild and Chinese landrace barley.
Fifty-two SSR markers were used to evaluate the genetic diversity of 33 Qinghai-Tibetan wild barley accessions, 56 landraces collected primarily from other parts of China, and 1 Israeli wild barley accession. At the 52 SSR loci, 206 alleles were detected for the 90 accessions, among which 111 were common alleles. The number of alleles per locus ranged from 1 to 9, with an average of 4.0. Polymorphism information content (PIC) values ranged from 0 to 0.856 among all the markers, with an average of 0.547. The PIC value of Qinghai-Tibetan wild barley varied from 0 to 0.813 with an average of 0.543, while in landraces, the markers showed a range of 0 to 0.790 with an average of 0.490. The SSR markers could clearly differentiate the Qinghai-Tibetan wild barley from the landraces. Twenty-four unique alleles were observed in Qinghai-Tibetan wild barley, and the frequency of unique alleles in Qinghai-Tibetan wild barley was about 2.1 times higher than that in the landraces, on average. Five of the 7 chromosomes had more unique alleles in the Qinghai-Tibetan wild barley, but chromosome 2H had more unique alleles in the landraces. The presence of many unique alleles may reflect the adaptation of this barley germplasm to diverse environments and production systems.


Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039.
Programmed cell death or apoptosis of infected host cells is an important defense mechanism in response to viral infections. This process is regulated by proapoptotic and prosurvival members of the B-cell lymphoma 2 (Bcl-2) protein family. To counter premature death of a virus-infected cell, poxviruses use a range of different molecular strategies including the mimicry of prosurvival Bcl-2 proteins. One such viral prosurvival protein is the fowlpox virus protein FPV039, which is a potent apoptosis inhibitor, but the precise molecular mechanism by which FPV039 inhibits apoptosis is unknown. To understand how fowlpox virus inhibits apoptosis, we examined FPV039 using isothermal titration calorimetry, small-angle X-ray scattering, and X-ray crystallography. Here, we report that the fowlpox virus prosurvival protein FPV039 promiscuously binds to cellular proapoptotic Bcl-2 and engages all major proapoptotic Bcl-2 proteins. Unlike other identified viral Bcl-2 proteins to date, FPV039 engaged with cellular proapoptotic Bcl-2 with affinities comparable with those of Bcl-2's endogenous cellular counterparts. Structural studies revealed that FPV039 adopts the conserved Bcl-2 fold observed in cellular prosurvival Bcl-2 proteins and closely mimics the structure of the prosurvival Bcl-2 family protein Mcl-1. Our findings suggest that FPV039 is a pan-Bcl-2 protein inhibitor that can engage all host BH3-only proteins, as well as Bcl-2-associated X, apoptosis regulator (Bax) and Bcl-2 antagonist/killer (Bak) proteins to inhibit premature apoptosis of an infected host cell. This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition.


Electron microscopic findings in corneal epithelial basement membrane degeneration.
In an attempt to correlate basement membrane changes with clinical symptoms we examined 29 specimens from 28 patients who had undergone corneal epithelial basement membranectomy for corneal epithelial basement membrane degeneration (CEBMD). Twenty-two of the 28 patients were women. Recurrent erosion was the most frequent symptom and occurred in 24 of the 29 eyes. The most common electron microscopic finding was reduplication of the basement membrane with loculated connective tissue. The electron microscopic finding that predicted clinical symptoms was absence of the basement membrane and hemidesmosomes, which occurred in 4 eyes with severe recurrent erosion.


A novel allele of Saccharomyces cerevisiae NDC1 reveals a potential role for the spindle pole body component Ndc1p in nuclear pore assembly.
Both the spindle pole body (SPB) and the nuclear pore complex (NPC) are essential organelles embedded in the nuclear envelope throughout the life cycle of the budding yeast Saccharomyces cerevisiae. However, the mechanism by which these two multisubunit structures are inserted into the nuclear envelope during their biogenesis is not well understood. We have previously shown that Ndc1p is the only known integral membrane protein that localizes to both the SPBs and the NPCs and is required for SPB duplication. For this study, we generated a novel temperature-sensitive (ts) allele of NDC1 to investigate the role of Ndc1p at the NPCs. Yeast cells carrying this allele (ndc1-39) failed to insert the SPB into the nuclear envelope at the restrictive temperature. Importantly, the double mutation of ndc1-39 and NPC assembly mutant nic96-1 resulted in cells with enhanced growth defects. While nuclear protein import and NPC distribution in the nuclear envelope were unaffected, ndc1-39 mutants failed to properly incorporate the nucleoporin Nup49p into NPCs. These results provide evidence that Ndc1p is required for NPC assembly in addition to its role in SPB duplication. We postulate that Ndc1p is crucial for the biogenesis of both the SPBs and the NPCs at the step of insertion into the nuclear envelope.


Ibogan, Aspidosperman, Vincamine, and Bisindole Alkaloids from a Malayan Tabernaemontana corymbosa: Iboga Alkaloids with C-20α Substitution.
Ten new indole alkaloids (1-10) comprising five ibogan, two aspidosperman, one vincamine, and two bisindole alkaloids, in addition to 32 known alkaloids, were isolated from the stem-bark extract of a Malayan Tabernaemontana corymbosa. The structures of these alkaloids were determined based on analysis of the NMR and MS data and, in five instances (1, 3, 5, 6, 8), confirmed by X-ray diffraction analysis. Two of the iboga alkaloids, conodusines B (2) and C (3), and the iboga-containing bisindole tabernamidine B (10) are notable for the presence of an α-substituted acetyl group at C-20 of the iboga carbon skeleton. The iboga alkaloid (+)-conodusine E (5) had MS and NMR data that were identical to those of (-)-ervatamine I, recently isolated from Ervatamia hainanensis. Establishment of the absolute configuration of (+)-conodusine E (5) was based on analysis of the ECD data, correlation with (-)-heyneanine, and X-ray analysis, which showed that (+)-5 belongs to the same enantiomeric series as exemplified by (-)-coronaridine. The configuration at C-20' of the previously reported Tabernaemontana bisindole alkaloid 19'-oxotabernamine (renamed tabernamidine B) required revision based on the present results. Several of the bisindoles showed pronounced in vitro growth inhibitory activity against drug-sensitive and vincristine-resistant KB cells.


Specificity of synapse formation in the cockroach.
The synaptic connection between the filiform hair sensory neurons (FHSNs) and the giant interneurons (GIs) in the terminal abdominal ganglion of the first-instar cockroach Periplaneta americana has been used as a model system for investigating the mechanism of synaptic specificity. Electrophysiological and electron microscopical techniques were used to determine the normal patterns of connectivity between FHSNs and GIs. It was found that, even during synaptogenesis, no incorrect synapses were formed between the sensory axons and the interneuronal dendrites. Studies of a mutant in which there is a supernumerary filiform hair have given an insight into the role of positional information in determining the shape of a sensory neuron, and its connectivity with the GIs. There is electrophysiological evidence for competitive interactions between the supernumerary sensory axon and the original.


Sufficient informed consent to medical treatment of adults: legal and ethical perspectives from Malawi.
This special communication discusses the current legal and ethical requirements for informed consent to medical treatment of adults in Malawi. It analyzes the scope of the laws and code of ethics on professional discipline, including criminal privilege for surgeries and clarifies when insufficient disclosures entitle patients to compensation under civil law. Inconsistencies and uncertainties in the law are made apparent. It evaluates to which degree disclosure standards of other Commonwealth jurisdictions (e.g. the case of Montgomery) would be suitable for the health care setting of a country like Malawi that is characterized by shortages of resources, high illiteracy rates and a communitarian cultural context. Doctor-patient communication is not alien to African culture and part of sufficient informed consent. In order to balance the need for efficiency in health care delivery, accountability for quality care, fairness and effective patient-doctor communication the authors suggest to adopt the reasonable patient test only, if a defence of heavy workload on case-to-case basis is introduced at the same time. This does not dispense the need for organisational diligence on part of the institutional health care provider within its capacity.


Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal Metastases.
Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually switch off the shunt function can be used for intraventricular injections of therapeutics in patients suffering from a communicating hydrocephalus caused by leptomeningeal metastases. These shunt devices avoid the risk of injecting therapeutics through the distal leg of the shunt system into the intraperitoneal space, which may cause toxicity. Furthermore, regular intraventricular injections of chemotherapeutics help to maintain sufficient concentrations in the ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off valve are a useful tool to reliably inject chemotherapeutics into the ventricles. In order to systematically assess feasibility, safety, and efficacy of this procedure, we performed a retrospective analysis of all patients with leptomeningeal metastases who had received a shunt system at our institution. In total, six adult patients had a ventriculoperitoneal shunt equipped with an on-off valve implanted. Out of these six patients, two patients subsequently received intraventricular injections of chemotherapeutics. The configuration of the valve setting and the intraventricular injections were easily feasible in the setting of a neuro-oncology department. The complication of a shunt leakage occurred in one patient following the first intraventricular injection. No extra-central nervous system (CNS) toxicities were observed. In summary, ventriculoperitoneal shunts with on-off valves are useful tools for reliable intraventricular administration of therapeutics.


Transcriptomic biomarkers for individual risk assessment in new-onset heart failure.
Prediction of prognosis remains a major unmet need in new-onset heart failure (HF). Although several clinical tests are in use, none accurately distinguish between patients with poor versus excellent survival. We hypothesized that a transcriptomic signature, generated from a single endomyocardial biopsy, could serve as a novel prognostic biomarker in HF. Endomyocardial biopsy samples and clinical data were collected from all patients presenting with new-onset HF from 1997 to 2006. Among a total of 350 endomyocardial biopsy samples, 180 were identified as idiopathic dilated cardiomyopathy. Patients with phenotypic extremes in survival were selected: good prognosis (event-free survival for at least 5 years; n=25) and poor prognosis (events [death, requirement for left ventricular assist device, or cardiac transplant] within the first 2 years of presentation with HF symptoms; n=18). We used human U133 Plus 2.0 microarrays (Affymetrix) and analyzed the data with significance analysis of microarrays and prediction analysis of microarrays. We identified 46 overexpressed genes in patients with good versus poor prognosis, of which 45 genes were selected by prediction analysis of microarrays for prediction of prognosis in a train set (n=29) with subsequent validation in test sets (n=14 each). The biomarker performed with 74% sensitivity (95% CI 69% to 79%) and 90% specificity (95% CI 87% to 93%) after 50 random partitions. These findings suggest the potential of transcriptomic biomarkers to predict prognosis in patients with new-onset HF from a single endomyocardial biopsy sample. In addition, our findings offer potential novel therapeutic targets for HF and cardiomyopathy.


Hip axis length variation: its correlation with anthropometric measurements in women from three ethnic groups.
We compared hip axis length (HAL) in 157 non-Hispanic white women, 292 African-American women, and 210 Mexican-American women. After adjusting for maximal hip girth, there were no residual differences in HAL by ethnicity. Differences in hip fracture risk seen between these groups cannot be explained by ethnic differences in HAL. Hip axis length (HAL) has been reported to be an independent predictor of hip fracture. Significant ethnic differences in HAL have been noted, but no direct comparison has been made between African-American, Mexican-American, and non-Hispanic white women using the same protocol. We compared 157 non-Hispanic white women from the Rancho Bernardo Study, 292 women from the Health Assessment Study of African-American Women, and 210 women from the Skeletal Health of Mexican-American Women Project. A standardized questionnaire was used to obtain medical history; height, weight, waist girth, and hip girth were measured; and percentage body fat and HAL were obtained using dual energy X-ray absorptiometry. All HAL comparisons were adjusted for maximum hip girth to control for differences in size magnification by fan-beam absorptiometry. Though there were ethnic differences in the unadjusted HAL measurement, after adjusting for hip circumference, there were no residual differences in HAL with regard to ethnicity: 10.7 cm in Mexican-American women vs. 10.8 in non-Hispanic white women and African-American women (p = 0.61). There were no ethnic differences in HAL in women from the three ethnic groups. Differences in fracture risk among these groups cannot be explained by ethnic differences in HAL.


Shear bond strength of a novel porcelain repair system for different computer-aided design/computer-assisted manufacturing ceramic materials.
The purpose of this study was to compare the shear bond strength of a novel repair system, Nova Compo SF with Ceramic Repair, Ivoclar, to computer-aided design/computer-assisted manufacturing (CAD/CAM) restorative materials (IPS e.max CAD and Empress CAD). The specimens of each CAD/CAM restorative material were randomly divided into two subgroups of nine specimens, using one of two repair systems. All specimens were etched with hydrofluoric acid and rinsed under a water spray for 10 s, then air-dried for 10 s. Next, repair systems were applied according to the manufacturer's instructions. All specimens were stored in distilled water at 37°C for 24 h and then additionally aged for 5000 thermal cycles. A shear bond strength test was performed using a universal testing machine. Each fracture type was examined under a stereomicroscope at ×12.5 magnification. A two-way ANOVA test was used to detect significant differences between the CAD/CAM restorative materials and the composite repair systems. Subgroup analyses were performed using Tukey's honest significant difference. No statistically significant differences were observed between the repair systems (P = 0.9). The bond strength values from Empress CAD were statistically higher than those from e.max CAD (P < 0.05). Within limitations, SuperFlow may be an alternative to the ceramic repair materials we routinely used in the clinic. Empress CAD can be preferable to e.max CAD in terms of esthetically suitable clinical indications.


Social bet-hedging in vampire bats.
Helping kin or nonkin can provide direct fitness benefits, but helping kin also benefits indirect fitness. Why then should organisms invest in cooperative partnerships with nonkin, if kin relationships are available and more beneficial? One explanation is that a kin-limited support network is too small and risky. Even if additional weaker partnerships reduce immediate net cooperative returns, individuals extending cooperation to nonkin can maintain a larger social network which reduces the potential costs associated with losing a primary cooperation partner. Just as financial or evolutionary bet-hedging strategies can reduce risk, investing in quantity of social relationships at the expense of relationship quality ('social bet-hedging') can reduce the risks posed by unpredictable social environments. Here, we provide evidence for social bet-hedging in food-sharing vampire bats. When we experimentally removed a key food-sharing partner, females that previously fed a greater number of unrelated females suffered a smaller reduction in food received. Females that invested in more nonkin bonds did not do better under normal conditions, but they coped better with partner loss. Hence, loss of a key partner revealed the importance of weaker nonkin bonds. Social bet-hedging can have important implications for social network structure by influencing how individuals form relationships.


[Development of a special controlled-releasing long effect fertilizer used in controlled ecological life support system].
To develop a special controlled-releasing long effect fertilizer (SCRLEF) for growing higher plant in controlled ecological life support system (CELSS). First, a plan was designed. According to requirements, some original fertilizers were chosen and compounded in proper proportions, and a granule product was obtained and encapsulated in certain materials to form SCRLEF. Then, experiments were done by measuring the content and releasing-rate of the fertilizer, and cultivating plants with the fertilizer. The fertilizer contains nutrients for plant growing, such as: N 18.0%, P2O5 14.3%, K2O 12.6%, Ca 2.6%, S 3.5%, Mg 0.12%, and other micro-nutrients. The granules of the SCRLEF are uniform in size with diameters form 2.5 mm to 4.0 mm. Under 20-25 degrees C, the cumulative amounts of released nutrients from the fertilizer in 10 d, 20 d, 30 d, 40 d, and 50 d, are 7.9%, 21.6%, 40.5%, 50.2%, 60.9% respectively, within 10 d, 20 d, 30 d, 40 d, 50 d. By cultivating lettuce with the fertilizer, we found that the vegetable could grow normally, and there wasn't any deficiency symptom in the plants within 45 d. The design consideration of the SCRLEF is reasonable. The fertilizer provides total nutrients for plant growing, and can be used to supply the required nutrients for the plants grown in the CELSS.


Bedside sonographic-guided versus blind nasoenteric feeding tube placement in critically ill patients.
To compare a blind manual bedside method for placing feeding tubes into the small bowel vs. a sonographic bedside technique in critically ill patients. Prospective study with a random sample. Multidisciplinary intensive care unit in a tertiary care university hospital. Thirty-five adult patients. All patients were hemodynamically stable, mechanically ventilated, and required a nasoenteric tube placement for short-term enteral feeding due to impaired gastric emptying. A well-known, blind, manual, bedside method for postpyloric tube placement was always attempted first in all cases. The technique was considered successful when a postpyloric location of the tip of the tube was achieved as shown by abdominal roentgenogram. However, if after 30 mins we failed to enter the small bowel, a radiologist attempted a sonographic bedside technique for postpyloric tube insertion. Finally, when the feeding tube was in place, before starting enteral nutrition, a nasogastric tube was inserted into the stomach. The blind manual method was successful in nine (25.7%) of the 35 patients and the final location of these feeding tubes was the proximal jejunum. The average time for placement of the feeding tubes with this manual technique was 13.9 +/- 7.4 mins (range 5 to 30). The sonographic technique was successful in 22 (84.6%) of the remaining patients and the final location of the feeding tubes was three (11%) tubes in the second portion of the duodenum, eight (31%) tubes in the third portion of the duodenum, and 11 (42%) tubes in the proximal jejunum. The average time for placement with the sonographic technique was 18.3 +/- 8.2 mins (range 5 to 35). The pyloric outlet was sonographically akinetic or severely hypokinetic in 13 patients, and in four of them, we were unable to achieve postpyloric tube placement. In these four patients, the tubes were subsequently placed by endoscopy. The sonographic bedside technique for placing feeding tubes into the small bowel in critically III patients has a success rate of 84.6% (confidence interval 71% to 98%) after the failure of the blind bedside manual method, proving that the former is significantly more successful. This sonographic technique facilitates the insertion of the tubes in patients who cannot be moved and in those patients with severe impairment of the peristaltic activity of the stomach.


Nonindependent continuous-time random walks.
The usual development of the continuous-time random walk (CTRW) assumes that jumps and time intervals are a two-dimensional set of independent and identically distributed random variables. In this paper, we address the theoretical setting of nonindependent CTRWs where consecutive jumps and/or time intervals are correlated. An exact solution to the problem is obtained for the special but relevant case in which the correlation solely depends on the signs of consecutive jumps. Even in this simple case, some interesting features arise, such as transitions from unimodal to bimodal distributions due to correlation. We also develop the necessary analytical techniques and approximations to handle more general situations that can appear in practice.


Competence in critical care: what it is and how to gain it: a qualitative study from the staff's point of view.
Modern theories about competence at work state that the workers' conceptions about their work and work tasks are decisive for the workers' way of carrying out their work tasks. The present study is from a larger project studying the intensive care staff's way of perceiving intensive care and their work on the unit. With the aim of clarifying a specific concept, 5 complementary interviews were conducted to ask the staff about their understanding of competence. The staff described 5 different ways of understanding competence in intensive care: ability to cooperate, being able to perceive the situation correctly, being aware of abilities and limitations, being able to act, and being able to disregard the technology, when that is the most correct way of caring for a patient. The respondents had 2 different ways of understanding competence development: a question of personal traits and a question of organizational climate. The results confirm that competence is an understanding-based concept and that personal maturity and the right kind of attitude are the most important foundations for a competent nurse in intensive care.


Heartbeat Classification and Arrhythmia Detection Using a Multi-Model Deep-Learning Technique.
Cardiac arrhythmias pose a significant danger to human life; therefore, it is of utmost importance to be able to efficiently diagnose these arrhythmias promptly. There exist many techniques for the detection of arrhythmias; however, the most widely adopted method is the use of an Electrocardiogram (ECG). The manual analysis of ECGs by medical experts is often inefficient. Therefore, the detection and recognition of ECG characteristics via machine-learning techniques have become prevalent. There are two major drawbacks of existing machine-learning approaches: (a) they require extensive training time; and (b) they require manual feature selection. To address these issues, this paper presents a novel deep-learning framework that integrates various networks by stacking similar layers in each network to produce a single robust model. The proposed framework has been tested on two publicly available datasets for the recognition of five micro-classes of arrhythmias. The overall classification sensitivity, specificity, positive predictive value, and accuracy of the proposed approach are 98.37%, 99.59%, 98.41%, and 99.35%, respectively. The results are compared with state-of-the-art approaches. The proposed approach outperformed the existing approaches in terms of sensitivity, specificity, positive predictive value, accuracy and computational cost.


Evaluation of (1R,2R)-1-(5'-methylfur-3'-yl)propane-1,2,3-triol, a sphydrofuran derivative isolated from a Streptomyces species, as an anti-herpesvirus drug.
(1R,2R)-1-(5'-Methylfur-3'-yl)propane-1,2,3-triol (MFPT), a stable anhydro derivative of sphydrofuran, was obtained from the culture broth of STREPTOMYCES: sp. strain FV60 as an inhibitor of herpes simplex virus type 1 (HSV-1). The compound showed antiherpetic activity with a 50% inhibitory concentration of 1.2 IM in an in vitro assay system. Although the binding of virus to host cells was not inhibited, the penetration of virus into cells was moderately blocked by MFPT. Some of the viruses, once they had penetrated cells, failed to form plaques in the presence of MFPT. When added to the late stages of HSV-1 replication, MFPT also inhibited virus production. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis of isotope-labelled HSV-specific proteins revealed that a protein or proteins with reduced molecular weight (about 120 kDa) was clearly detected in cells treated with MFPT. Western blot analysis with antibodies against three HSV-specific glycoproteins (gB, gC and gD) showed a significant difference in gC synthesis between untreated and MFPT-treated cells. Release of progeny viruses was suppressed by MFPT. Syncytium formation by HSV-1 strain HF was inhibited and small plaques with rounded cells were formed in MFPT-treated cell cultures. When wild-type HSV-1 was serially propagated under the selective pressure of MFPT, resistant virus emerged. MFPT-resistant progeny were accompanied by the formation of plaques with rounded cells. These results, taken together, suggest that MFPT might act by limiting the maturation of HSV-specific glycoproteins, particularly of HSV-1 gC.


Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort.
The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifies patients with chronic obstructive pulmonary disease (COPD) into four groups (A to D). We explored the characteristics, stability and relationship to outcomes of these groups within the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points) (n = 2101). Main results showed that: 1) these groups differed in several clinical, functional, imaging and biological characteristics in addition to those used for their own definition; 2) A and D groups were relatively stable over time, whereas groups B and C showed more temporal variability; 3) the risk of exacerbation over 3 years increased progressively from A to D, whereas that of hospitalisation and mortality were lowest in A, highest in D and intermediate and similar in B and C, despite the former having milder airflow limitation. The prevalence of comorbidities and persistent systemic inflammation were highest in group B. The different longitudinal behaviour of group A versus B and C versus D (each pair with similar forced expiratory volume in1 s (FEV1) values supports the 2011 GOLD proposal of assessing COPD patients by more than FEV1 only. However the assumption that symptoms do not equate to risk appears to be naïve, as groups B and C carry equally poor clinical outcomes, though for different reasons.